Combinatorial and High-Throughput Screening of Materials ...

ACS Combinatorial Science
REVIEW
Figure 43. Results of the accelerated aging of 2-D combinatorial library of Rh/Pd film. Chemical response images to 1000 ppm of hydrogen (A) before
and (B) after the accelerated aging. (C) Differential response after and before the accelerated aging, the most stable regions have the darkest color. 343
Also, due to the advances in analytical techniques and nanosciences,
biomaterials research has seen the emergence of nanoscaled
biomaterials in the areas of drug or gene delivery, tissue
426 430
regeneration, and in materials for body implants.
Biomaterials should meet biocompatibility and other application-specific
requirements summarized by the International Organization
for Standardization (ISO). 431 Biomaterials used for in vivo
applications should be also biocompatible. The lack of consensus
on the standardization of biocompatibility tests has hampered this
field for years. However, recently, toxicity tests for biocompatibility
and safety assessments and becoming more standardized 432 due to
intensive efforts from various research groups and governments to
identify routine testing cascades for biocompatibility of
materials. 433,434 The interactions between the material and the
body or more particularly to the different subsystems are usually
complex. Thus, exploration of these multiple dimensions can be
daunting. Advances in CHT techniques in surface chemistry,
analytical chemistry, and materials chemistry have enabled the
rapid and effective evaluation of these complex spaces. 12,435,436
One of significant areas of biomaterials research is to develop
artificial materials for use in the human body to restore, repair
and replace diseased tissue to enhance survival and quality of life.
There has been an explosion of research activity on the work on
biomaterials made from polymers as well as peptides that has
been used in biological systems and more particularly in the
delivery of drugs or genes for therapeutic applications. In light of
these recent trends, polymeric biomaterials that are degradable in
nature are the preferred candidates, especially for tissue engineering
applications, drug delivery, and temporary therapeutic
devices. These materials are ultimately made into a system and
injected post formulation into the body, typically for therapeutic
applications. In most cases, the biomaterials have been made and
tested combinatorially as discrete arrays or gradient 2D films for
further biological testing. 435,437
Surfaces of biomaterials can be also used to trigger biological
responses and their interaction with biological systems. These
surfaces are being used in evaluating the viability of materials in
regenerative medicine and more particularly in triggering the
growth of stem cells for tissue regeneration as well as repair. 438
Being able to rapidly make, characterize and test these materials
enables the accelerated discovery of new materials in regenerative
medicine. 439,440
In the last few decades, small molecules have played a central
role in many areas of research, especially in drug discovery but
also in materials research and development. With the explosion
of laboratory automation and high throughput synthesis and
characterization techniques, interest in libraries of small molecules
to support drug discovery and materials research have
grown significantly. 441 443 In a recent review, Wu and Schultz
have reviewed selected examples of synthesis of unnatural
aminoacids by genetically modified organisms. 441 These materials
are typically difficult to access in a synthetic point of view and
may find unique applications in the realm of biomaterials/
biopolymers but also been used in medicine for gene delivery.
Biomaterials can also be synthesized and fabricated by using
bioorganisms to access building blocks that are traditionally
difficult to make. 444,445 This technology allows chemists to
probe, and change, the properties of proteins, in vitro or
in vivo, by directing novel, lab-synthesized chemical moieties
specifically into any chosen site of any protein of interest.
Biomaterials that have been generated by combinatorial phage
display have been reviewed elsewhere. 444,445
3.5.1. Biomaterials Used for Drug/Gene Delivery. Polymeric
biomaterials are among the most important materials in drug and
gene delivery for in vivo applications. When new classes of
pharmaceuticals and biologics (peptides, proteins and DNAbased
therapeutics) are being introduced, these new drugs
typically require efficient delivery to the therapeutic targets.
Additionally, for many conventional pharmaceutical therapies,
the efficacy may be improved and the side effects reduced if the
therapy is administered continuously, in a controlled fashion,
rather than through conventional burst release techniques (oral
ingestion, injection, etc). Development of materials that can
enable the encapsulation of these pharmaceuticals and biologics
has attracted significant interest. 435
The main advantages of these polymeric materials are ease
of synthesis, reproducibility but also the access to materials
platforms that can be tuned easily to achieve the desired physicochemical
properties, such as water solubility and biodegradability/release.
A wide range of highly diverse but also focused
materials has been used and considered in this field and especially
polymeric backbones such as PLGA (poly lactic and glycolic
acid) or polycaprolactam and polyhydroxyethylmethacrylate
moieties, which typically break down in in vivo into innocuous
byproducts. In recent years, due to more stringent regulations
from a materials requirement standpoint, synthetic approaches
have shown an increasing level of sophistication employing
nanotechnology, microfluidics, and micropatterning. The CHT
618 dx.doi.org/10.1021/co200007w |ACS Comb. Sci. 2011, 13, 579–633