Profilaksa DVT kod velikih ortopedskih operacija - Depol ...

FINAL PROGRAM 

BOOK OF ABSTRACTS 

ORGANIZED BY 

Croatian Academy of Sciences and Arts - Department of Medical Sciences 

IN COOPERATION WITH 

University of Rijeka - Department of Biotechnology 

GUEST SOCIETIES 

Croatian Society for Rheumatology 

International Society for Applied Biological Sciences 

Croatian Society for Allergology and Clinical Immunology

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Hospitalija trgovina d.o.o. 

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©2012 ConMed Linvatec All rights reserved. M2012284

CONTENTS 

20 - 22 September 2012, Opatija, Croatia 

Welcome to the 2 st International Conference on Regenerative Orthopedics and Tissue Engineering........................ 2 

Sponsors ........................................................................................................................................................................................................ 4 

Final Program ............................................................................................................................................................................................... 5 

General Information .................................................................................................................................................................................. 8 

Book of Abstracts ....................................................................................................................................................................................... 11 

Lecturers’ Resumes .................................................................................................................................................................................... 47 

Poster Presentations ................................................................................................................................................................................. 77 

Index of Authors ......................................................................................................................................................................................... 91 

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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS 

Dear Colleagues and Friends, 

The Department of Medical Sciences of The Croatian Academy of Sciences and Arts in cooperation with the Department 

of Biotechnology University of Rijeka is proud to announce the 2nd edition of the “International Conference 

on Regenerative Orthopedics and Tissue Engineering”, to be held in Opatija, Croatia on September 20-22, 

2012. 

In line with the spirit of the successful first edition, that was held in July 2010, this Conference’s goal is to present 

the latest scientific and clinical innovations in the field of bone and cartilage regeneration, osteoporosis treatment 

and stem cell research and application. We also propose a new topic that aims to cover novel treatment options 

in rheumatology, including biological and gene therapy. Once more, the Conference will be a multidisciplinary 

program of research and practice, giving the opportunity to interact and share clinical and research experiences 

with colleagues from the orthopaedic and musculoskeletal community. Prominent domestic and international 

speakers will provide comprehensive, up-to-date, research-based answers to the most frequent questions that 

arise in this rapidly evolving field of medicine. 

We would like to strongly encourage you to submit your abstracts and to attend in order to share your achievements 

in the fields of musculoskeletal regeneration and tissue engineering. 

The Conference will take place in the unique city of Opatija that radiates with quiet elegance and sumptuous 

beauty. Here, where the Adriatic Sea softly kisses the shore and the romantic spirit pervades every corner, buildings 

that still evoke the beauty of the old aristocracy (who visited them lovingly) were erected. Even today, many 

years later, Opatija, like a beautiful lady, enjoys her riches and fullness of life. 

Once again, on behalf of your Croatian hosts, we welcome you with the conviction that our Conference will prove 

to be the place to revive old and form new friendships, and with the hope that you will find it stimulating, informative 

and a pleasure. 

Sincerely yours, 

Christopher H. Evans 

Marko Pećina 

Krešimir Pavelić 

Presidents of the Conference 

Alan Ivković 

General Secretary of the Conference

Organized by: 

Croatian Academy of Sciences and Arts 

Department of Medical Sciences 

In cooperation with: 

University of Rijeka 

The Department of Biotechnology 

Guest societies: 

Croatian Society for Rheumatology 

International Society for Applied Biological Sciences 

Croatian Society for Allergology and Clinical Immunology 

Organizing Committee 

Presidents 

Christopher H. Evans (USA) 

Marko Pećina (Croatia) 

Krešimir Pavelić (Croatia) 

Vice Presidents 

Miroslav Hašpl (Croatia) 

Ivan Martin (Switzerland) 

Secretary General 

Alan Ivković (Croatia) 

Members 

Đurđica Babić-Naglić (Croatia) 

Tamas Bardos (UK) 

Matej Drobnič (Slovenia) 

Simeon Grazio (Croatia) 

Damir Hudetz (Croatia) 

Mislav Jelić (Croatia) 

Dražen Matičić (Croatia) 

Ryan M. Porter (USA) 

Gian M. Salzmann (Germany) 

Martin Stoddart (Switzerland) 

Andre Terzic (USA) 

Gamze Torun Kose (Turkey) 

Matjaž Vogrin (Slovenia) 

Stanimir Vuk-Pavlović (USA) 

Slobodan Vukičević (Croatia) 

Local Organizing Committee 

Roberto Antolović 

Nikica Daraboš 

Miljenko Franić 

Željko Jeleč 

Petar Kostešić 

Inga Marijanović 

Radovan Mihelić 

Tomislav Vlahović 

Andreja Vukasović 

Topics: 

Cartilage Regeneration 

Bone Regeneration 

Osteoporosis 

Stem Cells 

Rheumatology 


Language: 

The official language of the Conference is English. 

Scientific Committee 

Full members of the Department of Medical Sciences 

of the Croatian Academy of Sciences and Arts 

Slavko Cvetnić 

Ivo Čikeš 

Dragan Dekaris 

Vida Demarin 

Vladimir Goldner 

Drago Ikić 

Ivica Kostović 

Zvonko Kusić 

Josip Madić 

Davor Miličić 

Marko Pećina 

Ivan Prpić 

Željko Reiner 

Daniel Rukavina 

Marko Šarić 

Zdenko Škrabalo 

Eugen Topolnik 

Teodor Wikerhauser 

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Exhibitors and Sponsors 

Endorsed by:

CONFERENCE PROGRAMME: September 21 st and 22 nd 2012. 

Friday September 21 st 

09:00 - 09:20 Welcome Address 

09:00 - 09:05 Marko Pećina, President of the 2nd ICRO 

09:05 - 09:10 Pero Lučin, Dean Univesity of Rijeka 

09:10 - 09:15 Alan Ivković, Secretary General of the 2nd ICRO 

09:20 - 10:35 Bone Regeneration and Tissue Engineering 

Chairmen: Ivan Martin, Gamze Torun Kose, Alan Ivković 


09:20 - 09:35 “Evolution of Bone Tissue Engineering Strategies” 

Ivan Martin, Institute for Surgical Research and Hospital Management, University Hospital Basel, Switzerland 

09:35 - 09:50 “Use of Biodegradable Materials and Stem Cells in the Treatment of Bone Defects” 

Gamze Torun Köse, Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey 

09:50 - 10:00 “Fibrin-encapsulated, Genetically Modified Adipose-derived Stem Cells for Use in Bone Repair” 

Martina Shinhan, Medical University of Vienna, Austria 

10:00 - 10:10 “Non-nion Treatment with New Bone-regeneration Solving by FIXAs” 

Nedžad Šabić, Poliklinika dr. Šabić, Zenica, Bosnia and Herzegovina 

10:10 - 10:20 Discussion 

10:20 - 10:50 “Durolane Mini Symposium by Smith&Nephew: Single Injection Treatment for Osteoarthritis” 

Mislav Jelić, Dept. of Orthopaedic Surgery, Clinical Hospital Center Zagreb and School of Medicine University of Zagreb, 

Croatia 

10:50 - 11:05 Coffee Break 

11:05 - 12:50 Cartilage Repair and Regeneration 

Organized by Arthroscopy and Sports Traumatology Section Croatian Society for Sports Medicine 

Chairmen: Marko Pećina, Mahmut Nedim Doral, Mislav Jelić 

11:05 - 11:20 “Autologous Chondrocyte Transplantation Today and Tomorrow” 

Giann M. Salzman, Dept. of Orthopaedic and Trauma Surgery, University Medical Center, Albert-Ludwigs University, 

Freiburg, Germany 

11:20 - 11:35 “Characterized Chondrocyte Implantation Versus Microfracture for Symptomatic Cartilage Defects 

of the Knee” 

Mislav Jelić, Dept. of Orthopaedic Surgery, Clinical Hospital Center Zagreb and School of Medicine University of Zagreb, 

Croatia 

11:35 - 11:50 “Biological vs. Non-Biological Joint Reconstruction” 

Tahsin Beyzadeoglu, Dept. of Orthopaedic Surgery, Yeditepe University Hospital, Istanbul, Turkey 

11:50 - 12:05 “The Biological Tropism Between Synovial and Chondral Tissues” 

Mahmut Nedim Doral, Hacettepe University, Faculty of Medicine, Department of Orthopaedics and Traumatology, Ankara, 

Turkey 

12:05 - 12:20 “Cadaveric Models for Cartilage Repair Studies” 

Matej Drobnič, Department of Orthopedic Surgery, Medical School University of Ljubljana, Slovenia 

12:20 - 12:30 “Incidence of Cartilage Lesions During Knee Arthroscopy” 

Miroslav Hašpl, Denis Tršek, Nenad Medančić, Special Hospital for Orthopaedic Surgery and Traumatology Akromion, 

Krapinske toplice, Croatia 

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12:30 - 12:40 “Sequentially Programmed Magnetic Field (SPMF) Therapy, an Effective Treatment for Knee Osteoarthritis” 

Vishwanath Gopalakrishna Vasishta, SBF Healthcare and Research Centre Pvt Ltd, Bangalore, India 


12:50 - 13:50 Lunch 

13:50 - 15:20 Stem Cells in Regenerative Medicine and Tissue Engineering 

Chairmen: Andre Terzic, Krešimir Pavelić, Stanimir Vuk-Pavlović 

13:50 - 14:05 “Stem Cells for the Curious” 

Stanimir Vuk-Pavlović, Stem Cell Laboratory, Mayo Clinic, Rochester, USA 

14:05 - 14:20 “Human Stem Cell Research and Regenerative Medicine – A European Perspective on Scientific, 

Ethical and Legal Issues” 

Krešimir Pavelić, Department of Biotechnology, University of Rijeka, Croatia 

14:20 - 14:35 “Stem Cells and Prediction of Phenotype Through Transcriptome Deconvolution” 

Carmen M. Terzic, Department Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, USA 

14:35 -14:50 “Mechanoregulation of Stem Cell Fate” 

Martin Stoddart, Musculoskeletal Regeneration Program, AO Research Institute Davos, Switzerland 

14:50 - 15:00 “Human Tendon Perivascular Cells Are Multipotent and Express Embryonic Stem Cell Associated 

Markers” 

Herbert Tempfer, Paracelsus Medical University, Salzburg, Austria 

15:00 - 15:10 “Tendon Stem/Progenitor Cells: Nutrition Matters!” 

Christine Lehner, University Hospital Salzburg, Austria 


15:20 - 16:00 Mini Symposium by Linvatec: “Sequent - Meniscal Repair with an All-Inside and Stay Inside System” 

Patrick Weninger, The Knee Institute,Vienna, Austria 


16:15 – 16:30 Spotlight Lecture: „Current Concepts in Osteogenesis Imperfecta“ 

Dragan Primorac, University of Split, Split, University of Osijek, Osijek, Croatia, The Pennsylvania State University, USA, 

University of New Haven, USA 

16:30 - 17:25 Platelet-rich Plasma in Orthopedics and Sports Medicine 

Chairmen: Miroslav Hašpl, Matjaž Vogrin, Damir Hudetz 

16:30 - 16:45 “The Role of Platelet Rich Plasma in Sports Medicine” 

Matjaž Vogrin, Department of Orthopaedic Surgery, University Clinical Center Maribor, Slovenia 

16:45 - 16:55 “Double Bundle Technique Combined with a Biologic Regenerative Treatment Give the Best Result 

of ACL Surgery” 

Nikica Daraboš, Department of Traumatology, Clinical Hospital Center “Sestre milosrdnice”, Zagreb, Croatia 

16:55 - 17:05 “Platelet-rich Plasma Derived Growth Factors and TGF-β Antagonists Promote Muscle Regeneration 

in Vitro” 

Robi Kelc, Department of Anatomy, Faculty of Medicine Maribor, Slovenia 

17:05 - 17:15 “Significant Pain Reduction in Osteoarthritis of the Knee by ACP Administration” 

Michael Borsky, Etzelclinic, Pfaffikon, Switzerland


20:00 Social Dinner 

Saturday September 22 nd 

9:00 - 9:30 Spotlight Lecture: Regenerative Medicine - Transforming healthcare solutions 

Andre Terzic, Dept. of Regenerative Medicine, Mayo Clinic, Rochester, USA 

9:30 - 13:00 Emerging New Biological Therapies for Rheumatoid Arthritis 

Chairmen: Christopher H. Evans , Asja Stipić Marković, Srđan Novak 

9:30 - 9:45 “Update on the Pathogenesis and Treatment of Rheumatoid Arthritis” 

Asja Stipić Marković, Dept. of Internal Medicine, University Hospital Sveti Duh, Zagreb, Croatia 


9:45 - 10:30 “Gene Therapy for Rheumatoid Arthritis” 

Christopher H. Evans, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical 

School, Boston, MA 


10:45 - 11:00 “Biological Agents in Rheumatoid Arthritis” 

Srđan Novak, Dept. of Iternal Medicine, Clinical Hospital Center Rijeka, Croatia 

11:00 - 11:15 “The Future of Rheumatoid Arthtritis Treatment - Combining Pharmacology and Surgery” 

Duška Kaliterna, Dept. of Iternal Medicine, Clinical Hospital Center Split, Croatia 

11:15 - 11:25 “Enhanced Osteoclastogenesis in Arthritis is Paralleled with the Increased Expression of Proinflammatory 

Mediators CCL2, IL-17 and IL-18” 

Marina Ikić, Dept. of Internal Medicine, University Hospital Sveti Duh, Zagreb, Croatia 

11:25 - 12:00 Mini Symposium by BioTissue AG: “Cell-based and Cell-free Joint Implants for Cartilage Repair” 

Michaela Endres, TransTissue Technologies GmbH - RD Department of BioTissue AG., Berlin, Germany 

12:00 – 12:15 Spotlight Lecture: “SPECT/CT a Novel Diagnostic Tool for Evaluation of Loading Pattern of the Knee” 

Michael T. Hirschmann, Department of Orthopedics and Traumatology, Kantonspittal Bruderholz, Basel, Switzerland 

12:15 - 13:05 Emerging Concepts in Osteoporosis Treatment 

Chairmen: Danka Grčević, Željko Jeleč 

12:15 - 12:30 “Osteoporosis: Common Feature Underlined by Different Pathogenetic Mechanisms” 

Danka Grčević, Dept. of Physiology and Immunology, School of Medicine, University of Zagreb 

12.30 - 12:45 “Effect of Quercetin on Osteoporosis Caused by Retinoic Acid in Rats” 

Željko Jeleč, Department of Orthopaedic Surgery, General Hospital Sisak, Croatia 

12:45 – 12:55 “The Treatment of the Proximal Femoral Fractures in County Hospital Dubrovnik in a Period April 

2011 - April 2012” 

Marijo Bekić, County Hospital Dubrovnik, Croatia 


13:05 End of the Conference 

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Conference venue: 

Grand hotel Adriatic, Opatija - Croatia 

Registration Fee 

Early registration fee Late registration fee 

(before June 5st 2012) (after June 5st 2012) 

Participants 1.250 HRK/ 175 EUR 1.400 HRK/ 195 EUR 

Residents* 650 HRK/ 90 EUR 750 HRK/ 105 EUR 

Sponsors 750 HRK/105 EUR 750 HRK/105 EUR 

Undergraduate students 350 HRK/ 50 EUR 350 HRK/50 EUR 

Accompanying persons 750 HRK/105 EUR 750 HRK/105 EUR 

*PhD students and Post Doc students are welcome to register for subsidized registration fee. 

Registration fee covers: 

Admission to all lectures and access to the exhibition area 

Conference bag with conference materials 

Admission to the Welcome Drink on Thursday Sep 20 st 

Coffee Breaks, Lunch on Friday, Sept. 21 st and Social Dinner on Friday Sep 21 st 

Certificate of Attendance 

REGISTRATION DESK 

From Thursday 20 th September from 15:00 till Saturday 22 nd September 14:00 

SPEAKER PREVIEW ROOM 

The Speaker Preview Room, located close to the entrance of the conference room in hotel Adriatic, will bi open 

from Thursday 20 th September from 15:00 till Saturday 22 nd September till 14:00 

Presenters are asked to check their MS Power Point presentations to the Speaker Preview Room at least two 

hours before the session. Posters will be presented at the exhibition area. 

LANGUAGE 

The official language of the meeting is English. 

About Croatia 

Despite the hype, Croatia’s pleasures are more timeless than trendy. Along its 1778 km coastline, a glistening sea 

winds around rocky coves, lapping at pine-fringed beaches. Istrian ports bustle with f ishermen while children 

dive into the sparkling water. In Dalmatia, cities throb with nightlife amid ancient Roman ruins. Yachts glide up the 

coast, movie stars discreetly arrange to buy one of Croatia’s 1185 islands and no Mediterranean cruise is complete 

without a stop in Dubrovnik. The interior landscape is as beguiling, even though less visited. Soak in a thermal 

spa at Istarske Toplice in Istria. Hike through pristine forests watered by mountain streams in the west. Let the 

waterfalls of Plitvice moisten your face. And then there’s the culture. The country that endured Roman, Venetian, 

Italian and Austro-Hungarian rule has a unique and slightly schizoid identity. You’ll find a strong central European 

flavour in the baroque architecture of Zagreb, and Italian devotion to the good life percolates up from the coast, 

permeating Croatian food and style. During holidays and festivals the country’s Slavic soul emerges, as colourfully 

costumed dancers whirl about to traditional folk melodies.


About Opatija 

Opatija, often called the pearl of the Adriatic, is one of Croatia’s most famous destinations, boasting a tradition of 

welcoming visitors dating back more than 160 years. Located at the edge of the Mediterranean, on the slopes of 

Mount Učka gently descending towards the coast of Kvarner Bay, Opatija with its local climate, beautiful architecture, 

quality hotels and luxurious, well-tended parks and promenades, offers plenty of possibilities for a pleasant 

stay throughout the year. The notable person who first discovered the magic of Opatija was Iginio Scarpa, a merchant 

from Rijeka who built his holiday home here in 1844 and named it the Villa Angiolina after his late wife. This 

event marked the beginning of tourism in Opatija. 

After that, Opatija started intensely developing under the supervision of the Austro-Hungarian Empire. Director 

of the Austrian Southern Railway Company Friedrich Schüler and its shareholders wanted to improve passenger 

traffic to the south. After choosing Opatija as the region’s most promising destination, they started building the 

first hotel in this new bathing and climatic health resort, advertising it widely as the “Austrian Nice”. 

Several important facilities were built alongside the first hotel: a pavilion with indoor pool for warm sea baths, a 

bathing place with separate areas for ladies and gentlemen, and the 12-kilometre-long coastal promenade from 

Volosko to Opatija and further to Lovran. The hotel was opened on the 27th March 1884. Its original name was 

Hotel Quarnero, and it offered its visitors 60 rooms. 

The second hotel that was built in Opatija after the Quarnero was the Hotel Kronprinzessin Stephanie. In 1885, 

the Austrian Southern Railway Company organised the first congress of balneologists in Opatija, during which 

the decision was made to declare Opatija a climatic health resort, which was officially done in 1889. Some of the 

Monarchy’s most eminent physicians opened their sanatoriums in Opatija; numerous promenades and bathing 

places were being built. This all turned Opatija into one of Europe’s most important health resorts of the 19th and 

the first half of the 20th century, alongside Nice, Karlovy Vary, Cannes and Biarritz. Kings and emperors, writers, 

philosophers, poets and composers used to stay here – let us mention some of them: the emperors Franz Joseph 

and William II, the queen of Romania Elisabeth who used to publish poems under the pseudonym of Carmen Sylva, 

then the empress Sissi, the writers A. P. Chekhov and James Joyce, the ballet dancer Isadora Duncan, and the 

composers Gustav Mahler and Giacomo Puccini. To see and be seen – this was the motto for those who came to 

Opatija. 

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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS

BOOK OF 

ABSTRACTS 


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EVOLUTION OF BONE TISSUE ENGINEERING STRATEGIES 

Ivan Martin, University Hospital Basel, Switzerland 

Despite the large clinical needs in bone regeneration and the advances in scaffold production and regulation 

of osteoprogenitor cell function, the adoption of cell-based bone graft substitutes in the clinical practice is yet 

limited. Indeed no study has yet convincingly demonstrated reproducible clinical performance of tissue engineered 

bone graft substitutes and at least equivalent cost-effectiveness as compared to the current treatment 

standards. This lecture will describe and discuss three alternative approaches currently pursued by the author’s 

team to evolve classical tissue engineering paradigms towards possibly more effective products. The perspective 

will address issues related to quality standardization, process control and regulatory compliance in manufacturing 

cell-based products and highlight the need not only to automate, but also to streamline and simplify typical production 

processes. An alternative strategy based on the intraoperative use of autologous fat-derived cells will be 

presented and critically discussed. Finally, as a next generation paradigm, the lecture will propose and exemplify 

the concept of engineering regenerative strategies following principles of developmental biology, using the own 

body as the in vivo bioreactor. 

Oral


USE OF BIODEGRADABLE MATERIALS AND STEM CELLS IN THE 

TREATMENT OF BONE DEFECTS 

Gamze Torun Kose, Yeditepe University, Faculty of Engineering and Architecture, Department of Genetics 

and Bioengineering, Istanbul, Turkey, BIOMATEN, METU Center of Excellence in Biomaterials and Tissue 

Engineering, Ankara, Turkey 

There are a large number of people suffering from an organ or tissue loss due to injury, infection, or disease. Currently, 

major approaches to solve this problem are surgical reconstruction, transplantation or use of prosthesis. 

Although these therapies have saved and improved countless lives, they remain imperfect solutions due to occurrence 

of infection, chronic irritation, donor shortages, tissue rejection, and longer term complications such as 

development of malignant tumor. 

Tissue engineering, the development of cell seeded 3D biomaterials for introduction to the defect area is the current 

solution for all of the problems mentioned above. 

Cell Guidance is a branch of tissue engineering that offers controlled tissue regeneration and allows the repair 

of the tissue by mimicking its natural organization to achieve better and faster integration with the native tissue. 

Guidance is important especially for constructs for nerve and bone tissues because of their significant levels of 

organization and anisotropy. 

