The Emergence of Tissue Engineering as a ... - Abt Associates

The 

Emergence of 

Tissue 

Engineering 

as a Research 

Field 

Cambridge, MA 

Lexington, MA 

Hadley, MA 

Bethesda, MD 

Washington, DC 

Chicago, IL 

Cairo, Egypt 

Johannesburg, South Africa 

Contract # 

EEC-9815425 

Task Order A-07 

October 14, 2003 

Prepared for 

The National Science 

Foundation 

4201 Wilson Boulevard 

Arlington, VA 22230 

Prepared by 

Jessica Viola 

Bhavya Lal 

Oren Grad 

Abt Associates Inc. 

55 Wheeler Street 

Cambridge, MA 02138

Acknowledgements 

The authors would like to thank all who participated in this study, especially the researchers and leaders 

in academia and industry who agreed to be interviewed and who shared their insights and experiences in 

the field. We also thank the efforts of Dr. Rosemarie Hunziker, formerly at the National Institute for 

Standards and Technology, Dr. Kiki Hellman of the Food and Drug Administration, Dr. Christine Kelley 

of the National Institutes of Health, and Dr. Steven Davison of the National Aeronautics and Space 

Administration, who helped us gather relevant agency data to contribute to our study. 

We would like to give special thanks to the project team in the Directorate for Engineering at the National 

Science Foundation, including Drs. Joanne Culbertson, Bruce Hamilton, Frederick Heineken, and Linda 

Parker, who provided ongoing information and technical support integral to our data collection and 

analysis. Without their involvement, many aspects of our research would have been difficult, if not 

impossible. 

The work was sponsored by the Directorate for Engineering of the National Science Foundation’s 

Directorate of Engineering through Task Order A-07, award 0212341, in NSF contract EEC-9815425. 

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the 

authors and do not necessarily reflect those of the National Science Foundation. 

Abt Associates Inc. Emergence of Tissue Engineering – Final Report 3

About the Authors 

Bhavya Lal. An engineer by training, Ms. Lal has applied her analytic problem-solving skills to social 

science projects for the National Science Foundation, National Institutes of Health, National Institute of 

Standards and Technology (in particular, the Advanced Technology Program), and other Federal 

Agencies for the last nine years. In these projects, she has led and herself designed and implemented case 

studies, literature reviews, surveys, and other qualitative data collection activities. In addition, she has 

analyzed and interpreted data, performed statistical analyses, written reports, and presented results at 

national and international conferences and workshops. Many of her NSF projects have required 

understanding historical underpinnings of NSF funded programs. Bhavya Lal is currently the Director of 

Abt Associates’ Center for Science and Technology Policy Studies. Ms. Lal has a bachelor's and a 

master's degree in nuclear engineering from the Massachusetts Institute of Technology (MIT), as well as a 

master's degree from the Technology and Policy Program (TPP) at MIT. 

Jessica Viola. Ms. Viola has been a science and technology policy analyst at Abt Associates for the past 

5 years. She has been most closely involved with NSF’s Government Performance and Results Act 

(GPRA) related activities and has participated in several process- and performance-based outcome 

measurement studies. She has experience in the design of data collection instruments and the analysis of 

that data for evaluative purposes. She has also participated in several qualitative and case-study based 

program evaluations involving expert interviews and focus groups. Ms. Viola also possess strong 

research and quantitative skills in both theoretical and laboratory science with a specialization in the 

chemical and biological sciences. Her undergraduate work involved independent laboratory research on 

cellular interactions at Harvard Medical School in their Department of Biological Chemistry and 

Molecular Pharmacology. Ms. Viola has an undergraduate degree from Harvard University in 

biochemical sciences. 

Dr. Diana Hicks, Ph.D. Dr. Hicks is a senior policy analyst at CHI Research, Inc. She is a student of 

science and technology policy by training and works in this area. Her career has focused on the scientific 

side, with a particular focus on using quantitative bibliometric tools to address policy and sociological 

questions of broad interest at the intersection of science and technology. At CHI she has used 

bibliometric and cyberbibliometric techniques to assess research institutes and programs for the 

Department of Energy, National Science Foundation and the American Cancer Society. She has recently 

spoken at the American Association for Advancement of Science workshop on Science Policy and at the 

first Gordon Research Conference on Science Policy and at a joint OECD/German government workshop 

on science-industry relations. She received her MSc and PhD from the University of Sussex in science 

and technology policy studies. 

Dr. Oren Grad, Ph.D., MD. Oren Grad is experienced in a full range of data collection and analytic 

techniques including historical reviews and policy analyses, case studies, interviews, focus groups, 

surveys, statistical analyses of quantitative data, and bibliometric analyses, and has focused especially on 

program outcomes which are primarily qualitative in nature and difficult to measure. Dr. Grad has played 

a key role in developing conceptual frameworks for evaluation design and data analysis on several major 

evaluations of NSF Programs, including the Coordinated Experimental Research in Computer Science 

(CER) Program, the Engineering Research Centers (ERC) Program, and the Science and Technology 

Centers (STC) Program, all of which have been concerned with the dynamics of emerging fields and the 

role of NSF in their support. Dr. Grad’s has a great breadth of interdisciplinary technical knowledge 

across the biological and physical sciences and clinical medicine, he has an MD and a Ph.D. in health 

policy and management from the Harvard/MIT Division of Health Science and Technology (HST), as 

well as extensive experience in writing historical analyses which interpret research programs in light of 

political and institutional perspectives. 


Executive Summary 

This report examines the emergence of the research field of tissue engineering (or TE), focusing on 

developments in the United States. Its purpose is to document the evolution of tissue engineering into a 

distinct area recognized as such by scholars, to document the involvement of the Directorate for 

Engineering at NSF, and to evaluate the significance of the Directorate for Engineering’s role in the 

broader context of the field’s evolution. A graphical genealogy of the field is also provided as a separate 

wall chart. 

Tissue engineering represents the confluence of a complex array of pre-existing lines of work from three 

quite different domains: the worlds of clinical medicine, engineering, and science. Its most obvious 

precursors lie in the clinical domain, and are best understood as specific examples of general problemsolving 

strategies employed by physicians. However, tissue engineering is also remarkable for the 

breadth of its “footprint” in fundamental and applied biomedical research, in areas such as cell and 

developmental biology, basic medical and veterinary sciences, transplantation science, biomaterials, 

biophysics and biomechanics, and biomedical engineering. Key developments in the prehistory of tissue 

engineering are reviewed briefly for several clinical areas, including vascular grafts, skin grafts, therapies 

for kidney, pancreatic and liver failure, and bone and cartilage repair. 

The origin of the term “tissue engineering”, and of the concept as we know it today can be traced to 

bioengineering pioneer Y.C. Fung of the University of California at San Diego (UCSD), who led the 

UCSD team that submitted an unsuccessful proposal to NSF in 1985 for an Engineering Research Center 

Program award under the title “Center for the Engineering of Living Tissues”. Fung proposed the term 

again at a 1987 panel meeting that was considering future directions for the NSF’s Directorate for 

Engineering Bioengineering and Research to Aid the Handicapped Program; strong interest in the concept 

within NSF led to a special panel meeting on tissue engineering at NSF in the fall of 1987 and then to the 

Lake Granlibakken, CA workshop of 1988, the first formal scientific meeting of this emerging field. This 

workshop, and succeeding symposia in 1990 and 1992 , helped “seed” the scientific literature with this 

new concept. More widespread awareness of the term tissue engineering appears to have followed with 

the 1993 publication of a review article in Science by Robert Langer and Joseph Vacanti, a paper which 

cites, among others, funding support from NSF. 

The definitions of the concept presented in the published proceedings of the Granlibakken workshop and 

in the Langer/Vacanti review have provided the framework within which most researchers who published 

later have situated their work. Langer and Vacanti defined tissue engineering as “an interdisciplinary 

field that applies the principles of engineering and life sciences toward the development of biological 

substitutes that restore, maintain, or improve tissue function”, and identified three general strategies 

employed in tissue engineering: use of isolated cells or cell substitutes, use of tissue-inducing substances, 

and use of cells placed on or within matrices. However, actual usage of the term reflects an ongoing 

ambiguity in scope and focus, notably with respect to how far applications can stray into purely molecular 

(rather than cellular) approaches and still be considered tissue engineering, and with respect to the role of 

hybrid and external organ replacement devices. Experts interviewed in the study used the recently-coined 

terms “reparative medicine” and “regenerative medicine” largely as synonyms of “tissue engineering.” 

During the years since 1987, the number of researchers who consider themselves to be working in tissue 

engineering has grown substantially, as newly-trained and established researchers have entered the field, 

as established researchers have come to recognize their existing lines of work as tissue engineering, and 

as the scope of tissue engineering has implicitly expanded when adjacent fields report advances that 

address core challenges in tissue engineering. 


Based on discussions with figures prominent in the tissue engineering community, the single most 

influential research paper in the field from a substantive point of view is a 1988 paper, also by the 

Langer/Vacanti team, that described the method of using resorbable polymer matrices as a vehicle for cell 

transplantation. This method rapidly became the most important enabling technology and organizing 

concept in the field and catalyzed a flurry of work on a wide range of tissue and organ systems, 

overshadowing to some extent fundamental efforts to address other knowledge gaps in areas such as 

scaffold materials, cell sourcing, immune response, chemical signaling, vascularization, bioreactors and 

bioprocessing, tissue preservation, and methods for characterization and functional assessment of 

bioengineered tissues. 

Given the range of topics/foci characteristic of the field, we find an assortment of investigators pursuing 

work in TE. Analysis of a sample of 231 individuals representing a majority of non-physician faculty 

active in tissue engineering as well as a selection of prominent clinician-researchers and individuals active 

in the corporate sector pointed to some generalizations about the cadre of tissue engineers (please see 

Appendices 1 and 2 for a discussion on methodology and for the list of tissue engineers). While not 

meant to be an exhaustive listing of tissue engineers, some trends are apparent. They are indeed 

predominantly engineers, with chemical engineering the most frequent field of their training by a wide 

margin, followed by bioengineering and mechanical engineering. Current academic department 

affiliations are also strongly weighted toward engineering, but with bioengineering or biomedical 

engineering the leading disciplinary affiliation by a wide margin, followed by chemical engineering and, 

distantly, by mechanical engineering. Biological science affiliations are few, and are weighted toward 

basic medical science departments. Clinical and clinical science affiliations are strongly weighted toward 

surgery and surgical specialties, notably orthopedics. 

More than 70 universities are represented in the list of institutions from which tissue engineers in this 

sample set received their non-clinical doctorates and more are sure to exist. Of the major institutions with 

groups of researchers in this list pursuing tissue engineering, MIT trained the largest number of 

individuals, followed by the University of Pennsylvania, Rice University, the University of Michigan, the 

University of Minnesota, Columbia University, Stanford University, and the University of California at 

Berkeley. When postdoctoral training relationships are traced as well, the relative weight of MIT in this 

group increases further. Finally, within this cohort the great majority of individuals active in tissue 

engineering are involved on a part-time basis, simultaneously maintaining a number of lines of research 

both in tissue engineering and in other areas. 

A separate analysis of key genealogic relationships within this emerging field is also described. 

Discussions with experts in the field, document review, and analysis of funding abstracts pointed to six 

major centers of activity in the United States, the focus of the study, as having played central roles in 

research or training since the earliest days of the field. These six were selected for further analysis and 

included: Boston (MIT and Harvard), the University of California at San Diego, Rice University, Georgia 

Tech/Emory University, Columbia University, and the University of Pennsylvania. Research suggests 

that, to date, MIT has played the most prominent role, and within MIT the laboratory of Robert Langer. 

There is fair but not complete overlap between the key players identified in the bibliometric review and 

the literature review. 

While academia remains the primary source of fundamental advancement in the field, the corporate sector 

has also played a notable role in the development of this unique field, mostly due to the high level of 

corporate R&D funding injected into the field as compared to the relatively small influx of funds from the 

federal government. Given TE’s traditional perception as a high-risk investment, few agencies in the 

government were willing to support early work in the field forcing those pursuing research objectives to 

locate alternate sources of funding, such as by bootstrapping funds from other grants, patent revenue, or 

by bringing their ideas to the private sector. Corporate R&D has focused on the creation of proprietary 

intellectual content centered on the challenges of bringing products to market, and less on the solution of 


oader challenges in science or engineering. Today, there are over 70 start-up companies in the field 

specializing in structural, metabolic, and cellular TE applications, and other enabling technologies, many 

of these with founding links to major universities with TE programs. 

Patenting in the area is increasing steadily. Patenting in tissue engineering has been trending up since 

1980 and has not yet peaked. In particular, in the last 5 years patenting has increased 226% over the 

previous 5 years, which in turn was an increase of 138% over the prior 5 years. Most of the patents are 

coming from US inventors and assignees. The bulk of the innovation is coming from the US (especially 

from MIT, Advanced Tissue Sciences, and Regen Biologics Inc.). Over seventy percent of the global 

tissue engineering patents are invented in the US, followed by 18% in Europe (led by Germany and UK) 

and 6% in Japan. The highest cited patents are also US-based. MIT has the most highly cited patents. 

Among the most effective patenting companies is Regen Biologics Inc., which has 8 of its 11 patents 

among the highly cited set. 

Today tissue engineering remains an eclectic mix of topical foci and research styles, with work of an ad 

hoc character continuing to play a strong role not only in the corporate sector but in academia as well. An 

important contribution of engineers during the events that led to the emergence of the field in the 1980s 

was to articulate the need for rationalization and systematization of the field. However, to date little 

progress has been made in this respect. Assessed in terms of the number and character of its products that 

have either reached or approached commercialization, tissue engineering has made only incremental 

progress toward its ultimate goal of developing practical and viable therapeutic products. 

The National Science Foundation, in particular the Directorate for Engineering, appears to have played an 

important role in the emergence of tissue engineering as a recognized field of activity, and in shaping the 

character and determining the direction of the field. Prescient leaders in the Directorate, such as Allan 

Zelman and Frederick Heineken, were instrumental in making tissue engineering a priority within their 

Divisions and in gaining the support and involvement of other agencies in TE activities, such as the 

MATES working group and the WTEC study on TE. 

In terms of financial support, the amount of NSF funding for tissue engineering has been growing over 

time, but represents a relatively small fraction of the total resources available to support academic 

research in the field. In terms of absolute dollar amounts, a more important early sponsor of institutional 

development in support of tissue engineering has been the Whitaker Foundation, through its role in 

building the field of biomedical engineering, and especially in providing institutional development funds 

for the creation and expansion of bioengineering departments. The Directorate for Engineering has been 

able to leave a mark on the field, however, through its provision of support to several important 

conferences, workshops, and other networking activities since the field’s inception. They have also 

provided targeted support to Tissue Engineering Centers at MIT, the University of Washington, and the 

Georgia Institute of Technology—groups that currently represent hubs of training and research activity in 

the field. 

The NSF Directorate for Engineering has also provided important early career development support for a 

large number of promising young researchers in tissue engineering, a role that may not be fully 

appreciated by researchers who have not themselves been direct beneficiaries of NSF’s support. NSF also 

appears to have played a role in bringing the biomechanics community into this emerging field in a timely 

way, and more recently, is working to address a key gap in the field by exerting a similar effort to engage 

biologists. The role of Frederick Heineken in particular is key in the Directorate especially in initiating 

cross-agency coordination. This is reflected in NSF’s recent collaborations with other federal agencies, 

through the Multi-Agency Tissue Engineering Science Working Group (MATES) which also sponsored a 

WTEC report to document international Tissue Engineering research, and with the National Institutes of 

Health’s National Institute for Biomedical Imaging and Bioengineering (NIBIB). 


1.0 Introduction 

NSF provides the funding that sustains many research fields as advances in these fields expand 

the boundaries of knowledge. Equally important, the agency provides seed capital to catalyze 

emerging opportunities in research and education. It supports a portfolio of investments that 

reflects the interdependence among fields, promoting disciplinary strength while embracing 

interdisciplinary activities. Its investments promote the emergence of new disciplines, fields and 

technologies. 1 

Engineering and technology are not static bodies of knowledge and practice, but dynamic processes 

characterized by constant change. In supporting fundamental research in engineering, the National 

Science Foundation is necessarily planting the seeds of continued change, for the knowledge gained is 

itself the fuel for this ongoing transformation. 

But new knowledge does not affect solely the particulars of specific technologies and branches of 

engineering. More fundamentally, it may transform our understanding of knowledge itself, of its 

organization and of the means of creating and utilizing it most effectively, pointing to new ways of 

thinking about engineering challenges and, ultimately to the emergence of new areas of research and 

practice that in time come to be recognized as distinct fields of activity. Thus, in fulfilling its mission to 

preserve and enhance the vitality of engineering in service of the nation, NSF must constantly be alert not 

only to opportunities for continuing advances within established lines of inquiry, but also to the 

possibility that entirely new directions for research may offer compelling benefits for engineering and for 

society – indeed, that they may be essential to continued progress. 

In practice, to what extent has NSF served as a catalyst for the timely emergence of productive new 

domains of engineering research? What are the specific mechanisms by which it has done so? 

They are difficult questions to answer, for the innovation system of which engineering research is a part – 

and in which NSF plays an important role – is actually a complex ecosystem characterized by noisy 

signals traversing tangled pathways of influence and feedback among the system components. Gathering 

the data that may enable one to make sense of the system is challenging, both because the system is only 

imperfectly “instrumented” with routine measures of its behavior, and because ad hoc observations are 

costly both to the system and to its observers. Finally, the complexity of the pathways of influence that 

govern the system can make attribution of causality problematic, and the idiosyncratic variety of the 

particulars in different domains of engineering and innovation make generalization perilous. 

This report examines the emergence of the research field of tissue engineering (TE), focusing on 

developments in the United States. Its purpose is to document the evolution of tissue engineering into a 

distinct area recognized as such by scholars, to document NSF’s involvement through its Directorate for 

Engineering, and to evaluate the significance of NSF’s role in the broader context of the field’s evolution. 

As a topic of study, tissue engineering is interesting for several reasons. First is the field’s inherent 

human interest. The ultimate goal of the field is to develop powerful new therapies – “biological 

substitutes” – for structural and functional disorders of human health that have proven difficult or 

impossible to address successfully with the existing tools of medicine. This goal is made all the more 

provocative by its science-fiction vision of man-made, living “replacement parts” for the human body, 

1 

“NSF’s Role”, p. iv, NSF GPRA Strategic Plan FY 2001-2006, September 30, 2000, 

http://www.nsf.gov/pubs/2001/nsf0104/nsf0104.pdf (URL verified December 30, 2002). 


and more compelling by its framing in terms of the lives lost through the ultimately irremediable shortage 

of transplantable organs. 

Of special interest to research managers is the unusual breadth and depth of TE’s interdisciplinarity: the 

knowledge needed to meet the technical challenges posed by TE spans many subdisciplines not only of 

engineering, but also of science and of clinical medicine. To reach their ultimate goal – successful 

therapies – tissue engineers must integrate many very different kinds of knowledge and ways of thinking. 

Finally, from the perspective of an evaluator, the study of an emerging, strongly interdisciplinary field – a 

complex, ill-defined, moving target – represents a challenge of the first order, demanding ingenuity and 

flexibility as much as narrowly-defined methodological rigor, in pursuit of the real prize: qualitative 

insight that is well-founded in empirical observation and credible in its logic. 

Where does one begin such a study? In the contemporaneous historical analysis of an emerging, strongly 

cross-disciplinary field, it can be difficult to specify the object or scope of the inquiry precisely at the 

outset. Almost by definition, the conceptual frameworks that define the substantive extent of the field 

remain fluid, while the field’s institutional infrastructure is typically both limited and not fully apparent to 

a superficial review. The investigation will often take on a “bootstrap” character, in which part of the task 

of the inquiry is to delimit its own scope through analysis of the evidence that is gathered. 

Within a biomedical context, the term “tissue engineering” points naturally to a central concept that is 

simple, powerful and intuitive: the creation of living tissues for therapeutic purposes. It is not obvious, 

however, how far this concept should extend. What counts as a “tissue”? (For example, are encapsulated 

pancreatic cells that function autonomously a tissue? Is blood a tissue? Are unorganized stem cells a 

tissue?) Must the “engineering” be done in vitro, or is induction of tissue growth in situ in a living 

organism also “tissue engineering”? Must the engineered product be implanted, or is improvement of the 

function of extracorporeal devices through the introduction of living cells to be considered “tissue 

engineering”? Must the product be directly therapeutic, or is the use of complex, cell-based products in 

diagnostic applications also a type of “tissue engineering”? To what extent or under what circumstances 

should fundamental research on underlying concepts or enabling technologies be considered tissue 

engineering? 

Thus, the present study began not with a precise definition of tissue engineering, but rather with a set of 

plausible entry points for inquiry: the names of a few key researchers widely considered synonymous 

with the field, a handful of review papers, a list of NSF awards in support of TE research and ancillary 

activities – and the term “tissue engineering” itself, which could be presented as a filter to search engines 

used to scan bibliographic and research funding databases as well as the Internet. Following a chain of 

referrals, citations and links from these initial sources, the investigation accumulated many alternative 

definitions for the term, as well as a growing list of suggestions by expert interviewees of domains of 

research activity that they believed could or should be considered part of the field. 

A central and ongoing task of the study was to analyze the character and overall coherence of the scope of 

activity delineated in this way. Specific findings in this respect are presented in appropriate context in the 

later sections of this report. However, it is worth noting here that no simple boundary-setting rule could 

be identified that maps cleanly to the scope of activity of researchers who think of themselves, or who are 

thought of by others, as being tissue engineers. In the end, our own concept of tissue engineering 

remained a pragmatic and operational one. In particular, because part of the charge for this project was to 

understand the role of NSF in shaping the field, and because funding agencies act through support of 

people and their activities, final judgment of what to include in the story was shaped as much by the 

sociological structure of the field – the people and institutions involved – as by its intellectual or 

substantive structure. 


To understand the emergence of a research field, one must understand also something of what came 

before. Thus, we begin in Chapter 2 by examining the roots of tissue engineering in existing areas of 

research. In Chapter 3, we discuss the emergence and evolution of a shared concept for this new 

enterprise, delineating what participants believed to be its essence, through an examination of the origin 

and varying meanings and usages of the term “tissue engineering”. Chapters 4 and 5 address the reality 

of tissue engineering: Chapter 4 discusses its scope and substantive character and Chapter 5 describes the 

community of tissue engineers, outlining some of its general characteristics and introducing specific 

individuals and institutions that have played central roles in the emergence and growth of the field and the 

most important genealogic relationships among them. Chapter 6 provides an overview to activities and 

major contributions in the emerging years of the corporate sector. Chapter 7 completes the spectrum of 

participants in the field by reviewing other prominent institutions participating in the goal of tissue 

engineering. Finally, we end in Chapter 8 with a discussion of the role of the National Science 

Foundation and its Directorate for Engineering in the emergence of tissue engineering. Supporting 

material is presented in the appendices. Appendix 1 describes our approach to data collection for the 

study; Appendix 2 presents a roster of individuals currently active or who have previously played an 

important role in tissue engineering, with information about their training and (where applicable) current 

employment; Appendix 3 lists the personnel interviewed for this study; and Appendix 4 contains our 

interview protocols. Finally, Appendix 5 includes a separate analysis conducted by CHI research on 

bibliometrics and patents, key findings from which are also included in the main report. A separate wall 

chart graphically illustrates the genealogy of the field. 


2.0 Precursors of Tissue Engineering 

Tissue engineering represents the confluence of a complex array of pre-existing 2 lines of work from three 

quite different domains: the worlds of clinical medicine, engineering, and science. This section offers a 

brief overview of the range and character of these different contributing elements, to provide a context for 

the discussion in later sections of intellectual and institutional developments in TE. 

2.1 Roots in Clinical Medicine 

Perhaps the most obvious precursors to TE lie in the clinical domain. These are best understood as 

specific examples of general problem-solving strategies employed by physicians. 

Consider, for example, the basic dilemma faced by a surgeon. While the removal of organs or body 

structures that are damaged beyond repair by disease or trauma can be life-saving, the patient must cope 

with the functional effects of tissue loss and, in some cases, the psychological impacts of disfigurement. 

And for those vital organs whose complete removal is incompatible with life, the surgeon’s hard-earned 

skill is, by itself, of no avail: the procedure cannot be done unless there is some way of replacing or 

reconstituting essential functions. 

The resourceful application of virtuosic craft through the tools and materials at hand to meet the 

distinctive needs of each patient is central to the ethos of surgery. Thus, surgeons have sought to 

reconstruct anatomic structures using the patient’s own tissues as raw material; they have pressed 

artificial materials into service as prostheses; and, most spectacularly, they have brought patients back 

from the brink of death by transplanting an ever-wider range of vital organs – primarily living organs, but 

in a few cases, with only very limited success to date, prototype artificial organs as well. 

However, with experience, surgeons have come to understand in detail not only the benefits of such 

measures, but their limitations as well. Anatomic reconstruction using the patient’s own tissues can cause 

substantial morbidity at the donor site; the improvised structures are usually functionally inferior to the 

natural organs they replace, and less durable as well. Poor compatibility between artificial materials and 

mechanical systems and the internal environment and physiologic requirements of the human body can 

lead to dysfunctional interactions and new failure modes. Transplantation of living organs brings with it 

profound immunologic complications, and the number of patients who can be treated in this way will 

always be severely constrained by the limited supply of organs suitable for use. 

For a surgeon, then, the development of engineered tissues is a logical next step in the ongoing effort to 

improve the match between the surgeon’s various reparative and reconstructive contrivances and the 

requirements of human anatomy and physiology. 

Physicians in a range of internal medicine specialties as well have found themselves impelled to explore 

clinical solutions that incorporate living cells. Generally, internists seek to identify therapies that can 

repair or reconstitute physiologic functions with sufficient effectiveness to enable patients to avoid 

surgery. Often these therapies are pharmacologic – physicians may use small molecules, or, increasingly, 

complex, genetically-engineered biological macromolecules, to replace critical molecular species that are 

in short supply within the body, to counter the effects of molecules that are in harmful oversupply, or to 

intervene in more subtle ways in regulatory pathways that control critical functions. Other therapies rely 

on physico-chemical effects – sometimes implemented through external artificial devices – to replace 

2 

For present purposes, a substantively relevant line of work is considered to have been “pre-existing” if it was 

underway prior to 1987, the point at which the conscious involvement of NSF in tissue engineering began. 


critical filtering functions that maintain electrolyte balance and remove metabolic wastes from the body. 

Yet the metabolic functions of human organs are so complex and interrelated that simple pharmacologic 

or physico-chemical approaches, while they can be life-saving, nevertheless often constitute highly 

imperfect solutions whose limitations become increasingly apparent in chronic use. In such situations, the 

notion of leveraging the kinds of complex, integrated physiologic functions that are accessible only at the 

level of intact cells or tissues becomes compelling. 

2.2 Contributing Research Domains in Engineering and Science 

The clinical perspective on tissue engineering is strongly applications-oriented. Viewed the “other way 

around”, in terms of enabling knowledge and technologies, TE is remarkable for the breadth of its 

“footprint” in fundamental and applied biomedical research. Table 2.1 identifies a range of fields and 

subfields that have played important roles in TE. 3 Research in all of these areas substantially predates the 

emergence of a generalized concept of tissue engineering, and continues in parallel with TE. 

Table 2.1: Research Fields and Subfields that have Contributed to Tissue Engineering 

Cell and developmental biology 

Cell differentiation, morphogenesis and tissue assembly 

Cell-cell and cell-matrix interactions 

Growth factors 

Cell isolation and selection 

Cell culture 

Angiogenesis 

Stem cells 

Basic medical and veterinary sciences 

anatomy 

cytology 

physiology and pathophysiology 

Transplantation science 

Applied immunology – immunosuppression, immunomodulation and immunoisolation 

Organ preservation 

Biomaterials 

Natural and synthetic, biodegradable and non-biodegradable polymers 

Polymer chemistry 

Ceramics 

Cell interactions with biomaterials 

Controlled release of bioactive molecules 

Microencapsulation 

Microfabrication techniques 

3D fabrication techniques 

Surface Chemistry 

3 

The list of fields presented here is not intended to represent a definitive taxonomy of the knowledge underlying 

tissue engineering; the intent is simply to provide a qualitative appreciation for the breadth, depth and character 

of the “inputs” to the field. 


Biophysics and biomechanics 

Molecular and cell transport 

Micro- and macrocirculatory dynamics 

Cell and tissue mechanics 

Biomedical engineering 

Bioreactors 

Membranes and filtration 

Musculoskeletal joint engineering 

Biomedical sensors 

Biomedical signal processing, feedback and control 

Electrical and mechanical engineering of biohybrid systems 

Engineering design and systems analysis 

Quantitative tissue characterization 

Biosensors and biolectronics 

2.3 Examples 

Landmark conceptual developments prerequisite for a concept of tissue engineering have emerged over a 

period of decades within the problem-solving traditions of clinical medicine. In some clinical domains, 

physicians and non-clinician researchers reached the stage of incorporating living cells into prototype 

tissue-engineered clinical solutions years before the emergence of a generalized concept of tissue 

engineering. The following examples illustrate the depth and breadth of activity prior to 1987: 

Vascular grafts The earliest explorations by surgeons of the possibility of transplanting blood vessels 

took place more than a century ago; the renowned surgical researcher Alexis Carrel was awarded the 1912 

Nobel prize in physiology or medicine for his demonstration of successful techniques for the anastomosis 

of blood vessels and the extension of these techniques from the transplantation of vessels to the 

transplantation of entire solid organs. 4 Over the succeeding decades, experimental use of rigid glass and 

metal tubes as vascular grafts yielded disappointing results. 5 In the early 1950s, Voorhees demonstrated 

the first use of tubes of synthetic fabric as arterial prostheses. With the expanded use of a range of 

synthetic grafts in clinical practice and ongoing research into the characteristics of a range of alternative 

materials, surgeons and biomaterials researchers gained a deeper appreciation of thrombogenesis and 

other problems arising from the interaction between synthetic materials and the blood and perigraft tissues 

with which they came in contact. 6 The concept of a resorbable vascular graft was introduced in the 

1960s, and the first fully-resorbable graft was reported in 1979. Improvement in the healing process of 

Dacron vascular grafts via pre-seeding with endothelial cells was reported in 1978. Finally, the first 

attempt to create entirely biologic vascular structures in vitro, using collagen and cultured vascular cells, 

was reported in 1982. 7 

4 

5 

6 

7 

Alexis Carrel – Biography and Nobel Lecture, http://www.nobel.se/medicine/laureates/1912/carrel-bio.html and 

http://www.nobel.se/medicine/laureates/1912/carrel-lecture.html (URL verified July 13, 2002). 

Voorhees AB, “How it all Began”, pp. 3-4 in Sawyer PN, Kaplitt MJ, Vascular Grafts (New York: Appleton- 

Century-Crofts, 1978). 

Callow AD, “Historical Overview of Experimental and Clinical Development of Vascular Grafts”, pp. 11-25 in 

Stanley JC, Burkel WE, Lindenauer SM et al., eds., Biologic and Synthetic Vascular Prostheses (New York: 

Grune & Stratton, 1982). 

Xue L and Greisler HP, “Blood Vessels”, pp. 427-446 in Lanza RP et al., eds., Principles of Tissue 

Engineering; Burkel WE, Ford JW, Vinter DW et al., “Endothelial Seeding of Enzymatically Derived and 


Skin grafts For centuries, physicians have attempted to cover severe wounds with grafts from a variety of 

sources, including cadavers and living humans. By the early decades of the 20 th century, researchers were 

investigating the immunologic basis for rejection of skin allografts, though there was no apparent 

progress toward any practical solution. 8 The marked increase during World War II in the number of burn 

victims for whom a skin allograft was not feasible provided a renewed impetus for research on skin 

replacement. During this era, the distinguished immunologist Peter Medawar made important 

contributions both to further progress in the understanding of the immunology of graft rejection, 9 and to 

the in vitro culture of epithelial cells drawn from a patient. By 1953, Billingham and Reynolds 

demonstrated in animal models that the products of a brief culture of epidermal cells could be applied to a 

graft bed to reconstitute an epidermis. 10 

Despite these early successes, more efficient means of cultivation were needed to provide enough cells to 

sustain transplantation. Overgrowth of certain cell types, such as fibroblasts, suggested that existing 

culture techniques would not be effective in producing large quantities of cells. Research in the 1960s 

and 70s identified growth factors that could be added to culture medium to induce greater proliferation of 

epidermal cells. 11 Starting in the mid-1970s, three research groups working independently at MIT 

reported a series of milestones in the development of skin replacements. In 1975, Green and Rheinwald 

described the co-culture method, a technique for serial cultivation of human epidermal keratinocytes from 

small biopsy samples. 12 Using the technique, one sample of cells was sufficient to generate enough thick, 

multilayered skin to resurface the entire body of a burn victim. Some differentiation among epidermal 

cells to mimic that of the epidermis was also visible. In 1979, Green and colleagues, building on the 

work of Bellingham and Reynolds, demonstrated that cultured cells can be grown in sheets in a petri dish 

and transferred intact, rather than as disaggregated cells, to a graft wound bed. 13 

That same year, Bell and colleagues described the use of fibroblasts to condense a hydrated collagen 

lattice to a tissue-like structure potentially suitable for wound healing. 14 These findings led to the first 

functional living skin equivalent (LSE) in 1981, consisting of fibroblasts suspended in a collagenglycosaminoglycan 

matrix. 15 Yannas identified the components of the underlying matrix structure of skin 

Cultured Cells on Prosthetic Grafts”, 1982. pp. 631-651 in Stanley JC et al., eds., Biologic and Synthetic 

Vascular Prostheses, 1992. 

8 

9 

10 

11 

12 

13 

14 

15 

Duquesnoy RJ, “History of Transplant Immunobiology (Part 1 of 2)”, 

http://tpis.upmc.edu/tpis/immuno/wwwHISTpart1.htm (URL verified December 31, 2002). 

Duquesnoy RJ, “Early History of Transplantation Immunology (Part 2 of 2)”, 

http://tpis.upmc.edu/tpis/immuno/wwwHistpart2.html (URL verified December 31, 2002). 

Billingham RE, Reynolds J, “Transplantation Studies on Sheets of Pure Epidermal Epithelium and on 

Epidermal Cell Suspensions”, Br J Plast Surg 1953;6:25-36. 

Cohen S, “Epidermal Growth Factor”, Nobel lecture, 8 December 1986, 

http://www.nobel.se/medicine/laureates/1986/cohen-lecture.pdf (URL verified December 31, 2002). 

Rheinwald JG, Green H, “Serial Cultivation of Human Epidermal Keratinocytes: the Formation of Keratinizing 

Colonies from Single Cells”, Cell 1975 Nov;6(3):331-43. 

Green H, Kehinde O, Thomas J, “Growth of Cultured Human Epidermal Cells into Multiple Epithelia Suitable 

for Grafting”, Proc. Natl. Acad. Sci. U.S.A. 1979 Nov;76(11):5665-68. 

Bell E, Ivarsson B, Merrill E, “Production of a Tissue-Like Structure by Contraction of Collagen Lattices by 

Human Fibroblasts of Different Proliferative Potential In Vitro”, Proc. Natl. Acad. Sci. U.S.A. 1979 

Mar;76(3):1274. 

Bell E, Ehrlich HP, Buttle DJ, Nakatsuji T, “Living Tissue Formed In Vitro and Accepted as Skin Equivalent 

Tissue of Full Thickness”, Science 1981 Mar 6;211:1052-54. 


and used this knowledge to develop a dermal regeneration template which, when implanted and seeded 

with autologous basal cells, stimulated re-growth of functional skin. 16 All of these lines of research, 

continuing into the 1990s, proceeded to the development of commercial products. 

Kidney A number of investigators experimented sporadically with kidney transplantation during the early 

part of the 20 th century, but planned renal transplantation efforts began only in the late 1940s. During the 

war years in the Netherlands, Kolff developed the first dialysis machine; its design was refined at the 

Peter Bent Brigham Hospital in Boston and used in patients for the first time in 1948. In turn, the 

availability of effective short-term dialysis facilitated progress on transplantation, culminating in the 

successful transplant of a donated kidney from a twin by Murray and colleagues at Brigham and 

Women’a Hospital in 1954. 17 Subsequent advances in immunosuppression for transplantation and further 

development of Kolff’s dialysis machine made both techniques practical for widespread, routine use, 

transforming the management of end-stage renal disease. However, the limited supply of organs suitable 

for transplantation, combined with recognition of the therapeutic limitations of the dialysis machine, 

motivated the formulation of the concept of the bioartificial kidney, which would mimic more faithfully 

the physiologic functions of the kidney and thus avoid the debilitating side effects of chronic dialysis. 

During the late 1960s and early 1970s, Wolf experimented with combinations of kidney cells with hollow 

synthetic fibers as conduits for nutrients and waste. Subsequent work on growing liver cells on the 

outside of hollow fibers by Wolf and independently by Knazek led to the demonstration of hollow-fiber 

bioreactors. 18 In the mid-1980s Galletti and colleagues furthered development of the bioartificial kidney 

concept through their research on hollow-fiber bioreactors employing renal epithelial cells. 19 

Pancreas / islet cells Although the introduction of insulin more than 70 years ago had a miraculous 

impact on the lives of diabetes patients, with prolonged survival it became apparent that the highly 

imperfect glycemic control typical of routine insulin therapy was associated with severe long-term 

complications for a variety of organ systems. The first insulin pumps appeared in the 1960s, but the 

sensor and control technology required for a complete “closed loop” system to mimic the adaptive 

character of physiologic glucose control was not available. The first pancreas transplant, in conjunction 

with a simultaneous kidney transplant, was performed by Lillehei in 1966. 20 Lacy reported a method for 

isolation of intact islets in 1967, and isolated islet cells were first transplanted in 1970, though without a 

solution to the problem of immune rejection. The use of microencapsulated islets as artificial beta cells 

was proposed by Chang as early as the mid-1960s. 21 During the 1970s, Chick and colleagues, building on 

the work of Knazek, developed a “hybrid artificial pancreas” consisting of beta cells cultured on synthetic 

semipermeable hollow fibers, and demonstrated the ability of this device to restore glucose homeostasis 

16 

17 

18 

19 

20 

21 

Yannas IV, Burke JF, Orgill DP, Skrabut EM, “Wound Tissue Can Utilize a Polymeric Template to Synthesize 

a Functional Extension of Skin”, Science 1982 Jan 8;215:174-76. 

Alexis Carrel – Nobel Lecture, see note 2; Joseph E. Murray – Nobel Lecture, 

http://www.nobel.se/medicine/laureates/1990/murray-lecture.html, accessed July 20, 2002. 

Lewis R, “A Compelling Need”, The Scientist 1995 Jul 24;9(15), http://www.thescientist.com/yr1995/july/tissue_950724.html, 

accessed July 20, 2002. 

Aebischer P, Ip TK, Panol G, Galletti PM, “The Bioartificial Kidney: Progress Towards an Ultrafiltration 

Device with Renal Epithelial Cells Processing”, Life Support Syst 1987 Apr-Jun;5(2):159-68. 

United Network for Organ Sharing, “Milestones”, http://www.unos.org/Newsroom/critdata_milestones.htm, 

accessed July 21, 2002. 

Chang TMS, Artificial Cells (Springfield, IL: Charles C. Thomas, 1972). 


in rats when connected to the circulatory system via shunt. 22 Sun and colleagues reported similar work in 

the 1970s, followed by studies of implanted microencapsulated islets beginning in 1980. 23 Investigation 

of different ways of “packaging” islet cells to provide effective and durable glycemic control continued 

through the 1980s and beyond. 

Liver The first successful liver transplant was carried out by Starzl in 1967, 24 but in the absence of an 

adequate supply of transplantable organs, researchers and clinicians have continued to pursue alternative 

approaches to the replacement of hepatic function. Over more than four decades, clinicians have 

attempted in a variety of ways to provide extracorporeal support to patients suffering from liver failure. 

Nonbiological approaches that have been explored include hemodialysis, hemoperfusion over charcoal or 

resins or immobilized enzymes, plasmapheresis, and plasma exchange. However, these approaches have 

met with limited success, presumably because the complex synthetic and metabolic functions of the liver 

are inadequately replaced by these systems. 25 Work on cell-based therapies and bioartificial systems has 

reflected the same themes observed in the case of pancreatic islet cells. Wolf and Munkelt reported in 

1975 on a bioreactor containing a rat hepatoma cell line cultured on the surface of semipermeable hollow 

fibers within a plastic housing. 26 Sutherland and colleagues reported in 1977 on the use of transplanted 

hepatocytes in the treatment of drug-induced liver failure in rats, 27 and Sun and colleagues in the mid- 

1980s explored approaches to microencapsulation of hepatocytes. 28 

Bone and cartilage A variety of materials generally perceived as chemically inert, such as various metals 

and alloys, have been used for many years to replace damaged bone or to provide support for healing 

bones. With experience, however, it has become clear that non-biologic materials do not remain 

biologically inert in the environment of the human body, but rather elicit reactions whose intensity is 

related to a variety of factors such as implantation site, the type of trauma at the time of surgery, and the 

precise material in use. Beginning in the 1970’s, bioactive materials, such as porous glass and 

hydroxyapatite ceramic, were examined as alternatives, as they were shown to elicit the formation of 

normal tissue on their surfaces. 29 

Aside from novel biomaterial development, the growth and regenerative capacities inherent in bone have 

also been intense topics of scientific and clinical study for decades. In a 1945 publication in Nature, 

Lacroix hypothesized that osteogenin, a substance in bone, was responsible for its growth. Twenty years 

later in 1965, Marshall Urist proved that there was, indeed, some substance or combination of substances 

22 

23 

24 

25 

26 

27 

28 

29 

Chick WL, Like AA, Lauris V et al., “A Hybrid Artificial Pancreas”, Trans Am Soc Artif Intern Organs 

1975;21:8-15; Whittemor AD, Chick WL, Galletti PM et al.,”Effects of the Hybrid Artificial Pancreas in 

Diabetic Rats”, Trans Am Soc Artif Intern Organs 1977;23:336-41. 

Lim AF, Sun AM, “Microencapsulated Islets as Bioartificial Endocrine Pancreas”, Science 1980 Nov 

21;210:908-10. 

UNOS, “Milestones”, see note 19. 

Allen JA, Hassanein T, Bhatia SN, “Advances in Bioartificial Liver Devices”, Hepatology 2001;34(3):447-55. 

Wolf CF, Munkelt BE; “Bilirubin Conjugation by an Artificial Liver Composed of Cultured Cells and 

Synthetic Capillaries”, Trans Am Soc Artif Intern Organs 1975; 21:16-27. 

Sutherland DE, Numata M, Matas AJ et al., “Hepatocellular Transplantation in Acute Liver Failure”, Surgery 

1977 Jul;82(1):124-32. 

Sun AM, Cai Z, Shi Z et al., “Microencapsulated Hepatocytes: an In Vitro and In Vivo Study”, Biomater Artif 

Cells Artif Organs 1987;15(2):483-96. 

Ducheyne P, El-Ghannam A, Shapiro I, “Effect of Bioactive Glass Templates on Osteoblast Proliferation and In 

Vitro Synthesis of Bone-Like Tissue”, J Cell Biochem 1994; 56: 162-167. 


present in demineralized bone, which when transplanted, could induce growth of new bone. 30 Urist’s 

landmark finding encouraged many to investigate the precise factors which trigger bone induction. 

During the 1970s and 80s, research demonstrated that the process is mediated by a category of growth 

factors, termed bone morphogenetic proteins or BMPs, which act in a multistep cascade highly 

reminiscent of embryonic bone morphogenesis. 31 Reddi and colleagues developed techniques to isolate 

these proteins from the extracellular matrix of bone. 32 The findings are promising, too, for induction of 

cartilage as BMPs initially induce a cascade of chondrogenesis and might just as easily be called cartilage 

morphogenetic proteins. 33 Work on isolation, purification, and proliferation of BMPs continued 

throughout the 1980s. 

30 

31 

32 

33 

Urist, MR, “Bone Formation by Autoinduction”, Science 1965; 150: 893-899. 

Reddi, AH, “Morphogenetic Messages are in the Extracellular Matrix: Biotechnology from Bench to Bedside”, 

Biochem Soc Trans 2000; 28: 345-349. 

Sampath TK, Reddi AH, “Dissociative Extraction and Reconstitution of Extracellular Matrix Components 

Involved in Local Bone Differentiation”, Proc Natl Acad Sci USA 1981 Dec; 78(12): 7599-603. 

Reddi, AH, “Morphogenetic Messages”, see note 30. 


3.0 Emergence and Evolution of a Shared Concept 

It is unclear who first used the term “tissue engineering” to mean what it does today. Not surprisingly for 

a coinage that seems so natural in hindsight, a number of the individuals interviewed for this study 

suggested that the term may have been invented several times independently before it came into 

sufficiently broad usage that a wide range of researchers can be expected to have encountered it in 

publications or in discussion. Indeed, the first appearance of the term in print of which the study team is 

aware – also the earliest revealed through a PubMed search – was an incidental, almost offhand usage in a 

1984 publication that described the organization of an endothelium-like membrane on the surface of a 

long-implanted, synthetic ophthalmic prosthesis. 34 

However, the origin of “tissue engineering” as it is recognized today can be clearly traced to a specific 

individual. In 1985, Y.C. Fung, a pioneer of the field of biomechanics and of bioengineering more 

broadly, submitted a proposal to NSF for an Engineering Research Center to be entitled “Center for the 

Engineering of Living Tissues”. 35 Fung’s concept drew on the traditional definition of “tissue” as a 

fundamental level of analysis of living organisms, between cells and organs: 

The study of organs and organ systems has historically been the domain of the physiologist and 

physician. There is, therefore, a relative wealth of practical information about organs, codified in 

terms of medical practice. On the other hand, tissues are composed of cells, having specialized 

internal organelles and, ultimately, chemical constituents. The composition of the cell and its 

constituents has been dealt with by cell biologist and biochemist [sic]. There are relatively few 

focused efforts at bridging the gap between these extremes. A clear understanding of phenomena 

at the tissue level is prerequisite to the engineering of tissues [emphasis in original]… 

Fung’s proposal was not accepted. Nevertheless, the concept of an engineering approach to the level of 

biological organization between cells and organs surfaced again at NSF in the spring of 1987, at a panel 

meeting convened to review proposals to the Bioengineering and Research to Aid the Handicapped 

(BRAH) Program within the Engineering Directorate. Fung was present at this meeting, and is recalled as 

having volunteered the term “tissue engineering” in the course of a discussion that was seeking to 

crystallize the concept. 36 

34 

Wolter JR, Meyer RF, “Sessile Macrophages Forming Clear Endothelium-like Membrane on Inside of 

Successful Keratoprosthesis”, Trans Am Ophthalmol Soc 1984;82:187-202. “After observing the facts of the 

present case, one is drawn to the conclusion that the reactive cellular components contribute toward the eye’s 

purpose by attempting to prevent light scattering even under totally unusual conditions…. Nature impresses us 

with a great variety of reactive possibilities in the adaptation of its tissues to new conditions and substances. 

Sound progress in medicine is easiest when we work along with the physiological currents of beneficial reaction 

and adaptation. To understand the direction and limits of nature’s reactions is always the first step toward 

progress in tissue engineering [emphasis added]. It is in this sense that the observations in the unusual present 

case will contribute to progress in the creation of artificial windows in the shell of the eye with the aim to 

maintain and possibly also to correct vision.” Interestingly, the chapter on the cornea in Principles of Tissue 

Engineering does not cite this paper, even though, despite 16 years of scientific progress, it retains its 

predecessor’s focus on the body’s response to corneal replacements made of purely synthetic materials, placing 

it similarly outside of the TE mainstream. 

35 

36 

“A Proposal to the National Science Foundation for An Engineering Research Center at UCSD, CENTER FOR 

THE ENGINEERING OF LIVING TISSUES”, UCSD #865023, courtesy of Y.C. Fung, August 23, 2001. 

Allen Zelman, interview, July 17, 2001; Y.C. Fung, interview, August 23, 2001. 


Further discussions between the program directors for the BRAH Program, which looked at whole 

organs, and the Directoratefor Engineering’s Biotechnology (BIOTECH) Program, which focused on the 

cellular level, led to the convening of a special Panel Meeting on Tissue Engineering at NSF on October 

28, 1987. For this meeting, Allen Zelman, a Program Director for BRAH, prepared a draft definition of 

tissue engineering: 

The term “tissue engineering” indicates a new inter-disciplinary initiative which has the goal of 

growing tissues or organs directly from a single cell taken from an individual. 

Interestingly, in his “statement of the problem”, Zelman pointed to the avoidance of immune rejection 

through the growth of tissues or organs from a patient’s own cells as the key benefit of tissue engineering. 

Zelman envisioned the development of a large and vigorous new industry producing internal organs, but 

tempered this vision with the caveat that production of complex internal organs, such as the kidney, 

“would be considered far too ambitious as a starting point” and that “tissues, being more simple than 

organs, should be investigated initially”. 37 

During the discussions at the October 28 meeting, Maurice Averner, Program manager for NASA’s 

Controlled Ecological Life Support Systems Program, proposed another definition of tissue engineering: 

the production of large amounts of functional tissues for research and applications through the elucidation 

of basic mechanisms of tissue development combined with fundamental engineering production 

processes. This definition reflected the tenor of the discussion more generally, in which problems of 

production and distribution of tissue-engineered materials featured prominently. In the end, however, 

after different opinions were expressed concerning how precise and explicit a field definition needed to 

be, no formal definition was adopted; further clarification on this point was left as a task for an envisioned 

workshop. 38 

Subsequent to this meeting, a Forum on Issues, Expectations, and Prospects for Emerging Technology 

Initiation was held in Washington, DC, under the sponsorship of the Division of Emerging Engineering 

Technologies within NSF. This forum recommended that tissue engineering be designated as an 

emerging engineering technology, and that a workshop be held to identify appropriate areas for research 

in this technology. This proposed workshop, organized by Zelman, Frederick Heineken, and Duane 

Bruley –all of NSF—was held at Granlibakken Resort, Lake Tahoe, California, in February 1988. 39 

With the exception of a re-publication of the 1984 ophthalmology paper in another ophthalmology journal 

in 1985, the next known appearance of the term “tissue engineering” in print was in the proceedings of 

the Granlibakken workshop. 40 A preface to these proceedings defined the term more broadly than did any 

of the provisional definitions floated up to that point, to encompass a wider range of potential therapeutic 

interventions that could be enabled by research carried out under this new perspective: 

“Tissue Engineering” is the application of principles and methods of engineering and life sciences 

toward fundamental understanding of structure-function relationships in normal and pathological 

mammalian tissues and the development of biological substitutes to restore, maintain, or improve 

tissue function. 

37 

38 

39 

40 

Zelman A, “Tissue Engineering: A Fundamentally New Concept in Health Care”, internal discussion memo, 

first draft, Sept. 22, 1987, courtesy of NSF. 

Skalak R, notes from Panel Meeting on Tissue Engineering , Oct. 28, 1987, courtesy of NSF. 

Heineken FG, Skalak R, “Tissue Engineering: A Brief Overview”, J Biomech Eng 1991 May;113(2):111-2. 

Skalak R, Fox CF, eds., Tissue Engineering (New York: Alan R. Liss, Inc., 1988). 


The basic point of the above definition is that tissue engineering involves the use of living cells 

plus their extracellular products in development of biological substitutes for replacements as 

opposed to the use of inert implants. The definition is intended to encompass procedures in 

which the replacements may consist of cells in suspension, cells implanted on a scaffold such as 

collagen and cases in which the replacement consists entirely of cells and their extracellular 

products. 

The term did not appear in the title or abstract of an indexed biomedical journal again until 1989, 41 after 

the proceedings of the February 1988 Granlibakken workshop had been published in book form, but again 

representing the publication of meeting proceedings. Abstracts of the April 1990 UCLA symposium 

(later to become the Keystone symposia) in tissue engineering were published in 1990 42 and selected 

papers in 1991. 43 

At the 1992 UCLA symposium on tissue engineering, Eugene Bell defined tissue engineering in terms of 

a more specific list of goals: 

1) providing cellular prostheses or replacement parts for the human body; 

2) providing formed acellular replacement parts capable of inducing regeneration; 

3) providing tissue or organ-like model systems populated with cells for basic research and for 

many applied uses such as the study of disease states using aberrant cells; 

4) providing vehicles for delivering engineered cells to the organism; and 

5) surfacing non-biological devices. 44 

These early meeting proceedings can be said to have “seeded” the term tissue engineering into the 

biomedical literature. However, on the whole, interviews conducted for the present study made clear that 

broad awareness of the term “tissue engineering”, and its usage as a unifying concept for a wide range of 

concurrent lines of research, can be dated to the publication of a review paper by Robert Langer and 

Joseph P. Vacanti in the May 14, 1993 issue of Science. 45 This paper acknowledges NSF support, as well 

as support from other sources. 

Langer and Vacanti referenced the definition from the Granlibakken proceedings, presenting it in 

condensed form: 

Tissue engineering is an interdisciplinary field that applies the principles of engineering and the 

life sciences toward the development of biological substitutes that restore, maintain, or improve 

tissue function. 

Thus, perhaps the single most cited and influential paper in the field, cites the Granlibakken workshop 

and builds upon its pioneering definition of the tissue engineering. With this definition as a foundation, 

they added substance to the notion of common themes underlying a seeming diversity of research by 

identifying three general strategies for the creation of new tissue – the use of: 

41 

42 

43 

44 

45 

Matsuda T, Akutsu T, Kira K, Matsumoto H, ”Development of Hybrid Compliant Graft: Rapid Preparative 

Method for Reconstruction of a Vascular Wall”, ASAIO Trans 1989 Jul-Sep;35(3):553-5. 

“19 th Annual UCLA Symposium: Tissue Engineering. Abstracts”, J Cell Biochem Suppl 1990;14E:227-56. 

“Tissue Engineering. Selected Papers from the UCLA Symposium of Tissue Engineering. Keystone, Colorado, 

April 6-12, 1990”, J Biomech Eng 1991 May;113(2):111-207. 

Bell E, “Tissue Engineering, an Overview”, pp. 3-15 in Bell E, ed., Tissue Engineering: Current Perspectives 

(Boston, MA: Birkhäuser, 1993). 

Langer R, Vacanti JP, “Tissue Engineering”, Science 1993 May 14;260:920-6. 


• isolated cells or cell substitutes; 

• tissue-inducing substances; or 

• cells placed on or within matrices. 

In the body of the paper, they briefly introduced ongoing efforts across a wide range of organ systems, 

classified by their embryologic origin – as ectoderm, endoderm, or mesoderm. Finally, they concluded by 

identifying further common themes, this time in the form of enabling knowledge or technologies of broad 

significance that should be targets for future research, in the areas of cell biology, cell sourcing and 

preservation, and materials. 

The number of PubMed title/abstract “hits” on the term “tissue engineering” first exceeded 10 in 1994, 

the year after the Langer/Vacanti review appeared (see Table 1) . The number of appearances doubled in 

1996, and again in 1998 and 1999, reaching 153 in 1999 and continuing to grow to 214 in 2000. 46 This 

figure surely understates the extent to which researchers associated the concept “tissue engineering” with 

their work; once the concept is established, there is no reason for a researcher to call it out explicitly in 

titles or abstracts unless there is a specific point to be made by doing so. 

46 

Bibliometric analysis by CHI Research, Inc. 


Table 1. Number of papers using the term “tissue engineering” in their titles or abstracts since 1984 47 

Category 1st Papers % 1984 1985 … 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 

year Share 

All papers 1984 685 100% 1 1 1 1 8 9 7 11 14 30 30 79 153 214 126 

Research 1984 466 68% 1 1 1 1 3 3 4 2 8 18 18 55 103 137 111 

Review 1991 199 29% 4 5 3 8 6 11 11 23 46 71 11 

Other 1991 20 3% 1 1 1 1 1 1 4 6 4 

Ophthalmology 1984 6 1% 1 1 3 1 

Cardiovascular 1989 77 11% 1 1 2 2 2 1 1 2 11 15 28 11 

General 1990 83 12% 1 2 4 2 3 2 3 6 9 13 27 11 

Bone & Cartilage 1991 149 22% 2 4 3 5 5 18 38 49 25 

Basic 1991 147 21% 1 2 3 1 3 11 7 19 24 42 34 

Outside field 1991 48 7% 1 1 1 2 1 5 10 13 14 

Liver 1991 15 2% 1 1 1 1 1 2 5 3 

Skin 1995 38 6% 2 2 3 8 8 10 5 

Pancreas 1995 4 1% 1 1 1 1 

Neural 1996 16 2% 1 2 2 7 4 

Dentistry 1996 14 2% 1 1 1 3 6 2 

Tendon & 1996 10 1% 1 7 2 

Ligament 

Kidney 1996 7 1% 2 2 2 1 

Muscle 1997 9 1% 2 1 4 2 

Genitourinary 1998 27 4% 2 5 13 7 

Gene Therapy 1999 9 1% 7 2 

Other tissue 1999 9 1% 3 4 2 

Meniscus 1999 6 1% 4 2 

Stem Cells 1999 4 1% 1 3 

Digestive 1999 4 1% 2 2 

Lung 2001 3 0% 3 

The definitions elaborated during the 1987-93 period provided the basic terms of reference for discussions 

of tissue engineering through the 1990s. Tissue engineering researchers seeking to situate their work 

within a broader context typically cited either the Granlibakken workshop definition or the 

Langer/Vacanti framing of the field. Even those who did not directly cite these sources offered 

definitions that reflected some combination of the elements contained in the definitions outlined here, 

with the exception of Eugene Bell’s final point about surfacing non-biological devices, which seems to 

have been ignored for the most part. 

These early definitions left at least two important ambiguities. One involved the role of cells in tissue 

engineering. In many formulations of the concept, the unique aspect of tissue engineering compared to 

traditional biomedical engineering or to pharmaceutical development was that its products incorporated 

living cells. Bell’s 1992 definition, allowing for “acellular replacement parts capable of inducing 

regeneration”, reflected an emerging recognition that physiologic reactions to biomaterials were not 

necessarily just a nuisance to be suppressed, but might under some circumstances offer a means of 

inducing useful adaptations in the body. However, this conceptual advance also blurred the distinction 

between this new field and the studies of acellular biomaterials that had been a mainstay of biomedical 

engineering and materials science. Langer and Vacanti went one step further, defining the use of “tissue- 

47 See Bibliometric Analysis by CHI Research Inc., Appendix 5 


inducing substances” more generally as one of the strategies of tissue engineering. Including growth 

factors or other “signaling molecules” within the domain of tissue engineering represented progress 

toward an integrated understanding of the factors that govern tissue development in vivo, but also broke 

down the boundaries between tissue engineering and modern pharmaceutical research, which draws 

increasingly on the latest findings of cellular and molecular biologists. In the words of tissue engineer 

Jeffrey Hubbell, “Doing tissue engineering with factors to stimulate cells in the body is really just fancy 

drug delivery. One is delivering a drug – like a protein, a morphogenic factor – that stimulates cellular 

responses at a site with the goal of ending up with some overall tissue reconstruction or regeneration at 

that site.” 48 

A second ambiguity concerned the role of hybrid devices in tissue engineering, and the related question of 

whether therapeutic products of tissue engineering were necessarily intended to be implanted into the 

body. Several lines of research typically referred to as tissue engineering pursue the development of 

external bioreactors that can replace critical metabolic functions. From both a conceptual and a historical 

perspective, this work arguably represents an incremental advance on the dialysis machine. The longterm 

vision of researchers working on hybrid devices typically extends to more compact, self-contained 

versions that can be implanted. However, even when miniaturized, current “bioartificial organs” remain 

more machines than living organs, closer to today’s mechanical artificial heart than to the vision of an 

adaptive biological implant that is seamlessly incorporated into the body’s reparative and homeostatic 

mechanisms. 

The linkage of TE research with clinical medicine, although inevitable and desirable in view of the goals 

of the endeavor, nevertheless has also served as something of an obstacle to the sharpening of a definition 

of tissue engineering as an academic discipline. For example, orthopedic surgeons have been 

investigating many different kinds of implant that may promote bone regeneration. From a clinical 

perspective, what matters is not so much whether the active agent in an implanted matrix consists of stem 

cells, bone morphogenetic proteins, or gene therapy vectors, but whether it is therapeutically effective. 

Similarly, a nephrologist may view the dialysis machine, the external biohybrid “artificial kidney” or 

functional, histocompatible “microrenal” units created via nuclear transplantation as possibilities along a 

seamless spectrum of therapeutic options rather than in terms of the radically different underlying 

technologies they represent. 

Recent developments in nomenclature reflect this persistent ambiguity in scope and focus. The National 

Institutes of Health Bioengineering Consortium (BECON) symposium on tissue engineering, held at NIH 

in June, 2001, was entitled “Reparative Medicine: Growing Tissues and Organs”. The proceedings of the 

symposium offer multiple competing – and to some extent conflicting – definitions of reparative 

medicine, of tissue engineering, and of the relationship between the two. At one extreme, reparative 

medicine is defined very broadly as “the replacement, repair, or functional enhancement of tissues and 

organs”, a definition that is not much narrower than all of clinical medicine, although most of the 

examples cited have a surgical flavor; tissue engineering is viewed as one strategy among many for 

reparative medicine. 49 At the other, reparative medicine is defined as a synonym for tissue engineering: 

48 

49 

Henry CM, “Drug Delivery”, Chemical & Engineering News 2002 Aug 26;80(34):39-47. NSF has itself, on at 

least one occasion, extended the definition of tissue engineering beyond even this point, to encompass the use of 

controlled release polymers to deliver anticancer drugs in the brain. “Nifty 50: Tissue Engineering”, 

http://www.nsf.gov/od/lpa/nsf50/nsfoutreach/htm/n50_z2/pages_z3/45_pg.htm (URL verified December 31, 

2002). 

Sipe JD, “Tissue Engineering and Reparative Medicine”, pp. 1-9 in Sipe JD, Kelley CA, McNicol LA, eds., 

Reparative Medicine: Growing Tissues and Organs (Annals of the New York Academy of Sciences, vol. 961, 

June 2002). 


Reparative medicine, sometimes referred to as regenerative medicine or tissue engineering, is the 

regeneration and remodeling of tissue in vivo for the purpose of repairing, replacing, maintaining 

or enhancing organ function, and the engineering and growing of functional tissue substitutes in 

vitro for implantation in vivo as a biological substitute for damaged or diseased tissues and 

organs. 50 

This definition of tissue engineering is noteworthy for excluding extracorporeal bioartifical organs, and 

indeed, such devices gain only a passing mention in the proceedings, 51 which otherwise cover a very 

broad scope. 

The term “regenerative medicine”, offered as a further synonym, appears to have been coined by William 

Haseltine, to capture for promotional purposes his view of the future of medicine. 52 Contrary to the usage 

at the BECON symposium, Haseltine’s conception positions TE as a subset – a “thread” or “phase” – of 

regenerative medicine, not as a synonym for it, emphasizing the in vitro construction of human organs for 

implantation, using specialized biocompatible materials, signaling molecules, and adult human cells. In 

practice, however, there is little to distinguish Haseltine’s “regenerative medicine” from other conceptions 

of tissue engineering. 

Despite these alternative forms of the term, however, the true sentiment of the field appears to have been 

captured early on at the NSF meetings of 1987 and 1988. It is this concept of the field, which has been 

carried on by its leading proponents and remains highly referenced today. 

50 

51 

52 

Nerem R, Sage H, Kelley CA, McNicol LA, “Symposium Summary”, pp. 386-9 in Sipe JD, Kelley CA, 

McNicol LA, eds., Reparative Medicine: Growing Tissues and Organs (Annals of the New York Academy of 

Sciences, vol. 961, June 2002). 

Niklason LE, Ratcliffe A, et al., “Bioreactors and Bioprocessing: Breakout Session Summary”, pp. 220-2 in 

Sipe JD, Kelley CA, McNicol LA, eds., Reparative Medicine: Growing Tissues and Organs (Annals of the 

New York Academy of Sciences, vol. 961, June 2002). 

Haseltine WA, “The Emergence of Regenerative Medicine: A New Field and a New Society”, e-biomed: The 

Journal of Regenerative Medicine 2001;2:17-23. 


4.0 Development of the Field: 1987-2002 

The publication record indicates that the volume of research carried out under the rubric of tissue 

engineering has increased substantially since 1987, and especially since the mid-1990s, though it is 

difficult to determine this volume exactly because of the challenge inherent in attempting to precisely 

specify the scope of the field. 

A convenient proxy for the scope of TE today is arguably the pair of reference volumes Principles of 

Tissue Engineering (first edition published in 1997, second edition in 2000) and Methods of Tissue 

Engineering (published in 2002), which cover an impressively broad range of research subtopics and 

researchers. 53 The chapter-end bibliographies of Methods alone record thousands of citations to the 

research literature, with well over 5,000 individual researchers represented in the corpus of research thus 

defined. 54 The scope of research referenced by these volumes overstates to some extent the reach of 

tissue engineering today, because many of the citations refer to prior art or to adjacent fields from which 

current lines of research have drawn concepts and methods. Much of the scope of knowledge represented 

in these volumes was created through research efforts not originally conceptualized as investigations in 

tissue engineering, but which have, nevertheless, contributed to the field’s emergence. 

Nevertheless, the growth in tissue engineering proper – defined here as work perceived or designated by 

its participants as TE – has been substantial. This growth derives from multiple sources: 

• New graduates or established researchers who have chosen to enter the field have initiated or 

expanded work under established research themes. 

• Established researchers who have begun to collaborate with tissue engineers, or who have 

recognized similarities between their own work and that of tissue engineers as awareness of the 

field has grown, have relabeled existing lines of research as TE. One example is an apparent 

increase in the propensity of researchers in orthopedic surgery to conceive of their work as tissue 

engineering. 

• The definition of the field undergoes an implicit expansion when adjacent fields report advances 

that appear to address core challenges in tissue engineering. A prominent example of this 

phenomenon is the explosion of research on stem cells within the past few years, in the wake of 

discoveries in the late 1990s related to embryonic stem cells. Sourcing and cultivation of cells 

with desired and stably expressed properties has been recognized as a central research challenge 

for TE since it was defined as a field. In the words of one prominent researcher, however, “prior 

to the burst of stem cell activity, there would have been surprisingly little to say regarding 

progress in living cell therapy or knowledge of the conditions that would enable the practical use 

of cells in tissue engineering beyond skin.” 55 Today, stem cell research is a vigorous and 

important component of TE, partly through pursuit by researchers who consider themselves tissue 

engineers, and partly by extension of the concept of TE to incorporate the freshly relevant work 

of investigators who see their research as situated within other intellectual domains. 

53 

54 

55 

Lanza RP, Langer R, Vacanti J, eds., Principles of Tissue Engineering (San Diego: Academic Press, 2000); 

Atala A, Lanza RP, eds., Methods of Tissue Engineering (San Diego: Academic Press, 2002). 

Abt Associates analysis. 

Parenteau NL, “Cells”, pp. 19-32 in McIntire LV, Greisler HP, Griffith L et al., WTEC Panel Report on Tissue 

Engineering Research (Baltimore, MD: International Technology Research Institute, January 2002), available 

at http://www.wtec.org/loyola/te/final/te_final.pdf (URL verified Sept. 7, 2002). 


The individuals interviewed for this study found it difficult to identify seminal papers, events or specific 

discoveries or technical advances that could be characterized as having defined the direction or character 

of the field. Tissue engineering’s growth and development might be better described as the result of 

incremental progress along several originally independent lines of work, rather than the product of a 

handful of major breakthroughs or discoveries. Interviews and bibliometric analysis, pointed to two early 

papers that have played especially important roles in shaping the overall character of the field. While the 

1987 Granlibakken conference officially presented and defined the term “tissue engineering”, the 1993 

Langer/Vacanti review paper in Science introduced the concept of tissue engineering to a wider audience, 

alerted many researchers who were independently pursuing related work that others shared similar 

interests within a larger framework, and provided a convenient label for these activities. The 

Langer/Vacanti collaboration was also responsible for the paper that has probably been most influential 

from a substantive point of view, an article published at the beginning of 1988 describing the method of 

using resorbable polymer matrices as a vehicle for cell transplantation. 56 

On the face of it, the work presented in this paper represented a modest advance. Conceptually, it 

reflected a logical combination of existing approaches – cell-seeding of two-dimensional matrices of 

biological origin, as in the early work on artificial skin; three-dimensional cell culture on synthetic 

matrices; 57 and selective cell transplantation, as in the early work on islet cell transplantation. However, 

the method of seeding cells on resorbable polymer scaffolds was unique and rapidly became both the 

most important enabling technology and the most important organizing concept in the field, serving as a 

common element across lines of research addressing a wide range of therapeutic challenges. As a 

technique for building tangible objects, it also became a vehicle for enhanced public visibility – if not 

enhanced public understanding – of the field and its goal of “growing organs”. 58 

The scaffolds-and-cell-seeding technique catalyzed a flurry of tinkering on a wide range of tissue and 

organ systems, overshadowing to some extent the more fundamental efforts proceeding in parallel to 

develop the underlying knowledge needed to make the products of this technique viable as therapies. 

Beyond the obvious need for new scaffold materials with properties optimized for specific tissue 

engineering applications, key knowledge gaps in the late 1980’s and early 1990’s included, among others: 

• sources of large quantities of cells reliably and controllably expressing desired phenotypes 

• details of the immune response to implanted tissues, and means of controlling it 

• the role of chemical and physical signals in morphogenesis and in the in vivo remodeling of 

implanted tissues 

• means of controlling angiogenesis in order to achieve adequate vascularization of threedimensional 

tissue constructs 

• design principles to create and optimize bioreactors and bioprocessing techniques for the 

manufacture of specific tissue-engineered products 

• means of preserving TE products between the point of manufacture and the time of usage 

56 

57 

58 

Vacanti JP, Morse MA, Saltzman WM et al., “Selective Cell Transplantation Using Bioabsorbable Polymers as 

Matrices”, J Pediatr Surg 1988 Jan;23(1 Pt 2):3-9. 

Bottaro DP, Liebmann-Vinson A, Heidaran MA, “Molecular Signaling in Bioengineered Tissue 

Microenvironments”, pp. 143-53 in Sipe JD, Kelley CA, McNicol LA, eds., Reparative Medicine: Growing 

Tissues and Organs (Annals of the New York Academy of Sciences, vol. 961, June 2002). 

This was notoriously so in the case of the tissue-engineered “ears” grown by implantation of suitably-shaped 

polymer templates, seeded with chondrocytes, on the backs of mice. Cao Y, Vacanti JP, Paige KT et al., 

“Transplantation of Chondrocytes Utilizing a Polymer-Cell Construct to Produce Tissue-Engineered Cartilage 

in the Shape of a Human Ear”, Plast Reconstr Surg 1997 Aug;100(2):297-302; “Artificial Liver ‘Could be 

Grown’”, BBC News Online, 25 April 2002, http://news.bbc.co.uk/1/low/health/1949073.stm (URL verified 

Dec. 26, 2002). 


• methods for characterization and functional assessment of engineered tissues both in vitro 

and in vivo 

Many researchers began – or continued – to pursue these questions in their own work, and to draw 

relevant insights from developments in research outside of tissue engineering. 

In 2002, after 15 years since the initial NSF meetings, TE remains a mix of topical foci and research 

styles, reflecting in part the heterogeneous origins, intellectual traditions, and disciplinary affiliations of 

the mix of clinicians, engineers and scientists who work in the field. 

Although recognition of the importance of gaps in the fundamental knowledge underlying tissue 

engineering is widespread, many of the individuals interviewed for this study referred to the persistently 

“Edisonian” 59 character of much of the work in TE, by which they meant a sort of inspired, ad hoc 

tinkering focused on the solution of specific practical problems in the creation of usable products. Some 

considered this a positive attribute while others viewed it as a drawback, reflecting a persistent tension 

between two different strategies for TE. Is it best to invest in fundamental research that will lay strong 

theoretical and methodological foundations for the long-term productivity of TE, or are clinicallysignificant 

products sufficiently close to being within reach as to warrant an Edisonian sprint toward their 

creation? 

It might be expected that Edisonian approaches would be most strongly associated with TE research and 

development efforts in the corporate sector, while the academic sector would be more strongly focused on 

fundamentals. The former is certainly true, and because the corporate sector has accounted for the great 

majority of the funds invested in TE, 60 it necessarily follows that the character of corporate R&D has had 

a substantial impact on the character of the TE enterprise overall. 

Many of our informants observed that corporate R&D efforts in tissue engineering have had a modest 

effect on the progress of the field. Corporate R&D has focused on the creation of proprietary intellectual 

content centered on the challenges of bringing products to market, and less on the solution of broader 

challenges in science or engineering. Knowledge transfer from industry back to academia has been 

limited. 

However, many respondents suggest that the Edisonian approach remains a powerful force within the 

academic sector as well. In part, this reflects the natural inclination of some workers in the field, many 

but not all of these clinicians who bring to their work a strong practical bent. Some observers believe that 

another influence – a deleterious one – has been the combined effect of a shortage of funding from 

traditional sources of support for academic research together with the incentives created by the venturecapital-funded 

boom in biotechnology startup companies during select periods in the 1980s and 1990s, 

that has induced some researchers to attempt prematurely to “productize” their ideas or research findings. 

Given the eclectic nature of the field, it is difficult to make judgments as to the level of progress that has 

been made in the years since 1987. One way of interpreting the significance of the events of 1987 is that 

they marked the beginning of an attempt by engineers to systematize and formalize the field of tissue 

engineering. The principle of rational design is central to the engineering approach. In turn, rational 

59 

60 

The term “Edisonian” was used independently by several researchers we spoke to during the course of our 

interviews. The term itself originates from the book Pasteur’s Quadrant: Basic Science and Technological 

Innovation (Brookings Institution Press, 1997) by Donald E. Stokes. 

Investment in TE has been tracked most systematically in a series of studies by Michael Lysaght; the most 

recently published installment in the series is Lysaght MJ, Reyes J, “The Growth of Tissue Engineering”, Tissue 

Eng 2001 Oct;7(5):485-493. 


design is made possible by the elucidation of theoretical principles of broad generalizability and by the 

systematic characterization of available materials and methods in terms of the parameters that comprise 

these theoretical models. In the tissue engineering context, some of these principles would need to come 

from engineering – for example, those related to mechanical aspects of tissues, the behavior of 

biomaterials, and processes for producing, preserving and distributing TE products. Others would need to 

come from biology – for example, the behavior of cells and of growth factors. Still others would need to 

come from clinical medicine – for example, principles of physiology and pathophysiology. No matter 

whether their disciplinary roots have been in medicine, in engineering or in biology, TE researchers have 

from the earliest days of their involvement recognized that the future success of the field depends heavily 

on strengthening the base of systematic knowledge underlying TE applications. Yet it was engineers who 

first sought to articulate this point clearly and make it the foundation for a formalization of the field. 61 

While this principle is sound, however, the development of the field since 1987 reflects little progress 

toward a systematization of TE through the creation of a foundation of broadly applicable theory or even 

a well-structured phenomenology. Although a great deal of new knowledge has been accumulated, 

deficits in fundamental understanding cataloged in recent reviews 62 are similar in general outline to those 

recognized in the late 1980s and early 1990s. Researchers today have gained a much more detailed and 

sophisticated understanding of the specific challenges that must be addressed, however, and some 

progress has been made in framing research challenges in particular areas of TE in a more systematic 

way. 63 

Perhaps the most important explanation for this slow progress is simply that the rationalization of TE 

represents an intellectual challenge of enormous magnitude. Construction of replacement tissues and 

organs, or controlled induction of endogenous reparative capacities to restore tissue structure and 

function, represent extraordinarily difficult systems engineering problems, and knowledge both of the 

behavior of the system components and of the necessary principles of systems integration remains 

primitive in relation to what is required. 

Another factor affecting the rate of progress may be important gaps in the intellectual resources that have 

been brought to bear on the challenges of tissue engineering, and in the degree of cross-disciplinary 

integration that has been achieved. In her plenary address at the 2001 BECON symposium, Nancy 

Parenteau articulated these concerns: 

The need for cell therapy is well recognized even by the nonscientist, as evidenced by the 

perceived need for some form of stem cell research. Yet the complex nature of dealing with 

actual cells themselves to achieve an outcome is still not fully realized. While there is 

burgeoning information on the genetics front, advances in technology for rapid proteomic 

analysis, rapidly growing information on factors that effect (sic) cell lineage, identification of 

transcription factors involved in the development of tissue structure and control of 

morphogenesis, and advancing preclinical and clinical research on cell implantation, there is a 

very important need to bring all aspects together. Engineers and physician scientists have been 

61 

62 

63 

The 1985 ERC proposal from UCSD is emphatic and articulate on this point. Pp. 8-9, “A Proposal to the 

National Science Foundation for An Engineering Research Center at UCSD, CENTER FOR THE 

ENGINEERING OF LIVING TISSUES”, UCSD #865023, courtesy of Y.C. Fung, August 23, 2001. 

WTEC Panel Report on Tissue Engineering Research (Baltimore, MD: International Technology Research 

Institute, January 2002), available at http://www.wtec.org/loyola/te/final/te_final.pdf (URL verified Sept. 7, 

2002); Sipe JD, Kelley CA, McNicol LA, eds., Reparative Medicine: Growing Tissues and Organs (Annals of 

the New York Academy of Sciences, vol. 961, June 2002). 

See, for example, Butler DL, Goldstein SA, Guilak F, “Functional Tissue Engineering; The Role of 

Biomechanics”, J Biomech Eng 2000 December;122:570-575. 


instrumental in leading the way in academic tissue engineering research, although they 

desperately need the participation of workers in other disciplines, such as molecular biologists 

and cell biologists, to fill the important gaps in understanding between them. We must not be 

naïve. 

How do we stimulate interest in critical areas such as applied research in cell biology and foster 

interdisciplinary collaboration? How do we provide academic recognition for being an important 

part of a significant achievement? Academic laboratories must be given an incentive to work on 

common goals…. New paradigms and metrics must be established both in academics and 

industry as we delve into complex biological problems that are well beyond a single scientific or 

engineering discipline…. 64 

With respect to its headline goal as well – to create living replacement parts for the human body – the 

progress of TE has been slow. As with the underlying scientific challenges, the work of the past fifteen 

years in tissue engineering has served above all to clarify our understanding of how difficult it will be to 

achieve the full extent of TE’s therapeutic vision. 