In one of the study conducted by our research group BIOMATEN on bone tissue engineering, the aim was to 

achieve improved attachment and uniform distribution of rat mesenchymal stem cell-derived osteoblasts by introducing 

chemical and topographical cues on biopolyester film surfaces. Various patterns such as microgrooves 

and micropits were introduced on the film surface by employing micropatterned silicon wafers. Results proved 

that microtopographies could improve osseointegration especially when combined with chemical cues, and that 

microgrooves and cell adhesive protein lines guided osteoblast adhesion on selective regions and improved alignment. 

Oral 

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FIBRIN-ENCAPSULATED, GENETICALLY MODIFIED ADIPOSE- 

DERIVED STEM CELLS FOR USE IN BONE REPAIR 

Martina Schinhan, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, 

Harvard Medical School, Boston, MA, 2Department of Orthopaedic Surgery, Vienna General Hospital, 

Medical University of Vienna, Vienna, Austria 

Marc Mueller, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard 

Medical School, Boston, MA, Departments of Surgery and of Biomedicine, University Hospital Basel, 

Basel, Switzerland 

Fangjun Liu, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard 

Medical School, Boston, United States 

Zhenxin Shen, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard 


Ryan Porter, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard 


Reinhard Windhager, 2Department of Orthopaedic Surgery, Vienna General Hospital, Medical University 

of Vienna, Vienna, Austria 

Christopher Evans, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, 

Harvard Medical School, Boston, United States 

Elizabete Ferreira, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, 

Harvard Medical School, Boston, United States 

Transplantation of stem cells engineered to express Bone Morphogenetic Protein-2 (BMP-2) remains an attractive 

approach for bone repair as it provides both BMP and osteoprogenitors. Adipose-derived stem cells (ADSCs) are 

of particular interest as they are obtained with lower donor-site morbidity and at greater yields than osteoprogenitors 

derived from bone marrow. This study aimed to develop an expedited method, using gene transfer, for 

preparing ADSC-loaded fibrin gels to serve as cell and BMP-2 delivery systems. 

hADSC suspensions were mixed with recombinant adenovirus carrying hBMP-2 or GFP cDNA. Transduction was 

carried out using a centrifugation method (2000g for 15min). The supernatant was removed and the cell pellets 

resuspended in media. Subsequently, transduced cells were transferred to fibrinogen solution which then polymerized 

into a fibrin gel encapsulating the cells. Cell viability and transgene expression were evaluated over a 

3-week study. 

Our centrifugation method resulted in at least 70% transduction efficiency. Cell viability and GFP expression within 

the scaffolds was maintained for at least 3 weeks. Ad.BMP-2 transduced cells produced ~170 ng BMP-2/24h/106 

cells at day 8, after which BMP-2 secretion progressively decreased to basal levels. 

These data suggested that ADSCs can be expeditiously engineered and encapsulated in fibrin gels to deliver high 

quantities of BMP-2. In vivo studies are underway to evaluate the potential of this system for healing rat segmental 

defects. 

Oral


NON UNION TREATMENT WITH NEW BONE REGENRATION- 

SOLVING BY FixAS 

Šabić Nedžad, Poliklinika Dr Šabić, Zenica, Bosnia and Herzegovina 

Tarik Kapidžić, Cantonal Hospital, Bosnia and Herzegovina 

Enver Šabić, Poliklinika Sunce, Bosnia and Herzegovina 

Faruk Hodžić, Cantonal Hospital, Bosnia and Herzegovina 

Intraduction:Getting the new-quality bone by distraction of pineal body (epiphysis-growth plate, Ring 1958, 

Zivyalov and Plaskin 1968, Ilizarov 1969, Monticelli and Spineli 1981) as well as by distraction calus after corticotomy 

and metaphysary lenghtening (Ilizarov 1971, 1988, 1989, Alberty 1990, Terjesen 1984, 1988, Adolphson 1990), 

has enabled treatment of larger bone defects without autografted cancellous bone with regenerate which is appropriate 

with its width and density. This has been, certainly, made easier with tehnical improvements of fixators 

and dynamic possibilities of structures with area, flexible and extrafocal stability. Methods: When solving infected 

non-union with bone defects, beside regaining bone continuity and length there is a problem of infection, which 

is the heaviest complication in bone-joint surgery..This work presents possibilities of compression – distraction 

method by Fix-AS. 

1 st GROUP: fixation with shortening of extremities and achieving the length after cover the soft tissue defect. 

2 nd GROUP: fixation of the non union with the full length of the extremity and levelling with the nearby joint areas 

and treatment of the defect, either by int. or exter. transport 

Results: Followed by ways at solving contractures, deformations achieving full length of extremity with simultaneous 

infection sanation and non-union consolidation in natural ways. For the last 25 years we*ve successfully 

treated 435 non-union, of which 241 infected ones, 185 with bone defect, 51 over 5 cm , which is especially 

emphasized in this work. This work analyses and presents infection – defect non-union, after war injuries and 

failed treatment by others methods. Conclusion: This way, extremity is saved even in heaviest cases, unlike other 

methods (bone grafting, free flap), which were more expensive and unformal, often ended by an amputation. 

Oral 

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CHARACTERIZED CHONDROCYTES IMPLANTATION COMPARED 

TO THE MICROFRACTURE IN TREATMENT OF A CHONDRAL 

LESION OF THE KNEE: 5 YEAR RESULTS OF A CONTROLLED 

RANDOMIZED TRIAL 

Mislav Jelić and TIG/ACT/01/2000&EXT Study Group, Department of Orthopaedic Surgery, Clinical 

Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia 

Characterized chondrocytes are an expanded population of cartilage cells that express a marker profile predictive 

for the formation of ectopic hyaline-like cartilage in vivo in a consistent and reproducible manner. A controlled 

and consistent manufacturing process was developed to maintain this phenotype stability. Characterized viable 

autologous cartilage cells expanded ex vivo expressing specific marker proteins were introduced in clinical practice 

in 2004. 

A prospective randomized multicenter controlled trial compared characterized chondrocyte implantation (CCI) to 

microfracture in the treatment of symptomatic cartilage defects of the femoral condyles. The primary endpoint 

was successfully reached at one year, with CCI showing superior tissue regeneration. Clinical outcome at 12 to 18 

months measured by the overall Knee injury and Osteoarthritis Outcome Score (KOOS) was comparable for both 

treatments. An extension at 3 and 5 years confirmed that a good clinical outcome was maintained over time for 

both treatments in the overall patient population. Strikingly, sub analysis of the long-term follow-up data revealed 

that early treatment by CCI resulted in statistically significant and most importantly clinically relevant better results 

when compared to microfracture, supporting a critical window of opportunity for genuine tissue regeneration. 

Oral


AUTOLOGOUS CHONDROCYTE TRANSPLANTATION TODAY 

AND TOMORROW 

Gian Salzmann, Department of Orthopaedic and Trauma Surgery, University Medical Center, Albert- 

Ludwigs University Freiburg, Germany 

Following the 1994 pioneer work by Brittberg and colleagues autologous chondrocyte implantation has evolved 

significantly until today. The traditional periosteum-covered technique has retrospectively been termed first generation 

ACI-P. In order to reduce operating time and as well to avoid graft hypertrophy the second generation 

ACI-C has been introduced by replacing the periost by an artificial membrane such as collagen. While the cells are 

applied beneath a cover when performing first or second generation ACI, third generation ACI is matrix-assisted 

(m-ACI). The chondrocytes are cultured within the matrix for a certain time prior to transplantation. The idea was 

to give better primary stability, handling and probably partial cellular redifferentiation. As further alternatives 

there are ACI-Cs, where the cells are seeded within the matrix intraoperatively and consecutevily implanted to 

have high vitality and mitotic activity. Also bioreactor-assembled implant-ready cartilage products are on the 

threshold to clinical implementation, which are sought to present with an already assembled extracellular matrix 

at time of implantation. Furthermore one-step cartilage repair techniques are on the rise in order to reduce the 

traditional 2-step into a 1-step procedure. 

Concerning outcome data, it is now becoming increasingly apparent that ACI gives better tissue quality when 

compared to the concurring methods foremost in the long-term and is much better suited for larger cartilage defects. 

Literary information on the younger techniques is sparse and one has to await longer-term follow-up among 

large patient cohorts to give out treatment suggestions. 

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BIOLOGICAL vs. NON-BIOLOGICAL JOINT RECONSTRUCTION 

Tahsin Beyzadeoglu, Yeditepe University, School of Medicine, Istanbul - TURKEY, Turkey 

Cartilage lesions of the knee joint if left untreated is likely to develop osteoarthrosis. While there are many biological 

treatment options in younger patients, focal degenerative cartilage lesions of moderate-to-advanced age are 

more difficult to treat due to the low success chance of biological methods. Cartilage lesion size, depth, quality of 

the subchondral bone, patient’s age are some of the main determinants for prognosis. The success of biological 

procedures depends on the quality of subchondral bone. Total arthroplasty is often considered as the last treatment 

option and limited resurfacing arthroplasty is increasingly becoming popular as a new treatment option 

with the biggest advantage of preserving the subchondral bone. 

In medial gonarthrosis accompanied with varus alignment, resurfacing can be done with simultaneous high tibial 

osteotomy. Correct alignment can slow the development of arthritis, however, at the presence of patellofemoral 

lesions, progression of patellofemoral arthrosis can be seen. At these patients, resufacing of the patellofemoral 

joint can relief the symptoms. Limited resurfacing fills the gap between biological methods and total knee arthroplasty. 

The presence of inflammatory arthritis, body mass index over 35, instability and malignment over 7 

degrees, limited resurfacing is relatively contraindicated and simultanous assistive surgeries like ligament reconstruction 

or HTO have to be considered. High demand patients with moderate-to-advanced age, yet relatively 

preserved joint width, and cannot be treated with existing biological methods are good candidates for limited 

surfacing arthroplasty. However, the implant as well as a new one needs long-term clinical follow-up studies. 

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THE BIOLOGICAL TROPISM BETWEEN SYNOVIAL AND 

CHONDRAL TISSUES 

Mahmut Nedim Doral, Hacettepe University Dept. of Orthopaedics & Traumatology, Dept. of Sports 

Medicine, Ankara, Turkey 

The importance of articular cartilage lesions was first described by William Hunter in 1743. Ever since, the efforts 

to repair the damaged joint cartilage have been accelerating intensively through basic and clinical investigations. 

Arthroscopic debridement with or without intra-articular injections, perichondrial or periosteal covering, abrasion 

arthroplasty, microfracture, transplantation of chondrocytes, meniscal allografts, osteochondral allografts/ 

otografts, autologous chondrocyte transplantation, tissue engineering and gene therapies are some methods to 

treat cartilage lesions. However, any treatment modality has enabled full restoration of the injured articular cartilage 

to its original phenotype yet. 

In recent years, mesenchymal stem cells (MSCs) have been recommended as a cell therapy to regenerate chondrocytes. 

MSCs are known to be present in the bone marrow and other tissues such as skeletal muscle, tendon, fatty 

tissue, neural tissue, hepatic tissue, periosteum and synovium. Morphological and functional characteristics of 

the chondral tissue formed from MSCs that are originated from various tissue types show some differences. MSCs 

derived from the synovium have been shown to be highly potential for chondrogenesis that presents them as an 

attractive source for the treatment of the damaged cartilage tissue. Intra-articular loose bodies are described as 

cartilaginous, osseous or osteochondral fragments located within the joint cavity and are known to be produced 

by the synovium. Free or pediculated ‘‘chondroosteophytes’’ that are frequently seen in arthroscopic observations 

and their close biological relationship with the synovial tissue formed the basis of our study, in which the hypothesis 

was that ‘‘the synovial tissue might have a pivotal role in the formation and growth of intra-articular 

chondro-osteophytes and might exert similar growth effects on transplanted cartilaginous tissue grafts’’. So we 

aimed to assess the applicability of the use of synovium as an in vivo chondrocyte culture medium and to evaluate 

the effects of the synovial tissue on chondrocyte growth in a rabbit model study. We tried to determine the 

effects of synovium on cartilage proliferation as “in-vivo” culture medium and to anticipate a new, biological and 

cheap treatment method for the articular cartilage pathologies. In our study, 12 New Zealand rabbits were used 

and standardized cartilage samples were taken from both knees. Two groups were formed: In group I (synovium 

group), the cartilage samples were placed into the synovial tissue on the supracondylar groove, and in group II (intraarticular 

group), behind the patellar tendon. After 4 months, we sized and analyzed samples histologically with 

the camera lucida method to count the chondrocyte numbers (Mann-Whitney U-Test and regression analysis). 

The chondrocyte numbers in the osteochondral samples were found to be higher than chondral samples (p

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HUMAN CADAVERIC MODELS FOR CARTILAGE REPAIR STUDIES 

Matej Drobnic, Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Slovenia 

Armin Alibegovic, Institute of Forensic Medicine, Medical Faculty, University of Ljubljana, Slovenia 

Marjana Hribernik, Institute of Anatomy, Medical Faculty, University of Ljubljana, Slovenia 

The research in the field of cartilage repair has been growing increasingly for the last two decade. The preclinical 

studies require an appropriate model to simulate the intra-articular milieu to which the graft or the repair tissue 

will be exposed in the clinical application. Cell cultures and experimental animals are most commonly used, but 

they are unable to stimulate the conditions in human joints entirely. Human cadaveric cartilage, which can be 

used as fresh or preserved, represents an additional spectrum of preclinical testings. Fresh cadaveric chondral 

samples provide a high number of viable chondrocytes as they are protected from the autolysis in the abundant 

chondral matrix. The duration of viability of such samples is long enough to study the impact of external physical 

or chemical stimuli and also to isolate viable chondrocytes for the research of cell cultures. The preserved, non-viable 

human material can be applied in the studies of biomechanics and surgical techniques. However, ethical 

approval has to be granted before any research on human cadaveric material is to be performed. 

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PREVALENCEOF THE CHONDRAL DEFECTS: A RETROSPECTIVE 

STUDY OF 1000 KNEE ARTHROSCOPIES 

Miroslav Hašpl, Special Hospital for Orthopaedic Surgery AKROMION, Krap inske Toplice, Croatia 

Denis Tršek, Special Hospital for Orthopaedic Surgery AKROMION, Krap inske Toplice, Croatia 

Borna Strahonja, Special Hospital for Orthopaedic Surgery AKROMION, Krap inske Toplice, Croatia 

PURPOSE: To determine the prevalence of chondral defects during knee arthroscopy. 

METHODS: We performed retrospective analysis of cartilage lesions in 1000 knee joints treated at our institution 

during 2010 and 2011 year.In all cases was performed arthroscopy for various indications. Age of our patients was 

44 (13-80) years. Males 629 (62.9%) and females 371 (37.1%). Chondral lesions are analyzed by location and classification 

according to ICRS (International Cartilage Repair Society). 

RESULTS: One or more chondral lesions had 679 (67.9%) knees. Chondral lesions were most often associated with 

other disease and were not primary indication for arthroscopy. Rupture of the medial meniscus we found at 645 

knees, lateral meniscusat 260, anterior cruciate ligament rupture at 286, parapatellarplicasyndroms in 58, patellofemoral 

instability in 26 patients, different etiology of synovitis at 33, stiff knee at 24, and of patellar enthesitis 

(jumpre’s knee) at 10 and other diseases and injuries at 24 knees (intrarticular tumors, intraarticular fractures, 

osteochondriotisdissecans etc.) 

Chondral patellar lesions were found in 436 knees (9.4% I; 25.7% II; 6.6% III; 1.9% IV degree ), at trochlear femoral 

part in 270 knees (1.5% I ; 7.3% II; 10.5% III; 8.3% IV degree), at medial femoral condyle in 448 (3.3% I; 17.0% II; 

11.4% III; 13.1% IV degree), lateral femoral condyle in 120 (1.1 I; 4.1% II; 2.5% III; 4.3% IV degree),medial tibial 

condyle in 117 (2.3% I; 4.1% II; 2.2% III; 3.1% IV degree) and the lateral tibial condyle in 131 patients (2.9% I; 6.2% 

II;2.1% II; 1.9% IV degree). 

In 498 (49.8%) knees underwent one or more surgical procedures on chondral lesions at one or more locations. 

Chondral debridemente was done on 437 (43.7.0%) knees, microfracture in 151 (15.1%) knees, mozaikplasty on 4 

(0.4%) and on 9 (0.9%) knees intraarticular osteosynthesis for osteochondral lesions. 

CONCLUSION: The present study shows that cartilage lesion is the most common finding during knee arthroscopy. 

Mostcartilagedamagewas found on medialcondyleof the femurandthepatella. Fourth degree of damageismost 

commonon themedialfemoralcondyle. In many cases surgery is required in such a damaged cartilage, especially 

the fourth grade. 

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SEQUENTIALLY PROGRAMMED MAGNETIC FIELD 

(SPMF) THERAPY, AN EFFECTIVE TREATMENT FOR KNEE 

OSTEOARTHRITIS 

Vishwanath Gopalakrishna Vasishta, SBF Healthcare and Research Centre Pvt Ltd, India 

Background: Sequentially Programmed Magnetic Field (SPMF) therapy utilizes magnetic fields of specific strength 

and frequencies which are generated from Magnetic Field Generators (MFG) that can be focused on the affected 

tissues. These are non-thermal, non-ionizing and has no known side effects. The efficacy of SPMF therapy in knee 

osteoarthritis was first published in the Scientific Medicine Journal in 2009. The current study is to evaluate the 

long term efficacy of SPMF Therapy in knee Osteoarthritis. 

Methods: 300 patients were enrolled for this follow up study to evaluate the long term results of SPMF therapy after 

12months of the treatment. All the patients underwent SPMF for 21consecutive days and were evaluated with 

Total Knee Score (TKS), Total Functional Score (TFS) and MRI to measure Cartilage thickness pre treatment, Post 

treatment at 21days, 3months and 12months. 

Result: Statistical analysis demonstrated that an improvement in TFS scores from 39.64 (SD=21.53) pre-treatment 

to 47.84 (SD=18.54) at 21days, 56.92 (SD=16.47) at 3months and 61.20(SD=16.63) at 12months. The TKS score was 

53.08 (SD=17.39) at pre-treatment, which improved to 73.44 (SD=13.61), 78.64 (SD=12.26), 83.32(SD=11.63) at 

21days, 3 months and 12months respectively. The cartilage thickness was 0.64mm (±0.02mm) at pre-treatment, 

which increased to 0.88mm (±0.07mm) at 3months and 1.24(±0.03mm). 

Conclusion: The results confirm significant improvement in the strength, stability and significant reduction of pain 

as shown in the TKS and TFS value. The result also shows significant regeneration of cartilage and progressive increase 

in the cartilage thickness in MRI, to show that SPMF being non invasive and without any side effect should 

be used as a first line of treatment for knee Osteoarthritis. 

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STEM CELLS FOR THE CURIOUS 

Stanimir Vuk-Pavlović, College of Medicine, Mayo Clinic, Rochester, United States 


Recent evidence for induction of stem cell characteristics in somatic cells by epithelial–mesenchymal transition, 

by induced activation of a small number of transcription factors, or by modification of microenvironment has 

invalidated the once held notion of differentiation as a strictly unidirectional deterministic process. Together with 

the broad interest elicited by current clinical trials testing different cellular preparations dubbed “stem cells,” this 

necessitates reconsideration of the very definition of the stem cell. As a result, the focus has shifted from consideration 

of “stem cells” as a class of cells to “stemness” as a property that can be acquired, conferred and/or retained 

by cells. What is stemness that allows a cell (population) to divide, maintain the size of its pool and differentiatiate 

at the same time? How is it defined, induced, maintained? A recent view posits “stemness as a cell default state” 

(cf. Casanova, EMBO Reports, 13: 396, 2012). It is based on experimental evidence compatible with a deterministic 

model of stemness maintained as long as maintained is the intrinsic/inherent inhibition to differentiation. Another 

model invokes stochastic gene and protein expression that drives transitions among deterministic attractors 

characterizing stemness and the possible differentiation states (MacArthur et al., Nature Rev. Mol. Cell Biol. 10: 672, 

2012). As a further development, one can interrogate the factors that define all levels of cell differentiation (i.e., 

attractors) as properties emergent within complex biological systems. 

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HUMAN STEM CELL RESEARCH AND REGENERATIVE MEDICINE 

- EUROPEAN PERSPECTIVES ON SCIENTIFIC, ETHICAL AND 

LEGAL ISSUESS 

Krešimir Pavelić, University of Rijeka, Department of Biotechnology, Rijeka, Croatia 

The concept of using stem cells for therapeutic purposes has much in common with the now conventional principle 

of organ transplantation. Today several applications of stem cell in therapies are recognized in humans: from 

bone marrow transplants through to more recent advances in skin and cornea repair. The cells used in these cases 

are adult stem cells. They exist in several adult tissues and they are usually rare. Primordial progenitor cells derived 

from the earliest stages of embryonic development are capable of producing all tissue types of the adult. 

Embryonic stem cells are very potent but difficult to control at the present time of knowledge. Research on both 

embryonic stem cells and adult stem cells is providing prospects of therapies for a variety of tissue-specific diseases, 

including major illnesses as type I diabetes, Parkinson’s disease as well as cancer. There are few obstacles in advancing 

stem cell research in Europe. Currently there is relatively little commercial support for, or industry engagement 

in, stem cell research and development in Europe. One of the major inhibitory factors is the European Patent 

Office’s interpretation of the morality clause in the European Biotechnology Directive (adopted into the European 

Patent Convention). European Patent Office is to exclude from patentability all inventions or claims relating to human 

embryonic stem cells. This position has its roots in rule 23d(c) of the European Patent Convention which stipulates 

that „European patents may not be granted in respect to biotechnological inventions which, in particular, 

concern uses of human embryos for industrial or commercial purposes according to current EPO interpretation, 

that excludes from patentability all claims to associated products necessitating the direct and unavoidable use 

of human embryo – including claims on cells derived from an embryo.” European stem cell research is concerned 

with the protection of intellectual property relating to the manipulation of established human embryonic stem 

cell research and differentiated derivatives. This situation renders the European biotechnology sector at a serious 

disadvantage compared with global competitors. The disparate national regulations governing stem cell research 

in Europe inhibit the field from benefiting from the internationality of approach inherent to scientific advance. 

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STEM CELLS AND PREDICTION OF PHENOTYPE THROUGH 

TRANSCRIPTOME DECONVOLUTION 

Carmen Terzic, Mayo Clinic, Rochester, United States 

Genomic perturbations that challenge normal signaling at the pluripotent stage may trigger unforeseen ontogenic 

aberrancies. Anticipatory systems biology identification of transcriptome landscapes that underlie latent 

phenotypes would offer molecular diagnosis before the onset of symptoms. Bioinformatic surveillance of calreticulin-null 

stem cells, a monogenic insult model, diagnosed a disruption in transcriptome dynamics, which re-prioritized 

essential cellular functions. Calreticulin-calibrated signaling axes were uncovered, and network-wide cartography 

of undifferentiated stem cell transcripts suggested cardiac manifestations. Calreticulin-deficient stem 

cell-derived cardiac cells verified disorganized sarcomerogenesis, mitochondrial paucity, and cytoarchitectural 

aberrations to validate calreticulin-dependent network forecasts. Furthermore, magnetic resonance imaging and 

histopathology detected a ventricular septal defect, revealing organogenic manifestation of calreticulin deletion. 

Thus, bioinformatic deciphering of a primordial calreticulin-deficient transcriptome decoded at the pluripotent 

stem cell stage a reconfigured multifunctional molecular registry to anticipate predifferentiation susceptibility 

toward abnormal cardiophenotype. 

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MECHANOREGULATION OF STEM CELL FATE 

Martin Stoddart, AO Research Institute Davos, Davos, Switzerland 

Bone marrow derived mesenchymal stem cells (MSCs) offer great promise in the repair of defects of the musculoskeletal 

system. Classical tissue engineering incorporates a source of cells, a scaffold to retain them, and biochemical 

cues. Increasingly mechanical force is being shown to regulate the phenotypic fate decisions in these cells. 

Mechanical stimuli are of crucial importance for the development and maintenance of articular cartilage. While a 

number of studies have shown a beneficial effect of load for chondrogenesis of MSCs there is some controversy 

as other studies have indicated an inhibitory effect. For conditioning of cartilaginous tissues, various bioreactor 

systems have been developed that have mainly aimed to produce cartilaginous grafts for tissue engineering applications. 

Emphasis has been on in vitro preconditioning, whereas the same devices could be used to attempt 

to predict the response of the cells in vivo or as a prescreening method before animal studies. As a result of the 

complexity of the load and motion patterns within an articulating joint, no bioreactor can completely recreate the 

in vivo situation. Using a custom built loading device, it is possible to apply compression, shear or a combination 

of both stimuli onto fibrin/polyurethane composites in which human mesenchymal stem cells were embedded. 

To simplify the system, and more accurately mimic the in vivo situation it is possible to perform studies where no 

exogenous growth-factors are added to the culture medium. Thus any chondrogenic induction is purely as a result 

of the loading protocol applied. Recent data would suggest that under these conditions, shear is a critical component 

when inducing chondrogenesis in human mesenchymal stem cells by mechanical means. In agreement with 

other groups, uniaxial load in isolation does not appear sufficient to induce chondrogenic differentiation. This may 

play a role in natural healing within the musculoskeletal system, whereby the same cell type (MSCs) initiates bone 

repair (uniaxial load) and cartilage repair (multiaxial load) resulting from different mechanical cues. 

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HUMAN TENDON PERIVASCULAR CELLS ARE MULTIPOTENT 

AND EXPRESS EMBRYONIC STEM CELL ASSOCIATED MARKERS 

Herbert Tempfer, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria 

Renate Gehwolf, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria 

Christine Lehner, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria 

Andrea Wagner, Paracelsus Medical University, University of Salzburg, Salzburg, Austria 

Hans-Christian Bauer, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria 

Tendon-derived stem cells are commonly considered to be of mesenchymal origin, having the capacity to differentiate 

into adipocytes, chondrocytes, osteoblasts and tendon cells. Earlier on we have shown that human tendon 

perivascular cells express markers associated with neural stem cells such as Nestin and Musashi1. 

Here we describe a so far unrecognized type of human tendon perivascular stem cells (hTPSC) expressing markers 

commonly associated with embryonic stem cells (ESC). By immunohistochemistry and single cell PCR on human 

tendon tissue we demonstrate that hTPSCs express Oct4, Nanog, Klf4, Cmyc and Sox2 in vivo. In cell culture, these 

cells give rise to clonal spheroid cell aggregates harbouring cells expressing the stem cell markers mentioned and 

markers associated with all three embryonic germ layers, such as Insulin and Glucagon, Collagens type 1 and 3 and 

GFAP and Galactosyl ceramidase. In differentiation experiments, hTPSC can give rise to adipocytes, osteoblasts, 

oligodendrocytes, astrocytes and insulin producing cells. 

Despite their ESC-like marker expression, these cells do not form tumors upon injection into immunodeficient 

mice. 

These findings suggest that TPSC represent a more undifferentiated cell type than mesenchymal stem cells. 

hTPSC may be a valuable source for future applications in tissue engineering and cell therapy. 

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TENDON STEM/ PROGENITOR CELLS: NUTRITION MATTERS! 

Renate Gehwolf, Paracelsus Medical University, Salzburg, Austria 

Christine Lehner, University Hospital Salzburg, Salzburg, Austria 

Andrea Wagner, Paracelsus Medical University, University of Salzburg, Salzburg, Austria 

Corinna Hirzinger, University Hospital Salzburg, Salzburg, Austria 

Verena Heu, University Hospital Salzburg, Salzburg, Austria 

Peter Augat, Trauma Center Murnau, Murnau, Germany 

Daniel Stephan, Trauma Center Murnau, Murnau, Germany 

Hans-Christian Bauer, Paracelsus Medical University, Salzburg, Austria 

Herbert Tempfer, Paracelsus Medical University, Salzburg, Austria 

Diabetes and obesity are known to be risk factors for tendinopathy, tendon injury and impaired tendon healing. 

Earlier on we described a so far unrecognized, insulin producing tendon cell type in humans and rats. These cells 

are responsive to glucose stimulation and their depletion leads to mechanical impairment in a rat model. 

We now hypothesize that dietary glucose levels influence the properties of human and rat tendons and test this 

hypothesis both by in vivo and in vitro experiments. 

We therefore fed healthy rats with either high glucose diet (HGD), low carbohydrate diet (LCD) and control diet 

(CD) for one month. Achilles tendons were then tested for their maximum tensile load and for the expression of 

Insulin and matrix degrading enzymes. 

Both HGD and LCD lead to an increased load to failure in rat Achilles tendons by 26% and 34%, respectively 

(p


CURRENT CONCEPTS OF OSTEOGENESIS IMPERFECTA 

Dragan Primorac, Penn State University, USA; University of Split, University of Osijek, Croatia 

Osteogenesis imperfecta (OI) or brittle bone disease is a heritable disorder of connective tissue that is associated 

with osteoporosis and variable amount of skeletal deformities. During the last years molecular concept of 

OI changed from a single gene disorder to multigenes disorder. Dominant negative mutations including glycin 

substitution mutations in COL1A1 or COL1A2 genes (the most common defect), helical splicing mutations (mainly 

mutations within donor or acceptor of either gene has been associated with exon skipping) produce abnormalities 

in the sequence of different regions of the type I collagen gene and result in expression of a mutant protein 

that drastically affects the normal triple-helix configuration. On the other hand, null allelic mutations may result 

in a 50% reduction of total collagen mRNA, creating a mild clinical phenotype of OI. Recent findings showed that 

mutations on CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1 and SP7 are responsible for autosomal recessive OI while 

dominant inheritance of OI is linked with mutations in COL1A1 or COL1A2 genes. Since bisphosphonates cannot 

correct the primary cause of OI, and their long-term use and effectiveness are still uncertain, new treatment options 

including mesenchymal stem cells and gene therapy are being developed by different group of scientists 

and clinicians. 

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THE ROLE OF PLATELET RICH PLASMA IN SPORTS MEDICINE 

Matjaz Vogrin, Department for orthopaedic surgery, Universtiy Medical Center Maribor, Maribor, Slovenia 

Robi Kelc, Department for orthopaedic surgery, Universtiy Medical Center Maribor, Maribor, Slovenia 

Among new therapeutical options for achieving more efficient healing, autologous thrombocytes have a very 

important place. Although there is no randomized prospective study confirming its value, platelet-rich plasma 

(PrP) as a source of autologous growth factors is speculated to be used by many sports physicians for treating 

muscle injuries. The use of platelet-derived preparations was prohibited by WADA until 2011 but was removed 

from the list after considering the lack of current evidence concerning the use of the method for the purposes of 

performance enhancement as current studies did not reveal a potential for performance enhancement beyond 

a therapeutic effect.PrP is today being widely used in therapy of tendinopathies and ligament injuries. Its place is 

being extensively investigated in case of muscle injuries, where the use seems to be more problematic due to the 

fibrotic scarring issue. 

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DOUBLE BUNDLE TECHNIQUE COMBINED WITH A BIOLOGIC 

REGENERATIVE TREATMENT GIVE THE BEST RESULT OF ACL 

SURGERY 

Nikica Daraboš, University Clinic for Traumatology, Clinical Hospital Center Sisters of Mercy, Zagreb, Croatia 

Miroslav Hašpl, Special Hospital Acromion, Krapinske Toplice, Croatia 

Denis Tršek, Special Hospital Acromion, Krapinske Toplice, Croatia 

Carsten Moser, Institute for Microtherapy, University Witten-Herdecke, Bochum, Germany 

The bone tunnel widening appear after knee anterior cruciate ligament (ACL) single bundle technique (SB) reconstruction 

and could result in a ligament laxity or lead to increased failure rates. It could be affected on the 

biomechanical and biomolecular base. This research was carried out to establish whether a double bundle technique 

(DB) in a combination with.biologic regenerative treatment of intra-articular application of Autologous Conditioned 

Serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and several growth 

factors, could enhance a result of ACL surgery. 

In a prospective, randomized, double-blind trial with four parallel groups, 124 patients were treated. We compared 

a tibial bone tunnel width measured by CT-scans in three different post-operative periods. The clinical efficacy was 

assessed by patient administered outcome instruments (IKDC 2000, LYSHOLM, TEGNER) up to two years following 

the ACL-reconstruction in 4 groups of patients regarding a different combination of treatment: A. SB + Placebo, B. 

SB + ACS, C. DB + Placebo, D. DB + ACS. 

Postoperative tibial tunnel diameters in all groups were significantly larger than they were directly after surgery. 

Bone tunnel enlargement was significantly less in Group D than in the other groups (p

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PLETELET-RICH PLASMA DERIVED GROWTH FACTORS AND 

TGF-β ANTAGONISTS PROMOTE MUSCLE REGENERATION IN 

VITRO 

Robi Kelc, Department of Orthopaedic Surgery, University Clinical Center Maribor, Maribor, Slovenia 

Martin Trapecar, Department of Biochemistry and Nutrition, Faculty of Medicine, University of Maribor, 

Maribor, Slovenia 

Lidija Gradisnik, Department of Biochemistry and Nutrition, Faculty of Medicine, University of Maribor, 


Rudi Mlakar, Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia 

Marjan Slak Rupnik, Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia 

Avrelija Cencic, Department of Biochemistry and Nutrition, Faculty of Medicine, University of Maribor, 


Matjaz Vogrin, Department of Orthopaedic Surgery, University Clinical Center Maribor, Maribor, Slovenia 

Injured skeletal muscle repairs spontaneously via regeneration; however, this process is often incomplete because 

of fibrotic tissue formation. Growth factors from platelet-rich plasma (PRP) with proven effects in tendinous and 

ligamentous healing have not yet been studied in skeletal muscles mainly due to the concern that exogenous 

TGF-β application could lead to even greater fibrosis development in an injured muscle. Therefore, only some 

TGF-β antagonists like decorin have shown their positive role in muscle repair so far. 

In our study, we have investigated the effects of PRP and decorin on skeletal muscle regeneration. A novel human 

myoblast cell culture, defined as CD56 (NCAM)+ and PAX7+ developed in our laboratory, was used for evaluation 

of potential bioactivity of PRP and decorin. The influence on the cells mitochondrial activity and expression of 

TGF-β was studied in parallel with cell proliferation. Further we have studied the ability of the therapeutic agents 

to influence the differential cascade of dormant myoblasts towards fully differentiated myotubes by monitoring 

step wise activation of single nuclear factors like PAX7, MyoD and Myogenin via multicolor flow cytometry. 

Our results clearly showed that PRP treated myoblasts have a significant increase in the mitochondrial activity and 

in the cell proliferation rate as compared to those treated with decorin and control cells. At the same time lower 

expression of TGF-β was evident in PRP treated myoblasts. We showed that PRP and decorin influence the activation 

of the differential cascade of satellite cells towards myotubes. 

Despite concerns about promoting fibrosis developement, PRP inhibits the TGF-β activity. We conclude that PRP 

can be a highly potential therapeutic agent for skeletal muscle regeneration and repair. 

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SIGNIFICANT PAIN REDUCTION IN OSTEOARTHRITIS OF THE 

KNEE BY ACP ADMINISTRATION 

Michael Borsky, Etzelclinic, Pfäffikon, Switzerland 

Jan Leuzinger, Etzelclinic, Pfäffikon, Switzerland 

Alexandro Pellegrino, Etzelclinic, Pfäffikon, Switzerland 

We report our experience with ACP administration in osteoarthritic knees. 53 patients were treated by four ACP 

injections weekly. Lequesne score and class as well as the VAS score were evaluated before and four weeks after 

treatment. 32 patient were scored as extremely or very severe before treatment, whereas only one patient remained 

in the very severe class after treatment. The reduction in the Lequesne and VAS score was 68 per cent. We 

observed 11 per cent non responders. 

In conclusion intraarticular ACP administration in osteoarthritic knees offers a simple and cheap pain reduction for 

the patient and prevents a knee arthroplasty in patient up to 3 years. 

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REGENERATIVE MEDICINE: TRANSFORMING HEATLH CARE 

SOLUTIONS 

Andre Terzic, Center for Regenerative Medicine; Mayo Clinic, Rochester, United States 

Regenerative medicine has begun to define a new perspective of future clinical practice. The U.S. Department of Health 

and Human Services report “2020: A new Vision” highlights that regenerative medicine is the vanguard of 21st century 

healthcare. Patients and society increasingly expect that regenerative medicine will lead to repair of diseased organs, 

injured tissues or congenital anomalies. Without the contribution of personalized products and services emerging 

from regenerative medicine technology, experts caution that healthcare will face an escalation in inefficient treatments 

and a rising global cost. Aimed on functional restoration of damaged tissues, not a mere abatement or moderation of 

symptoms, regenerative medicine offers a “disruptive innovation” strategy uniquely poised to add value and transform 

healthcare by providing tailored, curative solutions for the unmet needs of our patients. Indeed, the rapidly developing 

regenerative medicine armamentarium promises significant human health benefit with tangible outcomes for 

increased quality of life and improved patient care building on breakthroughs. Maximizing potential return mandates, 

however, an integrated roadmap across the translational continuum of discovery-development-regulation-use to ensure 

optimal application of regenerative medicine algorithms in medical and surgical practice.


THE IMMUNOPATHOGENESIS OF RHEUMATOID ARTHRITIS 

Asja Stipić Marković, Department of Clinical Immunology, Pulmology and Rheumatology, Clinic for Internal 

Medicine, Medical School University of Zagreb, University Hospital Sveti Duh, Zagreb, Croatia 

Rheumatoid arthritis (RA) is an autoimmune disease in which the synovial tissue transforms into a destructive pannus 

leading to erosions and lost of joint functions.Why the systemic loss of immune tolerance is linked to a localized onset 

of inflammation in the joint is still unclear. Distinct disease mechanisms are at play in RA pathology. The heterogeneity 

is consequence of the multifactorial nature of the disease and specific combination of environmental factors with polygenetic 

background. Environmental factors have a major role in developing RA as it is shown in genetically identical 

twins. 

Factors that facilitate autoimmunity 

Proliferation of synovial, oligoclonal, antigen-specific, autoreactive CD4+T cells is key event in RA pathogenesis. Etiological 

antigens are selfproteins, formed, for example, after alterations in citrullination of mucosal proteins upon influence 

of environmental stressors on barrier tissues (ie, smoking on pulmonary tissue). Several citrullinated self-proteins with 

neoepitopes are recognized, but most of the patients with seropositive RA have antibodies for citrullinated α-enolase 

(anticyclic citrullinated peptide antibodies).That is accompanied with strong association with smoking and common 

aminoacid motif (QKRAA) in HLA-DRB1*04,PTPN22 genotype. Other citrullinated self-proteins are: keratin, fibrinogen, 

collagen, vimetin and fibronectin, all showing similar interactions with smoking and same risk alleles. Altered citrullination 

of mucosal proteins also could be induced in periodontal disease by bacteria Porphyromonas gingivalis, microorganism 

expressing PADI4 (peptidyl arginine deiminase type IV). 

Other important causes facilitating autoimmunity in articular compartment are various microorganisms (bacteria, viruses) 

and their products.They induce specific T response which crossreact with human antigens (mechanism named 

molecular mimicry). Another mechanism in RA pathophysiology is autoantibody production against Fc portion of human 

immunoglobulin, in the course of infection in which immune complexes are produced. 

Furthermore, an new mechanism in autoantibody-positive RA is mediated by gastrointestinal microbiome. 

Perpetuation of synovial inflammation 

Specific,autoreactive CD4+Th-1 cells, which infiltrate synovial tissue, migrate from lymph nodes where they got information 

about autoantigen from dendritic cells (DC). However, specific antigen induce proliferation of other T cell subsets: 

Th-17 (producing IL-17A,IL-17F,TNF-α) and T regulatory cells (Tregs), Foxp3 positive (important arm of the immune 

system responsible for suppression of the response). DCs, another key players in immune response, are patrolling and 

scanning peripheral tissue. They take antigens and transfer it through lymphatic system to local lymph nodes. In the 

lymph nodes, DCs present antigen to naive T cells and act somehow altering the morphology of subcapsular sinus floor 

what divert the homing route of T lymphocites, which trafficking through 

efferent lymph vessel infiltrate synovial membrane. In synovium, there is no balance (T cell homeostasis) between 

Th-17 and T regs, because macrophages and DC provide a milieu supporting Th-17 differentiation. Parallely, Tregs are 

blocked. Cytokines, macrophage-derived (TGF-β,IL-1β,IL-6,IL-21,IL-23,TNF-α), DC-derived (TGF-β,IL-12,IL-15,IL-18,IL-23,), 

Th-17 derived (IL-17A, IL-17F,IL-21,IL-22,TNF-α), and IFN-γ, create hierarchy with TNF-α at its peak. TNF-α is essential for 

persistence of the joint inflammation. Exclusive cytokine expression patterns are characteristic for distinct autoimmune 

disease. IFNs, early mediators of the innate immune response, affect initiation and amplification of autoimmunity in 

SLE. However, in a subgroup of patients with RA, IFN type I molecular signature is upregulated, but it could mean that 

this cytokine profile is patient-specific rather than a disease-specific phenomenon. Further characteristic of this subgroup 

of patients is increased activitiy of complement and coagulation cascades. IFN/STAT-1 activation in RA synovium 

could be an attempt to limit inflammation. Upregulation of IFN-induced genes has been observed in peripheral blood 

cells of patients with other auatoimmune disease as a common hallmark in chronic autoimmunity. Besides T cells, the 

synovium in rheumatoid arthritis contains B cells, plasma cells, plasmablasts, macrophages and plasmacytoid dendritic 

cells. B cells, localized in T-cell-B-cell aggregates, form humoral part of adaptive autoimmunity.A pathogenic role of B 

cells is confirmed by the efficacy of rituximab. The autoantibody level is variably altered after rituximab therapy which, 

with the fact that plasma cells are not targeted, suggests that these cells are not only antibody producers but have role 

in autoantigen presentation and cytokine production. Plasmacytoid DCs in synovium continue presentation and T cells 

activation. Macrophages,(M1 phenotype), represent innate immunity arm along with mast cells (produce vasoactive 

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amines,cytokines,chemokines,proteases) and NK cells, while neutrophils reside mainly in synovial fluid. Macrophages 

are the central effectors of synovitis. Their “weapons” are cytokines TNF-α, IL-6,reactive oxygen intermediates, nitrogen 

intermediates, product of prostanoids and matrix-degrading enzymes. Macrophages act also as phagocytes and 

antigen-presenting cells. Macrophages are activated by Toll-like receptors 2,3,4,8 and by NOD-like receptors. By these 

receptors macrophages recognize various microorganisms and antigens deliberate after tissue damage. 

Signalling in RA 

A network of intercellular signaling cytokines is central controlling mechanism in the pathogenesis of RA.Cytokine 

patterns vary over time: early RA involves IL-4, IL-13 and IL-15, while in chronic disease the central role of TNF-α and IL-6 

has been confirmed by successful therapeutic blockade in clinical settings.Besides intercellular, there are many intracellular 

signaling molecules (particulary kinases) that regulate cytokine-receptor-mediated functions. Janus kinase 1 

(JAK1) mediate the function of several cytokines, interferons and growth factors what is confirmed in positive clinical 

outcomes of JAK1 blockade. 

Semiautonomous phenotype of synoviocytes 

The normal synovium contains mesenchymal-derived fibroblast-like synoviocytes. In RA this synoviocytes assume a 

semiautonomous phenotype characaterized by independence,loss of contact inhibition and expression of high levels 

of cytokines, chemokines, adhesion molekules,matrix metalloproteinases and tissue inhibitors of metalloproteinases. 

Fibroblast-like synoviocytes contribute directly to local cartilage destruction by adhesion and invasion of the cartilage 

surface.A hyperplastic synovium is the major cause of cartilage damage. 

Bone erosions 

Bone erosions occurs rapidly, within one year after diagnosis. Central effectors of bone destruction are osteoclasts 

which have the acidic enzymatic machinery necessary to destroy mineralized cartilage and subhondral bone. Osteoclasts, 

activated by network of synovial cytokines, invade periosteal surface adjacent to articular cartilage.”Mechanically 

vulnerable” sites such as the second and third metacarpals are prone to erosive changes.Eroded periarticular bone 

shows little evidence of repair, unlike bone in other inflammatory arthropathies because differentiation of mesenchymal 

precursors into chondroblasts and osteoblasts is inhibited by dickkopf-1 and frizzled-related protein 1, mediators 

induced by synovial cytokines.However,mesenchimal stem cells can be detected in the synovium. They have potential 

to differentiate into chondrocytes and osteoblasts. 