In his 1987 draft concept memo, NSF’s Allan Zelman identified a list of “types of tissues most likely to 

bring early success”. In Zelman’s words, these were: 

1. Skin: replacement of existing skin damaged from burns, scars, etc. 

2. Bone: present artificial hips and other joints could be replaced with hips and joints composed 

primarily from the patients’ own tissue 

3. Blood vessels: arteriovenous shunts for hemodialysis patients and heart bypass patients 

would benefit greatly 

4. Cornea: this could eliminate rejection, bring sight to those who reject corneal transplants and 

as success grows possibly provide an alternative to eye glasses 

5. Cartilage: providing cartilage replacement for arthritic patients could bring relief from pain 

to millions 

6. Nerves: every year thousands of paraplegics are generated and this may be the means to 

reconnect nervous tissue too damaged for self-repair 

7. Blood or blood components: production of viral free blood and blood components could 

justify a great research effort 65 

Preliminary progress has been made in the development of many of these tissues, though it is understood 

that much more work is required before “off-the-shelf” products will be available: 

Skin. Skin is perhaps the most successful of the tissue engineered therapies, with several products having 

completed clinical trials, met with FDA approval, and made the transition to market. In 1997, the FDA 

approved TransCyte 66 , a skin replacement tissue made by Advanced Tissue Sciences, which consists of 

dermal keratinocytes grown on a biodegradable polymer. TransCyte serves as a temporary wound cover 

64 

65 

66 

Parenteau NL, Young JH, “The Use of Cells in Reparative Medicine”, pp. 27-39 in Sipe JD, Kelley CA, 

McNicol LA, eds., Reparative Medicine: Growing Tissues and Organs (Annals of the New York Academy of 

Sciences, vol. 961, June 2002). 

Zelman A, “Tissue Engineering: A Fundamentally New Concept in Health Care”, internal discussion memo, 

first draft, Sept. 22, 1987, courtesy of NSF. 

TransCyte is now sold by Smith 7 Nephew, see: http://www.smith-nephew.com/businesses/W_TransCyte.html 


for burns as new tissue forms. Apligraf 67 , manufactured by Organogenesis, utilizes live human skin cells 

to form a dual layer skin equivalent approved by the FDA to treat diabetic leg and foot ulcers. 

Recent advances in skin tissue engineering have resulted in the following examples of products in the last 

5 or so years: 

- EpiDex 68 , from Swiss-based Modex Therapeutics for treatment of chronic skin ulcers; EpiDex 

grafts are grown from hair follicle stem cells. 

- Dermagraft 69 was introduced in 1998 by Advanced Tissue Sciences. Dermagraft is a 

cryopreserved human fibroblast-derived dermal substitute, composed of fibroblasts, extracellular 

matrix, and a bioabsorbable scaffold. 

- Integra – Integra is a two-layered dressing and is completely acellular. The top layer serves as a 

temporary synthetic epidermis; the layer below serves as a foundation for re-growth of dermal 

tissue. The underlying layer is made of collagen fibers that act as a lattice through which the body 

can begin to align cells to recreate its own dermal tissue. 

- Epicel, also manufactured by Genzyme Biosurgery, is the only autologous skin graft that can 

permanently close a burn wound 70 . Epicel was developed based on original research done by 

Howard Green. 

- Alloderm 71 (LifeCell) is a cell-seeded allogenic skin replacement. The product consists of human 

dermal collagen seeded with allogenic fibroblasts. The material has recently been launched in the 

US - initially for patients with third degree burns and limited donor-site tissue. 

- Xenoderm, another product from LifeCell consists of porcine dermis used as a replacement for 

burn wounds. LifeCell claims that experimental data shows consistent incorporation of the matrix 

into the wound bed, low immunogenicity, and re-population with host cells. 

Companies have approached the development of skin equivalents from different perspectives: autologous 

cellular replacements (Genzyme Biosurgery), allogeneic cellular replacements (Advanced Tissue 

Sciences and Organogenesis), and completely acellular replacements (Integra). Each of these appear to 

achieve success as wound coverings. However, scar tissue formation and wound contraction issues 

remain problematic. Available products also fail in several ways to mimic the structure and function of 

native skin. Substitutes have long acted as passive wound covers, lacking certain essential 

67 

68 

69 

70 

71 

Apligraf is indicated for the treatment of non-infected partial and full-thickness skin ulcers due to venous 

insufficiency of greater than 1 month duration and which have not adequately responded to conventional 

therapy, and also for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than three weeks 

duration which have not adequately responded to conventional ulcer therapy and which extend through the 

dermis but without tendon, muscle, capsule or bone exposure. Apligraf prescribing information, Novartis 

Pharmaceuticals Corporation, June 2000. 

http://www.epidex.com 

Dermagraft is now marketed by Smith and Nephew, see: http://wound2.snwmdus.com/us/Product.asp?NodeId=2550 

(URL verified April 12, 2002) 

Epicel was first introduced in 1987, but is still a popular treatment for severe burns: 

www.genzymebiosurgery.com (URL verified April 12, 2002) 

http://www.lifecell.com/healthcare/products/alloderm/index.cfm (URL verified April 12, 2002) 


functions/components—including hair follicles, and glands 72 . Development of such enhancements are the 

focus of current research in living skin equivalents and suggests the use of stem cells as a basis for 

development of fully differentiated skin equivalents. Choice of matrix support to maintain fibroblasts and 

keratinocytes is also still being investigated. 

Vascular grafting. Progress to date in the development of tissue engineered vascular grafts has focused 

on mimicking the three layers of the normal muscular artery, using combinations of live cells, 

bioresorbable and non-bioresorbable scaffolding constructs. At present, there are no FDA approved live 

vascular replacement therapies. Several techniques are in pre-clinical trial but face challenges that may 

prevent their widespread use/application in the near future.” 73 

Huynh and colleagues at Organogenesis and Duke University, for example have used porcine intestine as 

a graft base for seeding of endothelial cells, which will grow and develop into vessel like structures 74 . 

The use of porcine cells, while important for clinical research, have unknown effects if transplanted into 

humans. Other sources for graft bases are also being explored, including fibrillar collagen and bovine 

collagen gels. However, none of these have produced a vascular substitute with the mechanical properties 

and strength of native blood vessels. Traditional problems plaguing the field, including clotting and scar 

tissue formation also persist in cellular replacements and prevent laboratory products from making it to 

the clinical trial stage. To combat such problems, researchers have attempted to embed the graft materials 

with antibiotics and antithrombotic coatings with limited success. There is also the need to create a 

functional nerve supply and capillary network in vitro to support live vascular tissues. Until such 

challenges are remedied, prosthetic grafts, made of substances like Dacron and polytetrafluoroethylene, 

will continue to serve as the major therapy. 

Kidney. As a highly complex organ, whole kidney replacement organs are far from being a reality. 

However, progress has been made in development of temporary replacement devices, such as 

extracorporeal kidney assist devices. Dr. David Humes, Chairman of The Department of Internal 

Medicine at The University of Michigan, Ann Arbor, has successfully completed in vivo testing of a 

Renal Tubule Assist Device (RAD) for treating acute renal failure 75 . The only other treatments currently 

available for acute renal failure are hemofiltration and dialysis. Extracorporeal devices may improve the 

outcomes of these patients while making treatment much less costly. 

Pancreas/Islet cells. Islet cell transplantation techniques have consisted of two major approaches: 

perfusion devices and microencapsulation. Perfusion devices, though developed as early as 1970, have 

failed to make it to the clinical trial stage to due long-term biocompatibility issues, membrane breakage, 

and size limitations (a problem which plagues bioartificial implantable livers as well). 

Microencapsulation, has also been in existence for several decades. Refinements to this technique over 

time involved improving the biocompatibility of the encapsulating materials. Some researchers suggest 

that widespread clinical application of microencapsulation techniques is just around the corner. 76 

Several commercial tissue engineering approaches to repair/replace pancreatic function describe the 

current state of the field: 

72 

73 

74 

75 

76 

Bren L, “Helping Wounds Heal”, FDA Consumer, May-June 2002, 

http://www.fda.gov/fdac/features/2002/302_heal.html, (URL verified September 2, 2002). 

Niklason, LE. “Replacement Arteries Made to Order.” Science, 286: 19 November 1999; 1493-1494. 

Huynh T, et al. Nature Biotechnology. 17(1083); 1999. 

The technology is now being developed by Nephros Therapeutics; see 

http://www.nephrostherapeutics.com/news/pr/pr-20020918-01.htm (URL verified April 12, 2002) 

Macluf M., Atala A. “Tissue Engineering: Emerging Concepts.” Graft. 1(1): March-April, 1998. 


• Metabolex is developing proprietary technologies for the microencapsulation of insulin-producing 

tissues using thin, conforming, biocompatible coatings. 

• BetaGene is a privately held biotechnology company developing innovative strategies for the 

detection and treatment of diabetes. This company was formed for the purpose of developing 

proprietary technology originating at the University of Texas Southwestern Medical Center. 

BetaGene retains exclusive license to aspects of this technology including the use of engineered 

cell lines for the treatment of type I and Type 2 diabetes and the use of these cells for bulk insulin 

production. 

• Circe Biomedical has developed the PancreAssist System, consisting of a single tubular 

membrane surrounded by insulin-producing islets, which are, in turn, enclosed within a diskshaped 

housing. The tubular membrane is porous and permeable to glucose and insulin. 77 

Liver. Several bioartificial liver (BAL) bioreactor designs have been developed in the laboratory to 

replace liver function. The basic design of a BAL device consists of circulating patient plasma 

extracoporeally through a bioreactor that houses/maintains liver cells (hepatocytes) sandwiched between 

artificial plates or capillaries. 78 Bioreactor materials have either a spherical shape, large surface area, 

large pores or high porosity, or are hydrophilic and biocompatible. 79 These features can help to achieve 

the high density cultures of hepatocytes required. However, there is no one material that possess all of 

these desired properties. Researchers are actively seeking a support matrix that could provide all these 

properties in order to have a BAL with improved efficiency and effectiveness. Clinical trials of some 

BAL devices are already underway in the United States and the UK Circe Biomedical currently has the 

HepatAssist liver device in clinical trial, which is a extracorporeal device consisting of a hollow-fiber 

bioreactor lined with porcine cells 80 . 

Numerous other challenges plague the development of tissue engineered livers: 

• Human hepatocytes are limited in supply which make harvest and culture for liver assist 

devices difficult 

• Hepatocytes are extremely difficult to stabilize and maintain in culture and lose their 

specificity rapidly. Several devices have made it to clinical trial but fail to seek FDA 

approval based on the lack of stabilization of the cellular component. 

• The liver is so complex and varied in its functions that generating a replacement device that 

performs all these duties is far from a reality. 

• Microencapsulation techniques have also been tried, but have been unsuccessful, again, due 

to the rapid loss of functionality of liver cells once removed from the body. 

Bone, cartilage. Like skin, tissue engineering of bone and cartilage has experienced relative success as 

compared to other tissue engineered products. Current strategies consist of two major approaches: 

77 

78 

79 

80 

http://www.circebio.com/technology/pancreassist.html (URL verified April 12, 2002) 

Strain A, Neuberger JM. “A Bioartificial Liver—State of the Art.” Science. 295(5557): 8 Feb 2002; 1005-1009. 

http://mtel.ucsd.edu/publications/Advances_in_Bioartificial_Liver_Devices.pdf (URL verified April 12, 2002) 

http://www.circebio.com/technology/hepatassist.html (URL verified April 12, 2002) 


transplantation of osteochondral grafts and transplantation of chondrocytes 81 . Cell populations from 

cultured periosteum have the ability to form new bone and cartilage under the appropriate conditions and 

with the addition of the appropriate growth factors. 82 Transplantation of osteochondral grafts, however, 

runs a possible risk of rejection in the recipient. 

Current products and strategies include: 

• Carticel 83 , by Genzyme Biosurgery of Cambridge, MA, which has received FDA approval to 

replace damaged knee cartilage. The product uses autologous chondrocytes and grows them in a 

biodegradable matrix, which is then transplanted in place of the damaged tissue. 

• Stryker Biotech of Hopkinton, MA has an FDA approved OP-1 Implant under the Humanitarian 

Device Exemption (HDE). The OP-1 Implant is now available across the country and is indicated 

for use as an alternative to patients’ own bone in recalcitrant long bone nonunions where an 

autograft is unfeasible and alternative treatments have failed. 84 

• Arnold Caplan of Case Western Reserve has performed mesenchymal stem cell (MSC) 

transplants in animals, and is working on similar transplants in humans. MSC’s have been found 

to induce bone and connective tissue growth. 

• Antonios Mikos at Rice University has developed an injectable copolymer that hardens quickly in 

the body and provides a surface to guide severed long bone regeneration 85 . 

To our knowledge, no other allogeneic, cell-based organ- or tissue-replacement product is close to 

market. Autologous efforts remain dominant. Efforts to bring to market tissue-engineered products that 

address defects in complex metabolic functions or replace vital organs will require more time and effort 

before reaching success. Research and development programs on various approaches to the bioartificial 

pancreas are said to have consumed over $200 million of private sector funds to date, but designs capable 

of routine success in large animal models are yet unavailable, while encapsulated cell therapy has failed 

to demonstrate efficacy in phase III clinical trials. 86 Extracorporeal replacement of critical metabolic 

functions of the kidney and liver has reached the stage of small clinical trials – Phase I (safety) for the 

former and Phase II (preliminary safety and efficacy) for the latter. 87 In both cases, the devices’ mode of 

operation involves extracorporeal blood circulation comparable to that of a dialysis machine, and both are 

initially targeted toward treatment of acute, life-threatening metabolic failure. The tissue-engineered 

replacement heart remains a distant vision. 88 

81 

82 

83 

84 

85 

86 

87 

88 

Macluf M., Atala A. “Tissue Engineering: Emerging Concepts.” Graft. 1(1): March-April, 1998. 

Breitbart AS, Grande DA, Mason JM, Barcia M, James T, Grant RT. Gene-enhanced tissue engineering: 

applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene. Ann 

Plast Surg 1999; 42:488-495. 

http://www.carticel.com (URL verified April 14, 2003) 

http://www.op1.com (URL verified April 14, 2003) 

Ferber D. “From the Lab to the Clinic.” Science 284(5413); 16 April 1999: 423. 

Michael Lysaght, interview, July 2, 2001. 

See http://www.nephrostherapeutics.com (Nephros Therapeutics Renal Assist Device) and 

http://www.vgen.com (Vitagen ELAD ® Artificial Liver device) URLs verified September 6, 2002). 

Sefton MV, “The LIFE Initiative: Creating Transplant Organs Through Tissue Engineering”, e-biomed: The 

Journal of Regenerative Medicine 2002;3:25-28. 


As noted previously, from the beginning, more subtle conceptions of TE have extended its scope to 

encompass not only the production of replacement parts that embody the necessary structure and function, 

but the possibility of induction of endogenous reparative capabilities as well. In principle, such induction 

may be achieved via a variety of approaches, including implantation of cells that express growth factor 

molecules, implantation of non-living materials (for example, a collagen sponge) containing growth factor 

molecules, delivery of genes that encode the required growth factor, or by local or systemic infusion of 

growth factor molecules. The observed physiologic effects of the “skin replacement” products in 

promoting wound healing suggest that they might also be described as the first “induced repair” products 

rather than as replacement organs. Acellular “skin replacement” products on the market, such as the 

INTEGRA ® dermal regeneration template derived from the work of Yannas, 89 are designed to function in 

this way. After more than 30 years of research on bone morphogenetic proteins, a BMP product has also 

recently reached the market – Medtronic’s INFUSE bone graft product, incorporating recombinant 

human bone morphogenetic protein rhBMP-2. 90 Several companies market acellular matrix materials for 

bulk applications in orthopedic and reconstructive surgery. 

In bringing therapeutic products to market, tissue engineers must surmount not only daunting technical 

challenges, but regulatory and business obstacles as well. The regulatory environment for cell-containing 

products is complex and still at an early stage in its evolution; it imposes a substantial financial burden on 

the product development process, directly through the efficacy standards the product must meet and 

through the cost of funding the trials needed to demonstrate that efficacy, and indirectly through the 

financial effects of delay in bringing products to market. Finally, for a product to be viable, it must be 

possible to develop it, achieve regulatory approval, manufacture it, distribute it and market it at a price 

adequate to yield a positive economic return. 

The difficulty of companies like Organogenesis and Advanced Tissue Sciences in recent times also raises 

concerns around the financial viability of some tissue engineered products. As of this writing, both 

Organogenesis and Advanced Tissue Sciences are undergoing reorganization under Chapter 11 

bankruptcy protection, and on trends to date it appears unlikely that revenues from their artificial skin 

products will ever cover the cost of the capital invested in their development. At the aggregate level, 

cumulative investment in tissue engineering research has been estimated to exceed $3.5 billion, of which 

well over 90% has been provided by private sources, with negligible financial return. 91 Such concerns are 

well known by individuals in the public and private sectors and will be important considerations in 

strategy development for building not only clinically viable, but commercially viable products. 

It is clear from these examples that despite notable contributions and advancements, tissue engineering is 

still a field in its infancy. Whether tissue engineering as we know it today will prove to be a powerful 

general strategy for developing therapeutic products and methods that can meet the dual hurdles of 

therapeutic efficacy and commercial viability remains to be seen. A strong research effort is underway, 

89 

90 

91 

INTEGRA ® Dermal Regeneration Template product description, http://www.integra-ls.com/busskin_product.shtml 

(URL verified December 25, 2002). 

“INFUSE Bone Graft / LT-CAGE Lumbar Tapered Fusion Device”, Medtronic Sofamor Danek press 

release, July 2, 2002 (http://www.sofamordanek.com/press-infuse.html, accessed Sept. 7, 2002). An additional 

BMP, Curis’ OP-1, has been approved by the FDA for limited use under a Humanitarian Device Exemption, 

and has also been approved for sale in certain international markets. “Curis’ OP-1 Received HDE Status in the 

United States”, Curis press release, October 18, 2001 (http://www.curis.com/news_101801.html, URL verified 

Sept. 7, 2002). Hematopoietic growth factors (such as recombinant erythropoietin), have been on the market for 

a number of years, but this line of research has not been characterized as tissue engineering by any of the 

informants consulted by the study team. 

Lysaght MJ, Reyes J, “The Growth of Tissue Engineering”, Tissue Engineering 2001 Oct;7(5):485-493. 


however, and advances in other emerging areas of science, such as stem cell research, are likely to make 

significant contributions toward helping tissue engineering to become a viable field. 


5.0 Who Are the Tissue Engineers? 

This section examines the people and institutions that are active in tissue engineering or, in a few cases, 

played a key role in the past. We review some characteristics of the community of tissue engineers 

viewed in aggregate, introduce specific individuals and six major centers of activity that have played 

central roles in research or training since the earliest days of the emergence of tissue engineering, and 

conclude with a few observations on the corporate sector. Our focus here is on those who are actually 

doing tissue engineering; the role of funding agencies is addressed in a later section. 

Our analysis draws heavily on a roster of 231 tissue engineers compiled by the study team, and presented 

in Appendix 2. These include individuals who have published in the realm of tissue engineering, have 

trained with notable names in the field, or have otherwise self-proclaimed themselves as tissue engineers. 

The roster is not intended to be a definitive list of those who should be considered tissue engineers – 

rather, it should be viewed as a convenience sample intended to shed light in a qualitative sense on the 

nature of tissue engineering and its participants, and to provide an overall sense of trends affecting the 

character of the field. With that purpose in mind, however, we believe that the list does contain the great 

majority of academic, non-physician researchers with faculty appointments in the United States and 

Canada who have identified tissue engineering explicitly as an important component of their research 

interests. In addition, the list includes a selection of the most prominent physician-researchers in the 

field, along with a small sampling of individuals in the corporate sector. 

5.1 The Tissue Engineers as a Group 

Disciplinary affiliations of tissue engineers are difficult to analyze in a precise quantitative way, because 

the specific mix of research areas that are included in a department with a given name or are associated 

with a degree with a given designation, and the number and character of departmental affiliations awarded 

to faculty, vary from one institution to another in idiosyncratic ways. Nevertheless, overall trends emerge 

clearly from a rough tally of the available data. 

Viewed in terms of both the departments by which their doctoral degrees were awarded and the 

departments in which those who are in academia now hold faculty appointments, tissue engineers are 

indeed predominantly engineers. 

By training, more than half of the individuals for whom we have specific data are engineers. 

Approximately one fifth of the tissue engineers in our sample hold medical or dental degrees, often in 

conjunction with an engineering or science doctorate. In view of the critical importance of cells and of 

physiology in tissue engineering, the fraction of individuals who hold only a doctorate in biological 

sciences (for example, biology, biochemistry, or non-clinical medical sciences such as physiology or 

anatomy) is remarkably small – roughly one out of ten. Chemical engineering is by a wide margin the 

engineering discipline most frequently encountered in this cohort, followed by biomedical or 

bioengineering, and by mechanical engineering. A more liberal interpretation of which aspects of 

contemporary orthopedics and biomechanics research should be considered part of tissue engineering 

would perhaps have yielded somewhat increased weights for biomedical and mechanical engineering in 

the sample. 

Current academic departmental affiliations of these tissue engineers are also strongly weighted toward 

engineering. However, here bioengineering or biomedical engineering is the leading disciplinary 

affiliation by a wide margin, followed by chemical engineering and, in a distant third place, mechanical 

engineering. This pattern may reflect the relatively recent emergence of biomedical engineering as a 

discipline, and the migration of faculty – especially recent trainees taking their first faculty appointments 


– from some of the classical engineering disciplines to newer and often growing departments of 

biomedical engineering. 

Biological science affiliations are few, and are weighted toward basic medical science departments. 

Clinical and clinical science departmental affiliations are strongly weighted toward surgery and surgical 

specialties, notably orthopedics. This latter pattern may to some extent be an artifact of selection bias in 

construction of the sample; for example, it is likely that a more liberal definition of tissue engineering to 

include a greater part of islet cell transplantation research and a correspondingly more aggressive search 

for clinicians who have been involved in such work would have resulted in the inclusion of more 

endocrinologists in the roster. Nevertheless, we would expect surgeons to dominate in any reasonably 

representative sample of clinician-scientists active in tissue engineering. 

More than 70 universities are represented in the list of institutions from which the tissue engineers in our 

sample received their non-clinical (i.e., PhD and ScD) doctorates. Appendix 2 shows that MIT trained, 

by a wide margin, the largest number of individuals in this group, followed by the University of 

Pennsylvania, Rice University, the University of Michigan, the University of Minnesota, Columbia 

University, Stanford University, and the University of California at Berkeley. Again, a more liberal 

definition of relevant orthopedics and biomechanics research would perhaps have yielded a slightly 

stronger representation for Rice, Columbia, the University of California at San Diego (UCSD), and 

Georgia Tech. When postdoctoral training relationships are traced as well, the relative weight of MIT in 

this group increases further. 

At present, most of the individuals active in this representative sample of tissue engineers entered the 

field after completing dissertations in other areas. Because of the interdisciplinary character of tissue 

engineering, the field will likely continue to have a relatively high proportion of post-doctoral-training 

entrants. However, over time, the fraction of individuals whose thesis research was explicitly in tissue 

engineering, and the representation of universities other than MIT with broad platforms of research and 

training activity in tissue engineering, such as Rice, UCSD and Georgia Tech, should increase as a 

proportion of any roster of researchers active in TE. 

One last characteristic of this cohort is noteworthy here. The great majority of individuals are involved in 

TE on only a part-time basis. That is, academic tissue engineers typically maintain a number of lines of 

research, some of which meet any reasonable definition of tissue engineering, some of which straddle the 

ill-defined boundary that delineates the field, and some of which are clearly situated within other 

intellectual domains. By this measure, tissue engineering could be viewed more as a tactic than as a 

discipline – as part of an interdisciplinary assault on unsolved therapeutic challenges that draws 

opportunistically on an ever-wider range of knowledge and tools from science and engineering. 

5.2 Notable Participants in Tissue Engineering and Leading Centers in the 

Field 

A bibliometric analysis of papers important to the field of tissue engineering revealed a list of more than 

350 US institutions active in research. Our interviews with experts in the field as well as extensive 

secondary research 92 validated this list and also pointed toward several other institutions as being highly 

92 

In compiling these groups of researchers, we examined all major research universities in the country which had 

bioengineering departments—given the strong link between the field of bioengineering and tissue 

engineering—and scoured faculty research pages for individuals in those departments to see which of these may 

participate in TE. The research groups above were selected to appear in this report since, in our judgment, they 

had made significant research contributions or were comprised of multiple faculty or graduates who are 

considered major players in the field. 


influential in the field—not only in terms of their research contributions, but also in their training of 

personnel currently active in the field. Below we highlight a sample of the key loci of tissue engineering 

research. 

Boston Area: MIT and Harvard 

Perhaps the single most prominent geographical and institutional locus of research in tissue engineering 

has been in the Boston area, centered on the Massachusetts Institute of Technology (MIT) in Cambridge 

and the Harvard Medical School (HMS) in Boston, although researchers at other Boston-area institutions 

have been involved as well. 

MIT was the site of three independent, seminal lines of research on substitutes for human skin. During a 

period from the mid-1970s through the mid-1980s, the laboratory of cell biologist Howard Green, MD (in 

the biology department at MIT until 1980, subsequently in the cell biology department at Harvard 

Medical School) achieved a breakthrough in the cultivation of human keratinocytes, developed it into a 

method for growing epithelial grafts from a small piece of autologous epidermis, and demonstrated the 

viability of this method in the treatment of burn victims. 93 In 1987, this technique became the basis for a 

startup company called BioSurface Technology that offered cultured epidermal autografts commercially. 

The company was acquired by Genzyme in 1994 and became Genzyme Tissue Repair (now Genzyme 

Biosurgery), and the service is still offered under the name Epicel ® . 94 Dr. Green himself has continued 

his career as a cell biologist at HMS, but has not been prominent in the subsequent development of tissue 

engineering. 

Ioannis Yannas joined the faculty in the mechanical engineering department at MIT in 1966, after 

completing his PhD at Princeton. From the start, his research focused on the properties of collagen and its 

role in connective tissues, using approaches from chemistry, physics, and biomechanics. By the 1970s, 

Yannas was investigating the use of acellular collagen-glycosaminoglycan matrices as wound dressings 

designed to serve as biodegradable templates for the regeneration of viable skin. In 1977, Yannas, in 

collaboration with Massachusetts General Hospital and Shriners Burns Institute surgeon John F. Burke, 

was awarded a patent for a “multilayer membrane useful as synthetic skin”. 95 In 1980, they published the 

first in a series of papers outlining design considerations for what they called an “artificial skin”, and 

shortly thereafter, they reported the successful use of such an artificial skin in the treatment of extensive 

burn injury. 96 This research resulted in the development of a commercial product, Integra ® Dermal 

Regeneration Template, which is currently licensed to and manufactured by Integra LifeSciences 

93 

94 

95 

96 

Rheinwald JG, Green H, “Serial Cultivation of Strains of Human Epidermal Keratinocytes: the Formation of 

Keratinizing Colonies from Single Cells”, Cell 1975 Nov;6(3):331-43; Green H, Kehinde O, Thomas J, 

“Growth of Cultured Human Epidermal Cells into Multiple Epithelia Suitable for Grafting”, Proc Natl Acad Sci 

USA 1979 Nov;76(11)5665-8; and Gallico GG 3 rd , O’Connor NE, Compton CC et al., “Permanent Coverage of 

Large Burn Wounds with Autologous Cultured Human Epithelium”, N Engl J Med 1984 Aug 16;311(7):448-51. 

Epicel® (cultured epidermal autografts) product information, 

http://www.genzymebiosurgery.com/opage_print.asp?ogroup=1&olevel=2&opage=96 (URL verified October 

26, 2002). 

Yannas IV, Burke JF, Gordon PL, Huang C, “Multilayer Membrane Useful as Synthetic Skin”, US Patent 

4,060,081, November 29, 1977. 

Yannas IV, Burke JF, “Design of an Artificial Skin”, J Biomed Mater Res 1980 Jan;14(1):65-81; Burke JF, 

Yannas IV, Quinby WC Jr et al., “Successful Use of a Physiologically Acceptable Artificial Skin in the 

Treatment of Extensive Burn Injury”, Ann Surg 1981 Oct;194(4):413-28; and Yannas IV, Burke JF, Orgill JP, 

Skrabut EM, “Would Tissue Can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin”, 

Science 1982 Jan 8;215(4529):174-6. 


Corporation. 97 Prof. Yannas has continued to maintain an active research program on the principles and 

applications of induced tissue regeneration. 98 

Eugene Bell, a long-time faculty member in the biology department at MIT, also pursued in the 1970s a 

line of research that examined interactions between collagen and skin cells. In 1979, Bell and colleagues 

published a paper describing the production in vitro of a tissue-like structure, obtained via contraction of a 

collagen lattice seeded with fibroblasts. 99 In 1981 Bell’s group reported the successful grafting of a 

“living skin equivalent” consisting of fibroblasts cast in collagen lattices and seeded with epidermal 

cells. 100 A patent was obtained for this “tissue-equivalent” in 1984, 101 and Bell left MIT in 1986 to found 

Organogenesis, Inc. and pursue commercial development of the product. He left Organogenesis in 1991 

to return briefly to MIT, but left again in 1992 to found Tissue Engineering Inc. (now TEI Biosciences). 

Bell has led an active proprietary research program at TEI Biosciences, focusing on the further refinement 

of collagen fiber-based scaffolds and the enrichment of these scaffolds with signaling molecules that 

induce stem cell development and tissue regeneration, but has published little in the peer-reviewed 

biomedical literature in recent years. 102 

Although these three lines of research are widely recognized as milestones in the emergence of tissue 

engineering, in terms of visibility, and arguably in terms of scientific influence as well, they have long 

since been eclipsed by the network of TE researchers that grew up around Robert Langer and Joseph (Jay) 

Vacanti. Langer and Vacanti are widely recognized as coauthors on two seminal papers: the 1993 review 

article in Science that marked the “coming out” of tissue engineering as a field, and, with additional 

coauthors, the 1988 paper in the Journal of Pediatric Surgery that introduced the strategy of using 

resorbable artificial polymer matrices seeded with cells as a vehicle for cell transplantation. 103 However, 

their acquaintance and scientific collaboration predated these papers by more than a decade. 

Langer’s graduate studies were carried out under the supervision of yet another MIT researcher active 

during the “prehistory” of TE, Clark Colton of the chemical engineering department. Colton’s own PhD, 

completed in the same department in 1969 under the supervision of Kenneth A. Smith, was entitled 

Permeability and Transport Studies in Batch and Flow Dialyzers with Applications to Hemodialysis. 

Colton’s research on filtration technologies relevant to artificial organs continued following the 

completion of his PhD, and he collaborated with William Chick at Harvard Medical School, Pierre 

Galletti at Brown University and colleagues on the research which led to a 1975 publication in the 

97 

98 

99 

100 

101 

102 

103 

Integra® Dermal Regeneration Template Product Description, http://www.integra-ls.com/busskin_product.shtml 

(URL verified October 26, 2002). 

Yannas IV, “Synthesis of Organs: In vitro or In vivo?” Proc Natl Acad Sci USA 2000 Aug 15;97(17):9354-6; 

and Yannas IV, Tissue and Organ Regeneration in Adults (New York: Springer, 2001). 

Bell E, Ivarsson B, Merrill C, “Production of a Tissue-Like Structure by Contraction of Collagen Lattices by 

Human Fibroblasts of Different Proliferative Potential in Vitro”, Proc Natl Acad Sci USA 1979 

Mar;76(3):1274-8. 

Bell E, Ehrlich HP, Buttle DJ, Nakatsuji T, “Living Tissue Formed in Vitro and Accepted as Skin-Equivalent 

Tissue of Full Thickness”, Science 1981 Mar 6;211(4486):1052-4. 

Bell E, “Tissue-Equivalent and Method for Preparation Thereof”, US Patent 4,485,096, November 27, 1984. 

Dai J, Kumar J, Feng Y et al., “The Specificity of Phenotypic Induction of Mouse and Human Stem Cells by 

Signaling Complexes”, In Vitro Cell Dev Biol Anim 2002 Apr;38(4):198-204; and “Platform Technologies” 

description, TEI Biosciences web site, http://www.teibio.com (URL verified October 27, 2002). 

Langer R, Vacanti JP, “Tissue Engineering”, Science 1993 May 14;260(5110):920-6; and Vacanti JP, Morse 

MA, Saltzman WM et al., “Selective Cell Transplantation Using Bioabsorbable Artificial Polymers as 

Matrices”, J Pediatr Surg 1988 Jan;23(1 Pt 2):3-9. 


Transactions of the American Society for Artificial Internal Organs on a “hybrid artificial pancreas” for 

rats consisting of beta cells cultured on synthetic semipermeable hollow fibers. 104 Colton (with coauthors, 

graduate student Keith Dionne and postdoctoral fellow Martin Yarmush) was the only senior MIT 

researcher represented with a paper at the Granlibakken workshop in 1988. 

Although contemporaneous with this early work on artificial organ technologies in Colton’s lab, the 

research that formed the basis for Langer’s 1974 ScD in chemical engineering was part of a separate line 

of work being pursued by Colton in the area of enzyme engineering. 105 Langer proceeded to a 

postdoctoral fellowship in the laboratory of Dr. Judah Folkman at Harvard Medical School and Children’s 

Hospital in Boston. Folkman’s pathbreaking work on implantable drug delivery systems and on 

angiogenesis in cancer addressed a number of fundamental issues that were to be of broader significance 

for tissue engineering, including identification and analysis of the factors that govern the growth and 

differentiation of blood vessels, and the design of delivery systems to enable the sustained release of 

bioactive proteins and other molecules in a desired location in order to influence tissue growth. Langer’s 

first publication in the area of polymeric drug delivery systems, a line of research that was to become the 

foundation of the work of his own laboratory at MIT, was written in collaboration with Folkman and 

appeared in Nature in 1976. 106 

Langer’s entry into tissue engineering was catalyzed by a collaboration with Jay Vacanti. Vacanti earned 

his MD at the University of Nebraska, and came to Boston in 1974 to begin his postgraduate training in 

surgery. He completed a residency in general surgery at the Massachusetts General Hospital during 1974- 

1981, followed by a fellowship in pediatric surgery at Children’s Hospital from 1981-1983. During the 

period of his residency at MGH, he spent two years – from 1977 to 1979 – in the laboratory of Dr. 

Folkman, where his collaboration with Robert Langer began. Their first joint publication, written in 

collaboration with Folkman and two other colleagues, reported on experiments in the inhibition of tumor 

growth in animal models by regional infusion of a cartilage-derived angiogenesis inhibitor. 107 

Returning to MIT following his postdoctoral work with Folkman, Robert Langer built a highly productive 

research and training program focused primarily on polymer-based drug delivery systems and their 

applications. Vacanti, following his pediatric surgery fellowship, received two further years of clinical 

training in the renowned transplantation program at the University of Pittsburgh, then returned to Boston 

in 1985 to join the staff at Children’s Hospital and launch his own clinical and research program. 

Vacanti’s clinical experience in transplantation in Pittsburgh, and then in launching a pediatric liver 

transplantation program in Boston, confronted him with the intractable problem of organ supply. 

Following his return to Children’s Hospital in Boston in 1985, he began to explore with Langer the 

problem of how to extend to three dimensions the early success of Eugene Bell in growing flat sheets of 

tissue from skin cells. From this emerged the concept of using a porous, resorbable, three-dimensional 

polymer scaffold as a template for cell growth, and the 1988 paper the Journal of Pediatric Surgery 

reporting its experimental application. This technique was to be enormously influential in shaping the 

work of other investigators who entered the field – indeed, it could be said that it provided the intellectual 

104 

105 

106 

107 

Chick WL, Like AA, Lauris V et al., “A Hybrid Artificial Pancreas”, Trans Am Soc Artif Intern Organs 

1975;21:8-15. 

Langer RS, Enzymatic Regeneration of ATP, Thesis (ScD), Massachusetts Institute of Technology Department 

of Chemical Engineering, 1974. 

Langer R, Folkman J, “Polymers for the Sustained Release of Proteins and Other Macromolecules”, Nature 

1976 Oct 28;263(5580):797-800. 

Langer R, Conn H, Vacanti J et al., “Control of Tumor Growth in Animals by Infusion of an Angiogenesis 

Inhibitor”, Proc Natl Acad Sci USA 1980 Jul;77(7):4331-5. 


“scaffolding” for the work of an entire cadre of investigators who shared the long-term vision of creating 

“replacement” solid organs for therapeutic purposes. 

Although Langer himself is not primarily a tissue engineer, TE projects have remained an active line of 

research in his laboratory. He has mentored an extraordinary number of doctoral and postdoctoral 

trainees, some of whom focused their work specifically on tissue engineering applications. Many have 

gone on to establish independent academic careers in which tissue engineering research has played an 

important part. 

Most lead authors in Tissue Engineering have worked at least once with Langer and Jay Vacanti as shown 

in Table F.1 in Appendix 5. Papers by Langer and Vacanti list over 250 coauthors. Several leading 

authors appear to have started as students of Langer or Vacanti, and several more appear only as their coauthors. 

Important alumni of the Langer laboratory who are active in tissue engineering include former 

graduate students: 

• Elazer Edelman (PhD, 1984), currently Professor of Health Sciences and Technology at MIT and 

director of the Harvard-MIT Biomedical Engineering Center) 

• Cato Laurencin (PhD, 1987), currently Professor of Chemical Engineering at Drexel University) 

• W. Mark Saltzman (PhD, 1987), currently Goizueta Foundation Professor of Chemical and 

Biomedical Engineering at Yale University) 

• Lisa Freed (PhD, 1988), currently Principal Research Scientist in Langer’s laboratory) 

• David Mooney (PhD, 1992), currently Professor of Dentistry at the University of Michigan) 

• Michael Yaszemski (PhD, 1995), currently Associate Professor of Bioengineering at Mayo 

Medical School) 

• Jennifer Elisseeff (PhD, 1999), currently Assistant Professor of Biomedical Engineering at Johns 

Hopkins University) 

• Guillermo Ameer (ScD, 1999), currently Assistant Professor of Biomedical Engineering at 

Northwestern University 

Former Langer postdoctoral or research fellows include: 

• Kam W. Leong (currently Professor of Biomedical Engineering at Johns Hopkins University) 

• Linda Griffith (currently Associate Professor of Chemical Engineering at MIT) 

• Peter Ma (currently Associate Professor of Biologic and Materials Sciences at the University of 

Michigan School of Dentistry) 

• Antonios Mikos (currently Professor in Bioengineering and Chemical Engineering at Rice 

University) 

• Laura Niklason (currently Assistant Professor of Biomedical Engineering at Duke University) 

• Kristi Anseth (currently Associate Professor of Chemical Engineering at the University of 

Colorado) 

• Christine Schmidt (currently Associate Professor of Biomedical Engineering at the University of 

Texas at Austin) 

• Gordana Vunjak-Novakovic (currently Principal Research Scientist in Langer’s laboratory and 

Adjunct Professor of Chemical and Biological Engineering at Tufts University). 

• Michael Pishko (currently Associate Professor of Chemical Engineering at Penn State University) 

• Venkatram Prasad Shastri (currently Research Assistant Professor at the University of 

Pennsylvania School of Medicine) 

• David Lynn (currently Assistant Professor of Chemical Engineering at the University of 

Wisconsin, Madison) 

Jay Vacanti continues an active research program in his Tissue Engineering and Organ Fabrication 

Laboratory at the Massachusetts General Hospital. Together with junior colleagues including brother 


Charles Vacanti and Anthony Atala, he has helped define a branch of tissue engineering that has earned 

substantial public visibility with a fairly aggressive approach to early demonstration of potential new 

clinical applications. He has also played an important role in developing the infrastructure of the field 

through his active involvement in the creation and early leadership of the journal Tissue Engineering and 

the Tissue Engineering Society. 

Another prolific source of researchers who have gone on to be active in tissue engineering is the 

laboratory of Douglas Lauffenburger, Professor of Chemical Engineering and Director of the 

Biotechnology Process Engineering Center, an NSF-funded Engineering Research Center at MIT, and 

formerly a faculty member at the University of Pennsylvania and the University of Illinois. As with 

Langer, Lauffenburger’s own research has been centered away from the core of tissue engineering, 

focusing primarily at the molecular level on quantitative physicochemical principles governing ligandand 

architecture-controlled cell behavior. 

Graduates from Lauffenburger’s tenure at the University of Pennsylvania who are active in tissue 

engineering include: 

• Robert Tranquillo (PhD in Chemical Engineering, 1986), currently Distinguished McKnight 

University Professor of Bioengineering at the University of Minnesota 

• Helen Buettner (PhD in Chemical Engineering, 1987), currently Associate Professor of 

Biomedical Engineering at Rutgers University 

• Paul DiMilla (PhD in Chemical Engineering, 1991), who served as a postdoctoral fellow in the 

laboratory of George Whitesides at Harvard, was Assistant Professor of Chemical Engineering at 

Carnegie Mellon University and most recently served on the staff of Organogenesis, Inc. 

From Lauffenburger’s tenure at the University of Illinois: 

• Christine Schmidt (PhD in Chemical Engineering, 1995) completed a postdoctoral fellowship 

with Robert Langer and is now Associate Professor of Biomedical Engineering at the University 

of Texas at Austin. 

From Lauffenburger’s tenure at MIT: 

• Sean Palecek (PhD in Chemical Engineering, 1998) is now Assistant Professor of Chemical 

Engineering at the University of Wisconsin, Madison 

• David Schaffer (PhD in Chemical Engineering, 1998) is now Assistant Professor of Chemical 

Engineering at the University of California, Berkeley 

• Anand Asthagiri (PhD in Chemical Engineering, 2000) is now Assistant Professor of Chemical 

Engineering at the California Institute of Technology 

Former Lauffenburger postdoctoral fellows include: 

• Peter Zandstra, now Assistant Professor in the Department of Chemical Engineering and Applied 

Chemistry at the University of Toronto 

• Fred Allen, now Assistant Professor of Biomedical Engineering at Drexel University 


Another important laboratory active in tissue engineering, with links to both Harvard and MIT, is the 

Center for Engineering in Medicine / Laboratory of Surgical Science and Engineering at the 

Massachusetts General Hospital, led by Ronald G. Tompkins, who also serves as Chief of Staff and 

Director of Research at the Shriners Burns Hospital in Boston. Dr. Tompkins earned his MD at Tulane 

University in 1976, and his ScD in chemical engineering at MIT in 1983, under the supervision of Clark 

Colton and Kenneth A. Smith. Another long-serving senior member of the lab and Colton postdoctoral 

alumnus, Martin Yarmush, MD, PhD, has recently assumed the leadership of the Department of 

Biomedical Engineering at Rutgers University. A third lab member, Mehmet Toner, earned his PhD in 

1989 from the Medical Engineering and Medical Physics Program in the Harvard-MIT Division of Health 

Sciences and Technology, under the supervision of Ernest Cravalho. Tompkins, Toner, Yarmush and 

other colleagues have been collaborating on fundamental research intended to lay the foundations for 

rational design of a bioartificial liver. Yarmush/Tompkins postdoctoral fellow Howard Matthew has 

established a research group at Wayne State University focusing on biomaterials for tissue engineering. 

Toner alumna Sangeeta Bhatia (PhD in the HST Program, 1997) is now Associate Professor of 

Bioengineering and head of the Microscale Tissue Engineering Laboratory at the University of California, 

San Diego, and Toner/Cravalho alumnus Jens Karlsson (PhD in Mechanical Engineering, 1994) is now 

Associate Professor of Mechanical Engineering at Georgia Institute of Technology and a member of the 

Georgia Tech/Emory Center for the Engineering of Living Tissues. 

Alan Grodzinsky, who earned his ScD in electrical engineering at MIT in 1974, under the supervision of 

James Melcher, with a thesis on membrane electromechanics, is now Professor of Electrical, Mechanical, 

Bioengineering and Biological Engineering and Director of the Center for Biomedical Engineering at 

MIT. Grodzinsky leads a wide-ranging research program on the mechanical, chemical and electrical 

properties of connective tissue, including studies on cartilage tissue engineering. Grodzinsky lab alumnus 

Robert Sah (ScD in the HST Medical Engineering and Medical Physics Program, 1990) is now Associate 

Professor of Bioengineering and leads the Cartilage Tissue Engineering Laboratory at the University of 

California, San Diego. 

Donald Ingber, another physician-researcher who served as a postdoctoral fellow in Judah Folkman’s 

laboratory during the mid-1980’s, now maintains his own laboratory as a Professor of Pathology at 

Harvard Medical School and Children’s Hospital. Ingber’s work has been distinctive for its focus on 

mathematical and mechanical engineering approaches to molecular and cellular structures. Collaborators 

in recent years have included George Whitesides of the chemistry department at Harvard, and Whitesides’ 

postdoctoral fellow from 1994-96, Milan Mrksich, who is now associate professor in the chemistry 

department at the University of Chicago. 

Other Boston-area alumni prominent in tissue engineering through their own work and/or through those 

they have trained include: 

• Nicholas Peppas completed his ScD in Chemical Engineering at MIT in 1974, under the 

supervision of Edward Merrill, and did postdoctoral work at the MIT Arterisclerosis Center under 

HST faculty member Robert Lees. Peppas has been on the faculty at Purdue University since 

1976 and is presently the Showalter Distinguished Professor in the School of Chemical 

Engineering; he will be moving to the University of Texas at Austin in December, 2002. 

Peppas’s work has focused primarily on polymers and drug delivery technology. He supervised 

Antonios Mikos’s master’s and doctoral theses at Purdue. 

• Michael Sefton completed an ScD in Chemical Engineering at MIT in 1974, under the 

supervision of Edward Merrill, and is now director of the Institute of Biomaterials and 

Biomedical Engineering at the University of Toronto 


• Barry Solomon, PhD served as a postdoctoral fellow at MIT from 1975-77 and published in 

collaboration with Clark Colton, and has pursued research on biohybrid artificial organ systems at 

Amicon, WR Grace, and most recently at Circe Biomedical 

• Rena Bizios completed her PhD in Chemical Engineering at MIT in 1979 under the supervision 

of Robert Lees. She is presently Professor of Biomedical Engineering and leads an active TE 

research program at Rensselaer Polytechnic Institute. 

• Elliot Chaikof, MD, PhD completed a residency in general surgery at Massachusetts General 

Hospital and a PhD in Chemical Engineering at MIT in 1989, under the supervision of Edward 

Merrill; he is now Chief of the Division of Vascular Surgery at Emory University and a member 

of the Georgia Tech / Emory Center for the Engineering of Living Tissues 

There is no single institutional or programmatic locus for tissue engineering in the Boston area. 

“Regenerative biological technologies”, defined as encompassing tissue engineering, micro- and nanoscale 

biomedical engineering, and hybrid systems, has become one of three major research thrust areas of 

the Harvard-MIT Division of Health Sciences and Technology (HST). The Department of Chemical 

Engineering, the Division of Biological Engineering and the Center for Biomedical Engineering at MIT 

are also central to the network of tissue engineering researchers at Harvard and MIT, and most of the 

more prominent researchers have multiple appointments in these and other units while maintaining 

numerous collaborations that cross formal departmental or program boundaries. 

University of California, San Diego 

Tissue engineering at the University of California, San Diego (UCSD) is centered on the Department of 

Bioengineering, the latest incarnation of one of the oldest bioengineering programs in the United States. 

The program’s origins can be traced to 1964-65, when Benjamin Zweifach, a physiologist with a lifelong 

interest in the study of blood microcirculation, took a sabbatical from his professorship at New York 

University to serve as a visiting professor at the California Institute of Technology. While at Caltech, 

Zweifach had the opportunity to share ideas with Harold Wayland, a pioneer in the engineering study of 

microcirculation, and his colleagues Y.C. Fung, Professor of Aeronautics and Applied Mathematics at 

Caltech, and research fellow Marcos Intaglietta, who had completed his PhD in Applied Mechanics at 

Caltech in 1963. In 1966, Zweifach, Fung and Intaglietta moved to the then-new UCSD to launch a new 

bioengineering program in its Department of Applied Mechanics and Engineering Sciences. 

In addition to his pioneering activities in biomechanics and bioengineering, Fung was to play a central 

role in the creation of the concept of tissue engineering as we know it today. As noted previously in 

Chapter 3, in 1985, Fung submitted a proposal to NSF for an Engineering Research Center to be entitled 

“Center for the Engineering of Living Tissues”. 108 Reflecting its intellectual origins, the proposal 

envisioned a program of research with a strong biomechanics and engineering flavor. Although this 

proposal was not accepted, the UCSD research program continued to develop through support from other 

sources, notably the Whitaker Foundation, and the tissue engineering concept stayed alive, to be raised by 

Fung at the spring 1987 review panel meeting of NSF’s Bioengineering and Research to Aid the 

Handicapped Program. 

The development of the UCSD Program was bolstered during this period by the arrival from Columbia 

University in 1988 of two other pioneering researchers in biomechanics and the study of the 

microcirculation – Richard Skalak and Shu Chien. As Director of Columbia’s Bioengineering Institute, 

Skalak had been a participant in the special Panel Meeting on Tissue Engineering at NSF in October 

108 

“A Proposal to the National Science Foundation for An Engineering Research Center at UCSD, CENTER FOR 

THE ENGINEERING OF LIVING TISSUES”, UCSD #865023, courtesy of Y.C. Fung, August 23, 2001. 


1987, and helped to coordinate the Granlibakken workshop in February 1988 along with Fung and Fred 

Fox of the University of California, Los Angeles. Additional UCSD researchers represented at the 

Granlibakken workshop were John Hansbrough and Savio L.Y. Woo. Hansbrough, a surgeon and leader 

in research on burn treatment, had begun to investigate skin substitutes in the mid-1980s and maintained 

an active line of research in this area until his untimely death in 2001. Although not a member of the 

bioengineering program proper, Hansbrough held an affiliation with the cross-departmental UCSD 

Institute for Biomedical Engineering (now the Whitaker Institute of Biomedical Engineering). 109 Woo, an 

engineer who has focused on biomechanics of connective tissue, led the Orthopedic Bioengineering 

Laboratory at UCSD until his departure in 1990 for the University of Pittsburgh. 

At present, the Department of Bioengineering at UCSD supports a wide range of fundamental and applied 

research that is relevant to tissue engineering. Core faculty who specifically identify their research as 

focused at least in part on tissue engineering include: 

• Sangeeta Bhatia MD, PhD (PhD in Health Sciences and Technology, MIT, 1997, under Mehmet 

Toner) is Associate Professor of Bioengineering and head of the Microscale Tissue Engineering 

Laboratory, focusing on hepatic tissue engineering and BioMEMS (biological micro-electromechanical 

systems). 

• Shu Chien, MD, PhD, formerly of Columbia University, is Professor of Bioengineering and 

Medicine, and Director of WIBE, leads the Vascular Bioengineering Laboratory, investigating 

molecular mechanisms by which mechanical forces affect cellular functions such as proliferation, 

migration and apoptosis. 

• Andrew McCullough (PhD in Theoretical and Applied Mechanics, University of Auckland, NZ, 

1986) is Professor of Bioengineering, and leads the Cardiac Mechanics research group. Group 

member Jeffrey Omens (PhD in Applied Mechanics and Engineering Sciences (Bioengineering), 

UCSD, 1988, under Y.C. Fung) is Associate Adjunct Professor of Medicine and Bioengineering. 

• Bernhard Palsson, PhD, Professor of Bioengineering, joined the department in 1995 from a prior 

faculty position at the University of Michigan, and leads the Genetic Circuits research group; his 

TE-related work focuses on tissue engineering of bone marrow. 

• Robert Sah, MD, ScD (Medical Engineering and Medical Physics in the HST Program at MIT 

under Alan Grodzinsky, 1990) is Associate Professor of Bioengineering and leads the Cartilage 

Tissue Engineering laboratory. 

• John A. Frangos (PhD in Chemical Engineering (Bioengineering) at Rice University under Larry 

McIntire, 1987) was an active member of the department core faculty from 1994-2002; he is 

currently Adjunct Professor, and continues to lead research on bone and vascular tissue 

engineering as president of the new La Jolla Bioengineering Institute. 

109 

The UCSD Institute for Biomedical Engineering, which was renamed the Whitaker Institute for Biomedical 

Engineering (WIBE) in 1999 in recognition of support from the Whitaker Foundation, is a cross-departmental 

unit that promotes and coordinates interdisciplinary research at the interfaces of engineering, biology and 

medicine. The Institute includes among its membership faculty from the Department of Bioengineering as well 

as other departments from the schools of engineering, medicine and natural science and other affiliated 

organizations. WIBE, directed by Shu Chien, has identified “tissue engineering research” as one of its major 

research thrusts. 


Rice University 

At Rice University, faculty active in tissue engineering are based in the Institute of Biosciences and 

Bioengineering (IBB) and the Department of Bioengineering, both chaired by Larry McIntire. The IBB 

was founded in 1986, and serves as a coordinating mechanism for cross-disciplinary research in 

biological, chemical and engineering disciplines involving researchers at Rice and at Texas Medical 

Center, the Johnson Space Center, industry, and other collaborators. Early efforts to organize a research 

focus in tissue engineering at Rice were bolstered by a special opportunity award from the Whitaker 

Foundation to IBB in 1994, and a large development grant from the Whitaker Foundation in 1996 made 

possible the creation of the Department of Bioengineering. 

McIntire completed his PhD at Princeton University in 1970, with a thesis in the area of fluid dynamics. 

In connection with artificial heart-related research in Houston during the 1970s, he became involved in 

studies of the effects of hemodynamics on blood coagulation, later extending that work to effects on 

endothelial cells and blood vessels. Within this still-ongoing line of work, he has supervised the PhD 

research of the following individuals who have established independent careers in tissue engineering, 

including: 

• Jeffrey Hubbell (PhD in Chemical Engineering, 1986), now Professor of Biomedical Engineering 

and director of the Institute for Biomedical Engineering at the Eidgenössische Technische 

Hochschule (ETH) in Zürich 

• John A. Frangos (PhD in Chemical Engineering, 1987) 

• Timothy M. Wick (PhD in Chemical Engineering, 1988), currently Associate Professor of 

Chemical Engineering at Georgia Tech, and a member of the Georgia Tech/Emory Center for the 

Engineering of Living Tissues 

• B. Rita Alevriadou (PhD in Chemical Engineering, 1992), currently Assistant Professor of 

Biomedical Engineering at Johns Hopkins University 

• Charles W. Patrick, Jr. (PhD in Chemical Engineering, 1994), now Assistant Professor and 

Director of Research, Department of Plastic Surgery, MD Anderson Cancer Center, and Adjunct 

Assistant Professor in the Department of Bioengineering at Rice University 

• Julia M. Ross (PhD in Chemical Engineering, 1995), now Associate Professor of Chemical and 

Biomedical Engineering at the University of Maryland, Baltimore County 

Another cornerstone of the tissue engineering program at Rice has been Antonios Mikos, who earned his 

PhD in chemical engineering under Nicholas Peppas at Purdue, then completed a postdoctoral fellowship 

with Robert Langer at MIT. Mikos joined the faculty at Rice in 1992 and is now John W. Cox Professor 

of Bioengineering and Chemical Engineering. Mikos leads a broad research program known especially 

for contributions to bone tissue engineering and to the further development of polymer and scaffolding 

technology for TE applications. In 1993 he created the continuing education course “Advances in Tissue 

Engineering” that continues to be offered annually at Rice. Mikos lab alumni active in tissue engineering 

include: 

• Susan Ishaug-Riley (PhD in Chemical Engineering, 1996), who joined the staff of Advanced 

Tissue Sciences 

• Susan Peter (PhD in Chemical Engineering, 1998), who joined the staff of Osiris Therapeutics 


• Vasilios Sikavitsas (postdoctoral fellow) who is now Assistant Professor of Chemical 

Engineering and Materials Science at the University of Oklahoma 

• Aaron Goldstein (postdoctoral fellow) who is Assistant Professor of Chemical Engineering at 

Virginia Polytechnic Institute and State University 

• Julia Babensee (postdoctoral fellow) who is Assistant Professor of Biomedical Engineering at 

Georgia Institute of Technology, and is active in the Georgia Tech/Emory Center for the 

Engineering of Living Tissues 

Other Rice core faculty in TE include: 

• Kyriacos Athanasiou (PhD under Van Mow, Columbia University, 1989), leads the 

Musculoskeletal Bioengineering Laboratory. 

• Kyriacos Zygourakis, PhD, Professor of Bioengineering and Chair of the Chemical Engineering 

Department, maintains a research track in TE as part of a diverse research program in 

bioengineering and chemical engineering. 

• Jennifer West (PhD thesis under Jeffrey Hubbell during his tenure at the University of Texas at 

Austin, 1996) is Associate Professor in the Department of Bioengineering. 

Other Rice alumni active in TE include: 

• Konstantinos Konstantopoulos (PhD in Chemical Engineering under J. David Hellums, 1995), 

now Assistant Professor of Chemical Engineering at Johns Hopkins University 

• Brenda K. Mann, (PhD in Chemical Engineering, under Jacqueline V. Shanks, 1997), now 

Assistant Professor in the Keck Graduate Institute of Applied Life Science, Claremont, CA 

Georgia Institute of Technology / Emory University 

The Georgia Tech/Emory Center for the Engineering of Living Tissues (GTEC) is a National Science 

Foundation-sponsored Engineering Research Center established in 1998 within the context of an evolving 

institutional framework for research and education in biomedical engineering linking the Georgia Institute 

of Technology with the Emory University School of Medicine. A key milestone in the development of 

bioengineering at Georgia Tech was the 1993 receipt of a Whitaker Foundation Biomedical Engineering 

Development Award, which provided funds for faculty and institutional development and the creation of 

a new PhD program. Today, the major institutional elements in which bioengineering is centered are the 

Parker H. Pettit Institute for Bioengineering and Bioscience (IBB) at Georgia Tech and the joint Georgia 

Tech/Emory Wallace H. Coulter Department of Biomedical Engineering. 

Both GTEC and IBB are led by Robert Nerem, who joined the Georgia Tech faculty in 1987. Nerem 

received his PhD from Ohio State University in 1964, and served on the faculty of the Department of 

Aeronautical and Astronautical Engineering at Ohio State and the Department of Mechanical Engineering 

at the University of Houston before coming to Georgia Tech. He has been active in bioengineering 

research for more than thirty years, starting with work on cardiovascular fluid dynamics and expanding 

into the study of the effects of physical forces on anchorage-dependent mammalian cells, especially as 

found in blood vessels. Nerem was represented at the 1988 Granlibakken workshop with a paper on the 

implications for the development of endothelialized synthetic vascular grafts of cell responses to shear 

stress. 


This paper is among the top 10% papers 

most cited in the TE review articles. 

Ziegler T 

Nerem RM 

Sambanis A 

Nerem RM, 1991, Ann Biomed Eng p529 

Ziegler T, 1994, J Cell Biochem p204 

Ziegler T, 1995, Ann Biomed Eng p216 

Nerem RM, 1995, Tissue Engineering p3 

Tziampazis E, 1995, Biotechnol Progr p115 

Nerem RM, 2000, Yonsei Medical Journal p735 

Georgia Institute of Technology 

Legend 

* 

Paper Author 

Patent Inventor 

Lead Author 

Lead Inventor 

Paper or patent 

acknowledging 

NSF support 

Other author(s) 

appearing on one 

paper only 

Lead author 

institutions 

1991 

1994 

1995 

2000 

Figure 5.1: Nerem has been active in bioengineering for more than 25 years. He has conducted 

fundamental research on problems in cardiovascular fluid dynamics. This Figure shows his work 

on the influence of physical forces on anchorage-dependent mammalian cells, with much of this 

work focusing on the cells which make up a blood vessel, and some work on modeling the 

pancreas. (From CHI Report Appendix 5) 

The Georgia Tech/Emory tissue engineering program was initiated in 1994 and expanded with the support 

of the NSF ERC award beginning in 1998. GTEC lists 29 faculty participants, whose primary faculty 

appointments are concentrated in the joint Biomedical Engineering department, the Mechanical 

Engineering department at Georgia Tech, and the Surgery and Orthopedic Surgery departments at Emory. 

Georgia Tech/Emory alumni active in tissue engineering include: 

• Kacey Marra, now Assistant Professor of Surgery at the University of Pittsburgh, and Janine 

Orban, now a research scientist at the DePuy Orthobiologics division of Johnson & Johnson, 

former postdoctoral fellows of Elliot Chaikof 

• Naomi Chesler, currently Assistant Professor of Biomedical Engineering at the University of 

Wisconsin, Madison, who carried out postdoctoral research with David Ku and Zorina Galis 

Columbia University 

Bioengineering studies have been ongoing at Columbia University since 1962, notably in the areas of 

cardiac and orthopedic biomechanics, although a formal department of biomedical engineering was not 

created until 2000. Three of the leaders in the development of bioengineering at Columbia have played 

prominent roles in the emergence of tissue engineering. 


Richard Skalak received his PhD in civil engineering and engineering mechanics from Columbia in 1954, 

and joined the faculty in that department upon completing his doctorate. His early research was focused 

on fluid mechanics, but by the mid-1960s he began to combine engineering mechanics and biomedical 

sciences in a series of pioneering investigations, notably in the area of blood rheology. As noted 

previously, Skalak was a participant in the special Panel Meeting on Tissue Engineering at NSF in 

October 1987, and helped to coordinate the 1988 Granlibakken workshop. Skalak served as director of 

Columbia’s Bioengineering Institute, a forerunner of today’s academic department, until his departure for 

the University of California at San Diego in 1988. He died in 1997. 

Following completion of his medical training in Taiwan, Shu Chien came to the United States to study 

physiology at Columbia, receiving his PhD in 1957 with a thesis on the role of the sympathetic nervous 

system in compensatory mechanisms to hemorrhage. Chien continued this line of research as a faculty 

member at Columbia, and by the mid-1960s was focusing on blood rheology. Starting in the late 1960s 

he conducted important work in this area in collaboration with Richard Skalak. Shu Chien moved to 

UCSD in 1988 as well, where he has continued his research on blood rheology at the molecular and 

cellular level, and has served as director of WIBE and chair of the Department of Bioengineering. 

Van C. Mow earned his doctorate in applied mechanics at Rensselaer Polytechnic Institute in 1966. As a 

faculty member at RPI in the early 1970s, he began to focus on orthopedic biomechanics. He joined the 

Department of Orthopedic Surgery at the Columbia University College of Physicians and Surgeons and 

the Department of Mechanical Engineering in the School of Engineering and Applied Sciences at 

Columbia in 1986, and currently serves as director of the Orthopedic Research Laboratory and chairman 

of the new Department of Biomedical Engineering. Mow participated in the Granlibakken workshop in 

1988. Former Mow doctoral students active in tissue engineering include: 

• Kyriacos Athanasiou (PhD, 1989), now Professor of Bioengineering at Rice University 

• Gerard Ateshian (PhD, 1991), currently Professor of Mechanical Engineering and Bioengineering 

at Columbia 

• Louis Soslowsky (PhD, 1991), currently Associate Professor of Bioengineering at the University 

of Pennsylvania 

• Farshid Guilak (PhD, 1992), now Assistant Professor of Orthopedic Surgery at Duke University 

University of Pennsylvania 

The University of Pennsylvania has offered graduate degrees in bioengineering since 1961, and its 

Department of Bioengineering, established in 1973, was one of the earliest in the field. Penn currently 

offers a PhD program track in Cell and Tissue Engineering. More generally, however, as one of the most 

productive bioengineering departments, with long-standing research activities in many aspects of the 

application of mechanics to biomedical problems, the bioengineering department at Penn has trained a 

number of researchers currently active in tissue engineering. 

Current Penn bioengineering faculty active in tissue engineering include: 

• Paul Ducheyne (PhD in Materials Science, Katholieke Universiteit Leuven), Professor of 

Bioengineering 

• Keith Gooch (PhD in Chemical Engineering, Penn State, 1995, under John A. Frangos), Assistant 

Professor of Bioengineering 


• Steven Nicoll (PhD in Bioengineering, University of California, Berkeley and San Francisco, 

2000), Assistant Professor of Bioengineering 

• Solomon Pollack (PhD in Physics, University of Pennsylvania, 1961), Professor of 


• Louis Soslowsky (PhD in Engineering Mechanics, Columbia, 1991, under Van C. Mow), 

Associate Professor of Bioengineering 

Penn bioengineering alumni active in the field include: 

• Fred Allen (PhD, 1996, under Solomon Pollack) is Assistant Professor of Biomedical 

Engineering at Drexel University 

• Kristen Billiar (PhD, 1998, under Michael Sacks) worked at Organogenesis after completing her 

doctorate, and is now Assistant Professor of Biomedical Engineering at Worcester Polytechnic 

Institute 

• Andres Garcia (PhD, 1996, under David Boettiger and Paul Ducheyne) is Assistant Professor of 

Mechanical Engineering at Georgia Tech and a participant in GTEC 

• Kevin Healy (PhD, 1990, under Paul Ducheyne) is Associate Professor of Bioengineering and 

Materials Science and Engineering at the University of California, Berkeley 

• Clark Hung (PhD, 1995, under Solomon Pollack) is Assistant Professor of Biomedical 

Engineering at Columbia University 

• David Kohn (PhD, 1989, under Paul Ducheyne) is Associate Professor of Biologic and Materials 

Sciences at the University of Michigan School of Dentistry 

• Michelle LaPlaca (PhD, 1996, under Lawrence Thibault) is Assistant Professor of Biomedical 

Engineering at Georgia Tech, and a member of GTEC 

• Helen Lu (PhD, 1998, under Solomon Pollack) is Assistant Professor of Biomedical Engineering 

at Columbia University 

• David Shreiber (PhD, 1998, under David Meaney) is Assistant Professor of Biomedical 

Engineering at Rutgers University 

Chemical Engineering graduates from Douglas Lauffenburger’s tenure at the University of Pennsylvania 

have been noted previously. 

5.3 Collaborations Among Tissue Engineers 

We examined patterns of co-authorship for several prominent authors in tissue engineering in order to 

understand the nature of collaboration occurring in the field. Through an analysis of primary and 

secondary authors on a selection of tissue engineering papers, CHI Research found several core 

collaborations which appear to have produced fruitful results. Appendix 5 summarizes CHI’s conclusions 

about co-authorship patterns. The analysis revealed the interweaving of public and private knowledge 

and the public and private sectors in the development of tissue engineering research. Figure 5.3 is 

included as an illustration (with Figure 5.2 as legend). The Figure shows that Jay Vacanti and Langer are 

prominent not only because of their highly cited Science paper referred to above; nor because they have 


double or triple the number of papers compared to any other lead author; but also because of the highly 

collaborative nature of their work. Nine of the other lead authors shown in this Figure co-authored papers 

with Vacanti and/or Langer. Many of these might be PhD students who became established in their own 

right, including Mooney, Atala, Mikos and Ma. 

Authors A & B collaborated with Vacanti 

and/or Langer in 1993, 1994 and - for author 

A only - 1995 & 1996 

Authors A & B collaborated 

with Vacanti and/or Langer in 

1994 on the same paper. 

Author 

1st year 

Papers 

Pre-1990 

1990 

1991 

1992 

1993 

1994 

1995 

1996 

1997 

1998 

1999 

2000 

2001 

A 19XX T N = Number of N N N N N N N/M N N 

papers author 

B 19XX T 

published each year 

that are in the set. N N N N N N N N N 

C 19XX T N N N N N N N N N 

D 19XX T N N N N 

Authors B & C work 

together on all or almost all 

of their papers (i.e. 

equivalent to dots and bars 

connecting the authors in 

every year.) 

Total number of papers 

Year of author's first paper in the set. 

Authors C & D collaborated 

in 1994 & 1997. 

M = number of papers 

acknowledging NSF support. 

Figure 5.2: Legend for Overview of Lead Author Coauthorship (to explain Figure 5.3) 


1st year 

Papers 

Pre-1990 

1990 

1991 

Author 

Vacanti JP 1988 92 2 1 3 4 13/2 12/3 7/2 8/3 7/3 2 14 15 4 

Langer R 1985 76 2 3 7 1 11/3 11/3 8/3 6/3 8/3 6/2 9 2 2 

Vacanti CA 1991 31 2 3 10/1 2 3 2 1 1 2 5 

Mooney DJ 1990 53 1 1 2 2 5/2 4/2 5/3 4/1 7/5 10/2 10/2 2 

Ingber DE 1987 17 5 1 2 1 4 1 1 1 1 

Atala A 1992 28 2 4 2 2 1 5 4 7 1 

Yoo JJ 1997 10 1 2 3 3 1 

Mikos AG 1993 25 5/1 3/3 1 2 2 4 4 3 1 

Freed LE 1993 20 2 4 1 2 4 5 1 1 

Vunjaknovakovic G 1993 18 1 3 1 2 4 5 1 1 

Ma PX 1995 15 2 2 3 1 3 1 3 

Grande DA 1987 12 2 2 1 1 1 3 1 1 

Caplan AI 1989 27 2 2 4 4 3 2 4 4 2 

Goldberg VM 1989 17 2 2 3 2 1 1 4 3 1 

Bruder SP 1990 10 1 1 4 3 1 

Yannas IV 1967 21 7 2 1 1 2 5 1 1/1 1 

Spector M 1997 14 3 3 2 4/1 2 

1992 

1993 

1994 

Galletti PM 1977 10 9 1 

Aebischer P 1987 26 8 1 4 3/1 1 2 2 1 2 1 1 

Winn SR 1987 14 4 3 1 2 1 3 

Hollinger JO 1986 14 2 2 3 1 2 3 1 

Wozney JM 1988 11 1 2 2 3 2 1 

Boyan BD 1988 14 3 1 1 5/1 1/1 2 1 

Schwartz Z 1988 10 2 1 3/1 1/1 2 1 

Athanasiou KA 1995 11 1 3 1 2 3 1 

Reddi AH 1972 13 5 5 1 1 1 

Green H 1975 11 10 1 

Bell E 1981 11 8 3 

Hansbrough JF 1988 11 3 3 2 1 1 1 

Figure 5.3: Overview of Lead Author Coauthorship Patterns 

1995 

1996 

1997 

1998 

1999 

2000 

2001 


6.0 Activities in the Corporate Sector 

Tissue engineering remains, in many respects, an eclectic mix of topical foci and research styles, with 

work of an ad hoc or “Edisonian” character continuing to play a strong role especially in the corporate 

sector. Overall, the corporate sector is recognized as having played a notable role in the development of 

this unique field, mostly due to the high level of corporate R&D funding injected into the field as 

compared to the relatively small influx of funds from the federal government. 

As many of our interviewees note, TE has traditionally been considered a high-risk investment. As a 

result, few agencies or program officers in the government—NSF’s Division of Bioengineering and 

Environmental Systems (BES) being a notable exception—were willing to provide funds for such new 

and creative research. Many interested in pursuing research in TE were often forced to find alternate 

means of funding, such as by bootstrapping funds from other grants, patent revenue or clinical department 

revenues, or by bringing their ideas to the private sector. Thus, much of the work in tissue engineering in 

the corporate sector is a result of a direct transfer of academic work to industry in a rush to bring viable 

products to market. However, because corporate R&D has traditionally focused on the creation of 

proprietary intellectual content and less on the solution of broader challenges in science or engineering, 

knowledge transfer from industry back to academia has been limited. 

The WTEC 110 report on tissue engineering provides a brief overview to the corporate state of affairs: 

In a little over a decade, more than $3.5 billion has been invested in worldwide research and 

development in tissue engineering. Over 90% of this financial investment has been from the 

private sector (Lysaght and Reyes 2001). Currently there are over 70 start-up companies or 

business units in the world, with a combined annual expenditure of over $600 million dollars. 

Tissue-engineering firms have increased spending at a compound annual rate of 16% since 1990. 

An interesting recent tend has been the emergence of significant activity in tissue engineering 

outside the United States. At least 15 European companies are now active (Lysaght, MJ, and 

Reyes 2001). 

The types of TE firms can be divided into four major categories: (1) structural applications, (2) metabolic 

applications, (3) cellular applications, and (4) other enabling technologies (some firms may actually fall 

into multiple categories, but are classified here by their primary focus areas). In Chapter 4, we provided 

information on some of the major tissue engineered products and the companies which produce them. In 

this section, we examine 28 firms that started before 1994, in order to understand the character and 

influence of such firms during the period when tissue engineering was just beginning to emerge. Figure 

6.1 lists the years the companies began. Since our goal was to investigate private sector activity in the 

early years of tissue engineering, we limited our exploration to companies that started before 1994. Table 

6.1 on the next several pages lists US-based companies in the early days of the field, and (consistent with 

the theme of this report) examines their origins. 

110 http://www.wtec.org/loyola/te/final/te_final.pdf 


Table 6. 1: A Sample of Tissue Engineering Companies and their Origins 

Name 

Interpore Cross 

International, Inc. 

BioHybrid 

Technologies 

Year 

Started 

Founded By Founder Affiliation (if known) Origin/Institutional Links 

1975 Edwin Shors cofounder, 

Company founded on patent held The company originated as a product of the ideas of 3 people from Penn State University and 

Edward by inventor at Pennsylvania State Penn State College in early to mid 1970s. Eugene White, a material scientist from Penn was 

Funk, Ingeborg University 

interested in uses of a scanning electron microscope, he had a colleague (now deceased) at the 

Funk, 

Department of Marine Geology who was interested in corals as indicators of geological events. 

White's nephew Rodney White (now chief of vascular surgery at UCLA) was looking for a job. 

They collectively came up with the notion of making materials with inteconnected porosity (similar 

to corals) which may be optimal for connective tissue growth bone growth. They made a variety of 

implants and realized the medical value of the experiments (particularly in the area of 

cardivasicular applications paticularly prostheses). The company was eventually founded on that 

principle. The concept was patented with Penn State holding the patent. The group called their 

work tissue gardening . 

1985 Founded by Bill Harvard Medical School Bill Chick had set up a diabetes unit at U Mass Worcester, and was interested in developing 

Chick and John L. 

artificial pancreas using insulin-producing microreactors; found that expensive to fund with grants; 

Hayes 

started to look - together with John Hayes - for funding from industry. First 8 years of company 

supported by WR Grace. In 1992, WR Grace and Biohybrid parted, and Grace bank-rolled Cerce 

(put artifical pancreas project on ice). Biohybrid went on its own with microencapsulation 

technology; funded by NIST ATP 4 year grants, JDF grant; NSF SBIR grant; no university 

affiliations; had advisory boards that have academics and academic consultants 

Celox 

Laboratories, Inc. 

(merged with 

Protide in 2001) 

Creative 

BioMolecules, 

Inc.(now Curis Inc 

after merger with 

Ontogeny and 

Reprogenesis) 

1985 Milo R. Polovina 

has been President, 

Chief Executive 

Officer, Treasurer, 

and Secretary of 

the Company and 

has served as a 

Director since 

1985. 

1985 Charles Cohen, 

Fred Craves, 

Roberto Crea 

Company started to research, develop, manufacture and market cell biology products that are 

used in the propagation of cells derived from mammals, including humans and other species; 

Global marketing agreement with ICN Pharmaceuticals; signed an option agreement with the 

University of Minnesota Office of Patents and Technology Marketing for an infusible grade solution 

for non-cryopreserved human hematopoietic stem cells. This option agreement allowed Protide to 

have the exclusive right to evaluate the technology and possibly commence negotiations with the 

University for worldwide commercialization. 

Jay Vacanti and Bob Langer of MIT thought about a way of using polymers and cells to make new 

tissues, and that led to Neomorphics, which subsequently merged with Advanced Tissue 

Sciences. A portion of these patents got licensed to Reprogenesis, which is now part of Curis; 

Reprogenesis also had start-up support from Pfizer. Curis has collaborations with Stryker 

Corporation, Biogen, Inc. 

LifeCell 

Corporation 

1986 Steve Livesay University of Texas, Austin University of Texas, Austin; More than 15 years ago, in a laboratory at the University of Texas, Dr 

Stephen Livesey, MD, PhD, and his colleagues were studying the formation of different structures 

of ice. Their goal was to develop a method of freeze-drying biological tissues and cells without 

damaging their structural or biochemical integrity. What they invented was the first of the patented 

preservation technologies which form the basis of LifeCell's technology today. Livesay transferred 

this cryopreservation technology from the University into the start-up. Now company has links with 

Boston Scientific; has received many NIH SBIR grants and DOD ATP grants 


Organogenesis, 

Inc. 

Advanced Tissue 

Sciences, Inc. 

Protein Polymer 

Technologies 

Cytotherapeutics 

(Stem Cell Inc.) 

ETEX 

Corporation 

Integra 

LifeSciences 

Corporation 

REGEN Biologics, 

Inc. 

1986 Eugene Bell and 

two postdoctoral 

students (Christian 

Weinberg and 

unknown) 

MIT 

Product marketed by Novartis Pharma AG 

1987 Gail Naughton New York University Company based on Naughton patent; Jay Vacanti and Bob Langer thought about a way of using 

polymers and cells to make new tissues, and that led to Neomorphics, which subsequently merged 

with Advanced Tissue Sciences. Smith and Nephew has provided support for cartilage and skin 

development since 1994. 

1988 No information 

1989 David Scharp, Paul 

Lacy, Michael 

Lysaght (Baxter) 

Michael J. Lysaght, Associate 

Professor of Artificial Organs 

(Research) at Brown University. 

Abt Associates Inc. Emergence of Tissue Engineering – Final Report 55 

Brown University, Other partners include: California Institute of Technology (Technology Licensing 

Agreement), Oregon Health Science University, Scripps Institute. Company split into successor 

companies: Stem Cells Inc. (Palo Alto, CA), Neurotech Corp. (Lincoln, RI), and Modex 

Therapeutics SA (Lausunne Switzerland). In 1989, Lysaght left Baxter to help start 

CytoTherapeutics. He served as Vice President and chief technical executive at CytoTherapeutics 

from 1989 through 1994. 

1989 D. Duke Lee Lee is the Chairman, Chief Agreement with several pharma companies: Biomet Merck as the exclusive distributor of Biobon in 

Scientific Officer and the scientific Europe and Latin America; DePuy Orthopaedics, Inc. a Johnson & Johnson company, for 

founder of ETEX. He is on the distribution of ETEX alpha-BSM ®, Bone Substitute Material, for orthopaedic indications, and joint 

faculty of Harvard Medical School research and development of future products; Sofamor Danek Division of Medtronic, Inc, to jointly 

and also serves as Director of the develop products for spinal applications. 

Harvard/MIT Biomaterials 

Training Program. 