Molecular signature of RA subclases 

The heterogeneity of RA patients still remain a challenging problem.By genom-wide expression profiling technologies 

of disease-relevant gene coclusters and correlation analysis with clinical parameters, researchers are trying to provide 

evidence for molecular signature of the disease. Significant differential gene expression could be detected by web 

based tools - bioinformatic analysis using softwares for oligonucleotide microarrays, cDNA microarrays and hierachial 

cluster analysis available at web net. 

On the basis of proteoglycan 4 (PRG4) genes expression in a group of 66 patients, two RA subpopulations could be 

distinguish: PRG4 high and PRG4 low expressors. Low PRG4 expression in synovial fluid is associated with more aggressive 

disease stage, which, in accordance with PRG4 loss-of-function mutations, is causing campodactyly-arthropathy-coxavara-pericarditis 

syndrome. Level of PRG4 expression is associated with strong synovial stromal activation. 

Proteoglycan 4 gene product is major lubricating factor, and with PRG4-coexpressed genes has tissue protection and 

regeneration capabilities. 

Predictive power to identify seronegative (anti-citrullinated peptide antibody) patients with early arthritis, at risk of 

developing RA, belongs to a CD4 T cell gene signature which implicates interleukin 6-mediated STAT3 signalling. 

To distinguish between rheumatoid arthritis and other entities (ie. osteoarthritis) upregulation of SPP1-like cluster 

genes can serve. Higher level of SPP1 protein can be detected in synovial fluids from RA patients. SPP1 is a secreted 

phosphoglycoprotein, functioning as cytokine, DC activator and costimulator of T-cell proliferation. 

Conclusion 

In recent years there has been great progress towards understanding the molecular basis of RA immunopathophysiology. 

However, effective treatment is impeded by a paucity of accurate diagnostic and prognostic tests. There are wide 

variations in responsiveness to virtually any treatment in RA consistent with the heterogeneous nature of the disease 

why a molecular portrait reflecting the contribution of diverse cellular responses in general, and for classification of the 

disease subtypes, is necessary. 

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ARTHRITIS GENE THERAPY 

Christopher Evans, Harvard Medical School, Boston, United States 


Localizing therapeutics to joints in a sustained fashion is extremely difficult because of the rapid rate of egress of 

both small and large molecules - intra-articular dwell times are usually measured in hours whereas the diseases are 

chronic. Gene transfer to the joint is the only technology that can overcome this limitation in a clinically reasonable 

fashion. A variety of vectors and trans-genes have been used in pre-clinical models, establishing unequivocal 

proof of principle in both rheumatoid arthritis (RA) and osteoarthritis (OA). There have been four clinical trials for 

RA and two for OA. Only one of these has progressed to Phase II. 

The first human trial used a retrovirus to deliver the interleukin-1 receptor antagonist (IL-1Ra) cDNA in an ex vivo 

fashion into the metacarpophalangeal joints of nine subjects with RA. No safety issues were identified in this 

succesful Phase I trial. In a subsequent German study involving just two subjects, there was a remarkable clinical 

response in one of the patients. A different approach using adeno-associated virus (AAV) carrying etanercept 

cDNA progressed to Phase II, but was marred by the death of one subject; nevertheless, the FDA allowed this trial 

to continue to completion. No statistically significant improvement was noted, however. 

Phase I trials for the treatment of OA have been completed successfully in the USA and Korea. This protocol uses allografted 

chondrocytes that have been transduced with retrovirus to over-express transforming growth factor-β1. 

Phase II studies are underway. Our group is trying to initiate a Phase I trial in OA, using AAV to deliver IL-1Ra cDNA. 

Although the science and technology behind these studies are sound, progress in clinical implementation is limited 

by the high translational costs and the restrictive regulatory environment. 

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BIOLOGICAL AGENTS IN RHEUMATOID ARTHRITIS 

Srđan Novak, University Hospital Rijeka, Rijeka, Croatia 

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis. If untreated, persistent synovial 

inflammation can progress to cartilage and bone destruction. The goal of RA treatment today is to achieve 

remission. In clinical practice remission means the presence of one or less swollen and one or less tender joints. 

Methotrexate (MTX) is usually the first chosen synthetic disease modifying anti-rheumatic drug (DMARD) and 

administered appropriately in some patients it can lead to remission. If remission is not achieved with one or two 

DMARDs in six months biologic drugs have to be introduced. The main inflammatory mediators of joint inflammation 

and destruction in RA are tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), IL-6, chemokines and proteases. 

Advances in our understanding of the key cells and inflammatory cytokines have led to the development of targeted 

biologic agents. Among them anti-TNFα drug is usually the frst choice. As of 2012, 5 TNF-alpha inhibitors are 

approved for use by the FDA: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol. Etanercept 

is a soluble receptor which binds TNF alfa and all others are monoclonal antibodies. In randomized clinical 

trials, all these agents have shown to be effective in reducing clinical signs of inflammation in RA patients who 

have failed synthetic DMARDs. They are usually given in combination with synthetic DMARD although etanercept 

and adalimumab can be given alone. Multiple studies have demonstrated significant benefits of early treatment 

with TNF-alpha inhibitors combined with methotrexate. Other FDA-approved biologic agents for treating moderate-to-severe 

RA include abatacept which modulates co-stimulation between T lymphocytes, rituximab which 

deplets CD20 B cells, and tocilizumab which neutralises IL-6 activity by binding to IL-6 receptors. If ant-TNF drug 

fails instead another anti-TNFα drug or tocilizumab or rituximab or abatacept can be given. Generally all biologic 

drugs are given in combination with MTX or some other DMARD. If monotherapy is needed tocilizumab is the drug 

of choice. All biologic agents carry an increased risk of infections, especially of TB among patients on monoclonal 

anti –TNF antibodies although screening to latent TB infection prior to anti TNF therapy significantly reduce the 

number of TB cases. All patients being considered for biologic agents should be screened for tuberculosis and 

hepatitis B and C. Additional potential side effects include infusion and injection site reactions for intravenous and 

subcutaneously administered agents respectively. 

Oral


THE FUTURE OF RHEUMATOID ARTHRITIS TREATMENT - 

COMBINING PHARMACOLOGY AND SURGERY 

Dušanka Martinović Kaliterna, Department of Rheumatology and Clinical Immunology, University 

Hospital of Split, Split, Croatia 

Rheumatoid arthritis (RA) is widespread and complex multifactorial chronic inflammatory disorder with not always 

successful treatment. A great success of RA pharmacotherapy is characterised by novel genetically engineered 

biological medicines. The hallmark of RA is chronic synovial inflammation which leads to joint damage and 

destruction. The role of cytokines is important not only for local synovial autoimmune response but also for systemic 

features. In the last decades the cytokines role is stressed in RA especially tumour necrosis factor alpha and 

interleukins. Achievements of molecular biology and genetics promote an individual approach to RA treatment, 

with a new concept of personal medicine in the view of genomic sciences. Personalized genomic medicine and 

surgery represents a new approach to health care that customised patients’ medical treatment according to their 

own genetic information. Genomic information can also indicate the potential risk for certain diseases before the 

patient is symptomatic. It is clear that differences in genomes of individuals would likewise affect the effectiveness 

of medication. 

We are aware that although we have the choice of new biological drugs, it is not always effective. In the beginning 

of the disease the bone biopsy is sometimes needed for evaluating the disease, and later the cooperation with 

orthopaedist is mostly based in purpose of arthroscopy. Off course in some progressive RA cases surgical reconstruction 

and joint replacement may not be avoided. 

While the progress in DNA sequencing has been extensive in the last years, it promote the great challenge for 

utilizing genomic information for choosing the future more effective pharmacological and surgical therapy in RA. 

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ENHANCED OSTEOCLASTOGENESIS IN ARTHRITIS IS 

PARALLELED WITH THE INCREASED EXPRESSION OF 

PROINFLAMMATORY MEDIATORS CCL2, IL-17 AND IL-18 

Marina Ikić, University Hospital Sveti Duh, Zagreb, Croatia 

Zrinka Jajić, University Hospital Sestre Milosrdnice, Zagreb, Croatia 

Nataša Kovačić, University of Zagreb, School of Medicine, Department of Anatomy, Zagreb, Croatia 

Elvira Lazić, University of Zagreb, School of Medicine, Department of Anatomy, Zagreb, Croatia 

Sanja Ivčević, University of Zagreb, School of Medicine, Department of Physiology and Immunology, 

Zagreb, Croatia 

Frane Grubišić, University Hospital Sestre Milosrdnice, Zagreb, Croatia 

Ana Marušić, University of Split, School of Medicine, Department of Anatomy, Zagreb, Croatia 

Danka Grčević, University of Zagreb, School of Medicine, Department of Physiology and Immunology, 


Osteoclasts play a pivotal role in excessive bone destruction of arthritic joints. Many cytokines are involved in the 

pathogenesis of arthritis, acting as osteoclastogenic factors, but their effects are not fully revealed. Our aim was to 

compare the expression profile of selected proinflammatory factors and osteoclastogenic potential of peripheral-blood 

mononuclear cells (PBMC) between control subjects and arthritic patients (including rheumatoid arthritis 

(RA) and spondyloarthritis (SpA)). In addition, we assessed osteoclastogenic potential of PBMC and local synovial-fluid 

derived mononuclear cells (SFMC) in patients with RA and SpA. PBMC were collected from control subjects 

(n=12), whereas PBMC and SFMC were collected from RA patients (n=10) and SpA patients (n=15), either with ankylosing 

spondylitis (AS=5) or psoriatic arthritis (PsA=10), after the informed consent. Osteoclasts were stimulated 

with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and detected 

as tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells. RNA was extracted from PBMC/SFMC 

cells, reversely transcribed to cDNA, and amplified by quantitative PCR for the expression of osteoclast differentiation 

genes (RANK, cFms, TRAP) and inflammatory mediators (CCL2, VEGF, IL-17, IL-18, TNF-a, and FasL). In addition, 

serum and synovial fluid levels of the same mediators were determined by ELISA. Serum levels of inflammatory 

mediators CCL2, IL-17 and IL-18 were higher in arthritic patients compared with control subjects, whereas synovial 

fluid levels of CCL2, VEGF, TNF-a and IL-18 were higher in RA compared with other patient groups. In addition, 

gene expression of inflammatory mediators CCL2, IL-17 and IL18 were higher in PBMC and SFMC of arthritic patients 

compared with control subjects. In vitro osteoclastogenesis showed higher osteoclastogenic potential for 

PBMC but similar for SFMC in RA compared with AS and PsA patients. In parallel, gene expression of osteoclast 

differentiation genes RANK and TRAP was higher in osteoclastogenic cultures derived from PBMC of RA patients. 

Our results indicate that patients with RA have greater osteoclastogenic potential compared with control subjects 

and SpA patients, which is paralleled with the increased expression of proinflammatory mediators. These findings 

may be relevant for the development of therapeutic approaches aimed to modulate proinflammatory as well as 

osteoclastogenic effects of those factors. 

Oral


CELL-BASED AND CELL-FREE JOINT IMPLANTS FOR CARTILAGE 

REPAIR 

Michaela Endres, TransTissue Technologies GmbH Berlin/ Germany 

For 12 years now, BioTissue has been the pioneer in the field of regenerative cartilage treatment. BioTissue combines 

the state of the art in bioengineering industry with the growing demands of the orthopedic market and 

the future-oriented visions of science. This is achieved by a high-tech GMP lab, an independent R&D center, and of 

course by eager clinical interaction with the physicians. 

Articular cartilage cannot regenerate itself. Once damaged, the result is pain and loss of function. Treatment is 

absolutely essential to prevent deterioration in conditions such as joint disease. Tissue engineering research had 

led to the development of cell-based transplants for bone (BioSeed ® -oral bone) and cartilage repair (BioSeed ® -C). 

BioSeed ® -C is an autologous 3-dimensional chondrocyte graft which has been successfully used for many years 

to treat articular cartilage defects in the knee, ankle or hip. Therefore, a biopsy of cartilage tissue is taken from 

the patient and cells are isolated and expanded. After 3 weeks, these cells are re-transplanted within a no woven 

polymer matrix into the cartilage defect by mini-open or arthroscopic procedure. The autologous cell graft replaces 

the missing tissue and restores the original function. It provides the chondrocytes (cartilage cells) with an 

ideal three-dimensional but stable environment which stimulates them to redifferentiate and thus assume their 

original morphology and function. 

In contrast to cell-based cartilage repair, chondrotissue ® is a 1-step, CE marked, cell-free implant used to treat articular 

cartilage defects in the knee, ankle or hip. It is used after bone-marrow stimulating techniques to repair focal 

chondral defects by the possibility of an arthroscopic application. Within the defect it covers the microfractured 

area, protects the subchondral bone and insures a stable 3D environment and a chondrogenic cell differentiation 

into hyaline-like repair tissue formation. chondrotissue ® provides a unique stable 3D technology ensuring excellent 

cell differentiation and allowing for stable fixation. By an easy and fast operation technique and arthroscopic 

implantation possibility, cartilage defects can be treated using the cell-free one-step procedure with excellent 

clinical outcome. 

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SPECT/CT A NOVEL DIAGNOSTIC TOOL FOR EVALUATION OF 

LOADING PATTERN OF THE KNEE 

Michael T. Hirschmann, Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland, 

Bruderholz, Switzerland 

Stephan Schoen, Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland, 


Niklaus F. Friederich, Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland, 


SPECT/CT is a promising imaging technology, which promises the combined evaluation of mechanical and biological 

information. If the loading pattern and intensity values of the SPECT/CT correlate with the anatomical and 

mechanical alignment it could be used for evaluation of postoperative patients after realignment procedures such 

as high tibial osteotomies or patellofemoral surgery. 

99mTc-HDP-SPECT/CT of 76 patients (mean age 49±17) and 104 knees were analysed using a previously validated 

localisation and grading algorithm. The maximum intensity in each femoral, tibial and patellar joint compartment 

(medial, lateral, central, superior, inferior) was noted (0-10). In addition, anterior-posterior and lateral weight bearing 

radiographs as well as Rosenberg and skyline view were analysed with regards to the Kellgren-Lawrence osteoarthritis 

score. Long leg radiographs were used to assess the mechanical and anatomical leg alignment, which 

was then classified as varus, valgus or neutral. We correlated the mechanical and antomical alignment with the 

intensity of tracer uptake in each area of interest. In addition, the Kellgren Lawrence socre was also correlated. A 

sample size calculation was performed. The level of statistical significance was p< 0.05. 

The intensity of 99mTc-HDP tracer uptake on the medial compartment significantly correlated with anatomical 

and mechanical varus alignment of the knee (p< 0.05). The intensity of 99mTc-HDP tracer uptake on the lateral 

compartment significantly correlated with anatomical and mechanical valgus alignment of the knee (p< 0.05). In 

patients having higher Kellgren Lawrence scores, which reflects a higher degree of osteoarthritis, higher tracer 

uptake values were found in the corresponding joint compartments. 

SPECT/CT reflects the loading pattern of the knee joint with regards to the mechanical and anatomical alignment. 

SPECT/CT is then a promising imaging technology in particular for follow-up of high tibial osteotomies, deloader 

braces treatment and patellofemoral realignment procedures. 

Oral


OSTEOPOROSIS: COMMON FEATURE UNDERLINED BY 

DIFFERENT PATHOGENETIC MECHANISMS 

Danka Grčević, University of Zagreb School of Medicine, Zagreb, Croatia 

The misbalance in the differentiation and activity of principal bone cells, bone forming osteoblasts and bone 

resorbing osteoclasts, leads to osteoporosis, characterized by the loss of bone mass and increased risk of fragility 

fractures. There are multiple pathogenetic mechanisms underlying osteoporosis, involving not only the osteoblastic 

and osteoclastic cell lineages but also other bone-marrow cells, systemic hormones, local cytokines, 

and growth factors. The RANKL/RANK interaction is critical for osteoclastogenesis and hence represents a final 

common pathway for any pathogenetic factor in osteoporosis that acts by increasing osteoresorption. By using 

different mouse models, we investigated several aspects of the disease mechanism, addressing both bone formation 

and bone degradation. We used genetic mutation causing the osteogenesis imperfecta murine (OIM), 

to confirm that the osteoblastic lineage is under continuous stimulation, but with decreased ability for maturation. 

Moreover, immature osteoblasts strongly support osteoclastogenesis, through higher RANKL/OPG ratio and 

TNF-alpha expression. In view of the reports that human postmenopausal osteoblasts constitutively express Fas 

and our finding that Fas receptor activation directly inhibits osteoblast differentiation, we confirmed that Fas/FasL 

system has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and 

inhibiting differentiation of osteoblast lineage cells. Inflammatory processes alter the bone microenvironment to 

promote irreversible bone destruction. In pathologic states, activated T-lymphocytes produce RANKL and other 

proresorptive cytokines playing a role in osteoporosis as well as inflammation-induced bone loss. In the model of 

systemic inflammation, by endotoxin administration, and autoimmune reaction, in collagen-induced arthritis, we 

confirmed that there is a decrease in total bone mass mediated by increased number of identified bone-marrow 

and peripheral osteoclast progenitors and their enhanced activity maintained by proinflammatory factors. Finally, 

we hypothesize that cells expressing smooth muscle alpha-actin promoter (aSMA)-directed transgene represent 

mesenchymal progenitors of adult bone tissue and confirmed that aSMA+ cells serve as a pool of skeletal progenitors 

with a potential for terminal differentiation into mature osteoblasts during fracture healing. Although 

we identified a defined population of mesenchymal progenitors with the active role in bone regeneration, many 

puzzles are still missing before we would be able to achieve the full therapeutic success in osteoporosis treatment. 

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EFFECT OF QUERCETIN ON OSTEOPOROSIS CAUSED BY 

RETINOIC ACID IN RATS 

Željko Jeleč, General Hospital “Dr. Ivo Pedišić” Sisak, Sisak, Croatia 

Nada Oršolić, Faculty of Science, University of Zagreb, Zagreb, Croatia 

Osteoporosis is a disease characterised by the loss of bone density and deterioration of bone microarchitecture, 

leading to an increased risk of fracture. Several classes of drugs are available for the treatment of osteoporosis: antiresorptive 

drugs, oestrogen, selective oestrogen receptor modulators, bisphosphonates, parathyroid hormone, 

and strontium ranelate. Due to the adverse effects of these drugs, a natural alternative offered in the form of flavonoids 

is of interest. 

Research is conducted on rats in whom osteoporosis was induced by means of retinoic acid. Our aim was to assess 

the effectiveness of the flavonoid quercetin in the treatment of osteoporosis, as well as to determine whether 

flavonoid differ in antiosteoporotic activity from bisphosphonate alendronate, the effectiveness of which has previously 

been shown. 

We analised changes in masses of experimental animals, masses, length and diameter of femur, calcium and phosphorus 

content, as well as some biochemical and haematological variables. 

The analysis was carried out in two directions. First observed and analyzed the effect of quercetin in healthy rats, 

ie, the experimental animals before getting quercetin are not dealt with retinoic acid. On the other hand, was 

monitored and analyzed the effect of quercetin on animals in which the former providing retinoic acid occurred 

osteoporosis. We compared the effects of quercetin in relation to the control group and in relation to the bisphosphonate 

alendronate. 

Quercetin showed good therapeutical potential, and some potential showed in prevention of osteoporosis. Quercetin 

was superior to alendronate according to some criteria. 

Based on available data from the literature and the results obtained in this study, there is a high probability for 

success in the treatment of osteoporosis accounted antioxidant and estrogenic activity of quercetin. Because of 

the numerous adverse effects and cost of drugs is now being used on one side, and the proven effectiveness of 

quercetin on the other hand, believe that quercetin has a great potential in the treatment of osteoporosis 

Oral


THE TREATMENT OF PROXIMAL FEMORAL FRACTURES IN 

COUNTY HOSPITAL DUBROVNIK IN PERIOD APRIL 2011-APRIL 

2012. 

Marijo Bekić, Institute of Surgery, Division of Traumatology, County Hospital Dubrovnik, Dubrovnik, 

Croatia 

Jakiša Lojpur, Institute of Surgery, Division of Traumatology, County Hospital Dubrovnik, Dubrovnik, 

Croatia 

Nikša Kojić, Institute of Surgery, Division of Traumatology, County Hospital Dubrovnik, Dubrovnik, 

Croatia 

Marko Margaritoni, Institute of Surgery, Division of Plastic and Reconstructive Surgery, County Hospital 

Dubrovnik, Dubrovnik, Croatia 

Fractures of the proximal femur are associated with a greater number of deaths and disabilities and higher medical 

expenses than all the other osteoporotic fractures together and therefore represents a great social and economic 

problem. 

We reported a 65 consecutive patients admitted into the Institute of Surgery, Division of Traumatology, County 

Hospital Dubrovnik, Croatia, treated with a different type of implants depending on type of fracture of proximal 

femoral region. 

Fifteen men and 50 women aged 68 to 92 underwent fixation using an Dinamic Hip Screw (DHS), Short Gamma 

Nail, Locking Compression Plate and Partial Endoprothesis (PEP). 

All patients with unstable trochanteric femoral fractures were treated operatively using the Gamma Nail. Postoperatively 

patients were mobilised early without weight bearing. 

A Gamma Nail is useful for the treatment of trochanteric femoral fracture offering an early patient verticalisation 

and discharge from Hospital. 

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47

LECTURERS’ 

RESUMES 


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50 


Field of research: 

Cartilage, Osteonecrosis, Resurfacing, ACL 

Shoulder, Hand Surgery & Microsurgery 

Scientific Work 

Özler T., Güven M., Kocadal O., Beyzadeoğlu T., Altıntaş F., 

‘Is locked anatomic plate fixation out of problem in adult 

displaced clavicle fractures?’ 

Acta Orthop Traumatol Turc, Accepted, (2012). 

Beyzadeoğlu T., Köse G.T., Ekinci I.D., Bekler H., Yılmaz C., 

‘Local anaesthetics are cytotoxic to rats’ articular cartilage 

both invivo and invitro: Experimental study’ 

Acta Orthop Traumatol Turc, Accepted, (2012). 

Beyzadeoglu T., Akgun U., Tasdelen N., Karahan M., 

‘Prediction of Semitendinosus and Gracilis autograft sizes 

for ACL.’ 

Knee Surg Sports Traumatol Arthrosc. Nov 25. [Epub 

ahead of print] (2011). 