1989 Richard Caruso No further information 

1990 Kevin Robert Stone Privately funded by Sulzer Medica, Sanderling, Sequoia Capital, and Allen & Company 

Synthecon, Inc. 1990 Charles Anderson NASA contractor company Co-founders C.D. "Andy" Anderson and Ray Schwarz worked for a NASA medical services 

contract company. As members of a Space Bioreactor Project Team, their charge was to develop 

a bioreactor that would enable scientists to study the effects of space on human tissue and help 

them understand why astronauts suffered bone and muscle loss in orbit. With assistance from 

NASA astronaut David Wolf, M.D., and medical contractor Tinh Trinh, Schwarz invented a fluidfilled 

rotary wall vessel (RWV) bioreactor that enabled NASA scientists to successfully grow, 

maintain and study three-dimensional human tissue in space for extended periods of time. 

Aastrom 

Biosciences, Inc. 

1991 Bernhard Palsson, 

Michael Clarke, 

Stephen Emerson 

Hematologists at the U Mich 

School of Medicine; Palsson is 

now a Professor of 

Bioengineering and Adjunct 

Professor of Medicine at the 

University of California, San 

Diego 

A 1989 research agreement with the University of Michigan, and licensing patents based on 

University-conducted research (relating to the ex vivo production of human cells), collaborations 

also with University of Colorado (to insert cell-destruction genes into AIDS patients' stem cells, 

which then would be expanded in the bioreactor and transplanted back into the patient). First 

approached by large pharmaceutical firm but then given away to venture capital firm.

Layton 

BioScience, Inc. 

1991 James Eberwine, 

Virginia M.-Y. Lee, 

and John Q. 

Trojanowski 

The three founding scientists 

were all neuroscientists at 


The technologies initially being developed were discovered in the laboratories of the company's 

founding scientists and licensed from Stanford University (Stanford) and the University of 

Pennsylvania (Penn). Cooperation, Licensing and/or Other Agreements with: Incyte Genomics, 

Inc, Merck & Co, PerkinElmer Life Sciences, Stanford University, Stratagene Corp, University of 

Florida (U. S.), University of Pennsylvania, and University of Texas 

ORTEC 

INTERNATIONAL 

1991 Steven Katz, Ron 

Lipstein, Mark 

Eisenberg, Alain M 

Klapholz 

Orthovita, Inc. 1992 Paul Ducheyne University of Pennsylvania, 

Bioengineering and Orthopaedic 

Surgery Research 

Ortec’s technology is based on the technology developed by Mark Eisenberg, an Australian 

physician 

Ducheyne is currently Chairman Emeritus and Director of Orthovita. Since 1997, Dr. Ducheyne 

has been the Director of the Center for Bioactive Materials and Tissue Engineering at the 


TEI Biosciences 1992 Eugene Bell MIT No information provided 

Prizm 

Pharmaceuticals, 

Inc., (merged with 

1992 Andrew Baird, 

Samuel Ward 

Cassells, III, 

Andrew Baird (then at Scripps), 

Ward Cassells, University of 

Texas) started Prism. Steven 

Matrigen licensed technology from U Michigan; Prizm licensed technology from Scripps Clinic; 

Prizm started by private venture firms DOMAIN ASSOCIATES and OXFORD BIOSCIENCE 

PARTNERS they started it as a company to stop cell proliferation - toxin conjugated to a growth 

Matrigen, Inc. in (Prism) Steven Goldstein (University of Michigan) factor. Idea was that the body will internalize growth factor, body will stop cell proliferating. Was not 

1998 to form 

Selective 

Genetics) 

Goldstein, Robert 

Levy (Matrigen) 

and Robert Levy, (Childrens 

hospital) started Matrigen 

feasible. Method worked only with toxicity - had to abandon technology. In 1998, met up with 

another company simulating cell growth (matrigen) resulting company Selective Genetics to 

explore tissue repair and regeneration 

Fibrogen 1993 Thomas Neff Neff was an investment banker 

with both PaineWebber and 

Lazard Freres & Co., and for 

many years he has followed 

commercial and scientific 

developments relating to 

molecular biology 

Guilford 

Pharmaceuticals 

Osiris 

Therapeutics, Inc. 

1993 Scios Nova Inc., 

and Solomon 

Snyder and Craig 

Smith 

1993 Arnold Kaplan, 

Steven Hanesworth 

(cell biologist), 

Victor Goldberg 

(orthopedic 

surgeon), James 

Burns, VC and 

Unnamed 

Businessman 

Kaplan, Hanesworth, Case 

Western Reserve University, had 

collaborations with Goldberg at 

the University Hospital 

A 1996 collaborative agreement with the University of Pittsburgh Medical Center re: biotech liver 

system. 

Bob Langer of MIT conceived of degradable polyanhydride systems, and licensed that originally to 

a company called Nova Pharmaceuticals. They merged with Scios, and then they spun off 

Guilford. 

Kaplan worked with Burns in 1992 to get company started, founders stayed involved till 1997-98 

through their participation on a scientific review board, the company also continued collaboration 

with the founders through about 1995 when it moved to Baltimore. Current CSO Marshak also 

holds an appointment as Adjunct Associate Professor of Oncology and of Molecular Biology & 

Genetics at the Johns Hopkins University School of Medicine. Marshak has served on several NIH 

Study Sections, the Medical and Scientific Advisory Board of the Dystonia Medical Research 

Foundation, and the Editorial Board of the Journal of Biological Chemistry. 


OsteoBiologics, 

Inc. 

1993 cofounders faculty 

at Univeristy of 

Texas Heath 

Science Center 

(Barbara Boyan, 

Athanasiou) one 

business founder 

Therics 1993 Brad Vale (J&J 

development 

corporation), Walter 

Flamenbaum; serial 

founder of 

companies starting 

at NYC's Mt. Sinai 

School of Medicine) 

licenisng tech develoepd own, 

have R&D agreements with other 

cooperations, company, 

collaborators at Universities 

Licensed technology developed at 

MIT (work of Linda Griiffith, 

Michael Cima, and Ely Sachs) 

The technologies initially being developed were discovered in the laboratories of the company's 

founding scientists and licensed from Stanford University and the University of Pennsylvania. 

Began by licensing technology developed at the University of Texas Health Science Center 

Boston University (U. S.) (Technology Licensing Agreement), Massachusetts Institute of 

Technology (U. S.) (Technology Licensing Agreement) 

Ximerex 1993 William 

Beschorner. 

Founder was at Johns Hopkins 

Hospital came up with the idea, 

developed it, filed patent and 

started company, 

Has links with the University of Nebraska, started out at Johns Hopkins (1993-95), private lab, in 

1997 moved to Omaha 

Islet Technology 1994 Scott Wiele Founder's daughter diagnosed with Type1 diabetes; father wanted to know if cure (rather than 

management) was possible; starterd searching and found a program at UC Davis. Kent Cochrum 

had technology for encapsulating islets from transplants and was funded by another compay, but 

asked Wiele to help him raise more money. Wiele licensed technology. Company has worked 

closely with U Minn and Diabetes Institute (Barnard Hering) via licensing arrangment 

MultiCell 

Associates 

1994 Galletti and 

Jauregui with 

Jayanta Roy 

Chawdhury, and 

Alfred Vasconcellos 

Albert Einstein School of Medicine Wholly owned subsidiary (2001) of Exten CA 

Orquest, Inc. 1994 strategic partners are other firms http://www.orquest.com/wt/sec/strat_partners 


Figure 6.1: New Tissue Engineering Companies by Year (1994 and earlier) 

6 

5 

4 

3 

2 

1 

0 

Before 

1985 

1986 1988 1990 1992 1994 

The focus areas of these firms were as follows: 

Area 

Structural applications 

Cellular 

Metabolic 

Enabling technologies 

(bone, tissue, muscle, 

vasculature, scaffolding, 

extracellular matrix, anything 

related to structural support) 

(use of specialized cells, cell 

culture, stem cell research) 

(bioartificial organ 

development, including 

whole organ development, 

microencapsulation 

techniques) 

(anything related to the 

above, but indirectly, such as 

informatics) 

Number of Sample Companies 

Companies 

13 Interpore, Organogenesis, 

ATS, PPTI, Etex, Integra, 

Ortec, Orthovita, TEI 

Biosciences, Guildford, 

Osiris, Osteobiologics, 

Orquest 

8 Celox, Creative 

Biomolecules, Regen, 

Aastrom, Layton, TEI, 

Osiris,, Prizm 

3 Biohybrid, Islet 

Technology, Multicell 

3 Lifecell, Synthacon, 

Therics, TissueInformatics 

All others 1 Ximerics 

The companies listed above were clustered in specific parts of the country. Of the 28 companies 

examined, eight were in California, five in Massachusetts, three each in New Jersey and Texas, and 

two each in Minnesota and Rhode Island. Michigan, Delaware, Maryland, Nebraska, and New York, 

all had one company each. 

Their locations parallel the locations of many of the major research centers in TE, which supports the 

hypothesis that many of these companies have close ties to academia—at least at the start-up phase. 

In fact, sixteen of the 28 companies had at least one founder in academia. Only five of the 28 

companies had co-founders that were neither currently nor formerly academics (i.e. were based in 

business or venture capital) 111 . 

Twenty one companies licensed or transferred intellectual property from academia (without 

necessarily having an academic co-founder). Two did not (Synthecon – NASA contractor, and Ortec, 

111 We have no information on the founders of the remaining seven. 


Australian physician) 112 . Table 6.1 above summarizes the origins of these companies. As Table 6.2 

below shows, the universities involved in start-ups were: 

Table 6.2: University Start-ups in Tissue Engineering 

Name of University 

Number Name of Company 

MIT/Harvard 6 Creative Biomolecules, Organogenesis, Etex, 

TEI Biosciences, Guilford, Therics 

University of Pennsylvania 3 Layton Biosciences, Orthovita, 

Osteobiologics 

University of Michigan 2 Aastrom, Prizm 

University of Texas 2 Lifecell, Prizm 

Pennsyvania State University 1 Interpore 

University of Massachusetts, 

1 Biohybrid 

Worcester 

New York University 1 ATS 

Brown University 1 Cytotherapeutics 

University of California at Davis 1 Islet Technology 

Case Western Reserve University 1 Osiris 

Johns Hopkins University 1 Ximerics 

Stanford University 1 Osteobiologics 

Yeshiva University 1 Multicell 

University of Pittsburgh 1 Fibrogen 

Of the 28 companies, 12 are public and 14 continue to be privately held (no information was available 

on the status of the remaining two firms). 

Financial support for these companies came from a variety of sources as shown in Table 6.3 below. 

Table 6.3: Financial Support of Corporate Start-ups 

Supporter 

Number of Names of Companies 

companies 

NIH/SBIR 9 Organogenesis, ATS, Cytotherapeutics, Aastyrom, Osiris, 

Osteobiologics, Layon, Fobrogen, Ximerics 

NIST/ATP 7 Biohybrid, Organogenesis, ATS, Aastrom, TEI, Osiris, 

Ximerics 

Foundations 2 Lifecell, ATS 

Universities 2 Lifecell, ATS 

DOD/DARPA/Army 2 Lifecell, Osiris 

NSF/SBIR 1 Biohybrid 

NASA 1 Synthecon 

State 1 Aastrom 

Private Investors 

Almost all firms have had private investors 

All of the firms listed here were still in existence through the close of 2001 in one form or another 

(many have merged with others to form new companies, but none have disappeared altogether) and 

112 We have no information on five companies. 


collectively employ (in 2001) about 2000 people. The overall number of firms and, consequently, 

employees in tissue engineering, has steadily increased since 1994 113 . 

Little data is available on the specific training of the researchers employed by private companies 

active in tissue engineering, and it is very difficult to paint a precise picture of the characteristics of 

the individuals that make up this group. However, the fragmentary data available to the study team 

suggest that few of the scientists and engineers employed by companies active in tissue engineering 

possess formal credentials in the field. Rather, companies seek individuals who have broadlyapplicable 

technical knowledge and skills relevant to the research and development tasks they face, 

and assign these individuals to specific projects as required; employees in the corporate sector may 

enter or leave tissue engineering as an activity quite freely. Flexibility is especially important in that 

no start-up company in the field that has attempted to develop cell-based products has yet established 

a successful business, and the ability to redirect staff to the most promising lines of work – often 

away from initially ambitious product concepts to simpler ones with more likely prospects of 

reaching the market in the near term – can be critical for corporate survival. 

With the caveat that our data are limited, we encountered no evidence that movement of newlytrained 

junior researchers from academia to industry has been an important mechanism of technology 

transfer in tissue engineering. At the senior level, although a handful of investigators have left 

academia to assume full-time roles leading start-up companies, more frequently senior academics in 

the field will serve as advisors or board members for companies licensed to develop technologies or 

product concepts that emerge from their laboratories. 

Review of Patent Activity: Domestic and International 

As an alternative means of understanding the origins of tissue engineering and progress made in the 

field, we also examined patenting in the field over the past twenty or so years. The full patent analysis 

is included as Appendix 5 at the end of this report. 

As the adjoining figure shows, the earliest 

patenting activity occurred in the mid-tolate 

80’s with a more dramatic increase in 

the 1990s; consistent with the overall 

growth in awareness of the field. As the 

Figure shows, patenting in tissue 

engineering has been trending up since 

1980 and has not yet peaked. In 

particular, in the last 5 years, patenting has 

increased 226% over the previous 5 years, 

which in turn was an increase of 138% 

over the prior 5 years. 

The bulk of this innovation was USbased 

114 , as shown in Figure 6.2. Over 

No. of Patent Families 

120 

100 

80 

60 

40 

20 

0 

Figure 6.1 - Tissue Engineering Patent 

Families by Year 

80 83 85 87 89 91 93 95 97 99 01 

Year 

113 

There is considerable variation in employment estimates. For example, a study sponsored by the Pittsburgh 

Tissue Engineering Initiative (PTEI) conducted in the Spring of 2000 lists 67 active firms in tissue 

engineering employing a total of more than 4,700 employees. “An Industry Emerges: A Profile of 

Pittsburgh’s Growing TE Sector.” www.ptei.org/industry/pdf/industry.pdf. 

114 As Appendix 5 explains, to compile the database of international patenting in tissue engineering, patents 

from more than 60 countries were searched using CHI’s internal US, EP, and PCT databases as well as 

Derwent’s World Patent Index. 


seventy percent of the global tissue engineering patents are invented in the US, followed by 18% in 

Europe (led by Germany and UK) and 6% in Japan. 

Figure 6.2 - Priority (Inventor) Country of Worldwide Tissue 

Engineering Patents (1980-2001): N=567 

Japan 

6% 

Other 

5% 

Europe 

18% 

United States 

71% 

Given that most of the invention is coming from the US, it is not surprising to see that most of the 

patent assignees are US institutions as well. Figure 6.3 shows all assignees with 4 or more global 

patent families 115 . The institutions holding the most highly cited patents are listed in Table 6.4. 

International institutions are depicted in gray. 

A list of the 100 most highly cited tissue engineering patent families is also given in Appendix 5 in 

Table G. The Table shows that the highest relative cited patent family is a 1999 Isotis (a biosurgery 

company based in Netherlands founded in 1996) patent that has received 11 citations already. Since a 

typical 1999 patent family has just over 1 citation, this patent is cited 7.5 times as often as expected. 

The highest overall cited patent family is an Advanced Tissue Science invention “Three-dimensional 

cell and tissue culture system.” This 1990 patent has received 162 citations from later patents, which 

is almost 6 times the expected number (28.3) for a 1990 tissue engineering patent family. Many of the 

highly cited patents are coming from the patenting leaders. This is further illustrated in Table 6.4 

below, where we see that MIT and Advanced Tissue Sciences have the most highly cited patents by 

far. Among the most effective patenting companies is Regen Biologics Inc., which has 8 of its 11 

patents among the highly cited set. 

115 

Note that a patent family is a set of equivalent patent documents from different countries. For example, 

when a scientist invents something, he/she will typically file the patent in his/her home country, and then 

file equivalent patents in every country for which he/she wishes to have patent protection. 


Figure 6.3 - Assignees with 4 or more TE Global Patent Families 

(1980-2001) 

Advance Tissue Sciences 

MIT 

Procter & Gamble 

Regen Biologics 

University Of Michigan 

Isotis BV 

Johnson & Johnson 

NASA 

University Of California 

Childrens Medical Center Corp 

Grace (WR) & Co 

Organogenesis 

Baxter International 

Case Western Reserve University 

Cytotherapeutics 

Fidia Advanced Biopolymers Srl 

Focal 

Keraplast Technologies Ltd 

Osteobiologics 

Collagen Corp 

Cryolife 

Tissue Engineering 

University Of Pittsburgh 

University Of Texas 

Wl Gore & Assoc 

5 

5 

5 

5 

5 

5 

5 

4 

4 

4 

4 

4 

4 

12 

11 

10 

9 

9 

8 

8 

7 

7 

7 

44 

43 

*US Assignees in Black; Foreign 

Assignees in Gray. 

0 10 20 30 40 50 

# Patent Families 


Table 6.4: Share of patents that are highly cited by assignee 

% 

Standardized Assignee 

Families 

Highly 

Cited 

Highly 

Cited 

Advanced Tissue Sciences Inc 44 15 34% 

MIT 43 20 47% 

Procter & Gamble Co, The 12 0 0% 

Regen Biologics Inc 11 8 73% 

University Of Michigan 10 1 10% 

Isotis BV 9 1 11% 

Johnson & Johnson 9 0 0% 

NASA 8 2 25% 

University Of California 8 0 0% 

Childrens Medical Center Corp 7 3 43% 

Grace (W.R.) & Co 7 1 14% 

Organogenesis Inc 7 2 29% 

Baxter International Inc 5 1 20% 

Case Western Reserve University 5 2 40% 

Cytotherapeutics Inc 5 1 20% 

Fidia Advanced Biopolymers Srl 5 2 40% 

Focal Inc 5 3 60% 

Keraplast Technologies Ltd 5 2 40% 

Osteobiologics Inc 5 1 20% 

Collagen Corp 4 1 25% 

Cryolife Inc 4 2 50% 

Tissue Engineering Inc 4 0 0% 

University of Pittsburgh 4 0 0% 

University of Texas 4 2 50% 

Wl Gore & Assoc Inc 4 0 0% 

In terms of subject matter, of the top 100 most cited patents examined in this analysis, the majority 

can be classified as cellular, including those which describe methods for cell culture or differentiation 

and the medium used to support such methods; or structural, such as those which describe novel 

biomaterials, bone and cartilage substitutes. In terms of the organs or tissues targeted by many of the 

patents, bone and cartilage stand out, in keeping with the advanced state of research for these tissues 

as compared to other more complicated organ systems, such as the kidney, lung, or heart, which will 

require considerably more research and development before patents and supporting methodologies are 

seen. 

Finally, CHI found that of the 100 or so patents examined, nineteen were declared by the inventors to 

have resulted fully or partially from a government grant. Of these, NIH had eight, NASA six, NSF 

three, and DHEW 116 two. 

116 Currently organized as Health and Human Services (HHS) but formerly referred to as the Department of 

Health, Education and Welfare (DHEW). 


7.0 Institutional Support of Tissue Engineering 

In addition to the individual researchers in academia and industry, key players in a field can include 

the federal agencies that provide financial support, professional societies and other institutions 

designed to promote and advance a field’s mission. Professional societies may promote educational 

programs, research applications, and the development of professional standards in an overall effort to 

advance the dissemination of knowledge in a particular field or research area. As networking 

facilitators, conferences, meetings, and other symposia supported by societies may be instrumental in 

bringing together researchers who work on similar topics but may not otherwise collaborate. Several 

groups have emerged in tissue engineering’s development. 

The National Science Foundation is one of many organizations – including the U.S. Federal 

government and foreign governments, industry and non-profit foundations – that have funded tissue 

engineering research in the United States and around the world. The WTEC report estimates that 

nearly $3.5 billion dollars have been spent on tissue engineering in the last decade. Of this, less than 

10% has come from the U.S. Federal government 117 . According to their definition, the National 

Science Foundation, primarily through its Directorate for Engineering, provided less than 1% of 

worldwide support for tissue engineering, but nearly 7% of U.S. Federal government support. 

Table 7.1 below and the accompanying Figure 7.1 examine U.S. Federal government funding of 

tissue engineering in greater detail, using a more restrictive definition. They provide a partial glimpse 

into Federal support of TE using data from RaDiUS, a database that tracks the research and 

development activities and resources of the Federal government. 118 Of all Federal agencies supporting 

biomedical science and engineering, NSF is second only to NIH in providing financial support to TE, 

and has increased both its level and share of Federal funding in the past few years. This chapter 

summarizes the support of the field by the key federal agencies involved: National Institutes of Health 

(NIH), National Institute of Standards and Technology (NIST), National Aeronautics and Space 

Administration (NASA), Food and Drug Administration (FDA), and finally, NSF. 

Before turning to NSF’s role in supporting tissue engineering, we provide brief descriptions of major 

efforts of other Federal agencies that have been active in tissue engineering in different ways. 

117 It is worth pointing out that the WTEC analysis uses a more expansive definition of “tissue engineering”, 

which includes elements such as gene therapy/gene transfer, scaffolding, cell culturing, cell adhesion, DNA 

delivery, stem cell technology, functional tissue engineering (e.g., mechanical properties of tissues), and tissue 

preservation. This is in contrast with the more restrictive definition employed in a search of the RaDiUS 

database as shown in Table 7.1 or the definition employed in this study. 

118 Description of our approach and limitations of the tool are addressed in a separate memo to Linda Parker, 

COTR. 


Table 7.1 Federal Awards for Tissue Engineering Research 1993 – 2000, by Agency (000 $)* 

1993 1994 1995 1996 1997 1998 1999 2000 TOTAL 

NIST 0 0 620 0 3,612 2,454 2,749 600 10,035 

DOD* 0 0 0 0 0 0 0 0 

DOE 0 0 0 0 0 0 0 50 50 

NIH 2,317 3,892 9,519 13,259 5,625 16,761 6,797 8,917 67,086 

DVA 0 135 295 89 204 340 449 388 1,900 

NASA 0 0 1,033 1,274 1,394 776 1,147 496 6,120 

NSF 588 1,218 1,364 934 1,858 4,429 6,421 5,993 22,806 

TOTAL 2,905 5,244 12,831 15,557 12,693 24,760 17,563 16,445 107,997 

NSF % 20% 23% 11% 6% 15% 18% 37% 36% 21% 

* While RaDiUS did not pull any records from DOD, we are aware of DARPA’s role in supporting activities 

related to Tissue Engineering. In the last five years, DARPA has funded research in cell-based biosensors. 

$ (in thousands) 

18,000 

16,000 

14,000 

12,000 

10,000 

8,000 

6,000 

NIST 

DOE 

NIH 

DVA 

NASA 

NSF 

4,000 

2,000 

0 

1993 1994 1995 1996 1997 1998 1999 2000 

Figure 7.1 Federal Awards for Tissue Engineering Research, by Year and by Agency 

(1993 –2000 ) 

7.1 National Institutes of Health (NIH) 

* Source: RaDiUS database, grants containing term “tissue engineering” 

Support of tissue engineering from the NIH has come in several forms over the years. While an 

official program/focus area in tissue engineering did not begin until the late 1990’s, many key 

researchers in the field attribute much of the early support they received as coming from the NIH. 

Traditionally known for its support of fundamental research, NIH has supported many of the basic 

science advancements, which led to tissue engineering as we know it today. Much of the past work 


done on cell culture methods, for example, was supported by NIH funding. Nonetheless, NIH was a 

relative newcomer to tissue engineering per se. In a 1998 article in Science, for example, researchers 

berated NIH’s lack of interest in the field: 

“To a large extent, NIH really hasn't been responsive," charges Robert Nerem, then director 

of the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of 

Technology in Atlanta. Nerem chaired a consultants' group that in 1995 urged the creation of 

"a central focus for basic bioengineering research ... at the highest level" at NIH. But "we're 

still, as a community, waiting to see what NIH is going to do," Nerem says. 119 

In more recent years, NIH’s focus on TE has increased dramatically: 120 

• Division of Biomimetics, Biomaterials, and Tissue Engineering, headed by Dr. Elani 

Kousvelari of NIDR, has been in existence for the past 6 years. Biomimetics relies on the 

simulation of human “parts”. A major early goal of the program is to reconstruct cranial and 

facial constructs. Of the three (biomimetics, biomaterials , tissue engineering), tissue 

engineering is the only component which has a cellular focus. 

• In 1997, Harold Varmus centralized several research efforts in BECON, the Biomedical 

Engineering Consortium, which has been central for progress in TE, biomedical engineering, 

and bioengineering. 

In 2000, the NIH launched its newest institute, the National Institute for Biomedical Imaging and 

Bioengineering (NIBIB), which aims to “…improve health by promoting fundamental discoveries, 

design and development, and translation and assessment of technological capabilities in biomedical 

imaging and bioengineering, enabled by relevant areas of information science, physics, chemistry, 

mathematics, materials science, and computer sciences 121 .” 

7.2 National Institute for Standards and Technology (NIST) 

NIST’s Advanced Technology Program (ATP) began in 1988 and was designed to focus on 

commercial applications of high-risk cutting edge basic scientific research, such as biology, a field 

NIST did not yet participate in. The first ATP competition was held in 1990-91 and the first TE 

award was made in the 2 nd round of competition to Acerm Biosciences, a company growing stems 

cells from bone marrow. In the years subsequent, NIST added projects at the rate of 1-2 per year on 

topics such as building better scaffolding, bioreactors, and xenotransplantation. 122 

Serious efforts in tissue engineering, however, did not occur until the mid-late 1990s. In 1993-94, a 

two day conference was held on cutting-edge biotechnology and involved individuals from several 

agencies including Francis Collins of NIST, Fred Heineken of NSF, and Kiki Hellman of FDA. The 

group identified ‘hot topics’ in a hierarchy—tissue engineering being one of those near the top of the 

list. For each, a set of key issues was identified and listed: in what areas is there enough basic science 

research and where is there a black hole? Other technologies identified at this meeting included DNA 

diagnostics, TE, vaccines, gene therapy, and biosensors. Approaches for the development of specific 

industries was discussed. Stan Abramowitz, who headed the early NIST/ATP efforts was heavily 

119 http://www.becon.nih.gov/sciencebioengineeringarticle.htm 

120 Elani Kousvelari interview, August 23, 2001. 

121 see: http://www.nibib.nih.gov/about/mission.html 

122 Rosemarie Hunziker interview, May 29, 2001. 


involved in this. Staff attended conferences to “find the right people” to get advice, and to head these 

initiatives. As a follow-up to these efforts, a series of white papers were solicited in 1995 in 

preparation for a focused competition in TE. The first focused program was initiated in 1997 when 

56 proposals were submitted and 12 awarded (for a total of $12 million that year). Focused 

competitions in tissue engineering ended for ATP in 1998, however. 

The ATP Program has been instrumental in funding high-risk commercial applications of ideas that 

venture capitalists are unlikely to support—typically these are multidisciplinary projects which 

require academic collaboration. Dr. Rosemarie Hunziker, a former Program Officer at ATP, believes 

that NIST/ATP support of TE gave it credibility, an important action, especially in light of its heavy 

private sector orientation 123 . 

7.3 National Aeronautics and Space Administration (NASA) 

Beginning in the late 1970’s, NASA’s efforts in tissue engineering have focused on development of 

techniques for three-dimensional cell and tissue culture. The agency’s interest in tissue engineering 

comes from a need to understand how cells and tissue behave in space. Laboratory cultures which 

mimic live human tissue can be used as models to conduct space research and research on deadly 

diseases, such as cancer—eliminating the need for human test subjects. In the late 1980’s, the work 

of Milbourne and Wolf of the Johnson Space Center culminated in the development of the rotating 

bioreactor, a horizontal rotating wall vessel with a center oxygen membrane, which promoted cell and 

tissue growth under a variety of conditions. A patent on the device was filed in 1988 and issued in 

1991 124 . 

While initially referred to under the agency’s biotechnology heading, NASA officially recognized 

these efforts as “tissue engineering” when the term appeared for the first time in a 1994 program 

update. Since then, NASA has continued to fund selective research on bioreactors and related topics 

and has provided a steady stream of funding to individuals in this area. Much of the work done by 

Lisa Freed and Gordana Vunjak-Novakovic of MIT has been supported by NASA’s Cellular 

Biotechnology Area. 

7. 4 Food and Drug Administration (FDA) 

The FDA has taken an interest in tissue engineering since the early 1990’s. In 1990, the Center for 

Devices and Radiological Health (CDRH) in conjunction with the State of Maryland held a 

conference to examine biological applications with device use. Among the topics raised was tissue 

engineering. Dr. Kiki Hellman, head of the CDRH, saw potential in the field and became interested 

in exploring it further. Two years later, a workshop was held to examine promising new 

technologies—tissue engineering being one of them. 

From an agency perspective, the FDA was proactively involved in the technology’s development. 125 

According to Dr. Hellman, the FDA made a concerted effort to deal with in-house needs (staff 

training, education) so that they could anticipate the technology and be prepared to deal with the any 

technical or scientific issues that would arise. 

123 Kiki Hellman interview, August 3, 2001. 

124 Goodwin TJ, Jessup JM, Wolf DA. Morphologic differentiation of colon carcinoma cell lines HT-29 and 

HT-29 KM in rotating-wall vessels. In Vitro Cell Dev Biol 1992 Jan/ 28A(1):47-60. 

125 Kiki Hellman interview, August 3, 2001. 


Many of our interviewees also state that the FDA has been instrumental in allowing products to move 

to market, encouraging the development of standards to measure devices (in conjunction with the 

ASTM Committee F04 Medical and Surgical Materials and Devices). In all, many experts in the field 

laud their efforts, stating that the FDA is not a force standing in the way of progress. 

7.5 Other Institutions involved in Tissue Engineering 

The Tissue Engineering Society International (TESI) 

In 1995, Charles Vacanti started The Tissue Engineering Society (now known as Tissue Engineering 

Society International or TESI). In its early days, the society served to foster communication between 

individuals in the tissue engineering world through sponsorship of meetings and conferences. In 

1995, the Society published the first issue of Tissue Engineering, the first dedicated journal in the 

field. Despite the placement of several prominent tissue engineers on its editorial board, the journal 

lacked popularity. Many researchers continue to preferentially publish in more traditional 

disciplinary journals or general peer-reviewed publication like Science or Nature. More recently, the 

society has grown to include a more international focus and serves as a networking organization to 

foster dialogue between international researchers in the field 126 . 

The Pittsburgh Tissue Engineering Initiative 

A unique and somewhat unusual contributor to the field of tissue engineering has been the Pittsburgh 

Tissue Engineering Initiative (PTEI). The organization was founded by Peter Johnson (founded 

1994) a former surgeon at the University of Pittsburgh. After becoming chairman of the department 

of plastic surgery, Johnson was in a unique position to form a network of scientists in the Pittsburgh 

area. Based largely upon his own interest in tissue engineering and its potential, Johnson pushed to 

develop a joint technology transfer policy between the major Pittsburgh area universities, and PTEI 

was born. In its beginnings, PTEI served mostly as a networking mechanism—to raise funds to 

provide support to TE research in the surrounding area. The initiative had four key components: (1) 

technology development grants, (2) summer research internships to increase student base in TE, (3) 

biotech exposure (with a minority focus), and (4) a guest speaker program (a coordinated effort to 

bring big names in the field to Pittsburgh) 127 . PTEI raised money and support and led the 1 st TE 

biotech company in the area. Currently, there are at eight firms in the area. PTEI has encouraged an 

amalgamation and growth of the critical mass necessary to sustain development in TE for the 

Pittsburgh community. As a result, Pittsburgh is rapidly becoming a center for informatics—a new 

branch in the field of tissue engineering. PTEI also serves as a model for other cities to advance 

research and development in TE. Toronto is expanding their TE workforce utilizing the PTEI model. 

126 Vacanti, C. Interview June 20, 2001. 

127 www.ptei.org 


The Whitaker Institute for Biomedical Engineering 

The mission of The Whitaker Foundation is to promote better human health through advancements in 

medicine. This is accomplished through a series of competitive grant programs that support research 

and education in biomedical engineering at academic institutions in the United States and Canada 128 . 

Whitaker has been instrumental in funding bioengineering programs around the country. Most 

notable for TE, they, in 1999, established the Whitaker Institute for Biomedical Engineering (WIBE) 

at UCSD under the leadership of Y.C. Fung. Much of the fundamental work supported under this 

institute will contribute to advancements in the field of TE. However, the foundation has been 

reluctant to classify TE as an independent entity, but rather a sub-field of bioengineering 129 . 

Multi-Agency Tissue Engineering Sciences (MATES) Working Group 

More recently, many agencies of the federal government have become interested in supporting the 

mission of tissue engineering. In an effort to coordinate this support, representatives from each of 

several federal agencies came together in 2000, under the leadership of Drs. Fred Heineken (NSF) 

and Kiki Hellman (FDA) to form the Multi-Agency Tissue Engineering Science (MATES) Working 

Group. MATES has three major goals: (1) to facilitate communication (and prevent redundancy of 

funding) across departments/agencies by regular information exchanges and a common web site, and 

(2) enhance cooperation through co-sponsorship of scientific meetings and workshops, and facilitate 

the development of standards, and (3) to monitor technology by undertaking cooperative assessments 

of the status of the field 130 . MATES has developed a web-site which they hope will become “onestop-shopping” 

for those seeking information on the field (such as information about federal funding, 

scientific meetings, regulatory guidance and standards development). Participating agencies in 

MATES include the Department of Commerce (NIST), the Department of Energy (DOE), the 

Department of Defense (DARPA), the Department of Health and Human Services (FDA, NIH), the 

National Aeronautics and Space Administration (NASA), and the National Science Foundation 

(NSF). The panel, co-chaired by Drs. Frederick Heineken of NSF and Kiki Hellman of the FDA also 

focuses on some regulatory, legal, and ethical issues for TE. A particular area of interest has been a 

global regulatory initiative for TE—an effort that will require the development of standards for 

testing tissue engineered products. 

A major contribution of the MATES group is the recent World Technology Evaluation Center 

(WTEC) study on tissue engineering, which attempts to summarize the technical contributions of 

current work in TE and to estimate the funding for TE from each of the federal agencies 131 . The study 

has become a focal point for activities of the working group, under the auspices of the Subcommittee 

on Biotechnology, Committee on Science of the President’s National Science and Technology 

Council (NSTC). The results of the WTEC study were used by MATES to plan a joint interagency 

program announcement in tissue engineering issued under the new National Institute for Biomedical 

Imaging and Bioengineering, which solicits research aimed at addressing specific gaps in tissue 

engineering. 

128 www.whitaker.org 

129 Peter Katona, President, Whitaker Foundation, Interview, August 16, 2002. 

130 http://www.tissueengineering.gov/ 

131 see: http://www.wtec.org/loyola/te/ 


8.0 The Role of the National Science Foundation 

(NSF) 

The National Science Foundation, particularly through its Directorate for Engineering, appears to 

have played an important role in the emergence of tissue engineering as a recognized field of activity, 

and in shaping the character and in determining the direction of the field. In addition to introducing 

and defining the larger concept of tissue engineering, the Foundation has provided support to key 

people, ideas, and institutions as discussed below. 

8.1 Financial Support 

From an examination of Fastlane Award data as an illustration of NSF support for tissue engineering, 

it is evident that the majority of NSF support goes toward individual investigator awards and Centers 

research (Table 8.1) 132 . NSF is also a strong supporter of workshops, conferences and other meetings, 

which suggest a prominent role in support of networking activities among individuals active in the 

field. Analysis of NSF funding by division shows that the vast majority of the agency’s support of 

tissue engineering—more than 80%--emanates from the Bioengineering and Environmental Systems 

(BES) and Engineering, Education and Centers (EEC) Divisions—both of which reside under NSF’s 

Directorate for Engineering. The role NSF funding has played in research will be explored in the 

next section. 

Table 8.1: NSF Funding of Tissue Engineering 1988 – 2001, by Award Type 

Number of Awards (between 1988 - 2001) 92 

Total Dollar Value of NSF Awards (Current Dollars) (between 1988 - 2001) 70,543,307 

Awards for Individual Investigator Research (only) 12,576,301 17.8% 

Exploratory Awards (SGERs) 216,866 0.3% 

Awards for Instrumentation 851,689 1.2% 

Awards for Curriculum Development 820,602 1.2% 

Awards for Networking and Meetings 258,000 0.4% 

Awards for Diversity 1,000,000 1.4% 

Center Awards* 50,349,031 71.4% 

Career Development Awards (POWRE, PYI, etc.) 4,070,835 5.8% 

SBIR Awards 399,983 0.6% 

Total Dollar Value of NSF Awards (Current Dollars) 70,543,307 100.0% 

Source: FastLane Award Data keyword search using term “tissue engineering” supplemented by additional data from the 

Directorate of engineering 

* The Center Award supports includes funds for three Centers – the Georgia Tech/Emory Center for the Engineering of 

Live Tissues, the University of Washington Engineered Biomaterials (UWEB) ERC, and MIT’s Biotechnology Process 

Research Center (BPEC). Data on these last two Centers was not pulled from FastLane using the keyword “tissue 

engineering”. Their dollar amounts were added manually to the total represented here. As a result, the final dollar value 

of Table 8.1 does not match that of Table 8.2, which is exclusively pulled from FastLane. 

132 NSF FastLane search for the period 1988-2001 using the keyword “tissue engineering” 


Table 8.2: NSF Funding of Tissue Engineering 1988 – 2001, by Division 

Current Dollars Percent 

BCS Total 11,000 0.0% 

BES Total 12,671,526 38.5% 

CTS Total 311,798 0.9% 

DBI Total 1,919,379 5.8% 

DMI Total 399,983 1.2% 

DMR Total 1,008,863 3.1% 

DUE Total 74,780 0.2% 

EEC Total 13,535,560 41.1% 

EPS Total 2,316,325 7.0% 

HRD Total 117,579 0.4% 

IBN Total 214,441 0.7% 

INT Total 29,000 0.1% 

MCB Total 300,000 0.9% 

NSF Total 32,910,234 100.0% 

Source: FastLane Award Data kyword search using term “Tissue Engineering” 

Note: BCS: Behavioral and Cognitive Sciences, BES: Bioengineering & Environmental Systems, CTS: Chemical and 

Transport Systems, DBI: Biological Infrastructure, DMI: Design, Manufacture and Industry, DMR: Division of Materials 

Research, DUE: Division of Undergraduate Education, EEC: Engineering Education & Centers, EPS: Experimental 

Program to Stimulate Competitive Research, HRD: Human Resource Development, IBN: Integrative Biology and 

Neuroscience, INT: International; MCB: Molecular and Cellular Biosciences 

8.2 Researcher Support 

While the interviews did not shed much light on 

the role of NSF as a funder, bibliometric 

analysis (see Figure 8.1 and Table 8.3 below, as 

well as Appendix 5 for the full bibliometrics and 

patent analysis) revealed that NSF has had a 

significant role in supporting lead researchers in 

the field 133 . Figure 8.1 illustrates the relative 

role of NSF support of TE over the years. NSF 

support has been acknowledged on 12% of the 

papers revealed by the bibliometric analysis. 

The influence of NSF funding on top researchers 

in the field, however, has been 

disproportionately large. Table 8.3 shows that 

three of the most prolific researchers – Vacanti, 

Langer and Mooney - acknowledge NSF funding 

on 19%-37% of their papers, including on the 

Figure 8.1 Number of NSF Funded Papers 

80 

NSF 

70 

Other 

60 

No funding acknowledged 

50 

40 

30 

20 

10 

0 

61 70 75 80 85 90 95 00 

133 In an analysis carried out for this project, subcontractor CHI Research tallied the funding sources 

acknowledged by papers retrieved through a PubMed search carried out in September 2001, using a search 

filter that heavily weighted the scaffolds-and-cell-seeding concept of TE. In the group of 1,056 papers 

generated by this search, 727 explicitly acknowledged a funding source. Of these, 89 papers or 12% 

acknowledged NSF support. In the absence of an exhaustive manual review of the funding histories of 

individual researchers active in tissue engineering, there is no way to determine what the corresponding 

fraction would be for a more inclusive definition of tissue engineering [than used in the bibliometric study]. 


1993 Science paper (this percentage may, in fact, be even higher, as not all papers list 

acknowledgement of research funding and, further, some researchers fail to mention all of the funding 

sources that should be cited in acknowledgements). Given the wide range of tissue engineering 

activities, it is not surprising that NSF support of researchers varies considerably. Notable 

researchers such as Linda Griffith, Jeffrey Hubbell, P.M. Kaufmann, and Mark Saltzman also 

acknowledge NSF on a third or more of their papers, while NSF appears to have had no role in 

supporting other prominent researchers such as Arnold Caplan, Lisa Freed, V.M. Goldberg or 

Gordana Vunjak-Novakovic. 

Table 8.3: Sources of Support for Prominent Authors and Their Papers in Tissue Engineering 

Funding type 

Author 

TE 

Papers 

# 

agencies 

# of NIH 

institutes % NSF NSF Other 

No funding 

acknowledged 

Vacanti JP 92 10 8 19% 13 57 22 

Langer R 76 11 6 26% 17 48 11 

Mooney DJ 53 5 5 37% 17 29 7 

Vacanti CA 31 4 1 5% 1 18 12 

Atala A 28 2 1 3 25 

Caplan AI 27 4 5 27 

Aebischer P 26 4 2 6% 1 15 10 

Mikos AG 25 6 6 17% 4 20 1 

Yannas IV 21 8 4 7% 1 14 6 

Freed LE 20 4 3 20 

Goldberg VM 19 4 3 19 

Kim BS 18 4 2 43% 6 8 4 

Vunjaknovakovic G 18 4 3 18 

Ingber DE 17 8 3 25% 4 12 1 

Mayer JE 17 5 1 12 5 

Schloo B 16 3 13% 2 13 1 

Ma PX 15 5 2 8 7 

Boyan BD 14 7 3 15% 2 11 1 

Cima LG 14 5 3 40% 4 6 4 

Hollinger JO 14 4 6 6 8 

Hubbell JA 14 5 2 75% 9 3 2 

Spector M 14 5 8% 1 12 1 

Winn SR 14 2 4 6 8 

Reddi AH 13 4 2 6 7 

Upton J 13 4 1 10% 1 9 3 

Grande DA 12 4 1 9 3 

Allcock HR 11 5 1 11% 1 8 2 

Athanasiou KA 11 2 4 7 

Bell E 11 3 1 4 7 

Green H 11 3 3 9 2 

Hansbrough JF 11 2 2 8 3 

Wozney JM 11 5 2 7 4 

Bruder SP 10 2 4 10 

Galletti PM 10 4 3 4 6 

Schwartz Z 10 7 2 22% 2 7 1 

Yoo JJ 10 2 1 1 9 

See Appendix 5 for a more extensive listing of authors published in tissue engineering. 


NSF funding, however, is not evenly distributed across all aspects of tissue engineering. NSF support 

is clearly targeted toward the application of engineering principles, especially with the aim of 

advancing engineering knowledge. Table 8.4 uses the bibliometric study to identify the sub-fields of 

tissue engineering where NSF-funded researchers have been most active and demonstrates that the 

agency has held true to its stated mission and goals. Almost 90% of NSF-supported papers are in 

fields related to engineering or fields that promote the application of engineering principles to solve 

problems in a variety of realms. Table 8.4 also shows that NSF support has been highest for 

biomedical engineering (30 of 145 papers or 21%) and general/miscellaneous biomedical research (27 

of 212 papers or 13%). 

Both the interviews and the bibliometrics assessment explored the role of NSF in supporting the 

establishment and growth of TE in institutions. Table 8.5 below lists the top institutions with which 

authors of TE papers were affiliated according to acknowledgements in the papers (a more extensive 

listing of institutions involved in tissue engineering can be found in Appendix 5). 134 As the Table 

shows, NSF supported 12% of the papers produced by authors working at these institutions. The 

Table shows that, among the TE papers (1) by authors from the leading TE research institutions and 

(2) that contained acknowledgements of underlying research sponsorship(s), 17% of the papers 

contained acknowledgements of NSF support. 

134 Note that papers whose authors were at more than one institution were multiple-counted. Please see the 

Appendix for a more complete listing of institutions. Only the top publishing institutions appear in this 

excerpt. 


Table 8.4 Tissue Engineering Research Papers, by Acknowledged Sponsor, Field of Journal, and Character of Research 135 

% Share 

National Science Foundation Other funders No explicit funding acknowledgements 

TE Papers 

Field 

% Share 

TE Papers 

Field 

% Share 

TE Papers 

Field 

37% 30 Biomedical Engineering 14% 83 Orthopedics 15% 41 Urology 

22% 18 Misc Biomedical Research 13% 78 Biomedical Engineering 14% 40 Surgery 

11% 9 General Biomedical Research 12% 70 General Biomedical Research 14% 38 General Biomedical Research 

6% 5 Neurology & Neurosurg 11% 63 Surgery 13% 37 Biomedical Engineering 

6% 5 Cell Biology, Cytology & Histology 9% 53 Misc Biomedical Research 9% 24 Misc Biomedical Research 

5% 4 Biochemistry & Molec Biology 7% 39 Cell Biology, Cytology & Histology 8% 21 Orthopedics 

2% 2 Polymers 6% 37 Neurology & Neurosurg 7% 19 Biochemistry & Molec Biology 

2% 2 Biophysics 4% 26 Biochemistry & Molec Biology 4% 11 Dentistry 

2% 2 Endocrinology 4% 21 Dentistry 3% 9 Cell Biology, Cytology & Histology 

1% 1 Orthopedics 3% 19 Immunology 3% 7 Neurology & Neurosurg 

1% 1 Surgery 3% 17 General & Internal Medicine 2% 5 General & Internal Medicine 

1% 1 General Chemistry 2% 13 Dermatology & Venereal Disease 2% 5 Dermatology & Venereal Disease 

1% 1 General Biology 2% 10 Endocrinology 1% 4 Endocrinology 

100% 81 Total papers covered by ISI 1% 8 Urology 1% 4 Immunology 

8 Not covered by ISI 1% 5 Cancer 1% 4 Cardiovascular Systm 

1% 5 Polymers 1% 3 Misc Clinical Medicine 

1% 4 General Biology 1% 3 Pharmacology 

1% 4 Biophysics 1% 2 Otorhinolaryngology 

1% 3 Pharmacology 0% 1 Pathology 

1% 3 Cardiovascular System 0% 1 Gastroenterology 

1% 3 Hematology 0% 1 General Chemistry 

1% 3 Otorhinolaryngology 100% 280 Total papers covered by ISI 

0% 2 Pathology 49 Not covered by ISI 

0% 2 Inorganic & Nuclear Chemistry 

0% 2 Genetics & Heredity 

0% 1 Misc Clinical Medicine 

0% 1 Geriatrics 

0% 1 Physical Chemistry Notes: Papers not covered by ISI could 

0% 1 Embryology not be allocated to a field 

0% 1 Anatomy & Morphology 

0% 1 General Chemistry 

100% 579 Total papers covered by ISI 

59 Not covered by ISI 

135 ISI does not include new journals, some proceedings journals, and some technology journals. New journals are added periodically after they demonstrate 

quality and importance. 


Table 8.5: Tissue Engineering Papers by Lead Author’s US Institutional Affiliation and Research 

Sponsor Acknowledged in Papers 

Institution 

8.3 Institutional Development 

TE 

papers NSF Other 

Funding Source Cited 

No 

funding 

acknowle 

dged 

% funded 

that are 

NSF 

Harvard University 317 38 192 87 17% 

MIT 239 50 148 41 25% 

University of Michigan 156 34 75 47 31% 

Childrens Hospital Med Ctr/Boston 142 13 90 39 13% 

University of Texas 124 24 71 29 25% 

Case Western Reserve University 83 1 78 4 1% 

University of California at San Diego 81 5 62 14 7% 

Massachusetts General Hospital 62 1 42 19 2% 

Rice University 55 6 42 7 13% 

Johns Hopkins University 48 6 29 13 17% 

University of Pennsylvania 36 11 16 9 41% 

Brown University 35 2 18 15 10% 

University of Massachusetts 34 18 16 

Northwestern University 30 30 

University Miami 30 25 5 

Univeristy of Virginia 29 1 17 11 6% 

Brigham & Women's Hospital 28 1 21 6 5% 

New York University 26 17 9 

Yale University 26 23 3 

University Minnesota 25 12 9 4 57% 

University of Pittsburgh 25 1 17 7 6% 

Washington University 24 15 9 

University Washington 23 20 3 

Genet Inst Inc 22 13 9 

University Rochester 22 20 2 

NSF has played a small but significant role in developing institutions and networks in the field of 

Tissue Engineering. A sample set of activities is listed below. 

Conferences and Workshops As discussed in depth in earlier chapters, NSF has been an early 

sponsor of workshops and conferences related to TE. To repeat from Chapter 3, the term “tissue 

engineering” itself was proposed at a 1987 panel meeting convened to consider future directions for 

the Engineering Directorates’s Bioengineering and Research to Aid the Handicapped Program. 

Strong interest in this concept within the Engineering Directorate (especially through the efforts of 

Allan Zelman and Frederick Heineken) led to a special panel meeting on tissue engineering, again at 

NSF, in the fall of 1987, and then to the Granlibakken workshop of 1988, now considered to be the 


first formal scientific meeting of the emerging field of tissue engineering (see Executive Summary 

and Chapter 3 for a more in-depth discussion of these early conferences). 

In all, about one percent of NSF’s total TE support in the period 1987-2001 was devoted to 

networking and conference support, and many of the individual investigator awards in TE were funds 

to support presentations of results from research conducted with the NSF support and attendance at 

non-NSF conferences and meetings. 

MATES As a founder and critical participant in the MATES Working Group, the Engineering 

Directorate, through the leadership of Frederick Heineken, Kiki Hellman, and others, has made a 

pronounced effort in recent years to engage participation from a range of disciplines (a more detailed 

discussion of MATES purpose and objectives can be found in Chapter 7 above). The MATES group 

aims to enhance collaboration and cooperation amongst several federal agencies so that gaps in tissue 

engineering research can be addressed. An important example is an outgrowth of the MATES 

initiative, a study published through WTEC, which summarizes the global status of the field 136 and 

notes where progress is needed. 

NIBIB Aside from its participation in MATES, NSF continues to collaborate with other Federal 

agencies and programs on TE related research and education. In particular, NSF has ongoing 

collaboration with the newest of the NIH Institutes, the National Institute for Biomedical Imaging and 

Bioengineering (NIBIB), established in 2000. The first "official" NIBIB interagency activity was a 

joint NIH/NSF Workshop on Bioengineering and Bioinformatics Education and Training. Since then, 

the two agencies have established the Bioengineering and Bioinformatics Summer Institutes (BBSI) 

Program to provide students majoring in the biological sciences, computer sciences, engineering, 

mathematics, and physical sciences with interdisciplinary bioengineering or bioinformatics research 

and education experiences 137 . 

Another important outgrowth of the NIBIB is a recent solicitation (dated December 30, 2002), likely 

influenced by the work of MATES and the WTEC report, seeking proposals to address key research 

challenges in TE 138 . The initiative is expected to draw biologists, clinicians, and engineers to work 

together to address issues such as cell sourcing, cell identification and characterization, engineering 

design, and other enabling technologies necessary to move the field forward. A total of $8 million 

dollars has been earmarked for the initiative. 

Center Support NSF’s Directorate for Engineering has provided significant support toward 

institutional development for TE through its funding of Centers. These include the Georgia 

Tech/Emory ERC, which was awarded in 1998, and the University of Washington Engineered 

Biomaterials (UWEB) Center. Aside from NSF, the bulk of institutional support in TE has been 

provided by the Whitaker Foundation, through its role in building the field of biomedical engineering, 

and especially in providing institutional development funds for the creation and expansion of 

bioengineering departments– not only at the academic centers highlighted in Chapter 5, but at many 

other institutions across the nation. These departments are increasingly taking over from departments 

of chemical and mechanical engineering as the focus of academic research activity in tissue 

engineering, and the drive to create and expand TE focus areas in many of these emerging 

departments has created opportunities for young investigators completing their training at the 

institutions that have led the way in TE research. 

136 http://www.wtec.org/loyola/te/final/te_final.pdf 

137 http://bbsi.eeicom.com/ 

138 http://grants1.nih.gov/grants/guide/rfa-files/FRA-EB-010.html 


Not evident in these funding analyses, but worthy of note, is that NSF has been an important source 

of support over the years for the work of Douglas Lauffenburger, a highly productive researcher on 

the fringes of tissue engineering who has trained many younger investigators involved in the field. 

Since 1999, Lauffenburger has served as director of the MIT Biotechnology Process Engineering 

Center (BPEC), an NSF-funded ERC, in its second incarnation in 1995. BPEC has developed new 

research thrusts that have moved the focus of its activity toward the boundary between tissue 

engineering and several adjacent fields, with projects led by several MIT investigators prominent in 

tissue engineering. 

Young Researcher Support As a complement to the bibliometric study, review of NSF’s own 

records in FastLane indicates that during the 1987-2002 period NSF has provided important early 

career development support for a large number of promising young researchers in tissue engineering, 

both through specially-designated young investigator and career development awards and through 

regular project awards, including (listed with current affiliation) 139 : 

• Kristi Anseth (University of Colorado) 

• Ravi Bellamkonda (Case Western Reserve University) 

• John Frangos (La Jolla Bioengineering Institute) 

• Linda Griffith (MIT) 

• Jeffrey Hubbell (ETH Zurich) 

• Jens Karlsson (Georgia Tech) 

• Tony Keaveny (University of California Berkeley) 

• Michelle LaPlaca (Georgia Tech) 

• Cato Laurencin (Drexel University) 

• Surya Mallapragada (Iowa State University) 

• Howard Matthew (Wayne State University) 

• Andrew McCulloch (University of California, San Diego) 

• Prabhas Moghe (Rutgers University) 

• David Mooney (University of Michigan) 

• David Odde (University of Minnesota) 

• Michael V. Pishko (Penn State University) 

• Robert Sah (University of California, San Diego) 

• W. Mark Saltzman (Yale University) 

• Christine Schmidt (University of Texas, Austin) 

• Lonnie D. Shea (Northwestern University) 

• Darrell Velegol (Pennsylvania State University) 

• Jennifer West (Rice University) 

• Joyce Wong (Boston University) 

• Martin Yarmush (Rutgers University) 

8.4 Overall Assessment 

While available evidence suggests that no single organization engendered monumental changes in the 

field of tissue engineering, NSF’s Directorate for Engineering did create an environment that 

encouraged the crystallization of an emerging concept, both with its innovative Engineering Research 

Centers (ERC) Program and its ongoing internal efforts to define productive future directions for its 

bioengineering program. NSF hosted the first meetings at which the concept of tissue engineering as 

139 The data here are not meant to be exhaustive and was gathered by entering the names listed in Appendix 2: 

Roster of Tissue Engineers into the FastLane Awards database and manually filtering the records retrieved 

for those applicable to tissue engineering. 


a focus of research was defined and strategies for its future growth and potential discussed. The field 

definition drafted at the October NSF 1987 meeting and reported in the preface of the Granlibakken 

workshop proceedings was to become a standard citation in later articles, including the well-known 

1993 paper by Langer and Vacanti (which listed NSF as a funding source). 

While the Directorate for Engineering has no doubt provided funding support to key researchers in 

the field, it is more difficult to attribute specific research contributions and breakthroughs to the 

Directorate. In fact, in general, the broad and interdisciplinary nature of the field make it difficult to 

classify any number of research contributions as seminal. As documented in Chapter 2, efforts to 

“engineer” tissues to restore structure or function predate the events of 1987-88 by many years. 

However, if there is a research development that marked the emergence of a recognizably distinct 

field on this foundation of many related, pre-existing lines of research, it appears that the consensus in 

the research community and through our own best judgment points to the January 1988 publication by 

Langer, Vacanti and colleagues describing the strategy of using resorbable artificial polymer matrices 

seeded with cells as a vehicle for cell transplantation. This early phase of the Langer/Vacanti 

collaboration, catalyzed by the shared experience of working under Folkman, brought together at least 

four of the conceptual elements that are central to tissue engineering today: the use of polymeric 

materials in biological applications, the use of live cells to restore lost physiologic function, the vision 

of controlling tissue morphogenesis through the use of signaling molecules, and the powerful 

motivation of the shortage of transplantable organs. 

Further, the seminal development in awareness of tissue engineering in the scientific community as a 

distinct domain of research is also attributable to Langer and Vacanti. The October 1987 Panel 

Meeting at NSF and the subsequent Granlibakken workshop in 1988 and Keystone workshops in 

1990 and 1992, while significant, appear to have “spoken” to a much narrower audience; among our 

group of interviewees, few who were not directly involved in one or the other of these events report 

any awareness of their direct impact, although, again, the field definition drafted at the October 

meeting is acknowledged. 

So, where does NSF fit within the larger picture of support for tissue engineering over the fifteen 

years since 1987? Comments by our interviewees suggest that while NSF funding is highly valued by 

those who have received it, the agency is not widely perceived as a major force in the field. The 

Foundation is seen today to play a less critical overall role, but rather, an important and distinctive 

niche role related to its early career support for several now prominent young researchers and its role 

in bringing in new disciplines to the field. As a founder and critical participant in the MATES 

Working Group, NSF’s Directorate for Engineering has made a pronounced effort in recent years to 

engage participation from a range of agencies and disciplines. Examples of such efforts include 

support of the WTEC study, and the close collaboration with NIH, which has produced a new 

solicitation to support research in fundamental knowledge gaps in TE. 

NSF’s Directorate for Engineering also appears to have played a large role in incorporating the 

biomechanics community into the emerging field. The events of 1987-88 engaged pioneers of an 

engineering approach to orthopedics and hemodynamics, such as Richard Skalak, Van Mow, and 

Robert Nerem, in the development of a shared concept for the field just as the emergence of the 

scaffolds-and-cell-seeding approach, occurring in parallel with and independently of the Foundation’s 

activities, was providing a renewed and powerful impetus for efforts to construct cell-based 

therapeutic solutions. 

One might also note the delayed efforts of the Foundation to engage biologists in the endeavor. All of 

the participants in the Foundation’s 1987 discussions were well-aware of the importance of 

fundamental research in biology as part of the mix required to make tissue engineering a success. As 

an agency concerned with the full range of fundamental research and not directly with clinical 


applications, NSF might have been the natural locus for an effort to mobilize basic biological 

scientists as well. However, as an NSF initiative, tissue engineering arose from the engineering 

directorate, and judged by data available from the NSF FastLane grants database, remained largely 

contained within the engineering directorate. 

As noted earlier, tissue engineering continues to be characterized by a tension between ad hoc and 

more fundamental or systematic approaches, with many observers concerned that the balance remains 

too far toward the ad hoc. On this deeper level, the involvement of engineers should be an important 

contribution to making TE truly an engineering discipline, characterized by rational design based on 

integration of fundamental principles. In practice, however, this theoretical rationalization has not 

made much progress. The challenges addressed by tissue engineering are hard problems. This 

perception underlines a dilemma faced by the Foundation as a whole. In the future, NSF will be 

challenged to define and fulfill a role that allows it to continue to have a noticeable impact on the 

field. 


Appendix 1: Approach to Data Collection 

Literature Review 

Bibliographic searches, general Internet searches, advice from expert informants, and citations and 

other leads within retrieved documents pointed to a wide range of professional, institutional and 

popular literature relevant to the study. Documents of the following types were reviewed: 

• Articles in peer-reviewed scientific journals, including review articles and original research 

papers published in general scientific and medical journals such as Science, Nature, and the 

New England Journal of Medicine as well as in biological, medical and engineering specialty 

and subspecialty journals such as Journal of Cellular Biochemistry, Journal of Vascular 

Surgery, Journal of Biomedical Materials Research, and Tissue Engineering. 

• Conference agendas and proceedings, including key events such as the 1987 NSF special 

panel meeting, 1988 Granlibakken TE workshop, the 1992 Keystone symposium, and the 

2001 BECON symposium. 

• Prospectuses, promotional materials and other documents from professional societies and 

private-sector development initiatives, such as the Tissue Engineering Society and the 

Pittsburgh Tissue Engineering Initiative. 

• Program announcements, project abstracts, reports and background documents from 

Federal funding agencies and collaborative initiatives, including NSF, NIH, NIST, and 

NASA, and the NIH BECON and interagency MATES initiatives. 

• Annual reports and miscellaneous documents from private foundations such as the 

Whitaker Foundation. 

• Special task force reports, notably including the January 2002 WTEC Panel Report on 

Tissue Engineering Research. 

• Announcements, bulletins, research abstracts, course syllabi and other materials from 

academic programs in tissue engineering. 

• Textbooks, including two recently-published, comprehensive volumes: Principles of Tissue 

Engineering, 2 nd Ed. (Academic Press, 2000) and Methods of Tissue Engineering (Academic 

Press, 2002). 

• Promotional materials and annual reports from companies engaged in tissue engineering. 

• Articles from trade publications and general-interest periodicals such as The Scientist, 

Scientific American, Discover, Business Week, and Time. 

• A convenience sample of TE-related patents identified through exploratory searches of the 

US Patent and Trademark Office database, using the term “tissue engineering” or the names 

of researchers or organizations prominent in the field as search terms. 


Expert Interviews 

An iterative process of literature review, Internet searches, and discussions with expert informants 

produced a list of 126 individuals presently or formerly active as participants in or observers of TE, 

including researchers based in academia, researchers and managers from private companies, present 

and former program managers for funding agencies, and investment and venture capital professionals. 

The study team was able to interview a total of 46 people from this list, either in person or by 

telephone, including most of the individuals identified by consensus among our informants as 

especially influential in shaping the field during the earliest years of its emergence. 

A master protocol of study questions was developed, from which separate interview guides were 

derived for use in discussions with individuals working in academic, government, and corporate 

settings. A complete list of interviewees can be found in Appendix 3, and copies of the interview 

protocols can be found in Appendix 4. 

Bibliometric Analysis 

A formal bibliometric analysis was carried out by CHI Research, Inc., using reference sets of 

publications and patents identified as related to tissue engineering. Full details are provided in a 

separate Appendix 5 to this report. 140 

Search for Data on Research Sponsorship 

To inform analysis of NSF’s role as a research sponsor in the emergence of tissue engineering, an 

attempt was made to collect systematic data on the quantity and character of related research projects 

funded and on the amount of money expended by Federal agencies in support of TE. Sources utilized 

included the following: 

• RaDiUS, a comprehensive database on Federally-funded research and development, 

maintained by the RAND Corporation. 

• Project databases of individual Federal agencies, including NSF, NIH and NASA. 

• Documents provided by program managers at Federal agencies. 

• Bibliometric analysis of funding acknowledgments in published papers and patents. 

It became apparent from intensive exploratory analysis of RaDiUS and the agency-specific project 

databases that there is no way to construct either a definitive list of TE projects funded by the Federal 

government or to calculate anything more than an order-of-magnitude estimate of the amount of 

funding provided for TE by the government. In part, this is a consequence of the boundary-drawing 

problem, and of the related difficulty of specifying a search filter that is both sensitive and specific for 

TE-related research. However, technical limitations of these databases – notably in the consistency of 

the largely investigator-reported data on which these systems are based – imposed severe constraints 

on the analysis as well. 

Once the roster of tissue engineers was completed, the database of NSF awards accessible through 

FastLane was searched for evidence of NSF support for the listed researchers. 

140 

Bibliometric Analysis of Core Papers Fundamental to Tissue Engineering, CHI Research Inc., March 25, 

2002. 


Although it was impossible to develop a precise quantitative accounting of the roles of different 

research sponsors, the available data, combined with qualitative information obtained via interviews 

of program officers, funded researchers and other observers, provided substantial qualitative insight. 

Review of NSF Historical Data 

We also analyzed data in the NSF Awards Database provided via CD-ROM by Linda Parker for five 

key researchers: Eugene Bell, Howard Green, Robert Langer, Jay Vacanti, and Ioannis Yannas. A 

total of 28 records were retrieved for these 5 names. The breakdown of awards is as follows: 

Eugene Bell: 19 awards 

Howard Green: no awards 

Robert Langer: 4 awards 

Jay Vacanti: no awards 

Ioannis Yannas: 4 awards 

Based on the information provided in the database, it is unclear which Directorate at NSF sponsored 

these awards. For many of these awards, the records are so old they are tracked instead by a 

‘historical’ number HST#, rather than under a Directorate heading. Abstracts for these awards are 

also missing, which make it difficult to understand the precise scope of each award. 

Only one of Langer’s 4 awards retrieved by the database actually pertains to tissue engineering and 

describes “Novel Degradable Polymers for Cellular Adhesion.” The other 3 awards are more 

specifically related to his work on drug delivery technology, which Langer himself considers a largely 

separate line of work from his efforts in tissue engineering. 

In the case of Yannas and Bell, it appears that the awards listed in the NSF database supported 

research in basic and developmental biology, which are no doubt important inputs to the development 

of tissue engineering and most certainly contributed to the efforts of these two researchers in 

developing the methods and materials which allowed them to develop their early skin substitutes. 

Adoption of this viewpoint shows NSF as a key supporter of Eugene Bell in the years prior to his 

major discoveries in skin replacement technology. It should also be noted, however, that though NSF 

appears to have provided some initial support to these researchers, none of the awards listed represent 

work that directly related to the development of the first living skin equivalents, which took place in 

the late 1970’s and early 1980’s. Again, however, without the grant abstracts, this is a surface 

judgment based only on the title of the award and not necessarily the substance of the research. 

Thus, based on the information contained in this database, combined with our previous analysis of 

NSF award abstracts listed in FastLane, we do not believe there to be convincing evidence to support 

additional discussion in our final report which cites NSF has having provided a framework for key 

advances in tissue engineering (for these researchers or otherwise). It is true that there are some 

records missing, post-1996, which are contained under separate heading at NSF. However, given the 

late date of these awards, we do not believe that these provide evidence that NSF provided early 

support to enable fundamental advances in the field. 

Construction of Roster of Tissue Engineers 

To enable an analysis of genealogic relationships among researchers active in tissue engineering, a 

roster of tissue engineers was constructed with information about their training and employment. 

(Appendix 2). The majority of the information in this table was extracted from documents obtained 

via Google search of the World Wide Web, including investigators’ CVs and laboratory pages, 


departmental overviews and histories, news reports, and a variety of other articles and documents. 

References located via PubMed were used to identify research collaborations not otherwise 

documented and to corroborate relationships suggested by other sources. Additional information was 

obtained from other sources identified above under “Literature Review”. 

As with data on research project funding, the absence of a precise definition of the field makes 

decisions about the inclusion of a given individual somewhat arbitrary. Our selection was intended to 

include individuals who have identified themselves as active in the field, usually by describing their 

own work with the term “tissue engineering”, and for whom TE-related work constitutes an important 

component of their overall portfolio of activity. We believe that the list does contain the great 

majority of academic, non-physician researchers with faculty appointments in the United States and 

Canada who meet these criteria. 

In addition, the list includes several of the most prominent physician-researchers in the field, along 

with a small sampling of individuals in the corporate sector. In general, less information was 

available on the web about physicians whose primary academic appointments were in clinical 

departments than about faculty in engineering or basic science departments, and almost no 

information was available about employees of private companies. 

A few deceased individuals who played prominent roles in the emergence of the field are included in 

the roster. 


Appendix 2: Roster of Tissue Engineers 

Name 

Current 

Employment 

Prior Employment Doctoral Degrees Dissertation Title PhD/ScD 

Thesis 

Supervisors 

Key Research 

Fellowships / Staff 

Researcher 

Positions 

Doctoral 

Students 

Fellows 

Aebischer, Patrick 

Akins, Robert E. 

Prof., Ecole 

Polytechnique 

Federale de Lausanne, 

1995 to date; 

President of EPFL, 

2000 to date 

Research Assist. Prof., 

Thomas Jefferson 

Univ., head of Tissue 

Engineering and 

Regenerative 

Medicine lab, duPont 

Hospital for Children 

Brown Univ., 1984-92; 

CHUV Lausanne, 

1992-95 

MD, University of 

Geneva, 1980; PhD, 

Neuroscience, 

University of Geneva, 

1983 

PhD, Biology, Univ. 

of Pennsylvania, 1992 

L'activite Naturelle des 

Cellules de la Substance 

Noire du Primate 

Comme Image Positive 

de l'Akinesie 

Parkinsonienne 

Calcium Transport in 

the Chick 

Chorioallantoic 

Membrane: Isolation 

and Characterization of 

Constituent Cells, 

Evidence for Cellular 

Compartmentalization, 

and Techniques for the 

Biochemical Analysis of 

Transport Related 

Protein Components 

Rocky S. Tuan 

Orthopedics, 

Thomas Jefferson 

Univ.; research, 

duPont Hospital for 

Children, 

Wilmington, DE 

Robert F. 

Valentini 

(1993); Ravi 

V. 

Bellamkonda 

(1994); John 

P. Ranieri 

(1994) 

Alevriadou, B. Rita 

Allen, Fred D. 

Assist. Prof. of 

Biomedical 

Engineering, Johns 

Hopkins Univ., 1993 

to date 


Biomedical 

Engineering, Drexel 

Univ., 2000? to date 

PhD, Chemical 

Engineering, Rice 

Univ., 1992 

PhD, Bioengineering, 

Univ. of Pennsylvania, 

1996 

Interaction of Platelets 

in Flowing Blood with 

Collagen-Coated 

Surfaces: Effect of 

Inhibitors of Platelet 

Function or von 

Willebrand Factor 

Binding Domains 

A Study of Fluid Flow 

Induced Intracellular 

Calcium Changes in 

Osteoblast-Like Cells 

Larry V. 

McIntire 

Solomon R. 

Pollack? 

Scripps Research 

Institute, La Jolla, 

1992-93 

Douglas A. 

Lauffenburger, 

1997-2000 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Ameer, Guillermo A. Assist. Prof. of 

Biomedical 

Engineering, 

Northwestern Univ. 

Andreadis, Stelios T. 

Anseth, Kristi S. 

Applegate, Dawn R. 

Asthagiri, Anand R. 

Atala, Anthony 

Ateshian, Gerard 

Athanasiou, Kyriacos 

A. 

Assist. Prof., SUNY 

Buffalo, 1998 to date 

Assoc. Prof. of 

Chemical 

Engineering, Univ. of 

Colorado, Boulder, 

1996 to date 


Sciences Director of 

Technology 

Development; now ? 


Chemical 


California Institute of 

Technology, 2002 to 

date 

Prof. of Surgery, 

Harvard Medical 

School / Children's 

Hospital, 1992 to date 

Prof. of Mechanical 


Bioengineering, 

Columbia Univ. 

Prof. of 

Bioengineering, Rice 

Univ., 1990s to date 

ScD, Chemical 

Engineering, MIT, 

1999 

PhD, Chemical 


Michigan, 1996 

PhD, Chemical 


Colorado, Boulder, 

1994 

PhD, Chemical 


1993 

PhD, Chemical 


2000 

MD, Univ. of 

Louisville 

PhD, Mechanical 


Columbia Univ., 1991 

PhD, Columbia Univ., 

1989 

Investigation of 

Extracorporeal 

Immobilized Enzyme 

Device: a Potential 

Treatment for Blood 

Deheparinization 

Dynamics of Retrovirus- 

Mediated Gene Transfer 

Photopolymerization of 

Multifunctional 

Monomers: Reaction 

Mechanisms and 

Polymer Structural 

Evolution 

Quantitative and 

Mechanistic Effects of 

Bubble Aeration on 

Animal Cells in Culture 

Dynamics of Adhesionand 

Growth Factor- 

Mediated Signals 

Regulating Cell Cycle 

Progression 

Biomechanics of 

Diarthrodial Joints: 

Applications to the 

Thumb Carpometacarpal 

Joint 

Biomechanical 

Assessment of Articular 

Cartilage Healing and 

Interspecies Variability 

Robert S. 

Langer 

David J. 

Mooney, 

Bernhard O. 

Palsson 

Christopher N. 

Bowman 

Daniel I.C. 

Wang 


Lauffenburger 

Van C. Mow 

Van C. Mow? 

Langer postdoc? 

M. Yarmush, 

HMS, 1996-98 

Nicholas Peppas, 

Purdue Univ., 

1995; Robert S. 

Langer, MIT, 

1995-96 


School/Children's 

Hospital (J. 

Vacanti?), 1990-92 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Auger, Francois A. 

Babensee, Julia E. 

Badylak, Stephen F. 

Professor, Universite 

Laval 


Biomedical 

Engineering, Georgia 

Tech 

Senior Research 

Scientist, Dept. of 

Biomedical 

Engineering, Purdue 

Univ. 

PhD 

PhD, Chemical 


Applied Chemistry, 

Univ. of Toronto, 

1996 

DVM, Purdue Univ., 

1976; PhD, Purdue 

Univ., 1981; MD, 

Indiana Univ., 1985 

Morphological Michael V. 

Assessment of HEMA- Sefton 

MMA Microcapsules for 

Liver Cell 

Transplantation 

Clinicopathologic and 

Morphologic Alterations 

in Naturally-Occurring 

Hepatic Disease and 

Experimentally-Induced 

Glucocorticoid 

Hepatopathy in the Dog 

Antonios G. 

Mikos, Rice Univ., 

1996-99 

Nicolas 

L'Heureux 

(1996) 

Bagli, Darius J. 

Barocas, Victor H. 

Bell, Eugene 


Surgery, Univ. of 

Toronto, 1995 to date 


Bioengineering, Univ. 

of Minnesota, 2000 to 

date 


Inc. (TEI Biosciences) 

1992 to date 

Univ. of Colorado, 

Boulder, 1997-2000 

MIT, 1960s (?) until 

1986; Organogenesis 

1986-91; MIT 1991-92 

MD, McGill Univ., 

1984 

PhD, Chemical 


Minnesota, 1996 

PhD, Biology, Brown 

Univ., 1954 

Anisotropic Biphasic 

Modeling of Cell- 

Collagen Mechanical 

Interactions in Tissue 

Equivalents 

Some Effects of 

Ultrasound on the 

Mouse Liver 

Robert T. 

Tranquillo 

Urology residency, 

HMS/New 

England 

Deaconess, Glenn 

Steele, 1989-93 

Robert T. 

Tranquillo, Linda 

R. Petzold, Univ. 

of Minnesota, 1996 

Bellamkonda, Ravi 

V. 

Bhatia, Sangeeta N. 


Biomedical 

Engineering, Case 

Western Reserve 

Univ., 1995 to date 



UCSD, 1999? to date 

PhD, Medical 

Sciences, Section of 

Artificial Organs, 

Biomaterials and 

Cellular Technology, 

Brown Univ., 1994 

MD, Harvard Medical 

School, 1990; PhD, 

Health Sciences and 

Technology, 1997 

Development of a 

Three-Dimensional 

Extracellular Matrix 

Equivalent for Neural 

Cells and Nerve 

Regeneration 

Controlling Cell-Cell 

Interactions in Hepatic 


Using Microfabrication 

Patrick 

Aebischer 

Mehmet Toner 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Bhatnagar, Rajendra 

S. 

Billiar, Kristen L. 

Bischof, John C. 

Bizios, I. Rena 

Boden, Scott 

Bonadio, Jeffrey 

Prof. of Biochemistry, 

School of Dentistry, 

Univ. of California, 

San Francisco, 1974 to 

date 


Biomedical 


Worcester Polytechnic 

Inst., 2002 to date 


Mechanical 


Minnesota, 1993 to 

date 

Prof. of Biomedical 

Engineering, RPI, 

1981 to date 

Prof. of Orthopedics, 

Emory Univ. 



of Washington 

Organogenesis, 1998- 

2002 

Univ. of Michigan, 

1990s 

PhD, Biochemistry, 

Duke Univ., 1964 



1998 



California, Berkeley, 

1992 

PhD, Chemical 


1979 


Pennsylvania 

MD, Medical College 

of Wisconsin, 1979 

The Effect of 

Lathyrogens on 

Collagen Metabolism in 

Embryonic Chick Bones 

in Culture 

A Structurally Guided 

Constitutive Model for 

Aortic Valve Prostheses: 

Effects of 

Glutaraldehyde 

Treatment and 

Mechanical Fatigue 

The Freezing of 

Biological Tissue 

Metabolism of 

Arachidonic Acid by 

Platelets in 

Hyperlipoproteinemia 

Michael S. 

Sacks 

Boris Rubinsky HMS/Shriners 

Surgical Research 

Laboratory, 1992- 

93 

Robert S. Lees, 

Angelina C.A. 

Carvalho, Klaus 

Biemann 

Visiting prof. or 

scientist in 

chemical 

engineering, Rice 

Univ., 1987-88 and 

1996; and MIT, 

1995 

Steven Nicoll 

(2000) 

Bonassar, Lawrence 

J. 

Research Assist. Prof. 

of Anesthesiology and 

Cell Biology, Univ. of 

Massachusetts 

Medical School 

PhD, Materials 

Science and 


1995 

Matrix 

Metalloproteinase 

Activity and Inhibition 

in Articular Cartilage: 

Effects on Composition 

and Biophysical 

Properties and 

Relevance to 

Osteoarthritis 

Alan J. 

Grodzinsky 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Boyan, Barbara D. 



Tech, 2002 to date 

Univ. of Texas HSC 

San Antonio, 1981 - 

2002 

PhD, Biology, Rice 

Univ., 1974 (conferred 

1975) 

Mineral Metabolism in 

Pulmonate Molluscs 

Boyce, Steven T. 

Bruder, Scott P. 

Buettner, Helen M. 

Butler, David L. 

Cahn, Frederick 

Research Assoc. Prof. 

of Surgery, Univ. of 

Cincinnati 

Vice President, DePuy 

Orthobiologics 

Assoc, Prof. of 

Biomedical 

Engineering, Rutgers 

Univ. 

Adjunct. Prof. of 

Orthopedic Surgery, 

Univ. of Cincinnati 

Senior Vice President, 

Integra LifeSciences 

Corp. 

PhD, Molecular, 

Cellular and 

Developmental 

Biology, Univ. of 

Colorado, 1985 

MD, Case Western 

Reserve Univ., 1992; 

PhD, Biomedical 

Engineering, Case 


Univ., 1990 

PhD, Chemical 


Pennsylvania, 1987 

PhD, Engineering 

Mechanics and 

Biomechanics, 

Michigan State Univ., 

1976 

PhD, Biology, MIT, 

1972 

Cultured Human 

Epidermal 

Keratinocytes: Growth, 

Differentiation, and 

Feasibility Studies for 

Medical Applications 

Characterization of the 

Osteogenic Cell Lineage 

Quantitative Analysis of 

Leukocyte Chemotaxis 

in the Millipore Filter 

Assay 

A Constitutive Equation 

for Mammalian Skeletal 

Muscle Tissue in the 

Passive and Fully 

Stimulated States 

Chemical and Physical 

Alterations in Ribosome 

Structure and Function 

Arnold I. 