Beyzadeoglu T., Gokce A., Bekler H., 

‘Skin and subcutaneous tissue atrophy after corticosteroid 

injection for medial epicondylitis.’ 

Orthopaedics, 34:8, 570 (2011). 

Unalan P.C., Akan K., Orhun H., Akgun U., Poyanli O., Baykan 

A., Yavuz Y., Beyzadeoglu T., Nuran R., Kocaoglu B., Topsakal 

N., Akman M., Karahan M., 

‘A basic arthroscopy course based on motor skill training.’ 

Knee Surg Sports Traumatol Arthrosc. 18:10, 1395-1399 

(2010). 

Beyzadeoğlu T., Uluçay Ç. 

‘Microsurgical Approach for Acute Dislocations of the 

Knee’ 

Türkiye Klinikleri J Orthop & Traumatol-Special Topics, 

2:2, 104-108 (2009). 

Gokce A., Beyzadeoglu T., Ozyer F., Bekler H., Erdogan F., 

‘Does bone impaction technique reduce tunnel enlargement 

in ACL reconstruction?’ 

Int Orthop, 33:2 407-412 (2009). 

Bekler H., Beyzadeoğlu T., Gökçe A., Servet E., 

‘Aseptic drainage associated with polyglactine sutures 

used for repair of Achilles tendon ruptures’ 

Acta Orthop Traumatol Turc, 42:2, 135-138 (2008). 

Tahsin Beyzadeoğlu 

M.D., Assoc. Prof. of Orthopaedics & Traumatology 

ISTANBUL, TURKEY 

tbeyzade@superonline.com 

Bekler H., Bulut G., Usta M., Gokce A., Okyar F., Beyzadeoğlu 

T., 

‘The contribution of locked screw-plate fixation with varying 

angle configurations to stability of osteoporotic fractures: 

an experimental study’ 


Beyzadeoglu T., Gokce A., Bekler H., 

‘Osteochondritis dissecans of the medial femoral condyle 

associated with malformation of the menisci’ 

Orthopaedics, 31:5, 504 (2008). 

Beyzadeoglu T., Inan M., Bekler H., Altintas F., 

‘Arthroscopic excision of an ununited ossicle due to Osgood-Schlatter 

disease’ 

Arthroscopy, 24:9, 1081-1083 (2008). 

Bekler H., Beyzadeoglu T., Mercan A., 

‘Groin flap immobilization by axillary brachial plexus block 

anesthesia.’ 

Tech Hand Up Extrem Surg, 12:2, 68-70 (2008). 

Bekler H., Beyzadeoğlu T., Gökçe A., 

‘Tibialis posterior tendon transfer for drop foot deformity’ 


Gökçe A., Bekler H., Beyzadeoğlu T., Karacaoğlu E., Servet 

E., 

‘Our results for open Tibia fractures’ 

Yeditepe Medical Journal, 1:1, 43-46 (2007). 

Beyzadeoğlu T., Gökçe A., Bekler H., 

‘The effectiveness of dorsiflexion night splint added to 

conservative treatment for plantar fasciitis’ 


Bekler H., Gökçe A., Beyzadeoğlu T., 

‘Dissemination pathways in high-pressure injection injuries 

of the hand: an experimental animal model’ 


Altıntaş F., Özkut A.T., Beyzadeoğlu T., Eren A., Güven M., 

‘The effect of risedronate treatment on bone turnover 

markers in patients with hip fracture’ 

Acta Orthop Traumatol Turc, 41:2, 132-135 (2007).

Parmaksizoglu F., Beyzadeoglu T., 

‘Composite osteocutaneous groin flap combined with 

neurovascular island flap for thumb reconstruction’ 

J Hand Surg (Br), 28:5, 399-404 (2003). 


‘Role of side branches in determining suitable arterial segments 

for anastomosis in avulsion injuries: Experimental 

study’ 

J Reconstr Microsurg, 19:4, 279-284 (2003). 

Parmaksizoglu F., Beyzadeoglu T., Yildirim S., 

‘Hemangioma originating from a tendon sheath at the 

wrist as an unusual cause of trigger wrist: Case report’ 

Handchir Mikrochir Plast Chir, 35:1, 64-65 (2003). 


‘Functional latissimus dorsi island pedicle musculocutaneous 

flap to restore elbow flexion in replantation or revascularization 

of above-elbow amputations’ 

Handchir Mikrochir Plast Chir, 35:1, 51-56 (2003). 

Parmaksızoğlu F., Beyzadeoğlu T., 

‘Surgical approach to the hand injuries with multiple digital 

amputations: Case report’ 

The Journal of Kartal Training and Research Hospital, 

14 :1, 44-46 (2003). 

Parmaksızoğlu F., Beyzadeoğlu T., 

‘The treatment of bilaeral congenital radioulnar synostosis 

with derotation osteotomy: Case report’ 

Çukurova University Medical Journal, 28:2, 74-80 (2003). 

Nişan N., Öğüt T., Erdoğan F., Beyzadeoğlu T., 

‘The fixation of proximal Humerus fractures with modified 

tension band wiring’ 

Joint Diseases and Related Surgery, 13:3, 141-144 

(2002). 


‘Lengthening of replanted or revascularized lower limbs: 

Is length discrepancy a contraindication for limb salvage?’ 



‘A modified method of microvascular autogenous interposition 

vein grafting for vascular reconstruction’ 



Bilsel N., Beyzadeoglu T., Kafadar A., 

‘Application of Bailey-Dubow rods in the treatment of osteogenesis 

imperfecta’ 

Eur J Orthop Surg Trauma, 10:3, 183-187 (2000). 

Membership of Scientific Societies and/or Associations 

Since 2006, ICRS, Member of Membership and Bylaws 

Committee 

Since 2005, ISAKOS, Member of Arthroscopy Committee 

Since 2002, AAOS, International Member 

Since 2006, ESSKA, Member 

51

52 


Matej Drobnič 

MD, Ph.D. 

Assist Professor 

Consultant orthopaedic surgeon 

Leading physician for orthopaedic rehabilitation 

LJUBLJANA, SLOVENIA 

matej.drobnic@mf.uni-lj.si 

Institution 

University Medical Centre Ljubljana, Department of Orthopaedic Surgery 

Field of research 

Cartilage repair – basic and clinical research 

Knee and ankle reconstructive surgery 


Alibegović A, Balažic J, Petrovič D, Velikonja NK, Blagus R, Suput D, Drobnič M. The Optimal Combination of Cartilage 

Source and Apparatus for Long-Term In Vitro Chondrocyte Viability Analysis. J Forensic Sci. 2012 

Suhodolčan L, Brojan M, Kosel F, Drobnič M, Alibegović A, Brecelj J Cryopreservation with glycerol improves the 

in vitro biomechanical characteristics of human patellar tendon allografts. Knee Surg Sports Traumatol Arthrosc. 

2012 

Kon E, Filardo G, Drobnič M, Madry H, Jelić M, van Dijk N, Della Villa S. Non-surgical management of early knee 

osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):436-49 

Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J, Van Dijk CN. Biomechanical considerations 

in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):423- 

35. 

Malicev E, Barlič A, Kregar-Velikonja N, Stražar K, Drobnič M. Cartilage from the edge of a debrided articular defect 

is inferior to that from a standard donor site when used for autologous chondrocyte cultivation. J Bone Joint Surg 

Br. 2011 Mar;93(3):421-6. 


International Cartilage Repair Society (ICRS), member of YSOS committee 

European Society of Sports Traumatology Knee Surgery and Arthroscopy (ESSKA), member of cartilage repair 

committee 

Slovenian Orthopaedic Society (joined member to EFFORT), past secretary 

Cell and Tissue Engineering Society of Slovenia, board member

Michaela Endres 

MD 

Project manager 

TransTissue Technologies GmbH, R&D department 

BERLIN, GERMANY 

michaela.endres@transtissue.com 

Institution 

TransTissue Technologies GmbH, R&D department 


Medical and medical products, BioMedical Engineering, Tissue engineering 



Endres M, Andreas K, Kalwitz G, Freymann U, Neumann K, Ringe J, Sittinger M, Haupl T, Kaps C. 

Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10 

and XCL1 recruit human subchondral mesenchymal progenitor cells. 

Osteoarthritis Cartilage. 2010 Nov;18(11):1458-66. Epub 2010 Aug 13. 

Endres M, Abbushi A, Thomale UW, Cabraja M, Kroppenstedt SN, Morawietz L, Casalis PA, Zenclussen ML, Lemke 

AJ, Horn P, Kaps C, Woiciechowsky C. 

Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration 

model. Biomaterials. 2010 Aug;31(22):5836-41. Epub 2010 Apr 28. 

Endres M, Wenda N, Woehlecke H, Neumann K, Ringe J, Erggelet C, Lerche D, Kaps C. Microencapsulation and 

chondrogenic differentiation of human mesenchymal progenitor cells from subchondral bone marrow in Ca-alginate 

for cell injection. Acta Biomater. 2009 Jul 19. 

Endres M, Neumann K, Schroder SE, Vetterlein S, Morawietz L, Ringe J, Sittinger M, Kaps C. 

Human polymer-based cartilage grafts for the regeneration of articular cartilage defects. 

Tissue Cell. 2007 Oct;39(5):293-301. Epub 2007 Aug 3. 

Endres M, Neumann K, Haupl T, Erggelet C, Ringe J, Sittinger M, Kaps C. 

Synovial fluid recruits human mesenchymal progenitors from subchondral spongious bone marrow. 

J Orthop Res. 2007 Oct;25(10):1299-307. 

Endres M, Leinhase I, Kaps C, Wentges M, Unger M, Olze H, Ringe J, Sittinger M, Rotter N. Changes in the gene 

expression pattern of cytokeratins in human respiratory epithelial cells during culture. 

Eur Arch Otorhinolaryngol. 2005 May;262(5):390-6. Epub 2004 Nov 11. 

Endres M, Hutmacher OW, Salgado AJ, Kaps C, Ringe J, Reis RL, Sittinger M, Brandwood 

A, Schantz JT. Osteogenic induction of human bone marrow-derived mesenchymal progenitor cells in novel 

synthetic polymer-hydrogel matrices. Tissue Eng. 2003 Aug;9(4):689-702. 

Duda GN, Haisch A, Endres M, Gebert C, Schroeder D, Hoffmann JE, Sittinger M. Mechanical quality of tissue 

engineered cartilage: results after 6 and 12 weeks in vivo. J Biomed Mater Res. 2000;53(6):673-7. 

for more publications please visit http://www.ncbi.nlm.nih.gov/pubmed/ 

53

54 


Institution 

Department of Orthopaedic Surgery 

Harvard Medical School 


Gene Therapy 

Biology of Bone and Joint Disease 

Christopher Evans 

PhD, Maurice Mueller Professor of Orthopaedic Surgery, Center for Advanced 

Orthopaedic Studies,Harvard Medical School 

Director 

BOSTON, USA 

cevans@bidmc.harvard.edu 


Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Tarner IH, Robbins PD, Evans CH, Sturz H, 

Steinmeyer J, Gay S, Pap T, Muller-Ladner U, Neumann E: Rheumatoid arthritis - evidence for synovial fibroblasts 

spreading the disease. Nature Med 15: 1414-1420, 2009 

Wehling P, Reinecke J, Baltzer AWA, Granrath M, Schulitz KP, Schultz C, Krauspe R, Whiteside TW, Elder E, Ghivizzani 

SC, Robbins PD, Evans CH: Clinical responses to gene therapy in joints of two subjects with rheumatoid 

arthritis. Hum Gene Ther 20: 97-101, 2009 

Evans CH, Liu FJ, Glatt V, Hoyland JA, Kirker-Head C, Walsh A, Betz O, Wells JW, Betz V, Porter RM, Saad FA, Gerstenfeld 

LC, Einhorn TA, Harris MB, Vrahas MS: Use of genetically modified muscle and fat grafts to repair defects 

in bone and cartilage. Eur Cells Mater 18: 96-111, 2009 

Evans CH, Ghivizzani SC, Robbins PD: Getting arthritis gene therapy into the clinic. Nature Rev Rheumatol 7: 244 

- 249, 2011 

Liu F, Porter RM, Wells J, Glatt V, Pilapil C, Evans CH: Evaluation of BMP-2 gene-activated muscle grafts for cranial 

defect repair. J Orthop Res 30:1095 - 1102, 2012. 


1978 – present - Orthopaedic Research Society 

Past-President 

1981 – present - Royal Society of Chemistry 

Fellow 

1997 – present - Royal College of Pathologists 

Fellow 

2009 – present - Hastings Center 

Fellow

Danka Grčević 

MD, PhD 

Associate Professor 

ZAGREB, CROATIA 

dgrcevic@mef.hr 

Institution 

Department of Physiology and Immunology, Zagreb University School of Medicine 


Ostoimmunology, Bone biology 

Rheumatology, Hematology 



Cvija H, Kovacic N, Katavic V, Ivcevic S, Aguila HL, Marusic D, Grcevic D. Chemotactic and immunoregulatory 

properties of bone cells are modulated by endotoxin-stimulated lymphocytes. Inflammation 2012, accepted. 

Grcevic D, Pejda S, Matthews BG, Repic D, Wang L, Li H, Kronenberg MS, Jiang X, Maye P, Adams DJ, Rowe DW, 

Aguila HL, Kalajzic I. In vivo fate mapping identifies mesenchymal progenitor cells. Stem Cells 2012, doi: 10.1002/ 

stem.780. 

Li H, Jiang X, Delaney J, Franceschetti T, Bilic-Curcic I, Kalinovsky J, Lorenzo J, Grcevic D, Rowe DW, Kalajzic I. 

Immature osteoblast lineage cells increase osteoclastogenesis in osteogenesis imperfecta murine. Am J Pathol 

2010;176:2405-13. 

Grcevic D, Jajic Z, Kovacic N, Lukic IK, Velagic V, Grubisic F, Ivcevic S, Marusic A. Arthritic patients could be distinguished 

by the peripheral blood expression profile of BMPs, tumor-necrosis factor-superfamily molecules and 

transcription factor Runx2. J Rheumatol 2010;37:246-56. 

Grcevic D, Lee SK, Marusic A, Lorenzo JA. Depletion of CD4 and CD8 T lymphocytes in mice in vivo enhances 

1,25OH-D3-stimulated osteoclast-like cell formation in vitro by a mechanism that is dependent on PG synthesis. J 

Immunol 2000;165:4231-4238. 


European Calcified Tissue Society, since 2008 

American Association of Immunologists, since 2001 

Croatian Calcified Tissue Society, since 1999 

Croatian Immunological Society, since 1998; Vicepresident 

55

56 


Miroslav Hašpl 

MD, PhD, Full Professor 

Consultant Orthopaedic Surgeon and Head of Research 

KRAPINSKE TOPLICE, CROATIA 

miroslav.haspl@zg.t-com.hr 

Institution 

Special Hospital for Orthopaedic Surgery AKROMION 


Cartilage repair 

Knee surgery 


Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg 

F, Lagae K, van der Bauwhede J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, 

Luyten FP. 

Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage 

defects of the knee in a randomized controlled trial versus microfracture. 

Am J Sports Med. 2008 Feb;36(2):235-46. 

Hundrić-Haspl Z, Pecina M, Haspl M, Tomicic M, Jukic I. 

Plasma cytokines as markers of aseptic prosthesis loosening. 

Clin Orthop Relat Res. 2006 Dec;453:299-304 

Haspl M, Bićanić G, Jelić M, Pećina M. 

Unicondylar knee arthroplasty with “Repicci” model 

Lijec Vjesn. 2005 Jul-Aug;127(7-8):172-6. 

Haspl M, Jelić M, Pećina M. 

Arthroplasty in treating knee osteoarthritis and proximal tibia stress fracture. 

Acta Chir Orthop Traumatol Cech. 2003;70(5):303-5. 

Pecina M, Haspl M, Jelic M, Vukicevic S. 

Repair of a resistant tibial non-union with a recombinant bone morphogenetic protein-7 (rh-BMP-7). 

Int Orthop. 2003;27(5):320-1. Epub 2003 Jun 17. 


1995 EFORT (National delegate) 

1995 ESSKA 

1997 SICOT (National delegate) 

2000 UEMS, Section for Orthopaedics and Traumatology (National delegate)

Michael T. Hirschmann 

MD, PhD 

Consultant Orthopaedic Surgeon and Head of Research 

BRUDERHOLZ, SWITZERLAND 

Michael.Hirschmann@unibas.ch 

Institution 

Kantonsspital Baselland, Bruderholz, Department of Orthopaedic Surgery and Traumatology 


Orthopaedic imaging analysis 

Orthobiologic treatment (HTO, meniscal substitution, cartilage repair, deloader) 

Knee arthroplasty (UKR; TKR) 


39 Pubmed listed peer-reviewed scientific publications 

See pubmed Hirschmann MT 


ESSKA 

SGOT 

AGA 

ISAKOS 


57

58 


Alan Ivković 

MD, PhD, Assistant Professor 

Consultant orthopaedic surgeon 


alan.ivkovic@gmail.com 

Institution 

Department of Orthopaedic Surgery, University Hospital Sveti Duh, Zagreb 

Department of Orthopaedic Surgery, St. Catherine’s Hospital, Zabok 

Department of Biotechnology, University of Rijeka 


Regenerative and molecular orthopaedics 

Biological joint reconstruction 


Ivković A, Pascher A, Hudetz D, Jelić M, Matičić D, Hašpl M, Windhager R, Pećina M. Articular 

Cartilage Repair by Genetically Modified Bone Marrow Aspirate in Sheep. Gene Therapy, 2010. 

Miller MA, Ivković A, Porter RM, Harris MB, Estok DM 2nd, Smith RM, Evans CH, Vrahas MS. Autologous bone 

grafting on steroids: preliminary clinical results. A novel treatment for nonunions and segmental bone defects. 

Int Orthop, 2011. 

Ivkovic A, Marijanovic I, Hudetz D, Porter RM, Pecina M, Evans CH. Regenerative medicine and tissue engineering 

in orthopaedic surgery. Front Biosci (Elite Ed) 2011 

Ivković A, Pascher A, Hudetz D, Jelić M, Hašpl M, Windhager R, Pećina M. Gene therapy of the 

musculoskeletal system. Acta Ortho Traum Checosl, 2006. 

Beyzadeoglu T, Onal A, Ivkovic A. Matrix-induced autologous chondrocyte implantation (MACI) for a large chondral 

defect in a professional football player: a case report. J Med Case Rep, 2012. 


2003 – present, Croatian Orthopaedic and Traumatology Association, Member 

2007 – present, Orthopaedic Research Society, Junior Member 

2007 – present, International Cartilage Repair Society, Junior Member 

2007 – present, AO Alumni Organization, Instructor 

2007 – present, American Academy of Orthopaedic Surgeons, International Member 

2010 – present, Tissue Engineering International Regenerative Medicine Society, Member 

2012 - International Society of Orthopaedic Surgery and Traumatology,associate member

Mislav Jelić 

M.D.; Ph.D., Assistant Professor 

Head of the Biological Reconstruction Unit 


mjelic@mef.hr 


Institution 

Department of Orthopaedic Surgery, Clincal Hospital Center Zagreb, School of Medicine, University of Zagreb, 

Croatia 


Scaffolds and/or cells in articular cartilage regeneration 

Tendon grafts in ACL reconstruction 


Gomoll AH, Filardo G, Almqvist FK, Bugbee WD, Jelic M, Monllau JC, Puddu G, Rodkey WG, Verdonk P, Verdonk R, 

Zaffagnini S, Marcacci M. Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures. 

Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):468-86. 

Kon E, Filardo G, Drobnic M, Madry H, Jelic M, van Dijk N, Della Villa S. Non-surgical management of early knee 

osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):436-49. 

Vanlauwe J, Saris DB, Victor J, Almqvist KF, Bellemans J, Luyten FP; TIG/ACT/01/2000&EXT Study Group. Fiveyear 

outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects 

of the knee: early treatment matters. Am J Sports Med. 2011 Dec;39(12):2566-74. 

Grgurevic L, Macek B, Mercep M, Jelic M, Smoljanovic T, Erjavec I, Dumic-Cule I, Prgomet S, Durdevic D, Vnuk D, 

Lipar M, Stejskal M, Kufner V, Brkljacic J, Maticic D, Vukicevic S. Bone morphogenetic protein (BMP)1-3 enhances 

bone repair. Biochem Biophys Res Commun. Apr 29;408(1):25-31. 2011 

Ivkovic A, Pascher A, Hudetz D, Maticic D, Jelic M, Dickinson S, Loparic M, Haspl M, Windhager R, Pecina M. Articular 

cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther. 2010 Jun;17(6):779-89. 


ESSKA cartilage committee, member 

ICRS communication committee, member until 2011 

YSOS (Young Scientists and Orthopaedic Surgeons Society, founding member (one of 3) 

Croatian Calcified Tissue Society, Board member 

59

60 


Ivan Martin 

PhD, professor 

Director of a Research group on Tissue Engineering 

BASEL, SWITZERLAND 

imartin@uhbs.ch 

Institution 

IUniversity Hospital Basel, Institute for surgical research and hospital management, Hebelstrasse 20, 4031 Basel 


Tissue Engineering 

3D cell culture 

Skeletal Tissue Repair 


Jakob M, Saxer F, Scotti C, Schreiner S, Studer P, Scherberich A, Heberer M, Martin I. Perspective on the evolution of 

cell-based bone tissue engineering strategies. Eur Surg Res (In Press) 

Martin I, Baldomero H, Bocelli-Tyndall C, Passweg J, Saris D, Tyndall A. The survey on cellular and engineered tissue 

therapies in Europe in 2010. Tissue Eng-A (In Press) 

Gueven S, Mehrkens A, Saxer F, Schaefer DJ, Martinetti R, Martin I, Scherberich A. Engineering of large osteogenic 

grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose 

tissue. Biomaterials 32:5801-5809 (2011) 

Martin I, Smith T, Wendt D. A roadmap for the bioreactor-based translation of tissue engineering strategies into 

clinical products. Trends Biotech 27(9): 495-502 (2009) 

Scherberich A, Galli R, Jaquiery C, Farhadi J, Martin I. 3D perfusion culture of human adipose tissue-derived endothelial 

and osteoblastic progenitors generates osteogenic constructs with intrinsic vascularization capacity. Stem 

Cells 25:1823-1829 (2007) 


2010 – present, Journal “Biomaterials”, Editorial Board Member 

2008 – 2011, Journal “Tissue Engineering”, Executive Editorial Board Member 

2006 – present, Journal “Tissue Engineering and Regenerative Medicine”, Editorial Board Member 

2005 – 2011, TERMIS, Member of the Governing Board


Dušanka Martinović Kaliterna 

MD,PhD, Assist Professor, spec. of internal medicine, rheumatology and immunology 

Assist Professor 

Head of department 

SPLIT, CROATIA 

d.martinovic@inet.hr 

Institution 

Clinical hospital center of Split, Internal clinic, Department of rheumatology and clinical immunology 


clinical immunology and rheumatology 

rheumatology 

immunology 


Author of more than 50 papers, several books, mentor for 7 PhD, faculty member of EUSTAR course, investigator 

in two Croatian project and one EULAR project, member of org. comitty of Mediterranian congress of rheumatology. 

Nacci F, Righi A, Conforti ML, Miniati O, Fiori G, Martinovic D, Melchiorre D, Sapir T, Blank M, Shoenfeld Y, Moggi 

Pignone A, Matucci Cerinic M. Intravenous immunoglobulins (IVIG) improve the function and ameliorate joint 

involvement in systemic sclerosis: a pilot study. Ann Rheum Dis. 2007; 66:977-9. 

Buća A, Perković D, Martinović-Kaliterna D, Vlastelica M, Titlić M. Neuropsychiatric systemic lupus erythematosus: 

diagnostic and clinical features according to revised ACR criteria. Coll Antropol. 2009 Mar;33:281-8. 

Martinovic Kaliterna D, Perkovic D, Radic M. Churg-Strauss syndrome associated with montelukast therapy. J 

Asthma 2009;46:604-5. 

Radic M, Martinovic Kaliterna D, Fabijanic D, Radic J. Prevalence of systemic sclerosis in Split – Dalmatia county 

in Southern Croatia. Clin Rheumatol. 2010;29:419-21. 

Marasovic-Krstulovic D, Martinovic-Kaliterna D, Fabijanic D, Morovic-Vergles J. Are the anti-cyclic citrullinated 

peptide antibodies independent predictors of myocardial involvement in patients with active rheumatoid arthritis? 

Rheumatology (Oxford). 2011;50:1505-12. 


Croatian ethic committee 1997-2007, member 

HLZ- Split, 2007 – vice president 

MEF Split, ethic committee member 

Immunology association, 2007-member of the board, 

61

62 


Mahmut Nedim Doral 

MD,PhD, professor 

Chairman of Orthopaedics and Traumatology Dept, Chairman of Sports Medicine 

Dept. 

ANKARA, TURKEY 

mndoral@gmail.com, ndoral@hacettepe.edu.tr 

Institution 

Hacettepe University, Department of Orthopaedics and Traumatology, Department of Sports Medicine 


Knee Injuries, Arthroscopy 

Achilles Tendon Endoscopic Surgery 


Doral MN, Bilge O, Batmaz G, Donmez G, Turhan E, Demirel M, Atay OA, Uzumcugil A, Atesok K, Kaya D. Treatment 

of osteochondral lesions of the talus with microfracture technique and postoperative hyaluronan injection. Knee 

Surg Sports Traumatol Arthrosc. 2012 Jul;20(7):1398-403 

Atesok K, Matsumoto T, Karlsson J, Asahara T, Atala A, Doral MN, Verdonk R, Li R, Schemitsch E. An emerging 

cell-based strategy in orthopaedics: endothelial progenitor cells. Knee Surg Sports Traumatol Arthrosc. 2012 

Jul;20(7):1366-77 

Kaya D, Doral MN, Nyland J, Toprak U, Turhan E, Donmez G, Citaker S, Atay OA, Callaghan MJ. Proprioception level 

after endoscopically guided percutaneous Achilles Tendon. Knee Surg Sports Traumatol Arthrosc. 2012 Apr 20. 

[Epub ahead of print] 

Anoka N, Nyland J, McGinnis M, Lee D, Doral MN, Caborn DN. Consideration of growth factors and bio-scaffolds 

for treatment of combined grade II MCL and ACL injury. Knee Surg Sports Traumatol Arthrosc. 2012 

May;20(5):878-88 

Bilge O, Doral MN, Atesok K, Atay OA, Donmez G, Turhan E, Uzumcugil A, Leblebicioglu G, Kaya D, Bilgili H, Sargon 

M. The effects of the synovium on chondrocyte growth: an experimental study. Knee Surg Sports Traumatol 

Arthrosc. 2011 Jul;19(7):1214-23 


President Turkish Society of Orthopaedics & Traumatology (TOTBID) 2010-2011 

President European Federation of Sports Traumatology (EFOST) / 2001-2003 

President Asia-Pacific Knee Society (APKS / Knee Section of APOA) / 2004-2006 

Program Committee Member and Membership Committee Chairman of International Society of Arthroscopy, 

Knee Surgery & Orthopaedic Sports Medicine (ISAKOS) / 2007-2011

Srđan Novak 

MD,PhD, professor 

Head of Rheumatlogy and Clinical Immunology 

RIJEKA, CROATIA 

srdan.novak@ri.htnet.hr 

Institution 

KBC Rijeka, Department for internal medicine 


Rheumatoid arthritis 

Systemic sclerosis, systemic lupus erithematodes, spodyloarthrithis 



Novak S, Anic F, Luke-Vrbanic TS. Extremely high serum ferritin levels as a main diagnostic tool af adult-onset Stil`s 

disase. Rheumatol Int 2011: Feb26 

Novak S, Anić B, Anić F, Cerovac M, Čikeš N. Clinical significance of autoantibodies induced by infliximab treatment: 

two year follow–up after Infliximab discontinuation.Acta Dermatovenelol Croat 2011;19(3):156-160. 

Ravlić-Gulan J, Gulan G, Novak S, Duletic-Nacinovic A, Matovinovic D, Rukavina D.A comparison of lymphocyte 

subpopulations simultaneously on local and systemic levels in acute rheumatoid arthritis patients. Colll Antropol 

2005; 29:661-9 

Novak S, Čikeš N. Infliximab-induced lupus or rheumatoid arthriris (RA) overlapping with systemic lupus erythematosus 

(SLE) unmasked by infliximab. Clin Exp Rheumatol 2004; 22:268. 

Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F C, Bancel PE, Allanore DF, Müller-Ladner Y, Distler U, Iannone O, 

Pellerito F, Pileckyte R, Miniati M, Ananieva I, Gurman L, Damjanov AB, Mueller N, Valentini A, Riemekasten G, Tikly 

G, Hummers M, Henriques L, Caramaschi MJ, Scheja P, Rozman A, Ton B, Kumánovics E, Coleiro G, Feierl B, Szucs E, 

Von Mühlen G, Riccieri CA, Novak S, Chizzolini C, Kotulska A, Denton C, Coelho PC, Kötter I, Simsek I, de la Pena Lefebvre, 

Hachulla PG, Seibold E, Rednic JR, Stork S, Morovic-Vergles J, Walker JUA. Causes and risk factors for death 

in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 

2010; 69 (10): 1809-18015. 


Croatian Reheumatology Society 

Croatian Clinical Immunology Society, 

EUSTAR 

63

64 


Krešimir Pavelić 

MD, PhD, professor 

Institution 

Department of Biotechnology,University of Rijeka,Croatia 

Krešimir Pavelić (1952) medical doctor, professor of molecular biology, Head, Department 

of Biotechnology, University of Rijeka, former director and establisher of 

Division of Molecular Medicine, Ruder Bošković Institute, Secretary General of the 

European Molecular Biology Conference (EMBC), EMBO member, member of Croatian 

Academy of Sciences and Arts and many others international scientific organisations, former vice-president of 

European Molecular Biology Conference, EMBC, Delegate of Croatian Academy of Sciences and Arts in European 

Science Foundation, President of the National Scientific Council, Republic of Croatia, former member of the parliamentarian 

committee for national scientific awards, expert for molecular medicine of the Trans radical party in 

the European Parliament. Krešimir Pavelić is ex officio member of the EMBO Council and member of the European 

Molecular Biology Laboratory. He has published 280 scientific papers in world top scientific journals and several 

invited review papers and chapters in prestigious journals and book published by American and European publishers. 

He significantly contributed to the understanding of biology of the transformed cell.


Marko Pećina 

Academician 

Professor emeritus 

Secretary of the Department of Medical Sciences – Croatian Academy of Sciencey 

and Arts 

Editor-in-Chief of the journal “InternationalOrthopaedics” 


marko.pecina@zg.t-com.hr 

Institution 

Department of Orthopaedic Surgery School of Medicine University of Zagreb 

Croatian Academy of Sciences and Arts 

SICOT 

Field of research: 

Orthopaedic surgery – sports traumatology 

Reparation/regeneration of musculoskeletal system 


Jelić M, Pećina M, Hašpl M, Kos J, Taylor K, Matičić D, McCartney J, Yin S, Rueger D, Vukičević S. Regeneration of 

Articular Cartilage Chondral Defects by Osteogenic Protein-1 (Bone Morphogenetic Protein-7) in Sheep. Growth 

factors 19 : 101 - 113, 2001. 

Pećina M, Jelić M, Martinović S, Hašpl M, Vukičević S. Articular cartilage repair: the role of bone morphogenetic 

proteins, Int Orthop 26 : 131 - 136, 2002. 

Pećina M, Bojanić I. Overuse Injuries of the Musculoskeletal System, 2nd Edition, CRC Press, Boca Raton- London 

- New York - Washington,DC, 2003., 

Mihelić R, Pećina M, Jelić M, Zoričić S, Kušec V, Simić P, Bobinac D, Lah B, Legović D, Vukičević S. BMP-7 (OP-1) 

Promotes Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction in Sheep. Am J Sports Med 32 : 

1619 - 1625, 2004. 

Hundrić-Hašpl Ž, Pecina M, Haspl M, Tomicic M, Jukic I. Plasma Cytokines as Markers of Aseptic Prosthesis Loosening. 

Clin Orthop Relat Res 453 : 299 – 304, 2006. 


1964 Croatian Medical Association 

1970 Croatian Orthopaedic Society, president 1997-2005 

1970 Yougoslav Orthopaedic and Traumatology Association, president 1988-1990 

1979 International Society of Orthopaedic Surgery and Traumatology (SICOT) , national delegate 1984-1990 and 

1992-2009, Editor from 2008 

1980 Societe Francaise de Chirurgie Orthopaedique et Traumatologique (So.F.C.O.T.) 

1982 European Spinal Deformity Society (ESDS) founder and vice-president 1989-1992 

1983 International Knee Society (IKS) 

1984 European Society for Sports Traumatology,Knee Surgery and Arthroscopy (ESSKA) 

1986 Hellenic Orthopaedic and Traumatology Society, honoured member 

1990 College Europeen de Traumatologie du Sport 

1992 Internatiional Association of Olympic Medical Officers 

1997 American Academy of Orthopaedic Surgeons, International Affiliate Member 

1999 European Calcified Tissue Society 

2000 International Federation of Sports Medicine 

2004 Czech Society for Orthopaedics and Traumatology, honoured member 

2005 Bone and Joint Decade 2000-2010, ambassador and national coordinator 

65

66 


Dragan Primorac 

MD, Ph.D. 

Professor 

Office of Dragan Primorac 


office@draganprimroac.org 

Institution 

Penn State University and University of New Haven USA, University of Split and University of Osijek, Republic of 

Croatia 


Pediatrics, Forensics, Bone Biology, Gene and Cellular Therapy 

Pediatrics, Forensic Genetics 

Origin of European Man (Y Chromosome Analysis) 


Stover M.L., Primorac D., Liu S.C., McKinstry M.B., and Rowe D.W. Defective Splicing of mRNA from One COL1A 

Allele of Type I Collagen in Nondeforming (Type I) Osteogenesis Imperfecta. J. Clin. Invest. 1993;92:1994-2002. 

Johnson C.V., Primorac D., Kinstry M.Mc, Rowe D.W, Lawrence J.B.. Tracking COL1A1 RNA in Osteogenesis Imperfecta: 

Splice-defective Transcripts Initiate Transport from the Gene but are Retained within the SC35 Domain. J Cell 

Biol. 2000; 150: 417-432 

Semino O, Passarino G, Oefner JP, Lin AA, Arbuzova S, Beckman EL, De Benedictis G, Francalacci P, Kouvatsi A, 

Limborska S, Marcikic M, Mika A, Mika Genetic Legacy of Paleolithic Homo sapiens sapiens in Extant Europeans: A 

Y B, Primorac D, Santachiara-Benerecetti AS, Cavalli-Sforza LL, Underhill AP. The Chromosome Perspective. Science 

2000; 290: 1155-1159. 

Battaglia V, Fornarino S, Al-Zahery N, Olivieri A, Pala M, Myres NM, King RJ, Rootsi S, Marjanovic D, Primorac D, 

Hadziselimovic R, Vidovic S, Drobnic K, Durmishi N, Torroni A, Santachiara-Benerecetti AS, Underhill PA, Semino O. 

Y-chromosomal evidence of the cultural diffusion of agriculture in southeast Europe. Eur J Hum Genet. 2008;1-11. 

Mršić G, Gršković B, Vrdoljak A, Popović M, Valpotić I, Anđelinović Š, Stenzl V, Ehler E, Urban L, Lacković G, Underhill 

P, Primorac D. Croatian national reference Y-STR haplotype database. Mol Biol Rep. 2012;39(7):7727-41 


International Society of Applied Biological Sciences-ISABS (Founder) 

American Academy of Forensic Sciences-AAFS (Fellow) 

1997, ISABS, Founder 

1997, American Society for Human Genetics, Member 

1996, AAFS, Fellow 

2000, Hrvatsko društvo za humanu genetiku

Gian M. Salzmann 

MD,PhD 

Trauma and Knee surgery 

FREIBURG, GERMANY 

Gian.salzmann@uniklinik-freiburg.de 


Institution 

DepartmentDepartment of Orthopaedic and Trauma Surgery, University Medical Center, Albert-Ludwigs University 

Freiburg, Freiburg, Germany 


cartilage 


Schriftenverzeichnis 

entsprechend den Ausführungsbestimmungen der Habilitationsordnung 

(§ 6 Abs. 2 Nr. 5) 

(Stand 18.07.2012) 

a. Bei kumulativer Habilitationsschrift: Angabe 

der in die Habilitationsschrift einfließenden Arbeiten 

1. Salzmann GM, Nuernberger B, Schmitz P, Anton M, 

Stoddart MJ, Grad S, Milz S, Tischer T, Vogt S, Gansbacher 

B, Imhoff AB, Alini M. Physicobiochemical Synergism 

Through Gene Therapy and Functional Tissue Engineering 

for In Vitro Chondrogenesis. Tissue Eng Part A. 2009 

Mar 12. 

IF 4.636 

2. Salzmann GM, Paul J, Bauer JS, Woertler K, Sauerschnig 

M, Landwehr S, Imhoff AB, Schöttle PB. T2 assessment 

and clinical outcome following autologous 

matrix-assisted chondrocyte and osteochondral autograft 

transplantation. Osteoarthritis Cartilage. 2009 

Dec;17(12):1576-82. Epub 2009 Sep 1. 

IF 3.953 

3. Salzmann GM, Niemeyer P, Steinwachs M, Kreuz PC, 

Südkamp NP, Mayr HO. Cartilage repair approach and 

treatment characteristics across the knee joint: a European 

survey. Arch Orthop Trauma Surg. 2010 Jan 16. 

IF 1.196 

4. Salzmann GM, Buchberger MS, Stoddart MJ, Grad 

S, Milz S, Niemyer P, Sudkamp NP, Imhoff AB, Alini M. 

Varying regional topology within knee articular chondrocytes 

under simulated in vivo conditions. Tissue Eng 

Part A. 2011 Feb;17(3-4):451-61. Epub 2010 Oct 12. 

IF 4.636 

5. Salzmann GM, Sauerschnig M, Berninger MT, 

Kaltenhauser T, Schönfelder M, Vogt S, Wexel G, Tischer 

T, Sudkamp N, Niemeyer P, Imhoff AB, Schöttle PB. The 

dependence of autologous chondrocyte transplanta- 

tion on varying cellular passage, yield and culture duration. 

Biomaterials. 2011 Sep;32(25):5810-8. Epub 2011 

May 17. 

IF 7.882 

6. Grad S, Salzmann GM. Chondrocytes - one cell type, 

different subpopulations: Characteristics and behavior 

of different types of chondrocytes and implications for 

tissue engineering applications. Orthopade. 2009 Oct 4. 

IF 0.583 

7. Ueblacker P, Wagner B, Kruger A, Vogt S, DeSantis 

G, Kennerknecht E, Brill T, Hillemanns M, Salzmann GM, 

Imhoff AB, Plank C, Gansbacher B, Martinek V. Inducible 

nonviral gene expression in the treatment of osteochondral 

defects. Osteoarthritis and Cartilage. 2004 Sep;12(9) 

IF 3.953 

8. Ueblacker P, Wagner B, Vogt S, Salzmann G, Wexel G, 

Kruger A, Plank C, Brill T, Specht K, Hennig T, Schillinger 

U, Imhoff AB, Martinek V, Gansbacher B. In vivo analysis 

of retroviral gene transfer to chondrocytes within collagen 

scaffolds for the treatment of osteochondral defects. 

Biomaterials. 2007 Oct;28(30):4480-7. 

IF 7.882 

9. Vogt S, Wexel G, Tischer T, Schillinger U, Ueblacker 

P, Wagner B, Hensler D, Wilisch J, Geis C, Wübbenhorst 

D, Aigner J, Gerg M, Krüger A, Salzmann GM, Martinek 

V, Anton M, Plank C, Imhoff AB, Gansbacher B. The influence 

of the stable expression of BMP2 in fibrin clots 

on the remodelling and repair of osteochondral defects. 

Biomaterials. 2009 Apr;30(12):2385-92. Epub 2009 Jan 

31. 

IF 7.882 

10. Schätti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini 

M, Stoddart MJ. A combination of shear and dynamic 

compression leads to mechanically induced chondrogenesis 

of human mesenchymal stem cells. . Eur Cell 

Mater. 2011 Oct 11;22:214-25. 

IF 9.650 

67

68 


b. als Ersautor 

1. Salzmann GM, Naal FD, von Knoch F, Tuebel J; 

Gradinger R, Imhoff AB, Schauwecker J. Effects of Cefuroxime 

on human osteoblasts in vitro. J Biomed Mater 

Res A. 2007 Aug;82(2):462-8. 

IF 3.044 

2. Salzmann GM, Walz L, Schoettle PB, Imhoff AB. Arthroscopic 

anatomical reconstruction of the acromioclavicular 

joint. Acta Orthop Belg. 2008 Jun;74(3):397- 

400. 

IF 0.392 

3. Salzmann GM, Paul J, Sandmann GH, Imhoff AB, 

Schöttle PB. The Coracoidal Insertion of the Coracoclavicular 

Ligaments: An Anatomic Study. Am J Sports Med. 

2008 Aug 28. 

IF 3.821 

4. Salzmann GM, Ahrens P, Spang J, El-Azab H, Imhoff 

AB, Lorenz S. Sporting activity after high tibial osteotomy 

for the treatment of medial compartment knee osteoarthritis. 

Am J Sports Med. 2008 Nov 

IF 3.821 

5. Salzmann GM, Spang JT, Imhoff AB.Double-bundle 

anterior cruciate ligament reconstruction in a skeletally 

immature adolescent athlete. Arthroscopy. 2009 

Mar;25(3):321-4 

IF 3.317 

6. Salzmann GM, Nuernberger B, Schmitz P, Anton M, 

Stoddart MJ, Grad S, Milz S, Tischer T, Vogt S, Gansbacher 

B, Imhoff AB, Alini M. Physicobiochemical Synergism 

Through Gene Therapy and Functional Tissue Engineering 

for In Vitro Chondrogenesis. Tissue Eng Part A. 2009 

Mar 12. 

IF 4.636 

7. Salzmann GM, Weber TS, Spang JT, Imhoff AB, 

Schöttle PB. Comparison of native axial radiographs 

with axial MR imaging for determination of the trochlear 

morphology in patients with trochlear dysplasia. Arch 

Orthop Trauma Surg. 2009 Jun 6. 

IF 1.196 

8. Salzmann GM, Paul J, Bauer JS, Woertler K, Sauerschnig 

M, Landwehr S, Imhoff AB, Schöttle PB. T2 assessment 

and clinical outcome following autologous 

matrix-assisted chondrocyte and osteochondral autograft 

transplantation. Osteoarthritis Cartilage. 2009 

Dec;17(12):1576-82. Epub 2009 Sep 1. 

IF 3.953 

9. Salzmann GM, Niemeyer P, Steinwachs M, Kreuz PC, 

Südkamp NP, Mayr HO. Cartilage repair approach and 

treatment characteristics across the knee joint: a European 

survey. Arch Orthop Trauma Surg. 2010 Jan 16. 

IF 1.196 

10. Salzmann GM, Buchberger MS, Stoddart MJ, Grad 

S, Milz S, Niemyer P, Sudkamp NP, Imhoff AB, Alini M. 

Varying regional topology within knee articular chondrocytes 

under simulated in vivo conditions. Tissue Eng 

Part A. 2011 Feb;17(3-4):451-61. Epub 2010 Oct 12. 

IF 4.636 

11. Salzmann GM, Walz L, Buchmann S, Glabgly P, Venjakob 

A, Imhoff AB. Arthroscopically assisted 2-bundle 

anatomical reduction of acute acromioclavicular joint 

separations. Am J Sports Med. 2010 Jun;38(6):1179-87. 

Epub 2010 May 4. 

IF 3.821 

12. Salzmann GM, Sauerschnig M, Berninger MT, 

Kaltenhauser T, Schönfelder M, Vogt S, Wexel G, Tischer 

T, Sudkamp N, Niemeyer P, Imhoff AB, Schöttle PB. The 

dependence of autologous chondrocyte transplantation 

on varying cellular passage, yield and culture duration. 

Biomaterials. 2011 Sep;32(25):5810-8. Epub 2011 

May 17. 