Caplan 


Lauffenburger 

Alexander Rich 

David J. Odde 

(1995) 

Campbell, Phil G. 


Scientist, CMU 

Institute for Complex 

Engineered Systems 

PhD, Physiology, 

Penn State Univ., 

1988 

Insulin-like Growth 

Factor-I and Insulin-like 

Growth Factor Binding 

Proteins in the Bovine 

Mammary Gland: 

Receptors, Endogenous 

Secretion, and 

Appearance in Milk 

C.R. 

Baumrucker 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Caplan, Arnold I. 

Prof. of Physiology 

and Biophysics, Case 



PhD, Physiological 

Chemistry, Johns 

Hopkins Univ. 

Medical School, 1966 

Carrier, Rebecca L. Pfizer ScD, Chemical 


2000 

Biochemical and 

Ultrastructural 

Properties of 

Osmotically Lysed Rat 

Liver Mitochondria 

Cardiac Tissue 

Engineering: Bioreactor 

Cultivation Parameters 

Robert S. 

Langer 

Scott P. 

Bruder (1990) 

Chaikof, Elliot L. 

Chancellor, Michael 

Prof. Of Surgery, 

Emory Univ. 1990s 

(?) to date 

Prof. of Urology, 

Univ. of Pittsburgh 

MD, Johns Hopkins 

Univ., 1982; PhD, 

Chemical Engineering, 

MIT, 1989 

MD 

Polyethylene Oxide- 

Polysiloxane Polymer 

Networks for Blood 

Contact 

Edward W. 

Merrill 

Kacey G. 

Marra (1996- 

97); Janine M. 

Orban (1999- 

2000) 

Chen, Christopher S. 

Cheng, Y.-L. 


Biomedical 


Hopkins Univ., 1999 

to date 

Prof. of Chemical 




1989 to date 


School / HST; PhD, 

Health Sciences and 

Technology, MIT, 

1997 

PhD, Stanford Univ., 

1984 

Cell Shape and 

Integrins: Determinants 

of Extracellular Matrix 

Regulation of Growth 

and Survival 

A Total Internal 

Reflection Fluorescence 

Study of Bovine Serum 

Albumin Absorption 

onto Polymer Surfaces 

Donald E. 

Ingber, George 

M. Whitesides 

Joe Tien (ca. 

1999-2001) 

Chesler, Naomi C. 

Chien, Shu 


Biomedical 


Wisconsin, Madison, 

2002 to date 

University Professor; 


Bioengineering and 

Medicine, UCSD, 

1988 to date 

Univ. of Vermont, ca. 

1998-2002 

PhD, Medical 


Medical Physics, HST, 

MIT, 1996 

MD, National Taiwan 

Univ., 1953; PhD, 


Ventricular Assist 

Device Design and 

Analysis: a 

Computational 

Approach 

Roger D. 

Kamm 

David N. Ku, 

Georgia Tech, and 

Zorina Galis, 

Emory Univ., 

1996-98 

Song Li 

(1997) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Colton, Clark K. 

Constantinidis, 

Ioannis 

Costa, Kevin D. 

Demetriou, Achilles 

A. 

Dennis, Robert G. 

Desai, Tejal A. 

DePaola, Natacha 

DiMilla, Paul A. 



1970s (?) to date 

Dept. of Medicine, 

Div. of Endocrinology 

and Metabolism, 

Univ. of Florida, 2002 

to date 


Biomedical 


Columbia Univ., 

1999? to date 



Los Angeles, 1992 to 

date 

Visiting Assistant 


and Biomedical 


Michigan, 2001 to 

date 


Biomedical 

Engineering, Boston 



Biomedical 


1994 to date 

Organogenesis (until 

?) 

Emory Univ., 1989- 

2001 

Albert Einstein College 

of Medicine; 

Vanderbilt Univ. 

Univ. of Illinois at 

Chicago, 1998-2002 

Northwestern Univ., 

1993-94 

Carnegie Mellon Univ., 

1993-98 

PhD, Chemical 


1969 

PhD, Chemistry, Univ. 

of New Mexico, 1987 


UCSD, 1996 

MD, Hebrew Univ.; 

PhD, Biochemistry, 

George Washington 

Univ., 1981 






San Francisco and 

Berkeley, 1998 

PhD, Health Sciences 

and Technology, MIT, 

1991 

PhD, Chemical 



Permeability and 

Transport Studies in 

Batch and Flow 

Dialyzers with 

Applications to 

Hemodialysis 

Antimalarial Drug 

Interaction with 

Porphyrins: 1H-NMR 

Study of G. dibranchiata 

Methemoglobins 

The Structural Basis of 


Ventricular Mechanics 

Studies on Polyamine 

Biosynthetic Enzymes 

Measurement of Pulse 

Propagation in Single 

Permeabilized Muscle 

Fibers by Optical 

Diffraction 

Microfabricated 

Biocapsules for the 

Immunoisolation of 

Pancreatic Islets of 

Langerhans 

Focal and Regional 

Responses of 

Endothelium to 

Disturbed Flow in Vitro 

Receptor-Mediated 

Tissue Cell Adhesion 

and Migration on 

Protein-Coated Surfaces 

Kenneth A. 

Smith 

Andrew D. 

McCulloch 

John A. 

Faulkner 

Mauro Ferrari 

C. Forbes 

Dewey 

John A. Quinn, 


Lauffenburger 

Frank C.P.Yin, 

Washington Univ. 

Edward F. 

Leonard, Columbia 

Univ., 1991-92 

George M. 

Whitesides, 

Harvard Univ., 

1991-93 

Robert S. 

Langer (1974) 

Aaron S. 

Goldstein 

(1997) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Dionne, Keith E. 

Dixit, Vivek 

VP, Millennium 


Prof. of Medicine, 



date 

CytoTherapeutics; 

ALZA Pharmaceuticals 

PhD, Chemical 


1990 

PhD, Physiology, 

McGill Univ., 1986 

Effect of Hypoxia on 

Insulin Secretion and 

Viability of Pancreatic 

Islet Tissue 

The Physiological 

Actions of Prostaglandin 

E2 on the Liver and 

Blood-Brain Barrier of 

Galactosamine-Induced 

Fulminant Hepatic 

Failure Rats 

Clark K. Colton 

Thomas M.S. 

Chang? 

Doctor, John S. 

Ducheyne, Paul 

Dunn, James C.Y. 

Dunn, Michael G. 


Biological Sciences, 

Duquesne Univ. 




Assist. Prof. in 

Pediatric Surgery, 



date 


UMDNJ / Rutgers 

PhD, Genetics, Univ. 

of California, 

Berkeley, 1985 


Science, Katholieke 

Universiteit Leuven 


School/HST, 1992; 

PhD, Chemical 


1992 



Univ., 1987 

Hormonal Control of 

Imaginal Disc 

Differentiation in 

Drosophila 

Melanogaster: Studies 

on the Biosynthesis of 

Chitin and Pupal Cuticle 

Proteins (20- 

Hydroxyeldysone) 

Long-Term Culture of 

Differentiated 

Hepatocytes in a 

Collagen Sandwich 

Configuration 

An Evaluation of Full 

Thickness Skin Excision 

Management by Wound 

Clips, Collagen Sponge 

and Electrical 

Stimulation 

Martin L. 

Yarmush, 

Daniel I.C. 

Wang 

Fred H. Silver 

Visiting prof., NIH 

sabbatical 

fellowship, CMU 

Bone Tissue 


Center, 2000 

David H. 

Kohn (1989); 

Kevin E. 

Healy (1990); 

Andres Garcia 

(1996) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Edelman, Elazer R. 

Elbert, Donald L. 

Prof. of Health 

Sciences and 

Technology, MIT 


Biomedical 




School/HST; PhD, 

HST Medical 


Medical Physics, MIT, 

1984 

PhD, Chemical 


Texas at Austin, 1997 

Regulation of Drug 

Delivery from Porous 

Polymer Matrices Using 

Oscillating Magnetic 

Fields 

Polymeric Steric 

Stabilization of Proteins, 

Cells and Tissues by 

Adsorption of 

Polycations and 

Biologically Inert 

Polymers 

Robert S. 

Langer 

Jeffrey A. 

Hubbell 

Elisseeff, Jennifer H. 


Biomedical 


Hopkins Univ. 

PhD, HST, MIT, 1999 Transdermal 

Photopolymerization of 

Hydrogels for Tissue 


Robert S. 

Langer 

Fishman, Harvey A. 

Folch, Albert 

Frangos, John A. 

Freed, Lisa E. 


Scientist, Director of 

Ophthalmic Tissue 


Laboratory, Stanford 

Univ. 



of Washington, 2000 

to date 

President and CEO, 

La Jolla 


Institute, 2002 to date 

Principal Research 

Scientist, Dept. of 

Chemical 

Engineering, MIT 

Penn State Univ., 1986- 

94; UCSD, 1994-2002 

MD, Stanford Univ.; 

PhD, Physical 

Chemistry/ 

Neuroscience, 

Stanford Univ., 1995 

PhD, Physics, Univ. of 

Barcelona 

PhD, Chemical 


Univ., 1987 

PhD, Applied 


MIT, 1988 

Neurochemical Analysis 

at the Single-Cell Level 

Using Capillary 

Electrophoresis 

Modification of Surfaces 

on the Nanometer Scale 

The Effect of Steady and 

Oscillatory Shear Stress 

on Endothelial Cell 

Function 

An Enzymatic Fluidized 

Bed Reactor for Blood 

Deheparinization: 

Development and 

Testing in Lambs on 

Extracorporeal 

Circulation 

Richard N. 

Zare, Richard 

H. Scheller 

Javier Tejada 

Larry V. 

McIntire 

Robert S. 

Langer 

Mehmet Toner, 

HMS Center for 

Engineering in 

Medicine, 1997- 

2000 

Keith J. Gooch 

(1995); Todd 

N. McAllister 

(2000) 

Nicolas 

L'Heureux (ca. 

1998-2000) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Fung, Y-C. 

Prof. Emeritus of 


Applied Mechanics, 

UCSD, 1960s to date 

PhD, California 

Institute of 


Elastostatic and 

Aeroelastic Problems 

Relating to Thin Wings 

of High Speed Airplanes 

Shu Q. Liu 

(1990) 

Galis, Zorina 

Assoc. Prof., School 

of Medicine, Div. of 

Cardiology, Emory 


Galletti, Pierre M. (deceased 1997) Emory Univ., 1958-67; 

Brown Univ. 1967- 

1997 

Garcia, Andres J. 

Gentile, Frank T. 

Ghanem, Amyl 

Giannobile, William 

V. 

Assist. Prof., 

Mechanical 



VP, Research, 

Hambrecht & Quist 

Capital Management, 

2002 to date 


Chemical 


Dalhousie Univ., 2001 

to date 


Dentistry, Univ. of 


date 

CytoTherapeutics, then 

Reprogenesis; Curis; 

Millennium 


Univ. of Maine 

Harvard School of 

Dental Medicine, 1997- 

98 

PhD, Pathology, 

McGill School of 

Medicine, 1992 


Lausanne, 1951; PhD, 

Physiology and 

Biophysics, Univ. of 

Lausanne, 1954 



1996 

PhD, Chemical 


1988 

PhD, Chemical 

Engineering, Cornell 

Univ., 1998 

DDS, Univ. of 

Missouri, Kansas City, 

1991; DMedSci, 

Harvard School of 

Dental Medicine, 1996 

Distribution of 

Endogenous 

Lipoproteins and 

Sulfated Proteoglycans 

in Normal Rabbit Aorta 

and in Atherosclerotic 

Lesions Induced by 

Endothelial Injury 

Quantitative Analysis of 

Fibronectin-Mediated 

Adhesion of Osteoblast- 

Like Cells to Bioactive 

Glass and 

Hydroxyapatite 

Constitutional 

Isomerism in Liquid 

Crystalline Polyamides 

Application of a Novel 

Packed Bed Cell Culture 

Analog Bioreactor and a 

Corresponding 

Pharmacokinetic Model 

to Naphthalene 

Toxicology 

Polypeptide Growth 

Factors: Roles in 

Periodontal Wound 

Healing and 

Osteogenesis 

David 

Boettiger, Paul 

Ducheyne 

Ulrich W. Suter 

Michael L. 

Shuler 

Peter Libby, 

Vascular Medicine, 

HMS/Brigham and 

Women's Hosp., 

1992-95 

Dept. of 

Microbiology, 

Univ. of 

Pennsylvania 

School of 

Medicine, 1996-98 

Naomi C. 

Chesler (1996- 

98) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Goldberg, Daniel P. 

Goldstein, Aaron S. 

Goldstein, Steven A. 

Gooch, Keith J. 

Gratzer, Paul F. 

Assist. Prof. of Plastic 

and Reconstructive 

Surgery, Case 




Chemical 

Engineering, Virginia 

Polytechnic Institute 

and State Univ. 

Prof. of Orthopedic 

Surgery and 


of Michigan 




Assist.Prof. of 

Biomedical 


Dalhousie Univ. 

MD, Northwestern 

University, 1986 

PhD, Carnegie Mellon 

Univ., 1997 



1981 

PhD, Chemical 


Pennsylvania State 

Univ., 1995 

PhD, Univ. of 

Toronto, 1999 

Strength, Dynamics and 

Mechanisms of Cell 

Detachment from 

Protein-Coated Surfaces 

under Hydrodynamic 

Shear 

Biomechanical Aspects 

of Cumulative Trauma 

to Tendons and Tendon 

Sheaths 

The Effects of Nitric 

Oxide on Endothelial 

Cell Proliferation and 

Viral Replication 

(Cytomegalovirus) 

The Effect of Chemical 

Modification on the 

Enzymatic Degradation 

of Acellular Matrix 

Processed Biomaterials 

Paul A. DiMilla Antonios G. 


1997-99 

John A. 

Frangos, 

Charles 

Dangler 

J.M. Lee, J.P. 

Santerre 

Scott J. 

Hollister 

(1991); 

Robert 

Guldberg 

(1995) 

Greisler, Howard P. 

Green, Howard 

Prof. of Surgery, Cell 

Biology, 

Neurobiology and 

Anatomy, Loyola 

Univ. Medical Center 

Prof. of Cell Biology, 


School, 1980 to date 

NYU School of 

Medicine, 1954-70; 

MIT, 1970-80 

MD, Penn State Univ., 

1975 

MD, Univ. of Toronto, 

1947 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Griffith, May 

Griffith, Linda G. 

Grodzinsky, Alan J. 

Guilak, Farshid 


Cellular and 

Molecular Medicine, 

Univ. of Ottawa, 1993 

to date 


Chemical 


1991 to date 

Prof. of Electrical, 

Mechanical, 


Biological 


1970s (?) to date 



Duke Univ., 1994 to 

date 

SUNY Stony Brook, 

1991-94 

PhD, Anatomy, Univ. 

of Toronto, 1990 

PhD, Chemical 



1988 

ScD, Electrical 


1974 




Retinoic Acid-Induced 

Spina Bifida: Early 

Events 

Anchorage-Dependent 

Mammalian Cell Culture 

in Hollow Fiber 

Reactors: Cell 

Metabolism and Mass 

Transfer Limitations 

Electromechanics of 

Deformable 

Polyelectrolyte 

Membranes 

Cell-Matrix Interactions 

and Metabolic Changes 

in Articular Cartilage 

Under Compression 

M.J. Wiley 

James R. 

Melcher 

Van C. Mow 

Esmond J. Sanders, 

Dept. of 

Physiology, Univ. 

of Alberta, 1989- 

90; Elizabeth D. 

Hay, Anatomy and 

Cellular Biology, 


School, 1990-93 

Robert S. Langer 

and Joseph P. 

Vacanti. ca. 1988- 

90 

Robert L-Y. 

Sah (1990); 

Lawrence J. 

Bonassar 

(1995) 

Marc E. 

Levenston 

(1995-98?) 

Guldberg, Robert 


Mechanical 






Hansbrough, John F. (deceased 2001) UCSD, 1980s - 2001 MD, Harvard Medical 

School, 1972 

Hansen, Linda K. 

Assist. Prof., Dept. of 

Laboratory Medicine 

and Pathology, Univ. 

of Minnesota 



Mechanical Adaptation 

of Trabecular Bone 

Formation in Vivo 

Proteins Synthesized in 

Response to Mitogenic 

Signals and Heat Stress 

in Human Peripheral 

Blood Lymphocytes 

Steven A. 

Goldstein, Scott 

J. Hollister 

James J. 

O'Leary 

Marine Biological 

Laboratory, Univ. 

of Michigan 

J. Vacanti, 

HMS/Children's 

Hospital, ca. 1992- 

94? 

Hanson, Stephen R. 


Engineering, Emory 

Univ. 

PhD, Chemical 


Washington, 1977 

In Vivo Evaluation of 

Biomaterial 

Thrombogenesis 

Buddy Ratner? 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Healy, Kevin E. 

Heidaran, 

Mohammad A. 



Materials Science and 



2000 to date 

BD Biosciences, 2001 

to date 


1989-99 

Orquest, Inc., ca. 1999- 

2000 



1990 

PhD, Univ. of South 

Carolina, 1987 

An Interface Approach 

to the Mechanisms of 

Passive Dissolution of 

Titanium in Biological 

Environments 

Transcriptional and 

Translational Control of 

the Message for 

Transition Protein 1, a 

Major Chromosomal 

Protein of Mammalian 

Spermatids 

Paul Ducheyne 

W. Stephen 

Kistler 

National Cancer 

Institute, ca. 1989- 

97 

Kyumin 

Whang 

(1997)? 

Hirschi, Karen K. 

Hoffman, Allan S. 


Pediatrics and 

Molecular and 

Cellular Biology, 

Baylor College of 

Medicine, 1998 to 

date 



of Washington 


Arizona, 1990 

ScD, Chemical 


1957 

Dietary and Hormonal 

Regulation of Pancreatic 

Digestive Enzymes 

The Mechanism of Graft 

Polymerization by High 

Energy Irradiation 

Patsy M. 

Brannon 

Edward W. 

Merrill, Edwin 

R. Gilliland 


School ca. 1995-97 

Hollinger, Jeffrey O. 

Hollister, Scott J. 

Hu, Wei-Shou 


Engineering, Carnegie 

Mellon Univ., 2000 to 

date 


Biomedical 



date 

Professor, Chemical 


Materials Science, 

Univ. of Minnesota, 

1983 to date 

Oregon Health 

Sciences Univ., 1993- 

2000 

DDS, Univ. of Facilitation of Osseous 

Maryland, 1973; PhD, Healing by a 

Univ. of Maryland at Proteolipid-Copolymer 

Baltimore, 1983 Matieral 



1991 

PhD, Nutrition and 

Food Science, MIT, 

1984 

Homogenization 

Analysis of Trabecular 

Bone and Prediction of 

Bone Ingrowth Using 

Topology Optimization 


Mechanistic Analysis of 

Mammalian Cell 

Cultivation on 

Microcarriers 

Steven A. 

Goldstein 

Daniel I.C. 

Wang 

Robert 

Guldberg 

(1995) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Huard, Johnny 



Pittsburgh 

PhD, Universite Laval, 

1993 

La Dystrophie 

Musculaire de 

Duchenne: Localisation 

de la Dystrophine dans 

le Systeme Nerveux et 

Recherche sur la Mise 

au Point d'un Traitement 

pour les Patients DMD 

Jacques P. 

Tremblay 

Hubbell, Jeffrey A. 

Hubel, Allison 


Engineering, ETH 

Zurich, 1997 to date 

Assist. Prof., Dept. of 

Laboratory Medicine 

and Pathology, Univ. 

of Minnesota 

Univ. of Texas at 

Austin, 1986-94; 


Technology, 1995-97 

PhD, Chemical 


Univ., 1986 



1989 

Visualization and 

Analysis of Mural 

Thrombogenesis 

Directional 

Solidification for the 

Freezing of Cell 

Suspensions 

Larry V. 

McIntire 

Ernest G. 

Cravalho 

William R. 

Wagner 

(1991); 

Jennifer L. 

West (1996); 

Donald L. 

Elbert (1997); 

Shelly E. 

Sakiyama- 

Elbert (2000) 

Weiyuan John 

Kao (1996-98) 

Humes, H. David 

Hung, Clark T. 

Ingber, Donald E. 

Prof. of Internal 

Medicine, Univ. of 


date 

Assist. Prof.of 

Biomedical 



Prof. of Pathology, 


School 


California, San 

Francisco, 1973 



1995 

MD, Yale Univ.; 

PhD, Cell Biology, 

Yale Univ., 1984 

Real-Time Calcium 

Response to Fluid Flow 

in Cultured Bone Cells 

Basement Membrane 

Polarizes Epithelial 

Cells and Its Loss Can 

Result in Neoplastic 

Disorganization 

Solomon R. 

Pollack 

Judah Folkman, 

HMS/ Children's 

Hospital, late '80searly 

90s 

Christopher S. 

Chen (1997) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Ishaug-Riley, Susan 

Johnson, Peter C. 

Kao, Weiyuan John 

Karlsson, Jens O.M. 


Sciences; now ? 

Chairman and CEO, 

Tissue Informatics, 

Inc. 


Biomedical 


Wisconsin, Madison 


Mechanical 



Univ. of Pittsburgh, 

1989-98 

Univ. of Chicago, 

1996? - 2002 

PhD, Chemical 


Univ., 1996 

MD, SUNY Health 

Sciences Center 

Syracuse, 1980 

PhD, Macromolecular 

Sciences, Case 


Univ., 1996 



1994 

Bone Formation by 


Osteoblast Culture in 

Biodegradable Poly(a- 

Hydroxy Ester) 

Scaffolds 

Biomechanisms of Giant 

Cell Formation and 

Leukocyte Adhesion on 

Polyurethanes 

Non-Equilibrium Phase 

Transformations of 

Intracellular Water: 

Applications to the 

Cryopreservation of 

Living Cells 

Antonios G. 

Mikos 

James M. 

Anderson 

Ernest G. 

Cravalho; 

Mehmet Toner 

Thrombosis, cell 

biology and 

biomaterials, 

Edwin Salzman, 


School, 1982-85 

Jeffrey A. Hubbell, 

California Institute 

of Technology and 

Swiss Federal 


Technology, 1996- 

98 

Katz, Adam J. 

Keaveny, Tony 



Virginia 


Mechanical 




Berkeley, 1993 to date 




Engineering, Cornell 

Univ., 1991 

A Finite Element 

Analysis of Load 

Transfer and Relative 

Motion for 

Contemporary 

Cementless Hip 

Implants in the Short 

and Long-Terms 

Plastic surgery 

training, Univ. of 

Pittsburgh 

Orthopedic 

Biomechanics 

Laboratory, 

HMS/Beth Israel 

Hospital, 1990-93 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Kohn, David H. 

Kohn, Joachim B. 


Biologic and Materials 

Sciences, Univ. of 

Michigan School of 

Dentistry, 1989 to date 

Prof. of Chemistry, 

Rutgers Univ. 



1989 

PhD, Weizmann 

Institute, 1983 

Mechanisms of Fatigue 

Failure in Porous Coated 

Ti-6Al-4V Implant 

Alloy 

The Chemistry of the 

Interaction of Cyanogen 

Bromide with 

Polysaccharide Resins 

Paul Ducheyne 

Meir Wilchek 



Pennsylvania, 

1984-89 

Ku, David N. 

Kumta, Prashant N. 




Prof. of Materials 

Science and 


Mellon Univ., 1990 to 

date 

MD, Emory Univ., 

1984; PhD, Georgia 

Tech, 1983 


Arizona, 1990 

Hemodynamics and 

Atherogenesis at the 

Human Carotid 

Bifurcation 

Synthesis and Structural 

Investigations of 

Infrared Transmitting 

Materials in Rare Earth 

Chalcogenide Systems 

Don P. Giddens Naomi C. 

Chesler (1996- 

98) 

Landis, William J. 

Prof. of Biochemistry 

and Molecular 

Pathology, Northeast 

Ohio Universities 

College of Medicine, 

1998 to date 

PhD, Biology, MIT, 

1972 

Macromolecular 

Interactions in Systems 

Containing Bovine 

Fibrinogen and 

Thrombin 

David F. 

Waugh 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Langer, Robert S. 

Lanza, Robert P. 



1977 to date 

VP of Medical and 

Scientific 

Development, 

Advanced Cell 

Technology, 1999 to 

date 

BioHybrid 

Technologies, 1993- 

99? 

ScD, Chemical 


1974 



Enzymatic Regeneration 

of ATP 

Clark K. 

Colton, Michael 

Archer 



Hospital, ca. 1974- 

77 

Elazer R. 

Edelman 

(1984); Cato 

T. Laurencin 

(1987); W. 

Mark 

Saltzman 

(1987); Lisa 

E. Freed 

(1988); David 

J. Mooney 

(1992); Joyce 

Y. Wong 

(1994); 

Michael J. 

Yaszemski 

(1995); 

Jennifer H. 

Elisseeff 

(1999); 

Guillermo A. 

Ameer (1999) 

Kam W. 

Leong (late 

1980s); Linda 

G. Griffith (ca. 

1988-90); 

Peter X. Ma 

(1993-96); 

Christine E. 

Schmidt 

(1994-96); 

Kristi S. 

Anseth (1995- 

96); Michael 

V. Pishko 

(1995-96); 

Laura E. 

Niklason 

(1995-98?); 

Surya K. 

Mallapragada 

(summer 

1996); 

Venkatram 

Prasad Shastri 

(ca. 1998- 

2000); 

Guillermo A. 

Ameer (ca. 

1999-2002?); 

David M. 

Lynn (1999- 

2002) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

LaPlaca, Michelle C. 



Laurencin, Cato T. 


Biomedical 


Tech 




Environmental Health, 

MIT, 1995 to date 



Univ. 


1979-90; Univ. of 

Illinois, 1990-94 



1996 

PhD, Chemical 



MD; PhD, Applied 


MIT, 1987 

Deformation Response 

and Cytosolic Calcium 

Increases in NTera2 

Neurons Subjected to 

Traumatic Levels of 

Hydrodynamic Shear 

Stress 

Effects of Motility and 

Chemotaxis in Cell 

Population Dynamical 

Systems 

Novel Bioerodible 

Polymers for Controlled 

Release Analyses of in 

Vitro / in Vivo 

Performance and 

Characterizations of 

Mechanism 

Lawrence E. 

Thibault 

Robert S. 

Langer 

Robert T. 

Tranquillo 

(1986); Helen 

M. Buettner 

(1987); Paul 

A. DiMilla 

(1991); 

Christine E. 

Schmidt 

(1995); Sean 

P. Palecek 

(1998); David 

V. Schaffer 

(1998); 

Anand R. 

Asthagiri 

(2000) 

Peter W. 

Zandstra 

(1997-98); 

Fred D. Allen 

(1997-2000) 

Helen H. Lu 

(ca. 1998- 

2001) 

LeDoux, Joseph M. 



Georgia Tech 

PhD, Chemical 


Univ., 1998 

Analysis of Retrovirus 

Production and 

Transduction 

Martin L. 

Yarmush 

Yarmush, Morgan 

et al., Laboratory 

of Surgical Science 

and Engineering, 

HMS/Shriners 

Burns Institute, 

1998-99 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Lee, Randall 

Lelkes, Peter I. 

Leong, Kam W. 

Levenston, Marc E. 

L'Heureux, Nicolas 

Li, Song 

Liu, Shu Q. 

Livesey, Stephen A. 


Medicine, University 

of California, San 

Francisco 

Calhoun Chair Prof. of 

Cellular Tissue 


Univ. 



Hopkins Univ. 


Mechanical 



Chief Scientific 

Officer, Cytograft 





Berkeley, 2001 to date 


Biomedical 



1995 to date 

Executive VP and 

Chief Science Officer, 

LifeCell, 1991 to date 

Univ. of Wisconsin, 

Madison 

MD, UCLA, 1984; 

PhD, Pharmacology, 

UCLA, 1984 

PhD, Technical Univ., 

Aachen 

PhD, Chemical 



PhD, Biomechanical 

Engineering, Stanford, 

1995 

PhD, Universite Laval, 

1996 


UCSD, 1997 


UCSD, 1990 


Melbourne; PhD, 

Univ. of Melbourne, 

1985 

Opioid and 

Neuropeptide 

Modulation of Seizures 

in the Mongolian Gerbil 

Synthesis and Insertion 

Mechanisms of Graphite 

Intercalation 

Compounds 

Simulation of Functional 

Adaptation in 

Trabecular and Cortical 

Bone 

Construction d'un 

Vaisseau Sanguin 

Humain par Ingenierie 

Tissulaire: une 

Nouvelle Approche 

Shear Stress-Induced 

Signaling in Vascular 

Endothelial Cells: Roles 

of Focal Adhesion 

Kinase, Small GTPases 

and Heat Shock Protein 

27 

Zero-Stress States and 

Tissue Remodeling of 

Rat Systemic and 

Pulmonary Arteries in 

Hypertension and 

Diabetes Mellitus 

(Systemic Arteries) 

Phosphorylation in the 

Action of Peptide 

Hormones 

Dennis R. 

Carter 

Francois A. 

Auger 

Shu Chien 

Y-C. Fung 

Robert S. Langer, 

MIT, late 1980s 

Alan J. 

Grodzinsky, 

Continuum 

Electromechanics 

Group, MIT, 1995- 

98 ? 

John A. Frangos, 

UCSD, late ca. 

1998-2000 


UCSD, 1990-92 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Longaker, Michael T. Prof. of Surgery, 

Stanford Univ., 2000 

to date 

Lotz, Jeffrey C. Assoc. Prof. of 



San Francisco, 1993 to 

date 

Lu, Helen H. Assist. Prof. of 

Biomedical 


Columbia Univ., 

2001? to date 

New York Univ. 


School, 1984 

PhD, HST Medical 



1988 



1998 

Hip Fracture Risk 

Predictions by X-Ray 

Computed Tomography 

45S5 Bioactive Glass 

Surface Zeta Potential 

Variations in Electrolyte 

Solutions With and 

Without Fibronectin 

Wilson C. 

Hayes 

Solomon R. 

Pollack 

Cato Laurencin, 

Drexel, ca. 1998- 

2001 

Lynn, David M. 

Lysaght, Michael J. 

Ma, Peter X. 

Macdonald, Jeffrey 

M. 


Chemical 


Wisconsin, Madison, 

2002 to date 

Professor (Research), 

Biomedical 

Engineering, Brown 




Sciences, Univ. of 

Michigan School of 

Dentistry, 1996 to date 


of Biomedical 


North Carolina 

Amicon, 1966-79; 

Baxter Int'l. 1984-89; 

CytoTherapeutics 

1989-94 

PhD, Organic 

Chemistry, California 





New South Wales 


Science and 


Univ., 1993 

PhD, Pharmaceutical 

Chemistry, Univ. of 

California, San 


Water-Soluble 

Ruthenium Alkylidene 

Complexes: Synthesis 

and Application to 

Olefin Metathesis in 

Protic Solvents 

Structure and 

Deformation Behavior 

of Amorphous 

Ionomers, their Blends 

and Plasticized Systems 

Toxicological 

Applications of Cell and 

Animal Models for in 

Vivo Nuclear Magnetic 

Resonance 

Robert H. 

Grubbs 


MIT, 1999-2002 


MIT, 1993-96 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Mallapragada, Surya 

K. 

Mann, Brenda K. 

Marra, Kacey G. 

Matthew, Howard 

McAllister, Todd N. 

McCulloch, Andrew 

D. 

McFetridge, Peter S. 


Chemical 

Engineering, Iowa 

State Univ. 

Assist. Prof., Keck 

Graduate Institute of 

Applied Life Science, 

2001 to date 



Pittsburgh, 2002 to 

date 


Chemical Engineering 

and Materials Science, 

Wayne State U. 

President and CEO, 

Cytograft Tissue 




UCSD, 1990s? to date 


Dept. of Chemical 


Materials Science, 

Univ. of Oklahoma, 

2002 to date 

Carnegie Mellon Univ., 

1998-2002 

PhD, Chemical 


Univ., 1996 

PhD, Chemical 



PhD, Organic 

Chemistry, University 

of Pittsburgh, 1996 

PhD, Chemical 

Engineering, Wayne 

State U., 1992 



San Diego, 2000 

PhD, Theoretical and 

Applied Mechanics, 

University of 

Auckland, 1986 

PhD, Univ. of Bath 

(UK), 2002 

Molecular Analysis and 

Experimental 

Investigation of 

Semicrystalline 

Polymers" 

In Vivo Phosphorus-31 

and Carbon-13 Nuclear 

Magnetic Resonance 

Spectroscopy to Study 

Cellular Metabolism 

Synthesis, 

Characterization, and 

Applications of Novel, 

Low-Surface Energy 

Poly(amide urethanes) 

Perfused 

Microencapsulated 

Hepatocytes: 

Evaluation of Potential 

for Extracorporeal Liver 

Support 

Fluid Flow-Induced 

Signal Transduction in 

Bone Cells 

Deformation and Stress 

in the Passive Heart 

The Use of Porcine 

Carotid Arteries as a 

Matrix Material for 

Tissue Engineered Small 

Diameter Vascular 

Grafts 

Nicholas A. 

Peppas 

Jacqueline V. 

Shanks 

John A. 

Frangos 

Visiting researcher 

w/Antonios Mikos, 

Rice Univ., May 

1996; visiting 

researcher 

w/Robert Langer, 

MIT, Summer 

1996 

Jennifer L. West, 

Rice Univ., 1998- 

2001 

Elliott L. Chaikof, 

Emory Univ., 

1996-97 

Martin Yarmush 

and Ronald 

Tompkins, HMS / 

Mass. General 



Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

McIntire, Larry V. 

Messersmith, Phillip 

B. 



Univ. 


Biomedical 



1998 to date 

Univ. of Illinois at 

Chicago, 1994-97; 

Dental School, 


1997-98 

PhD, Princeton Univ., 

1970 


Science and 


Illinois at Urbana- 

Champaign, 1993 

Hydrodynamic Stability 

of Selected Non- 

Newtonian Fluids in 

Two Simple Flows 

Synthesis and 

Characterization of 

Novel Polymer-Ceramic 

Nanocomposites: 

Organoceramics 

Samuel I. Stupp Materials science 

and engineering, 

Cornell Univ., 

1992-94 

Jeffrey A. 

Hubbell 

(1986); John 

A. Frangos 

(1987); 

Timothy M. 

Wick (1988); 

B. Rita 

Alevriadou 

(1992); 

Charles W. 

Patrick (1994); 

Julia M. Ross 

(1995) 

Mikos, Antonios G. 

Moghe, Prabhas V. 



Chemical 




Biomedical 



PhD, Chemical 


Univ., 1988 

PhD, Chemical 



Fracture of and 

Adhesion Between 

Biological and Synthetic 

Macromolecular 

Materials 

Phenomenological and 

Mechanistic Analyses of 

Leukocyte Chemotaxis 

Nicholas A. 

Peppas 

Robert T. 

Tranquillo 

MIT/HMS 1990-91 Susan Ishaug- 

Riley (1996); 

Susan Peter 

(1998) 

M. Yarmush, 

HMS, 1993-95 

Surya K. 

Mallapragada 

(May 1996); 

Julia E. 

Babensee 

(1996-99); 

Aaron S. 

Goldstein 

(1997-99); 

Vassilios I. 

Sikavitsas 

(2000-02) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Mooney, David J. 

Mow, Van C. 

Naughton, Gail K. 

Neitzel, G. Paul 

Nerem, Robert M. 

Nicoll, Steven 


Chemical 

Engineering, Prof. of 


Science, Univ. of 


date 




President and CEO of 


Sciences, 1987 to date 

(?) 




Institute Professor, 

Georgia Tech, 1987 to 

date 




NYU Medical Center, 

1983-85; CUNY 

Queensborough 

Community College, 

1985-87 

Arizona State Univ. 

Ohio State Univ., 1964- 

79; Univ. of Houston, 

1979-86 

PhD, Chemical 


1992 

PhD, Mechanics, 

Rensselaer 

Polytechnic Inst., 1966 

PhD, New York 


PhD, Johns Hopkins 

Univ., 1979 

PhD, Aeronautical and 

Astronautical 

Engineering, Ohio 

State Univ., 1964 



Berkeley and San 


Control of Hepatocyte 

Morphology and 

Function by the 

Extracellular Matrix 

Ultrastructural 

Localization of the 

Cellular Site of 

Extrarenal 

Erythropoietin 

Production 

Centrifugal Instability of 

Decelerating Swirl-Flow 

Within Finite and 

Infinite Circular 

Cylinders 

Shock Layer Radiative 

Emission During 

Hypervelocity Re-entry 

Induction of 

Chondrogenic 

Differentiation in 

Human Dermal 

Fibroblasts: Application 

to Cartilage Tissue 


Robert S. 

Langer 

NYU Dept. of 

Dermatology 

Stelios T. 

Andreadis 

(1996) 

Kyriacos 

Athanasiou? 

(1989); 

Gerard 

Ateshian 

(1991); Louis 

J. Soslowsky 

(1991); 

Farshid Guilak 

(1992) 

John D. Lee Jan P. 

Stegemann 

(2002) 

Rajendra S. 

Bhatnagar 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Niklason, Laura 

Odde, David J. 

Orban, Janine M. 

Oudega, Martin 


Biomedical 


Anesthesiology, 

Surgery, Duke Univ., 

1998 to date 

Assoc, Prof. of 

Biomedical 


Minnesota 

Research Scientist, 

DePuy Orthobiologics 

Division (Johnson & 

Johnson), 2002 to date 


of Neurological 


Miami 

Palecek, Sean P. Assist. Prof. of 

Chemical 


Wisconsin, Madison 

Palsson, Bernhard O. Prof. of 


UCSD, 1995 to date 

Parenteau, Nancy L. 

President of Amaranth 

Bio, 2002 to date 


1984-95 

Organogenesis until 

2002 


Michigan, 1991; PhD, 

Biophysics and 

Theoretical Biology, 

Univ. of Chicago, 

1988 

PhD, Chemical and 

Biochemical 


Univ., 1995 

PhD, Organic 

Chemistry, University 

of Pittsburgh, 1998 

PhD, University of 

Leiden (Netherlands), 

1990 

PhD, Chemical 


1998 

PhD, Chemical 


Wisconsin, 1984 

PhD, Georgetown 

Univ. Medical Center, 

1985 


Structural Analysis of 

Digital Angiographic 

Images 

Experimental and 

Theoretical 

Investigation of Nerve 

Growth Mechanisms: 

Contribution fo 

Microtubule Dynamics 

(Cytoskeleton) 

Synthesis, 


Applications of 

Poly(ether) grafted 

Poly(urethane)s 

Development of the Rat 

Spinal Cord: 

Histochemistry of Some 

Functional and 

Structural Parameters 

Regulation of Integrin- 

Mediated Linkages 

During Cell Migration 

Mathematical Modeling 

of Dynamics and 

Control in Metabolic 

Networks 

Antigen Distribution in 

Pancreatic Cells of the 

Chick Embryo and 

Adult Studied with 

Monoclonal Antibodies 

Helen M. 

Buettner 


Lauffenburger; 

A.F. Horwitz 


MIT, 1995-98 (?) 

Elliott L. Chaikof, 

Emory Univ., 

1999-2000; Lee 

Weiss and David 

Vorp, Institute for 

Complex 

Engineered 

Systems, PTEI 

Fellow, 2000-02 

Mary Bartlett 

Bunge, Cell 

Biology, Anatomy, 

Neurological 

Surgery and 

Neurology, Univ. 

of Miami 

Stelios T. 