IF 7.882 

13. Salzmann GM, Sah B, Südkamp NP, Niemeyer P. 

Reoperative characteristics after microfracture of knee 

cartilage lesions in 454 patients. Knee Surg Sports Traumatol 

Arthrosc. 2012 Apr 8. [Epub ahead of print] 

IF 1.857 

14. Salzmann GM, Sah BR, Schmal H, Niemeyer P, Sudkamp 

NP. Microfracture for treatment of knee cartilage 

defects in children and adolescents. Pediatr Rep. 2012 

Apr 2;4(2):e21. Epub 2012 Jun 19. 

Noch kein IF, aber Pubmed gelistet 

Gesamtsumme Impact Factor als Erstautor: 43.572 


AGA, ICRS; DGU


Asja Stipić Marković 

MD, PhD, professor of internal medicine, alergologist and clinical immunologist 

Head of department 


astipicm@inet.hr 

Institution 

Department of Clinical Immunology, Pulmology and Rheumatology, School of Medicine University of Zagreb, 

University Hospital “Sveti Duh”, Zagreb 


Allergology and clinical immunology 

allergology 

clinical immunology 


Pevec B, Radulovic Pevec M, Stipic Markovic A, Batista I, Rijavec M, Silar M, Kosnik M, Korosec P House dust 

mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes. Int Arch Allergy 

Immunol 2012;159:287-296 

Krmpotic D, Luzar-Stiffler V, Rakusic N, Stipic Markovic A, Hrga I, Pavlovic M.Effects of Traffic Air Pollution and 

Hornbeam Pollen on Adult Asthma Hospitalizations in Zagreb. Int Arch Allergy Immunol 2011;156:62-68 

Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet 

J, Braido F, Bruselle G, Canonica GW, Carlsen HK, Chanez P, Fokkens WJ, Garcia-Garcia M, Gjomarkai M, Haahtela 

T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska-Polak A, Lødrup-Carlsen K, Mäkelä M, 

Malkusova I, Mullol J, Nieto A, Østerberg-Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki I, Rukhadze 

M, Stipic-Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, M. Xatzipsalti M, 

Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations-A GA2LEN-DARE systematic review. 

Allergy 2011; 66(4): 458-68 

Pavlisa G, Pavlisa G, Kusec V, Kolonic SO, Markovic AS, Jaksic B. Serum Level of VEGF and bFGF in hypoxic patients 

with exacerbation of COPD. Eur Cytokine Network 2010; 21: 92-98 

Markovic AS, Pekic P, Schmidt S, Stulhofer-Buzina D. Small and large bowel manifestation of of leukocytoclastic 

vasculitis– A Case Report. Wien Klin Wochenschr 2005;115(9):302-308 


2004-present, Croatian Society of Allergology and Clinical Immunology, President 

2008-present, Croatian Society of Immunology,member of Executive Board 

2010-present, Croatian Society of Internal Medicine, Vicepresident 

1986-present, European Academy of Allergology and Clinical Immunology, member 

69

70 


Martin James Stoddart 

PhD, Principal Investigator 

DAVOS PLATZ, SWITZERLAND 

Martin.stoddart@aofoundation.org 

Institution 

AO Research Institute Davos, Musculoskeletal Regeneration Program 


Mesenchymal stem cells for regenerative medicine treatment of cartilage and bone defects 

Mechanoregulation of stem cell fate 


Stoddart MJ, Ettinger L, Hauselmann HJ. Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue 

subjected to compression and shear. Biotechnol Bioeng. 95(6):1043-51, 2006 

Palmer GD, Stoddart MJ, Gouze E, Gouze J-N , Ghivizzani SC, Porter RM, and Evans CH A simple, lanthanide-based 

method to enhance the transduction efficiency of adenovirus vectors. Gene Ther. 15(5):357-63, 2008 

Li Z, Kupcsik L, Yao S, Alini M, Stoddart MJ. Chondrogenesis of Human Bone Marrow Mesenchymal Stem Cells in 

Fibrin-polyurethane Composites Compared to Pellet Culture. Tissue Eng Part A. 2009 15(7):1729-37. 

Li Z, Kupcsik L, Yao SJ, Alini M, Stoddart MJ. Mechanical Load Modulates Chondrogenesis of Human Mesenchymal 

Stem Cells through the TGF-β Pathway. J Cell Mol Med. 2010 ;14(6A):1338-46. 

O Schätti, S Grad, J Goldhahn, G Salzmann, Z Li, M Alini, MJ Stoddart. A combination of shear and dynamic compression 

leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur Cell Mater. 2011 

Oct 11;22:214-25. 


Since 2001, ICRS, Member 

Since 2006, ORS, Member 

Since 2010, Faculty of 1000 Medicine- Associate Faculty Member 

Since 2011, eCells and Materials Journal, Scientific Editor


Carmen Terzic 

MD, PhD, Associate Professor of Medicine and Physical Medicine and Rehabilitation 

Chair, Department of Physical Medicine and Rehabilitation 

ROCHESTER, MN, USA 

terzic.carmen@mayo.edu 

Institution 

Mayo Clinic; Department of Physical Medicine and Rehabilitation 


Stem cell regenerative medicine 

Cardiovascular rehabilitation 


Faustino RS, Chiriac A, Niederlander N, Nelson TJ, Behfar A, Mishra PK, Macura S, Michalak M, Terzic A, Perez-Terzic 

C. Decoded calreticulin-deficient embryonic stem cell transcriptome resolves in latent cardiophenotype, Stem 

Cells 2010 

Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C, Terzic A. Somatic 

oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. 

Cell Metab 2011 

Baker DJ, Perez-Terzic C, Jin F, Pitel KS, Niederlander NJ, Jeganathan K, Yamada S, Reyes S, Rowe L, Hiddinga HJ, 

Eberhardt NL, Terzic A, van Deursen JM. Opposing roles for p16Ink4a and p19Arf in senescence and aging caused 

by BubR1 insufficiency. Nat Cell Biol 2008 

Perez-Terzic C, Faustino RS, Boorsma BJ, Arrell DK, Niederlander NJ, Behfar A, Terzic A. Stem cells transform into a 

cardiac phenotype with remodeling of the nuclear transport machinery. Nat Clin Pract Cardiovasc Med 2007 


2000-present, American Academy of Physical Medicine and Rehabilitation, Diplomate 

2000-present, American Board of Physical Medicine and Rehabilitation, Member 

2005-present, American Society of Clinical Pharmacology and Therapeutics, Member 

1998-present, American Medical Assocation, Member 

71

72 


Institution 

Mayo Clinic 


Regenerative medicine 

Cardiovascular medicine 

Stem cell biology 

Andre Terzic 

MD, PhD, Professor of Medicine and Pharmacology 

Director, Center for Regenerative Medicine; Mayo Clinic 

ROCHESTER, MN, USA 

terzic.andre@mayo.edu 


Behfar A, Terzic A. Derivation of a cardiopoietic population from human mesenchymal stem cells yields functional 

cardiac progeny. Nature Clin Pract Cardiovasc Med 2006. 

Perez-Terzic C, Faustino RS, Boorsma BJ, Arrell DK, Niederlander NJ, Behfar A, Terzic A. Stem cell transformation 

into cardiac phenotype guided by directed remodeling of nuclear transport machinery. Nature Clin Pract Cardiovasc 

Med, 2007 

Behfar A, Perez-Terzic C, Faustino RS, Arrell DK, Hodgson DM, Yamada S, Puceat M, Niederländer N, Alekseev AE, 

Zingman LV, Terzic A. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J Exp Med 

2007. 

Nelson TJ, Martinez-Fernandez A, Terzic A. Induced pluripotent stem cells: developmental biology to regenerative 

medicine. Nature Cardiol Rev, 2010. 

Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C, Terzic A. Somatic 

oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. 

Cell Metab, 2011 


Past President, American Society for Clinical Pharmacology and Therapeutics 

Chair, Functional Genomics and Translational Biology Council, American Heart Association 

Chair, Scientific Advisory Board, International Society for Cardiovascular Translational Research

Gamze Torun Köse 

PhD, professor 

Vice Head of Department 

ISTAMBUL, TURKEY 

gamzekose@yeditepe.edu.tr 


Institution 

Yeditepe University, Faculty of Engineering and Architecture, Department of Genetics and Bioengineering 


Cartilage repair – basic and clinical research 

Knee and ankle reconstructive surgery 


Ö.Karadas, D.Yücel, H.Kenar, G.T.Köse, V.Hasırcı, Bone Tissue Engineering Using Collagen Calcium Phosphate Composite 

Scaffolds And Stem Cells From Wharton’s Jelly And Menstrual Blood, Journal of Tissue Engineering and 

Regenerative Medicine, 2012 

A.B.Ertan, P.Yılgor, B.Bayyurt, Ayşe Ceren Çalıkoğlu, Ç.Kaspar, F.N.Kök, G.T.Köse*, V.Hasirci, Effect of Double Growth 

Factor Release on Cartilage Tissue Engineering, Journal of Tissue Engineering and Regenerative Medicine, DOİ: 

10.1002/term.509, 2011 

H.Kenar, G.Torun Kose, M.Toner, D.L. Kaplan, V.Hasirci, A 3D Aligned Microfibrous Myocardial Tissue Construct 

Cultured under Transient Perfusion, Biomaterials, 32:23, 5320-5329, 2011 

D.Yücel, G.T.Köse, V.Hasırcı, Tissue Engineered, Guided Nerve Tube Consisting of Aligned Neural Stem Cells and 

Astrocytes, Biomacromolecules, 11, 3584–3591, 2011. 

M.E.Yalvac, M.Ramazanoglu,A.A.Rizvanov, F.Sahin, O.F.Bayrak, U.Salli, A.Palota´s, G.T. Köse, Isolation and characterization 

of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, 

osteo-, adipo- and neurogenesis, Pharmacogenomics Journal, 10, 105-113, 2010 


2008+, Turkish Biomaterials and Tissue Engineering Society, One of the Founding Members 

2007+, Turkish Artificial Organs Society (TUYOD) 

2005+, Tissue Engineering and Regenerative Medicine International Society (TERMIS) 

2005, European Tissue Engineering Society (ETES) 

73

74 


Matjaž Vogrin 

MD, PhD 

Orthopaedic surgeon, Head of Orthopaedic Departement 

MARIBOR, SLOVENIA 

Matjaz.vogrin@ukc-mb.si 

Institution 

Department: Orthopaedic Surgery, University Hospital Maribor 


Sports medicine 

Arthroscopic surgery 


VOGRIN, Matjaž, RUPREHT, Mitja, DINEVSKI, Dejan, HAŠPL, Miroslav, KUHTA, Matevž, JEVŠEK, Marko, KNEŽEVIĆ, 

Miomir, ROŽMAN, Primož. Effects of a platelet gel on early graft revascularization after anterior cruciate ligament 

reconstruction: A prospective, randomized, double-blind, clinical trial. Eur. surg. res., 2010, vol. 45, no. 2, str. 77-85 

VOGRIN, Matjaž, RUPREHT, Mitja, CRNJAC, Anton, DINEVSKI, Dejan, KRAJNC, Zmago, REČNIK, Gregor. The effect 

of platelet-derived growth factors on knee stability after anterior cruciate ligament reconstruction: a prospective 

randomized clinical study. Wien. klin. Wochenschr., Suppl., 2010, vol. 122, suppl. 2, str. 91-95 

KRAJNC, Zmago, VOGRIN, Matjaž, REČNIK, Gregor, CRNJAC, Anton, DROBNIČ, Matej, ANTOLIČ, Vane. Increased 

risk of knee injuries and osteoarthritis in the non-dominant leg of former professional football players. Wien. klin. 

Wochenschr., Suppl., 2010, vol. 122, suppl. 2, str. 40-43 

VOGRIN, Matjaž. The role of growth factors in ACL surgery. V: DORAL, Mahmut Nedim (ur.). Sports injuries : prevention, 

diagnosis, treatment and rehabilitation. Berlin; Heidelberg: Springer, 2011, cop. 2012, str. 443-447 

VOGRIN, Matjaž, KUHTA, Matevž. Anterior ankle impingement. V: DORAL, Mahmut Nedim (ur.). Sports injuries : 

prevention, diagnosis, treatment and rehabilitation. Berlin; Heidelberg: Springer, 2011, cop. 2012, str. 635-638 


slovenia orthopaedic association 

EFOST

Institution 

College of Medicine, Mayo Clinic 


Cancer, immunotherapy, cellular therapy 


Stanimir Vuk-Pavlović 

Professor of Biochemistry and Molecular Biology 

Scientist; Consultant, Division of Hematology, Department of Internal Medicine, 

Mayo Clinic 

Director Emeritus (1996-2010), Stem Cell Laboratory, Mayo Clinic Cancer Center 

ROCHESTER, MINNESOTA, USA 

vuk@mayo.edu 


Kogan, Y., Halevi-Tobias, K., Elishmereni, M., Vuk Pavlović, S., Agur, Z.: Reconsidering the paradigm of cancer immunotherapy 

by computationally aided real-time personalization. 

Cancer Res., 72: 2218-2227, 2012. 

Agur, Z., Vuk-Pavlović, S.: Mathematical modeling in immunotherapy of cancer: Personalizing clinical trials. Molecular 

Therapy, 20: 1-2, 2012. 

Gomez, C.R., Knutson, G.J., Clifton, K.B., Schreiber, C.A., Vuk-Pavlović, S.: Age-dependent response of murine 

female bone marrow cells to hyperbaric oxygen. Biogerontology, DOI 10.1007/s10522-012-9373-8, 2012. 

Kronik, N., Kogan, Y., Elishmereni, M., Halevi–Tobias, K., Vuk Pavlović, S., Agur, Z.: Predicting outcomes of prostate 

cancer immunotherapy by personalized mathematical models. PLoS ONE 5(12), 2010: e15482. doi:10.1371/journal.pone.0015482. 

Vuk-Pavlović, S., Bulur, P.A., Lin, Y., Qin, R., Szumlanski, C.L., Zhao, X., Dietz, A.B.: Immunosuppressive CD14+H- 

LA-DRlow/– monocytes in prostate cancer. Prostate, 70: 443-455, 2010. 


American Association for Cancer Research (1987–) 

American Society of Biochemists and Molecular Biologists (1987–) 

International Society of Cell Therapy (1996–) 

International Society for Applied Biological Sciences (Zagreb; 2004–) 

75

76 


Institution 

Institution full name, Department 

Knie&Sport.Wien 

Soccerclinic Vienna 

Patrick Weninger 

Assoc. Professor MD 

Consultant orthopaedic sports and trauma surgeon 

Chief Medical Officer Austrian Tennis Federation 

CMO Austrian Badminton Federation 

CMO Austrian Hockey Federation 

Team Physician Austrian Soccer Board 

VIENNA, AUSTRIA 

ordination@dr-weninger.at 


Arthroscopic meniscal and ACL repair, bioscaffolds, PRP augmentation 

Biological ACL repair 

Biological meniscus repair 


Weninger et al. Single leg spinal anaesthesia for arthroscopic meniscus and ACL surgery, JBJS Am 2012. (accepted) 

Weninger et al. Outpatient meniscal repair: a cost-effectiveness analysis. Am J Sports Surg. 2012 (accepted) 

Weninger et al. Perfusion of the pes anserinus. Implcations for biological ACL repair using hamstring tendons. J 

Trauma, 2012. (accepted). 

Weninger et al. Anterior cruciate ligament reconstruction using autografts and double biodegradable femoral 

cross-pin fixation: functional, radiographic and MRI outcome after 2-year minimum follow-up. KSSTA. 2008 


Austrian Society of Trauma Surgery 

AGA 

ESSKA 

ISAKOS


77

fondaparinuks 

Profilaksa DVT kod velikih 

ortopedskih operacija 

ARIXTRA ® (fondaparinuksnatrij) 2,5 mg/0,5 ml otopina za injekciju u napunjenoj štrcaljki. Terapijske indikacije: Prevencija venskih tromboembolijskih događaja (VTD) u bolesnika 

koji se podvrgavaju velikom ortopedskom kirurškom zahvatu na donjim ektremitetima poput operacije frakture kuka, velike operacije koljena ili ugradnje umjetnog kuka; Prevencija 

venskih tromboembolijskih događaja (VTD) u bolesnika koji se podvrgavaju abdominalnom kirurškom zahvatu, a u kojih postoji visoki rizik nastanka tromboembolijskih komplikacija, npr. 

kod resekcije tumora u trbušnoj šupljini; Prevencija venskih tromboembolijskih događaja (VTD) u internističkih bolesnika za koje se procjenjuje da postoji visoki rizik nastanka VTD i koji su 

nepokretni zbog akutne bolesti, npr. srčane insuficijencije i/ili akutnih respiratornih bolesti i/ili akutnih zaraznih ili upalnih bolesti; Liječenje nestabilne angine pektoris ili infarkta miokarda 

bez elevacije ST-segmenta (UA/NSTEMI) u bolesnika u kojih nije indicirano hitno (

POSTER 

PRESENTATIONS 


79

80 


DNA DEMETHYLATING AGENT 5-AZACYTIDINE NEGATIVELY 

AFFECTS PROLIFERATION OF MAMMALIAN LIMB BUD CELLS IN 

AN ORGAN-CULTURE SYSTEM 

Vedrana Mužić, University of Zagreb, School of Medicine, Department of Biology, Department of 

Rehabilitation and Orthopaedic Devices, Clinical Hospital Centre Zagreb, Zagreb, Croatia 

Gordana Jurić-Lekić, University of Zagreb, School of Medicine, Departmentof Histology and Embryology 

Zagreb, Zagreb, Croatia 

Marta Himelreich, University of Zagreb, School of Medicine, Department of Histology and Embryology 


Željka Majić, University of Zagreb, School of Medicine, Department of Biology, Zagreb, Croatia 

Nino Sinčić, University of Zagreb, School of Medicine, Department of Biology Zagreb, Croatia 

Ana Katušić, University of Zagreb, School of Medicine, Department of Biology Zagreb, Croatia 

Maja Vlahović, University of Zagreb, School of Medicine, Department of Biology Zagreb, Croatia 

Ljiljana Šerman, University of Zagreb, School of Medicine, Department of Biology, Zagreb, Croatia 

Jelena Lončarević, University of Zagreb, School of Medicine, Departmentof Histology and Embryology, 


Floriana Bulić-Jakuš, University of Zagreb, School of Medicine, Department of Biology, Zagreb, Croatia 

Epigenetic drug, DNA demethylating agent 5-azacytidine (5azaC), impairs overall growth of ex vivo cultivated 

rat limb buds. The aim of this investigation was to assess proliferative capacity of rat limb buds cultivated with 

5azaC at the single cell level. 13-days-old embryos were isolated from pregnant Fisher rat females and limb buds 

were microsurgically isolated under the stereomicroscope. They were cultivated in an organ-culture system at the 

air-liquid interface in MEM and 50% rat serum. 5-azacytidine (5mmol) was added to the culture medium. During 

the second week, explants were processed for immunohistochemistry on Anti-Proliferating Cell Nuclear Antigen 

(PCNA). PCNA positive cells were stereologically evaluated using numerical density (Nv) and results were statistically 

compared with Student’s t-test. In both fore-limb and hind-limb explants, either treated or controls, differentiation 

proceeded in comparison to 13-days-old limb buds. PCNA was expressed in some cells of the cartilage, 

stratified squamous epithelium and mesenchyme. Nv values for PCNA were significantly lower (p


RESULTS OF 2 ND GENERATION AUTOLOGOUS CHONDROCYTE 

IMPLANTATION IN THE MANAGEMENT OF FOCAL ARTICULAR 

CARTILAGE DEFECTS 

Rutul Gandhi, B J Medical College, Ahmedabad, India 

BACKGROUND: Autologous Chondrocyte Implantation is the most widely used cell based surgical procedure for 

the repair of articular cartilage defects. Both short term and long term results are reported to be good or excellent 

in 80 to 95 percent of cases. MRI has emerged as the procedure of choice for assessment of graft survival and cartilage 

maturation after ACI and for predicting outcome and directing rehabilitation. In this study we intend to assess 

the results of ACI in patients with focal articular defects and correlating the MRI findings with clinical outcome. 

MATERIALS AND METHODS: Since July 2010, 12 patients with focal articular cartilage defects grade 3 or 4 according 

to ICRS grading were treated with ACI. IKDC knee scores were calculated pre operatively and then at 6 months 

and then at 12 months. All patients completed subjective knee evaluation forms before and at 6 months and 1 

year after surgery. MRI was performed post procedure at 12 weeks and then at 12 months and MOCART scoring 

done based on the studies. All adverse events recorded and all data analysed using appropriate tests. 

OBSERVATIONS AND RESULTS: 

1. Subjective evaluation and functional status: There was a significant improvement in the patients subjective 

knee score from a mean of 40.5 points to 88.5 points at the end of 12 months. Before operation only 25% 

graded their knee function as level I or II which significantly improved to 75% having grade I or II at 12 months 

2. IKDC clinical score: Before operation 75% were classified as A or B using the IKDC objective scoring criteria, 

which deteriorated to only 33.3% rated as A or B at 6 months. However again at 12 months there was a significant 

clinical recovery with 83.3% rated as A or B. 

3. MRI results and MOCART scores: The mean MOCART scores at 6 months were 80 which improved to 90 at 12 

months. At 6 months 50% lesions showed normal or nearly normal scores which improved to 83.3% lesions 

been graded as normal or nearly normal at 12 months. 

CONCLUSIONS: ACI has emerged as one of the leading treatment strategies in management of focal articular 

defects. These superior results are attributed to the capacity of ACI to produce hyaline articular cartilage. We recommend 

12 months MRI to be a reasonable non invasive means of assessing the maturation of the graft after ACI. 

Poster 

81

82 


ARTHROPLASTY BY DEMINERALIZED OSTEOCHONDRAL 

ALLOGRAFTS AS AN ALTERNATIVE TO EARLY TOTAL HIP 

ARTHROPLASTY IN CHILDREN WITH THE SEQUELAE OF 

OSTEOMYELITIS 

Yury Garkavenko, The Turner Scientific and Research Institute for Children’s Orthopedics, Saint-Petersburg – 

Pushkin, Russian Federation 

Alexandr Pozdeev, The Turner Scientific and Research Institute for Children’s Orthopedics, Saint-Petersburg – 

Pushkin, Russian Federation 

In the period from one to 26 years, the results were studied of the hip arthroplasty by demineralized osteochondral 

allografts in 52 patients with sequelae of osteomyelitis of the hip operated at the The Turner Research Institute 

for Children’s Orthopedics. 