Andreadis 

(1996) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Patrick, Charles W. 

Patzer, John F. 

Peppas, Nicholas A. 


Surgery, MD 

Anderson Cancer 

Center 



Pittsburgh, 1986? to 

date 



Biomedical 

Engineering, and 

Pharmaceutics, Univ. 

of Texas at Austin, 

starting 2003 

Gulf Research and 

Development Co. 

Purdue Univ., 1976 - 

2002 

PhD, Chemical 


Univ., 1994 

PhD, Chemical 

Engineering, Stanford 

Univ., 1980 

ScD, Chemical 


1973 

Video Microscopy and 

Digital Image 

Processing Applied to 

Tissue Engineering: 

Intracellular Ion and 

Cell Adhesion 

Measurements 

Stability in Spherical 

Systems: I. 

Hydrodynamic Stability 

of Thin, Spherically 

Concentric Fluid Shells. 

II. Global Stability of 

Transient Drop 

Extraction 

Crystalline Radiation- 

Crosslinked Hydrogels 

of Poly(vinyl-alcohol) as 

Potential Biomaterials: 

a Study of the Properties 

of Poly(vinyl-alcohol) 

Hydrogels in Relation to 

the Conditions of 

Primary Crosslinking by 

Irradiation and of 

Secondary Network 

Reinforcement by 

Crystallization 

Larry V. 

McIntire 

Edward W. 

Merrill 

Cox Lab, Rice 

Univ., 1994-96 

MIT 

Arteriosclerosis 

Center (Robert S. 

Lees?) 

Antonios G. 

Mikos (1988); 

Surya K. 

Mallapragada 

(1996) 

Kristi S. 

Anseth (1995) 

Peter, Susan 

Osiris Therapeutics (to 

date?) 

PhD, Chemical 


Univ., 1998 

Development of 

Poly(Propylene 

Fumarate-co-Ethylene 

Glycol): An Injectable, 

Biodegradable Implant 

for Cardiovascular 

Applications 

Antonios G. 

Mikos 

Pishko, Michael V. 


Chemical 

Engineering, Penn 

State Univ., 2000? to 

date 

Texas A&M Univ., 

1997-2000? 

PhD, Chemical 



Design and 

Characterization of 

Glucose Sensors for 

Subcutaneous 

Implantation 

Adam Heller 


MIT, 1995-96 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Pittenger, Mark F. 

Pollack, Solomon R. 

Ranieri, John P. 

Ratner, Buddy D. 

Reddi, A. Hari 

Reid, Lola M. 

VP, Research, Osiris 

Therapeutics, 1994 to 

date 




Vice President, 

DuPont Bio-Based 

Materials, 2002 to 

date 



Chemical 


Washington 


Research, Univ. of 

California, Davis, 

1997 to date 

Prof. of Cell and 

Molecular Physiology, 

UNC Chapel Hill, 

1994 to date 

Georgia Tech; Sulzer 

Biologics, ca. 2001; 

Aortech International, 

ca. 2001-2 

Univ. of Chicago; 

Johns Hopkins Univ. 

Albert Einstein College 

of Medicine, 1977-94 

PhD, Johns Hopkins 

Univ. School of 

Medicine, 1986 

PhD, Physics, Univ. of 


PhD, Medical 

Sciences, Section of 

Artificial Organs, 

Biomaterials and 

Cellular Technology, 

Brown Univ., 1994 

PhD, Polymer 

Chemistry, 

Polytechnic Institute 

of Brooklyn, 1972 

PhD, Endocrinology 

and Physiology of 

Reproduction 

(Delhi?), 1966 

PhD, 

Neuroendocrinology, 

UNC Chapel Hill, 

1974 

Autoregulation of 

Tubulin Synthesis: a 

Novel Cytoplasmic 

Mechanism Regulating 

Gene Expression 

The Specific Heat of 

Ferrites at Liquid 

Helium Temperatures 

Development of 

Biomaterials that 

Spatially Control 

Neuronal Cell 

Attachment and 

Differentiation 

The Interaction of Urea 

with Poly (2- 

Hydroxyethyl 

Methacrylate) 

Hydrogels 

A Study of the Structure 

and Inorganic 

Composition of the 

Cuticle over the Molt 

Cycle in the Spiders, 

Araneus diadematus, 

Araneus sericatus, 

Eurypelma anax, and 

Eurypelma sp., and of 

the Influence of 

Ecdysterone on the 

Cuticular Structure and 

Inorganic Composition 

in the Tarantula 

Patrick 

Aebischer 

H.G. Williams- 

Ashman, Johns 

Hopkins Univ. 

G. Sato and J. 

Holland, UCSD, 

1974-77 

Clark T. Hung 

(1995); Fred 

D. Allen 

(1996); Helen 

Lu (1998) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Remmel, Rory P. 

Ricordi, Camillo 

Ross, Julia M. 

Prof. of Medicinal 


Minnesota College of 

Pharmacy 

Prof. of Surgery and 

Medicine, Chief of 

Division of Cellular 

Transplantation, Univ. 

of Miami School of 

Medicine, 1994 to 

date 


Chemical and 

Biomedical 


Maryland Baltimore 

County 


1989-93 



MD (Italy) 

PhD, Chemical 


Univ., 1990 

Influence of the 

Intestinal Microflora on 

the Disposition and 

Metabolism of Warfarin 

and Clonazepam 

Platelet Interactions with 

Subendothelial Surfaces 

Under Physiological 

Shear Conditions: 

Response to Type VI 

Collagen and an 

Endothelial Cell Wound 

Model 

Larry V. 

McIntire 

Roth, Charles M. 

Russell, Alan J. 

Rutkowski, Greg E. 

Sabelman, Eric E. 


Biomedical 






date 


Chemical 


Louisville 

Consulting Assoc. 

Prof. of Functional 

Restoration, Stanford 

Univ. Biomechanical 

Engineering Div., to 

date 

PhD, Chemical 


Delaware, 1994 

PhD, Chemistry, 

Imperial College, 

1987 

PhD, Chemical 

Engineering, Iowa 


PhD, Stanford Univ., 

1976 

Electrostatic and van der 

Waals Contributions to 

Protein Adsorption 

Protein Engineering of 

the pH Dependence of 

Subtilisin BPN' 

Design of a Bioartificial 

Nerve Graft 

An Organ Culture 

Method for Study of 

Fetal Mouse Bone 

Under Stress 

Abraham M. 

Lenhoff 

Carole A. 

Heath 

M. L. Yarmush, 

HMS/MGH/ 

Shriners, 1995-97 

Alexander 

Klibanov, 

Chemistry, MIT, 

1987-89 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Sacks, Michael S. 

Sagen, Jacqueline 

Sah, Robert L-Y. 

Sakiyama-Elbert, 

Shelly E. 

Saltzman, W. Mark 

Sambanis, 

Athanassios 

Schaffer, David V. 

Assoc. Prof., 


of Pittsburgh, 1998 to 

date 

Prof. of Neurosurgery, 

Univ. of Miami, 1998 

to date 

Associate Prof. of 


UCSD, 1992 to date 


Biomedical 



Prof. of Chemical and 

Biomedical 

Engineering, Yale 



Chemical 


Tech 


Chemical 



1999 to date 

Univ. of Miami, 1993- 

98 

CytoTherapeutics/Brow 

n Univ. to 1998 

Johns Hopkins Univ., 

1987-95; Cornell 

Univ., 1996-2002 



Texas Southwestern 

Medical Center at 

Dallas, 1992 

PhD, Univ. of Illinois 

at Chicago Health 

Sciences Center, 1984 


School, 1991; ScD, 

HST Medical 



1990 

PhD, Chemical 







1987 



PhD, Chemical 


1998 

Active Wall Tension 

and Passive Constitutive 

Relation of the Right 

Ventricular Free Wall 

Modulation of 

Nociception by 

Brainstem 

Noradrenergic Neurons 

Biophysical Regulation 

of Matrix Synthesis, 

Assembly, and 

Degradation in 

Dynamically 

Compressed Calf 

Cartilage 

Biofunctional Polymers 

for Controlled Release 

of Growth Factors in the 

Peripheral Nervous 

System 

A Microstructural 

Approach for Modelling 

Diffusion of Bioactive 

Macromolecules in 

Porous Polymers 


Modeling Studies on the 

Dynamics of Cultures of 

the Ciliate Tetrahymena 

pyriformis Grown on 

Several Bacterial 

Species 

Epidermal Growth 

Factor Receptor- 

Mediated Gene 

Delivery: a Model 

System for Engineering 

Selective Gene Therapy 

Approaches 

C.J. Chuong 

Alan J. 

Grodzinsky 

Jeffrey A. 

Hubbell 

Robert S. 

Langer 


Lauffenburger 

Biomedical 


UTSWMCD, 

1992-93 

Postdoc at MIT 

Chemical 


(Gregory 

Stephanopoulos) 

and Whitehead 

Institute (Harvey 

Lodish), MIT, ca. 

1990 

Fred Gage, Salk 

Institute, 1998-99 

Kristen L. 

Billiar (1998) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Schmidt, Christine E. Assoc. Prof. of 

Biomedical 



(?) to date 

Schoen, Frederick J. Prof. of Pathology, 


School, faculty, 

Harvard-MIT HST 

PhD, Chemical 


Illinois at Urbana- 

Champaign, 1995 

MD, Univ. of Miami, 

1974; PhD, Materials 

Science, Cornell 

Univ., 1970 

Adhesion Receptor- 

Cytoskeleton 

Interactions in Migrating 

Tissue Cells 

A Model for the Growth 

of Martensite in Iron-(10 

Percent) Nickel Alloys 

Containing Carbon 


Lauffenburger 


MIT, 1994-96 

Sefton, Michael V. 

Sfeir, Charles S. 

Shastri, Venkatram 

Prasad 

Shea, Lonnie D. 

Sheardown, Heather 

D. 

Shoichet, Molly S. 





1974 to date 

Assist. Prof., Univ. of 


date 


Univ. of Pennsylvania 

School of Medicine 


Chemical 


Northwestern Univ. 


Chemical 


McMaster Univ. 

Assoc. Prof., Depts. of 

Chemistry, Chemical 




1995 to date 

Oregon Health 

Sciences Univ., 1999- 

2000 

CytoTherapeutics, 

1992-95 

ScD, Chemical 


1974 

DDS, Univ. Louis 

Pasteur, 1990; PhD, 

Molecular Biology, 


1996 

PhD, Chemistry, 

Rensselaer 

Polytechnic Institute, 

1995 

PhD, Chemical 


Scientific Computing, 


1997 

PhD, Chemical 




1995 

PhD, Polymer Science 

and Engineering, 


Massachusetts, 

Amherst, 1992 

Surface Hydroxylation 

of Styrene-Butadiene- 

Styrene Block 

Copolymers for 

Biomaterials 

Phosphorylation of 

Dentin Extracellular 

Matrix Proteins by 

Protein Kinases 

Evaluation of 

Polypyrrole Thin Films 

as Substratum for 

Mammalian Cell Culture 

Kinetics of Receptor, 

Ligand, and G Protein 

Interaction for Signal 

Transduction: a 

Modeling Study 

Mechanisms of Corneal 

Epithelial Wound 

Healing 

Synthesis and 

Adsorption of Polymers: 

Control of Polymer and 

Surface Structure 

Edward W. 

Merrill 

Arthur Veis 

Gary Wnek 

Jennifer J. 

Linderman 

Yu-Ling Cheng 

Thomas J. 

McCarthy 


Chemical 


ca. 1998-2000 

Julia E. 

Babensee 

(1996) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Shreiber, David I. 

Sielaff, Timothy D. 

Sikavitsas, Vassilios 

I. 


Biomedical 





Minnesota, 1998 to 

date 



and Materials Science, 

Univ. of Oklahoma, 

2002 to date 



1998 

MD, Medical College 

of Virginia, 1989; 



PhD, SUNY Buffalo, 

2000 


Computational 

Modeling of Traumatic 

Brain Injury: in Vivo 

Thresholds for 

Mechanical Disruption 

of the Blood-Brain 

Barrier 

Development and 

Characterization of a 

Porcine Hepatocyte 

Bioartificial Liver for 

the Treatment of 

Fulminant Hepatic 

Failure 

Dynamics of Antigen- 

Antibody Interactions 

and their Effect in the 

Performance of 

Immunosensors 

David F. 

Meaney 

Frank B. Cerra 

Robert T. 

Tranquillo, Univ. 

of Minnesota, ca. 

2000-02 

Antonios G. 


2000-02 

Skalak, Richard (deceased, 1997) Columbia Univ., 1954- 

88; UCSD, 1988-97 

Smith, Marc K. 

Solomon, Barry A. 

Soslowsky, Louis J. 

Spector, Myron 


Mechanical 



President and CSO, 

Circe Biomedical, 

1999-2002 





Surgery, Brigham and 

Women's Hospital / 


School 

Johns Hopkins Univ., 

until 1991 

1977-99 Amicon --> 

WR Grace 

PhD, Civil 




Sciences and Applied 

Mathematics, 


1982 

PhD, Chemical 

Engineering, Yale 

Univ., 1973 


Mechanics, Columbia 

Univ., 1991 

PhD, Carnegie Mellon 

Univ., 1971 

An Extension of the 

Theory of Water 

Hammer 

The Instabilities of 

Thermocapillary Shear 

Layers 

Open Tubular 

Heterogeneous Enzyme 

Reactors 

Studies on Diarthrodial 

Joint Biomechanics with 

Special Reference to the 

Shoulder 

A Study of the Mineral 

Phase Development 

Associated with Arterial 

Calcification 

Van C. Mow 

Chemical 

Engineering dept. 

MIT, 1975-77? 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Stegemann, Jan P. 

Stice, Steven L. 


Biomedical 


2002 to date 

Assoc. Prof., Animal 

and Dairy Science, 

Univ. of Georgia 

WR Grace; Circe 

Biomedical, mid-1990s 


Georgia Tech, 2002 

PhD, Animal Science, 


Massachusetts at 

Amherst, 1989 

Characterization and 

Control of Smooth 

Muscle Phenotype in 

Vascular Tissue 


The Characterization of 

a Factor in Mammalian 

Sperm Which Activates 

Mature Oocytes 

Robert M. 

Nerem 

James M. Robl 

Tien, Joe 


Biomedical 


Univ. 

Titus, F. Louisa Research Assist. Prof., 

Dept. of Medicine, 

Emory Univ., 1991 to 

date 

Tompkins, Ronald G. Prof. of Surgery, HMS 

/ Mass. General Hosp. 

/ Boston Shriners 

Hosp., 1990 to date 

Toner, Mehmet 

Prof. of Surgery, HMS 

/ Mass. General Hosp., 

1990s? to date 

Tranquillo, Robert T. Prof. of Biomedical 


Minnesota 

PhD, Physics, Harvard 

Univ., 1999 

PhD, Anatomy, Emory 

Univ., 1985 

MD, Tulane Univ., 

1976; ScD, Chemical 


1983 



Medical Physics, 1989 

PhD, Chemical 




Mesoscale Self- 

Assembly 

Regulation of Cardiac 

C-Protein 

Phosphorylation 

In Vivo Transport of 

Low-Density 

Lipoprotein in the 

Arterial Walls of the 

Squirrel Monkey 

Thermodynamics and 

Kinetics of Ice 

Nucleation Inside 

Biological Cells During 

Freezing: as Applied to 

Mouse Oocytes 

Phenomenological and 

Fundamental 

Descriptions of 

Leukocyte Random 

Motility and Chemotaxis 

George M. 

Whitesides 

H. Cris Hartzell 

Clark K. 

Colton, 

Kenneth A. 

Smith 

Ernest G. 

Cravalho 


Lauffenburger 

Christopher Chen, 

Biomedical 


Hopkins Univ., ca. 

1999-2001 

Jens O.M. 

Karlsson 

(1994); 

Sangeeta N. 

Bhatia (1997) 

Prabhas V. 

Moghe (1993); 

Victor H. 

Barocas 

(1996) 


Moghe (1993- 

95); Albert 

Folch (1997- 

2000) 

Victor H. 

Barocas 

(1996); David 

I. Shreiber (ca. 

2000-02) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Tuan, Rocky S. 

Unsworth, Brian R. 

Vacanti, Charles A. 

Vacanti, Joseph P. 

Valentini, Robert F. 


Surgery, Biochemistry 

and Molecular 

Biology, Thomas 

Jefferson Univ., 1988 

to date; Chief of 

Cartilage Biology and 

Orthopaedics Branch, 

NIH-NIAMS, 2001 to 

date 

Prof. of Biological 

Sciences, Marquette 



Anesthesiology, 

Perioperative and Pain 

Medicine, HMS / 

Brigham and 

Women's Hosp., 2002 

to date 


HMS/Massachusetts 

General Hospital 

Adjunct Assist. Prof. 

of Medical Science, 

Brown Univ., to date; 

Chief Executive 

Officer, Cell Based 

Delivery, 1999 to date 


1980-88 

HMS / Mass. General 

Hosp., 1980s - 1994; 

Univ. of Mass. Medical 

School, 1994-2002 


Hospital 

PhD, Rockefeller 

Univ., 1977 

PhD, Biochmistry, 

University College, 

London, 1965 


Nebraska, 1975 


Nebraska, 1974 

MD, Brown Univ., 

1993; PhD, Medical 

Science, Brown Univ., 

1993 

The Calcium Binding 

Protein of the Chick 

Chorioallantoic 

Membrane 

The Development of 

Electrically Charged, 

Covalently Modified 

Fluoropolymers for 

Patterned Neuronal Cell 

Attachment and 

Outgrowth 

Patrick 

Aebischer 


Wisconsin, 

Madison, 1965-67; 


San Diego, 1967- 

69 


HMS/ Children's 


Robert E. 

Akins (1992) 

Linda G. 

Griffith (ca. 

1988-90); 

Linda K. 

Hansen? (ca. 

1992-94) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Vandenburgh, 

Herman H. 

Prof. of Pathology and 

Cellular Technology 

(Research), Brown 

Univ., to date; Chief 

Scientific Officer, Cell 

Based Delivery, Inc., 

1999 to date 

PhD, Anatomy, Univ. 

of Pennsylvania, 1976 

A Membrane 

Ectoenzyme, 5' 

Nucleotidase, on 

Differentiating Chick 

Muscle Cells in Vitro 

Velegol, Darrell 

Vito, Raymond P. 


Chemical 

Engineering, Penn 

State Univ., 1999 to 

date 




PhD, Chemical 


Mellon Univ., 1997 

PhD, Cornell Univ., 

1971 

Determining the Forces 

Between Colloidal 

Particles Using 

Differential 

Electrophoresis 

Nonlinear Vibrations of 

Certain Conservative 

Systems with Two 

Degrees of Freedom 

John L. 

Anderson, 

Stephen Garoff 

Frederick Lanni, 

CMU Center for 

Light Microscope 

Imaging and 

Biotechnology, 

1997-99 

McMaster Univ., 

early 1970s 

Vorp, David A. 


Surgery and 



date 



Pittsburgh, 1992 

Finite Element 

Modelling and Analyses 

of Nonlinearly Elastic, 

Orthotropic, Vascular 

Tissue in Distension 

Janine M. 

Orban (2000- 

02) 

Vunjak-Novakovic, 

Gordana 

Wagner, William R. 

Watanabe, Frederick 

D. 

Adjunct Prof. of 

Chemical and 

Biological 

Engineering, Tufts 

Univ.; Principal 

Research Scientist, 

MIT 

Assoc. Prof., 



date 

Assist. Prof., Univ. of 

California, Los 

Angeles, School of 

Medicine 

PhD, Chemical 


Belgrade, 1980 

PhD, Univ. of Texas at 

Austin, 1991 

MD, Ohio State Univ. 

Biochemical and 

Biophysical 

Mechanisms of Mural 

Thrombosis on Natural 

Surfaces 

Jeffrey A. 

Hubbell 

Fulbright Fellow, 

MIT, 1986-87, 

visiting research 

scientist, MIT, 

1989, 1991, 1992 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Weber, Collin J. 

Weiss, Lee 


Emory Univ., 1992 to 

date 

Principal Research 

Scientist, CMU 

Robotics Institute, 

1984 to date 

MD, Columbia Univ., 

1971 

PhD, Electrical and 

Computer 


Mellon Univ., 1984 

Dynamic Visual Servo 

Control of Robots: an 

Adaptive Image-Based 

Approach 

Brenda K. 

Mann (1998- 

2001) 

West, Jennifer L. 

Whang, Kyumin 

Wick, Timothy M. 

Associate Prof. of 


Univ., late 1990s to 

date 


Restorative Dentistry, 

Univ. of Texas Health 

Sciences Center San 

Antonio, to date 


Chemical 


Tech 

PhD, Univ. of Texas at 

Austin, 1996 




1997 

PhD, Chemical 


Univ., 1988 

Photopolymerized 

Hydrogels for the 

Manipulation of Wound 

Healing 

A Novel Bioabsorbable 

Scaffold Useful for 

Controlled Drug Release 

and Tissue Regeneration 

Fibronectin and von 

Willebrand Factor 

Mediated Sickle 

Erythrocyte Adhesion to 

Human Endothelial 

Cells under Venous 

Flow Conditions 

Jeffrey A. 

Hubbell 

Kevin E. 

Healy? 

Larry V. 

McIntire 

Williams, Stuart K. 

Wong, Joyce Y. 

Woo, Savio L.Y. 

Prof. of Physiology, 

Univ. of Arizona, 

1991 to date 


Biomedical 


Univ. 





1990 to date 

Jefferson Medical 

College, 1981-91 

UCSD, 1970s - 1990 

PhD, Cell Biology, 

Univ. of Delaware, 

1979 


Science and 


1994 




Micropinocytosis in 

Isolated Capillary 

Endothelium 

Electrically Conducting 

Polymers for Non- 

Invasive Control of 

Mammal Cell Behavior 

Structural Analysis of a 

Corneo-Scleral Shell 

Roger C. 

Wagner 

Robert S. 

Langer 

Jacob N. 

Israelachvili, 

Chemical 

Engineering, Univ. 

of California, Santa 

Barbara, ca. 1997- 

2001 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Woodhouse, Kim A. 




Univ. of Toronto 

PhD, Chemical 


McMaster Univ., 1993 

The Interactions of 

Plasminogen with 

Model Surfaces and 

Derivatized Segmented 

Polyurethane Ureas 

John L. Brash 

Wright, James R. 

Wu, Benjamin 

Yannas, Ioannis V. 

Prof. of Pathology, 

Dalhousie Univ. 


Materials Science and 

Engineering, Univ, of 

California, Los 

Angeles 


Engineering, Health 

Sciences and 

Technology, and 


Environmental Health, 

MIT, 1966 to date 

MD, Ohio State 

College of Medicine; 

PhD, Pathology, Ohio 


DDS, Univ. of Pacific; 


Science and 


1998 

PhD, Princeton Univ., 

1966 

Characterization of the 

Spontaneously Diabetic 

BB Wistar Rat 

Microstructural Control 

During Three 

Dimensional Printing of 

Polymeric Medical 

Devices 

Viscoelastic Behavior 

and Certain Transitions 

of Gelatin-Nonaqueous 

Diluent Systems 

A.J. Yates 

Michael J. 

Cima 

Yarema, Kevin J. 

Yarmush, Martin L. 

Yaszemski, Michael 

J. 


Biomedical 


Hopkins Univ. 



Univ. 

Consultant, Dept. of 


Mayo Clinic 

PhD, Chemistry, MIT, 

1994 

MD, Yale Univ.; 

PhD, Rockefeller 

Univ., 1979 

MD, Georgetown 

Univ.; PhD, Chemical 


1995 

Cellular Responses to 

Platinum-Based 

Anticancer Drugs 

Idiotypes and Allotypes 

of Immunoglobulins: 

Probes for Inheritance 

and Gene Regulation 

The Design, Synthesis, 


Mechanical Testing of a 

Novel Degradable 

Polymeric Material for 

Use as a Bone Substitute 

John M. 

Essigman 

Robert S. 

Langer 

Orthopedics 

residency, Wilford 

Hall Medical 

Center, San 

Antonio 

James C.Y. 

Dunn (1992) 


Moghe (1993- 

95); Stelios T. 

Andreadis 

(1996-98) 


Name 

Current 

Employment 



Supervisors 

Key Research 


Researcher 

Positions 

Doctoral 

Students 

Fellows 

Zandstra, Peter W. Assist. Prof. of Tissue 

Engineering, Dept. of 


and Applied 


Toronto, 1999 to date; 

affiliated faculty, 

Biotechnology 

Process Engineering 

Center, MIT, 1998 to 

date 

Zygourakis, Kyriacos Prof. of Chemical 



Univ. 

PhD, Chemical and 

Bio-Resource 


British Columbia, 

1997 



Cytokine-Dependent 

Regulation of Human 

Hematopoietic Cell Self- 

Renewal and 

Differentiation on 

Suspension Cultures 

Studies on the Monolith 

Catalytic Reactor 

J. M. Piret Douglas A. 


MIT, 1997-98 


Appendix 3: List of Interviewees 

Name of Interviewee Organization Interview Date 

Researchers 

Anthony Atala Children's Hospital, Boston 8/17/2001 

Eugene Bell 

Prof. Emeritus, MIT; Founder of Organogenesis, TEI 

Biosciences 

7/26/2001 

Joseph Bronzino Trinity College, Hartford, CT 7/2/2001 

Duane Bruley University of Maryland, Baltimore County 3/20/2001 

Clark Colton MIT 7/13/2001 

Elazer Edelman 

HST/MIT 

Stephen Emerson University of Pennsylvania 8/16/2001 

Fred Fox University of California, Los Angeles 8/24/2001 

John Frangos University of California, San Diego 8/30/2001 

Y-C Fung University of California, San Diego 8/23/2001 

Steven Goldstein 

University of Michigan 

Howard Greisler Loyola University Medical Center 6/21/2001 

David Humes University of Michigan 6/29/2001 

Robert Langer MIT 7/10/2001 

Michael Lysaght Brown University 7/2/2001 

Larry McIntire Rice University 7/23/2001 

David Mooney University of Michigan, Ann Arbor 7/18/2001 

Van Mow Columbia University 7/16/2001 

Milan Mrksich University of Chicago 6/28/2001 

Robert Nerem Georgia Institute of Technology 9/14/2001 

Berhard Palsson University of California, San Diego 8/16/2001 

A.H. Reddi University of California, Davis 7/12/2001 

Lola Reid University of North Carolina at Chapel Hill 5/28/2001 

Mark Saltzman Cornell University 8/24/2001 

Charles Vacanti University of Massachusetts Medical Center 6/20/2001 

Joseph Vacanti Mass General Hospital 7/26/2001 

Ioannis Yannas MIT 7/17/2001 

Allen Zelman Rensselaer Polytechnic Institute 7/17/2001 

Federal Agencies 

Dean Cole 

DOE 

Steve Davison NASA 6/26/2001 

Kiki Hellman FDA 8/3/2001 

Rosemarie Hunziker ATP/NIST 5/29/2001 

Peter Johnson PTEI 6/24/2001 

Peter Katona Whitaker Foundation 7/30/2001 


Name of Interviewee Organization Interview Date 

Chris Kelley NIH 6/28/2001 

Eleni Kousvelari NIH 8/23/2001 

Peter Mayfield 

(Formerly of NSF) 

Paul Werbos NSF 8/24/2001 

Private Sector 

William Haseltine Human Genome Sciences 8/8/2001 

Peter Johnson Tissue Informatics 6/24/2001 

Steven Livesey 

LifeCell Corporation 

Gail Naughton Advanced Tissue Sciences 6/27/2001 

Nancy Parenteau Organogenesis, Inc. 6/18/2001 

Doros Platika Curis, Inc. 5/29/2001 

Gary Snable 

Alan Smith 

Layton Biosciences 

Osiris Therapeutics, Inc. 


Appendix 4: Interview Protocols 

_______________________________________________________________________________________ 

Interview Protocol: RESEARCHERS – PIONEERS 

Nature of Tissue Engineering 

We are first trying to establish the extent to which and in what ways is TE a unified, coherent field. Do the 

various sub-fields of TE (i.e. ??) share a single history or should we expect to see largely independent 

development histories of each of these sub-fields? 

Historical Profile 

We would like to understand what the definitions of TE in the mid-to-late 1980s reveal about the thinking 

and vision of the time. Could you tell us how researchers and funders at the time defined the bounds of TE? 

When was the first time the term TE was used (that you know of)? Who was using it and to describe what 

research? 

What were TE’s precursor fields? I.e., what fields came together to make TE recognizable as a distinct 

field? When? Why did it happen then? What characteristics made it recognizable as a distinct field? 

What were the key technical challenges in (what is now called) TE in the mid- to late-1980s (before the term 

TE was coined)? At the time, what was the relative importance of enabling technologies vs. applications? 

What was the relative weight of fundamental vs. applied research? How did these balances change over the 

years? 

What were the key discoveries, inventions, insights, and technological breakthroughs that contributed to the 

field’s emergence as a separate entity? Who/what were the people, institutes, and tools associated with 

these breakthroughs? What were the relationships between and among these entities? 

International Influences 

Who were the international players (people, places) in the late 1980s? How was the focus of research 

abroad different from research in the US? Are there some parts of the field that are further ahead 

internationally than others? How do US researchers leverage this? 

Do US researchers collaborate often with international counterparts? What gaps does international research 

fill? 

How is the funding or regulatory climate different in these countries? 

What has been the impact of international efforts (Japan, Europe etc.) on the emergence and evolution of the 

field in general and on the work of the US researchers in particular? 

Policy Lessons 

What, if anything, do the emergence and evolution of TE tell us about how to recognize new fields worthy 

of promotion, and how to encourage their growth? 


What were the earliest clues that pointed to the emergence of a concept for a new field? 

Who recognized these clues? When, how, and why? 

What steps were taken to "test" the concept? What were the results of the "tests", and what was done about 

it? 

What vision(s) existed for the field at the beginning? What steps were taken to realize them? To what 

extent and in what ways can we say these steps were successful? 

_______________________________________________________________________________________ 

Interview Protocol: RESEARCHERS – NEW ENTRANTS 

Nature of Tissue Engineering 

We are first trying to establish the extent to which and in what ways is TE a unified, coherent field. Do the 

various sub-fields of TE (i.e. ??) share a single history or should we expect to see largely independent 

development histories of each of these sub-fields? 





Early Evolution (1990s) 

How has the field migrated and evolved since the late 1980s? How have research priorities changed? What 

are the technical challenges today? 

How did creation of the formal field affect the development of research? Did it bring together, productively 

and to the advantage of the researchers, the various threads of research in different fields? Were there any 

advantages that came out of this “union?” How did the initial support shape the agenda of TE in the long 

run? 

What mechanisms were used in the early 1990s to further progress (setting up Centers, set-aside funding 

mechanism, cross-agency task forces etc.)? 

What is the status of the field today? Where are the major loci of research? What are the obstacles to 

progress today? How are they being addressed? Has there been any change in institutional or funding 

strategy? How about the involvement of the private sector? 

Is research in any of the sub-fields further ahead than others? Why? 

Given our goals for the project, who else would you recommend we speak with? 

_______________________________________________________________________________________ 

Interview Protocol: GOVERNMENT AGENCIES 


Role of Regulations 

What was the role of FDA (CDC depending on who we are talking to) in shaping the research agenda and 

progress (especially in more controversial areas like genetic manipulation, and use of stem cells)? 

Institutional Effects 

(for NSF only) How did creating the intend to) resolve umbrella field TE (technical challenges in the field? 

What was the role of your agency in deliberately or serendipitously (through funding related or support of 

precursor fields such as enzyme engineering) creating the field? 

Who was funding, what would today be considered TE research, in the 1970s and 80s? What was their 

focus (research, graduate education, clinical applications, networking etc.)? How did this support shape the 

agenda of TE and vice versa? 

What was the difference in the strategies used by the different funding organizations? How did they support 

the field in different but perhaps similarly effective ways? 

How did your organization mobilize the private sector (through SBIR or STTR grants or other programs like 

ATP)? 

Who were the people (“the visionaries”) at NSF and elsewhere who recognized the need and value of 

creating the field? What did they have to do to get the field launched? 

What was the role of the 1987 and 1988 NSF workshops and conferences? What other events or activities 

(funding students, establishing Centers, sponsoring meetings etc.) are relevant here? What was their 

direct/immediate impact? What is their long-term impact? 

What has been the role and impact of the cross-agency task force MATES? Whose ideas was it? Did the 

task force really enable better coordination among federal agencies? How? 

(for the head of PTEI, TES etc.) What other “institutional infrastructure” exists in TE? (E.g., professional 

societies, journals, regular meetings, formal consortia or other collaborative arrangements) What are the 

roles and relationships of these other entities? 

International Influences 

Were the 1987 activities in some way motivated by the perception of losing the “US edge” in the field? 







What steps were taken to "test" the concept? What were the results of the "tests", and what was done about 

it? 



_______________________________________________________________________________________ 

Interview Protocol: PRIVATE SECTOR 





years? 




Role of the Private Sector and Clinical Applications 

What are some of the most important TE firms today? Which of these have been around since the 1980s? 

What are some of the most important TE products in the market? What are TE firms developing other than 

a TE product (software, testing methods, materials, etc.) 

What was the role of the private sector and capital markets and your company in particular, in the 

emergence and early evolution of the field? In what ways did you contribute or change the nature or pace of 

research? Did you collaborate with any university-based or international researchers, or government 

agencies? For what purpose? How productive was this relationship? 

Approx. what is the ratio of investments made in TE: private vs public funding? How has this ratio 

changed over the years? 

What was the role of the clinical side? Did the urgency to develop clinical applications change the nature 

and direction of research or product development in industry? 

Role of Regulations and the Government in General 

What was the role of regulatory bodies (FDA, CDC) in shaping the research agenda and progress (especially 

in more controversial areas like genetic manipulation, and use of stem cells)? 

How did the government enhance or hinder the progress of TE in the marketplace? 

How is the situation of the private sector in TE different in Europe, Japan and other countries? 

What did the government do to support the private sector? What could it have done better? 

Early Evolution (1990s) 


How has the field migrated and evolved since the late 1980s? How have research or product development 

priorities changed? What are the technical challenges today? 

What is the status of the field today from the point of view of TE firms? Where are the major loci of 

research? What are the obstacles to progress today? How are they being addressed? Has there been any 

change in institutional or funding strategy? 

(for PTEI or other industry consortia) What are the employment patterns in the field? In academia and 

industry? How have they changed since the early years of the field? What are they expected to be in the 

coming years? 








_______________________________________________________________________________________ 

Interview Protocol: OTHERS WHO HAVE WRITTEN ON THE FIELD 


We would like to understand what the definitions of TE in the mid-to-late 1980s reveal about the thinking 

and vision of the time. Could you tell us how researchers and funders at the time defined the bounds of TE? 

When was the first time the term TE was used? Who was using it and to describe what research? 

What were TE’s precursor fields? I.e. what fields came together to make TE recognizable as a distinct 

field? When? Why did it happen then? What characteristics made it recognizable as a distinct field? 




years? 









Who recognized these clues? When, how, and why? What vision(s) existed for the field at the beginning? 

What steps were taken to realize them? To what extent and in what ways can we say these steps were 

successful? 


I. Executive Summary 

This bibliometric study of core papers fundamental to tissue engineering produced results in four 

areas: an overview of the growth of the field, an analysis of NSF’s role in the field, a mapping of 

co-authorship patterns, and an analysis of international patenting 

The foundation of the paper side of the study is a database of information on core papers 

fundamental to tissue engineering. This database was carefully constructed in a process 

developed to meet the challenge of identifying the boundaries of such an interdisciplinary area. 

The study focuses on research that synthesized many areas of biomedicine with the aim of 

seeding autologous cells and growth factors onto three-dimensional biodegradable scaffolds with 

the aim of forming new functional tissue. Papers and patents in this area were identified using 

search strategies or “filters” described in the appendices. The set of papers found using the 

filters was augmented by papers highly cited in the patents and in review papers. Of the papers 

analyzed in the study, 66% were cited in review articles or patents, and 33% were found using 

the search strategies described by the filter. 

The analytical results revealed that the number of core papers fundamental to tissue engineering 

has been growing strongly since about the mid 1980’s. The paper most cited in reviews of the 

field is: Langer & Vacanti, "Tissue Engineering," Science 1993 May 14;260(5110):920-6. This 

paper was cited 39 times in the reviews and 11 times in patents. This paper acknowledges 

funding from NSF as well as funding from other sources. 

Analysis of the use of the term “tissue engineering” in titles and abstracts of papers indexed in 

PubMed suggests that there were three phases in the spread of the concept of tissue engineering. 

In the first phase, researchers imagined the possibility of designing replacement tissue. This is 

exemplified by papers in 1984/85 by Wolter and Meyer examining a prosthesis removed from an 

eye after 20 years. Wolter and Meyer discussed: “the significance of the successful adaptation of 

the plastic materials of the prosthesis to the tissues of the cornea and the fluids of the inner eye 

for the future of tissue engineering in the region of the eye.” In the second phase, 1989 through 

1997, the term “tissue engineering” began to be used regularly in abstracts and titles. During this 

period, the term was applied to work concerning all the main organs closely connected to tissue 

engineering: bone, cartilage, blood vessels, liver, skin, neurons and also to biomedical materials. 

The third phase of dramatic growth began in 1998 and continues. In this phase we also see a few 

papers concerning other organs, and in fact the return of papers concerning eyes. Overall, the 

growth in the use of the term “tissue engineering” in titles and abstracts seems not unlike the 

growth in number of core papers fundamental to tissue engineering. 

We find that NSF supported about 12% of the papers in the field overall. However, NSF focused 

its support on basic research and biomaterials. Therefore, when clinical research is excluded 

from consideration, NSF's share rises to 20%. 86% of NSF-supported work is published in the 

most basic journals or in the two leading biomaterials journals: Biomaterials and the Journal of 

Biomedical Materials Research. In contrast, 52% of research supported by other funders is basic 

or in those two journals. NSF’s research is also focused on the core participants in the field. 

17% of the papers from leading institutions acknowledge NSF support compared to 2% of papers

from institutions that appeared only once on a core paper fundamental to tissue engineering. 

More peripheral, and one-off participants are much less likely to acknowledge NSF research 

support. Thus it is no surprise to find that NSF played a larger than expected role in supporting 

the work of leading researchers such as R Langer, JP Vacanti, and DJ Mooney. 

The patterns of co-authorship in the field are portrayed in an innovative series of figures, tables 

and maps developed for this study. These reveal the highly collaborative nature of the work 

undertaken by R Langer and JP Vacanti, with whom most lead authors in the area have worked 

at least once. Papers by Langer and Vacanti list over 250 coauthors. Several leading authors 

appear to have started as students of Langer or Vacanti, and several more appear only as their coauthors. 

Six multi-dimensional maps of the paper-by-paper development of lead authors’ work 

in the area were developed for authors supported by NSF. These reveal the interweaving of 

public and private knowledge and the public and private sectors in the development of tissue 

engineering research, and precisely position NSF support in relation to this. 

In parallel with the analysis of tissue engineering literature, CHI was engaged to do a patent 

analysis to study the international patenting trends in tissue engineering. We found: 

1. Patenting in the area is increasing steadily and has not yet peaked. 

2. Most of the patents are coming from US inventors and assignees. 

3. Most of the key inventions are coming from US assignees, especially MIT, Advanced 

Tissue Sciences, and Regen Biologics Inc.

The Emergence of Tissue Engineering as a ... - Abt Associates

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