The initial state of the affected hip with destructive hip dislocation was in 56 per cent of patients, in one third of 

patients was an ankylosis of the joint in a vicious position, and in 13% of patients was severe flexion-adduction 

contracture on the background of coxarthrosis, requiring joint stabilization and restoration of function. 

If indicated, the hip arthroplasty with the use of one or two demineralized osteochondral allografts was supplemented 

by shortening osteotomy of the femur in its lower third. 

The study has shown that in more than a half of the patients, namely in 27 (52%), flexion in the operated hip exceeded 

80°, reaching 100° or more in 7 (13.5%) patients. 

In the late followup, in all 16 patients with initial ankylosis of the hip the range of motion in at least two planes 

has preserved. However, only in four patients (25%) of them the flexion did not exceed 45°, while in the remaining 

cases (75%) it exceeded 60°, reaching 100° or more in 9 (56.2%) patients. 

Despite the increase in number of patients during later followup with limited range of motion in the operated hip, 

the preservation of a sufficient range of flexion beyond 80º was observed in patients even 10-15 years (33.3%), and 

even 16-20 years (66, 6%) after performed arthroplasty. 

The results presented here provide a basis to consider the arthroplasty with the use of demineralized osteochondral 

allografts as an alternative to the early total hip arthroplasty in children with destructive changes in the proximal 

femur. 

Poster


HIP AND KNEE OSTEOARTHRITIS SUSCEPTIBILITY AND 

ASSOCIATION WITH IL1 GENE CLUSTER IN CROATIAN 

POPULATION 

Zdravko Jotanovic, Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka, 

Croatia 

Marikken Heiland Kaarvatn, Molecular Genetics Laboratory, Department of Oral Biology, University of 

Oslo, Norway 

Godfrey Essien Etokebe, Molecular Genetics Laboratory, Department of Oral Biology, University of Oslo, 

Norway 

Radovan Mihelic, Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka, Croatia 

Biserka Mulac-Jericevic, Department of Physiology and Immunology, School of Medicine, University of 

Rijeka, Croatia 

Tamara Tijanic, Department of Physiology and Immunology, School of Medicine, University of Rijeka, 

Croatia 

Sanja Balen, Clinical Institute for Transfusion Medicine, Universal Hospital Center Rijeka, School of 

Medicine, University of Rijeka, Croatia 

Branko Sestan, Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka, Croatia 

Zlatko Dembic, Molecular Genetics Laboratory, Department of Oral Biology, University of Oslo, Norway 

Osteoarthritis (OA) is a degenerative, chronic, progressive and multifactorial disease of the joints that causes degenerative 

changes in articular cartilage, but also causes pathological changes in other parts of the joint. It is 

the most common chronic musculoskeletal disease with complex genetic risk, and represents a leading cause of 

disability in elderly population worldwide. The risk for primary OA is polygenic in nature, with risk differing among 

various human subpopulations. One of the factors involved in the genetic predisposition to both hip OA (HOA) 

and knee OA (KOA) is the interleukin-1 (IL-1) gene cluster located on chromosome 2. Using case-control study in 

a Croatian Caucasian population with 500 OA patients, of which 240 KOA patients with total knee replacement 

(TKR) or partial knee replacement (PKR) and 260 HOA patients with total hip replacement (THR), and 508 healthy 

blood donors as controls, we have mapped genetic polymorphisms at 4 loci, comprising three SNPs: IL1A -889 

(C>T), IL1B +3594 (C>T) and -511 (G>A), and a VNTR in the IL1RN gene. Further analyses were done by assembling 

haplotypes using our previous reports on markers for the same population (the IL1B -511C>T SNP and the IL1RN 

VNTR). Our results are consistent with a hypothesis that inflammatory factors like IL-1 are implicated in pathogenesis 

of primary OA. 

Poster 

83

84 


THE TENDON STEM/ PROGENITOR CELL NICHE: IS THERE A 

BLOOD TENDON BARRIER? 

Christine Lehner, University Hospital Salzburg, Salzburg, Austria 

Renate Gehwolf, Paracelsus Medical Univerity, Salzburg, Austria 

Andrea Wagner, Paracelsus Medical Univerity, Salzburg, Austria, University of Salzburg, Austria 

Hans-Christian Bauer, Paracelsus Medical Univerity, Salzburg, Austria 

Herbert Tempfer, Paracelsus Medical Univerity, Salzburg, Austria 

A major challenge for attempts to accelerate tendon healing is to understand the niche that regulates the differentiation 

of stem/ progenitor cells towards a tendon cell like phenotype. 

Along our attempts to characterize tendon cells we observed a population of perivascular cells expressing tendon- 

and neuronal stem cell associated markers. Moreover we observed that tendon endothelial cells express 

the tight junction (TJ) associated marker Occludin. We therefore hypothesise that tendon vessels form a barrier 

between blood and tendon tissue, establishing a privileged microenvironment. 

By immunohistochemistry, Lasermicrodissection, qRT-PCR and transmission electron microscopy we examined 

human biceps and semitendinosus tendons and mouse Achilles tendons for TJ associated markers and structures. 

Occludin, Claudin5 and ZO1 protein localize at the cell boundaries of tendon endothelial cells, as confirmed by 

confocal microscopy of isolated tendon vessels. Besides, these cells express mRNA encoding for the blood-brain 

barrier/ blood nerve barrier associated markers Occludin, Claudin1, Claudin5 and Claudin11. 

The finding of TJ- like structures in human tendons is confirmed by TEM images published by others. 

The finding of TJ- like structures in tendons may shed new light on the composition of the tendon niche. The functional 

properties and the role of this barrier in tendon de- and regeneration will have to be addressed by further 

studies. 

Poster


OSTEOGENIC POTENTIAL AND STEMNESS OF MESENCHYMAL 

STEM CELLS AFTER DEXAMETHASONE TREATMENT 

Igor Matić, Faculty of Science, University of Zagreb, Zagreb, Croatia 

Alan Ivković, Clinical Hospital Sveti Duh, Zagreb, Zagreb, Croatia 

Šime Brkić, Faculty of Science, University of Zagreb, Zagreb, Croatia 

Pavle Josipović, Faculty of Science, Univeristy of Zagreb, Zagreb, Croatia 

Ivan Karlak, Clinic for Traumatology, Zagreb, Zagreb, Croatia 

Marko Pećina, School of Medicine, University of Zagreb, Zagreb, Croatia 

Inga Marijanović, Faculty of Science, University of Zagreb, Zagreb, Croatia 

The purpose of the research was to improve osteogenic differentiation of human bone marrow derived-mesenchymal 

stem cells (hMSCs) and to evaluate the level of remaining undifferentiated stem cells in culture. Standard 

cell culture protocol includes continuous exposure to the dexamethasone which is not easy to reproduce in human 

body. Therefore, our experiment was designed to investigate the possibility of using short-term dexamethasone 

exposure in order to induce osteogenic differentiation. 

Human bone marrow-derived MSCs were expanded with FGF-2 supplemented media. Afterwards cells were cultured 

in osteogenic media (DMEM low glucose, 10% FBS, 10mM β-glycerophosphate, 5µg/ml ascorbic acid, 1mM 

piruvat) and treated with different concentrations of dexamethasone, both short-term and continuous. The differentiation 

status of the cells was estimated using several osteogenic markers - alkaline phosphatase (AP) activity, 

the bone sialoprotein (BSP) and dentin matrix protein 1 (DMP-1) mRNAs. The stemness of the cells was estimated 

by the presence of pluripotency markers - SRY (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription 

factor 4 (OCT4). The measurements were conducted on the days 7 and 14 after osteogenic conditions 

had been introduced. 

Our results show that continuous treatment induces the highest level of osteogenesis, but 2 hour exposure also induced 

differentiation in comparison with control. Overall, 10-5 M concentration of dexamethasone was the most 

powerful in the short-term induction of osteogenesis. SOX2 has not been detected in hMSCs. OCT4 was expressed 

in undifferentiated pluripotent hMSCs and its expression subsequently went down, indicating that the differentiation 

process is proceeding 

Poster 

85

86 


PLGA NANOFIBROUS MEMBRANES LOADED WITH 

HYDROXYAPATITE OR DIAMOND NANOPARTICLES AS 

SCAFFOLDS FOR BONE TISSUE ENGINEERING 

Katarina Novotna, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech 

Republic 

Martin Parizek, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic 

Timothy Douglas, Polymer Chemistry and Biomaterials Group, Ghent University, Ghent, Belgium 

Vera Lisa, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic 

Lucie Bacakova, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech 

Republic 

Various types of nanofiber scaffolds have been used in a wide range of tissue engineering applications, mainly 

for their ability to mimic the architecture of natural extracellular matrix. Composites of nanofibrous polymers and 

hydroxyapatite have been successfully tested for possible enhancement of bone regeneration. 

We have evaluated the proliferation of osteoblast-like MG-63 cells on 2 types of poly(lactide-co-glycolide) (PLGA) 

nanofibrous membranes, prepared by electrospinning using NanospiderTM device (Elmarco Ltd.). One type of 

membranes was loaded with hydroxyapatite nanoparticles (PLGA-HAp), the second with diamond nanoparticles 

(PLGA-ND), both about 23 wt% in dry PLGA. Besides the cell growth, we have also tested the possible immune activation 

of the cells, manifested by secretion of tumor necrosis factor-alpha (TNF-alpha), measured in the cell culture 

medium, and by concentration of intercellular adhesion molecule-1 (ICAM-1), measured in cell homogenates. As a 

positive control for TNF-alpha production, the cells stimulated with lipopolysaccharide from Escherichia coli were 

used. As MG-63 cells showed only a weak response to the lipopolysaccharide treatment, RAW 264.7 macrophages 

were used for the evaluation as well. 

The results have showed that both types of PLGA composites, as well as pristine PLGA represent a good support 

for attachment and subsequent proliferation of the MG-63 cells. However a notable difference between these 

PLGA composites was found in the TNF-alpha production. The concentration of TNF-alpha in the cell culture medium 

taken from RAW 264.7 cells grown on PLGA-HAp was significantly higher than on PLGA-ND and pristine PLGA, 

which makes PLGA-ND constructs suitable for its use in bone tissue engineering and for further research. 

Supported by the Academy of Sciences of the CR (grant No. IAAX00100902) and the Czech Science Foundation 

(grants No. P108/11/0794 and P108/12/G108). 

Poster


RISKS FACTORS FOR LOW BONE MINERAL DENSITY IN 

POST-MENOPAUSAL WOMEN WITH SYSTEMIC SCLEROSIS 

Anka Pranić-Kragić, Department of Nuclear Medicine, University Hospital Split, Split, Croatia 

Mislav Radić, Department of Rheumatology and Clinical Immunology, University Hospital Split, 

Split, Croatia 

Dušanka Martinović Kaliterna, University Hospital Split, Split, Croatia 

Josipa Radić, Department of Nephrology, University Hospital Split, Split, Croatia 

The aim of this study was to determine the prevalence and risk factors for low bone mineral density (BMD) in 

women with systemic sclerosis (SSc). A cross-sectional study was conducted among 32 post-menopausal SSc patients. 

Patients were evaluated using a questionnaire about the following variables: age, disease duration, disease 

activity, Medsger severity score, total skin score and history of fracture. Lumbar spine and hip measurements of 

BMD were performed by dual absorptiometry. Univariate and multivariate statistical analyses were used to assess 

the relationship between risk factors and BMD. The mean age was 52.8 +/- 10.7 years, and the median duration 

of SSc was 78.8 +/- 65 months. The mean BMD was 1.29 +/- 0.18 g/cm(2) in the lumbar spine and 1.09 +/- 0.14 g/ 

cm(2) in the hip. Osteopenia was present in 26.4 % of patients and osteoporosis in 15.6 %. In the multiple regression 

analysis, low BMD in the lumbar spine was associated with and low body mass index (BMI). Low BMD in the 

hip was associated with cumulative corticosteroid dose Medsger severity score and low BMI. Medsger severity 

score, low BMI, and total skin score are risks factors for low BMD in post-menopausal SSc patients. Osteopenia was 

found in 26.4 % of patients, while osteoporosis was found in 15.6%. Bone health should receive attention in care 

for persons with SSc. 

Poster 

87

88 


UNIVERSAL FIXATOR- Fix-AS NEW WAY FOR FULL 

STABILITY,REHABILITATION AND MAXIMUM COMFORT FOR 

PATIENTS 

Šabić Nedžad, Poliklinika Dr Šabić, Zenica, Bosnia and Herzegovina 

Question:Could one provide a full stability of the bone sequence, the full flexion and more comfort at heavy war 

injuries, big bone defects, and deformity corrections (even at the haviest cases)? Since 1985, compression-distraction 

method was successfully used in Cantonal Hospital in Zenica. First six years we only used Illizarov fixator, and 

last twenty years we are using our own fixator FixAS. 

This work will show advantages of FixAS apparatus at large deformation corrections, simultaneous lengthening by 

external or internal transport, and deformation correction, heavy war injuries, non union, big bone defects after 

tumor resection, lengthenings and other. 

Advantages are especially important for solving hip and femur problems, and knee deformation corrections. Our 

method provides full comfort during treatment, as well as easy rehabilitation – until full scope of joint movement. 

This way, extremity is saved even in heaviest cases, unlike other methods (bone grafting, free flap), which were 

more expensive and unformal, often ended by an amputation. This fully satisfies the principle minimum metal, 

maximum stability and comfort. Answer: Yes, indeed, it can be achieved – by using FixAS universal fixator! 

Poster


THE ROLE OF Nb IN OXIDIZED SURFACE OF A β-TiNb ALLOY ON 

ITS OSTEOINTEGRATION 

Marta Vandrovcova, Institute of Physiology AS CR, v.v.i, Prague, Czech Republic 

Ivan Jirka, J. Heyrovský Institute of Physical Chemistry AS CR, v.v.i., Prague, Czech Republic 

Otakar Frank, J. Heyrovský Institute of Physical Chemistry AS CR, v.v.i., Prague, Czech Republic 

Zdenek Tolde, Czech Technical University in Prague, Faculty of Mechanical Engineering, Prague, Czech 

Republic 

Thomas Luxbacher, Anton Paar GmbH, Graz, Austria 

Lucie Bacakova, Institute of Physiology AS CR, v.v.i , Prague, Czech Republic 

Vladimir Stary, Czech Technical University in Prague, Faculty of Mechanical Engineerin, Prague, Czech 

Republic 

The most commonly used Ti-based materials for bone implant fabrication are the alloys composed from titanium, 

aluminium and vanadium, particularly Ti6Al4V. These alloys fulfil many requirements for the implant material, i.e. 

they are characterized by their beneficial mechanical and chemical properties and high biocompatibility. However, 

substantial drawback of the TiAlV materials is the presence of small amounts of highly toxic Al and V oxide 

species in their surface region, or release of cytotoxic Al and V ions. Great attention thus has been paid to develop 

new materials which do not contain any toxic component. In this context, niobium is prospective as a non-toxic β 

stabilizing agent. 

In our study, the adhesion, growth and viability of human osteoblast-like MG63 cells on thermally oxidized surface 

of titanium (Ti600) and β-titanium-niobium (TiNb600) alloy were investigated. We also compared the influence 

-OH-group present on its surface (low concentration of OH-groups was observed after Piranha solution treatment). 

The role of sterilization in boiling water on the surface chemistry of the samples and the presence of Nb 

on the alloy surface on its interaction with cells was addressed. Sterilization of the samples caused extensive dehydroxylation 

of their surfaces. However, the overall acidity of the Ti600 and TiNb600 samples before and after 

sterilization is not affected by this treatment. 

The differences observed between Ti600 and TiNb600 samples which may participate in higher “osteointegration” 

can be summarized as follows: The surface of TiNb600 sample is more acidic. Moreover, the surface of TiNb600 

sample is negatively charged at physiological pH (6–7). This charge is, however, smaller than the charge on the 

surface of Ti600. 

The authors found that TiNb600 alloys showed improved colonization with MG63 cells. This was documented by 

significantly higher cell numbers on the TiNb600 (regardless of treatment by Piranha solution) compared with 

pure Ti600. In addition cell viability on day 7 after seeding was significantly higher on TiNb600 than on Ti600. Thus, 

niobium improves the mechanical properties of stainless steel, and it is suggested that addition of niobium to 

metallic alloys (especially to titanium alloys) could be useful for the fabrication of biomedical materials required 

definite mechanical features. 

Supported by the Grant Agency of the Czech Republic (grant No. P108/10/1858) 

Poster 

89

90 


COMPARISON BETWEEN TWO ICRS HISTOLOGY SCORING 

SYSTEMS FOR CARTILAGE REPAIR 

Andreja Vukasovic, Department of Histology and Embryology, School of Medicine, University of Zagreb, 


Davor Jezek, Department of Histology and Embryology, School of Medicine, University of Zagreb, Zagreb, 

Croatia 

Petar Kostesic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine, 

University of Zagreb, Zagreb, Croatia 

Damir Hudetz, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia 

Ivan Cerovecki, School of Medicine, University of Zagreb, Zagreb, Croatia 

Marin Kosovic, Department of Physics and Biophysics, School of Medicine, University of Zagreb, Zagreb, 

Croatia 

Tadija Petrovic, Clinic for Traumatology, Clinical Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia 

Drazen Maticic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine, 


Alan Ivkovic, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia 

Marko Pecina, School of Medicine, University of Zagreb, Zagreb, Croatia 

The histological quality of cartilage is considered to be one of the most important outcome tools to objectify 

success of different treatment modalities in regenerative orthopedics and tissue engineering. The aim of this pilot 

study was to compare the applicability of two International Cartilage Research Society (ICRS) visual histological assessment 

scales, ICRS I and ICRS II in the analysis of cartilage restoration after treatment with genetically modified 

autologous bone marrow clots. Chondral defects in 28 skeletally mature sheep which were randomly assigned to 

4 different groups; TGF group (TGF-β1 gene transduced bone marrow clot), GFP group (Green fluorescent protein 

transduced bone marrow clot), BMC group (untransduced bone marrow clot) and NC group (negative control, no 

treatment) were treated accordingly. After 6 months animals were sacrificed and osteochondral explants were 

analyzed. For histological assessment, slides were stained with hematoxylin - eosin and Safranin O. Two independent 

evaluators examined 112 slides blinded, 4 slides for each specimen using assessment scale ICRS I then ICRS 

II. Significant period of time passed between first and second examination, so the possibility of a bias with the 

respect to the first examination has been avoided entirely. ICRS I assesses 6 features that are graded with grades 

from 0 to 3. With ICRS II 14 features are evaluated on a visual analogue scale. Each parameter is scored on a scale 

from 0 to 100%. The ICRS I demonstrated lower inter-reader variability compared with ICRS II. Results yielded with 

ICRS I assessment scale were 98.7% coincident between two observers while those obtained with ICRS II assessment 

scale varied greatly. Subchondral bone and overall assessment scores had the best correlation coefficients 

for inter-reader variability (r = 0.82 and 0.76, respectively). ICRS I score revealed statistical significant difference in 

cell distribution between TGF and NC group (p=0.002). ICRS II showed statistical significant difference in surface 

and matrix staining score between TGF and NC group (p=0.009 and 0.007, respectively). ICRS II enabled better 

discrimination of scoring parameters but it is more suited for evaluators with strong background in cartilage histopathology. 

ICRS I remains easy to use for less experienced evaluators. 

Poster


OSTEOGENIC POTENTIAL AND STEMNESS OF MESENCHYMAL 

STEM CELLS AFTER DEXAMETHASONE TREATMENT 

Andreja Vukasovic, Department of Histology and Embryology, School of Medicine, University of Zagreb, 


Davor Jezek, Department of Histology and Embryology, School of Medicine, University of Zagreb, Zagreb, 

Croatia 

Petar Kostesic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine, 


Damir Hudetz, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia 

Ivan Cerovecki, School of Medicine, University of Zagreb, Zagreb, Croatia 

Marin Kosovic, Department of Physics and Biophysics, School of Medicine, University of Zagreb, Zagreb, 

Croatia 

Tadija Petrovic, Clinic for Traumatology, Clinical Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia 

Drazen Maticic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine, 


Alan Ivkovic, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia 

Marko Pecina, School of Medicine, University of Zagreb, Zagreb, Croatia 

The purpose of the research was to improve osteogenic differentiation of human bone marrow derived-mesenchymal 

stem cells (hMSCs) and to evaluate the level of remaining undifferentiated stem cells in culture. Standard 

cell culture protocol includes continuous exposure to the dexamethasone which is not easy to reproduce in human 

body. Therefore, our experiment was designed to investigate the possibility of using short-term dexamethasone 

exposure in order to induce osteogenic differentiation. 

Human bone marrow-derived MSCs were expanded with FGF-2 supplemented media. Afterwards cells were cultured 

in osteogenic media (DMEM low glucose, 10% FBS, 10mM β-glycerophosphate, 5µg/ml ascorbic acid, 1mM 

piruvat) and treated with different concentrations of dexamethasone, both short-term and continuous. The differentiation 

status of the cells was estimated using several osteogenic markers - alkaline phosphatase (AP) activity, 

the bone sialoprotein (BSP) and dentin matrix protein 1 (DMP-1) mRNAs. The stemness of the cells was estimated 

by the presence of pluripotency markers - SRY (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription 

factor 4 (OCT4). The measurements were conducted on the days 7 and 14 after osteogenic conditions 

had been introduced. 

Our results show that continuous treatment induces the highest level of osteogenesis, but 2 hour exposure also induced 

differentiation in comparison with control. Overall, 10-5 M concentration of dexamethasone was the most 

powerful in the short-term induction of osteogenesis. SOX2 has not been detected in hMSCs. OCT4 was expressed 

in undifferentiated pluripotent hMSCs and its expression subsequently went down, indicating that the differentiation 

process is proceeding. 

Poster 

91

92 


CELLULAR AND MOLECULAR ARCHITECTURE OF TENDON AND 

LIGAMENT 

Andrea Wagner, Paracelsus Medical Universtiy Salzburg, Tendon and Bone Regeneration, Salzburg, 

Austria 

Renate Gehwolf, Paracelsus Medical Universtiy Salzburg, Tendon and Bone Regeneration, Salzburg, 

Austria 

Corinna Hirzinger, Universtiy Hospital Salzburg, Traumatology and Sports Injuries, Salzbug, Austria 

Milan Toljan, Sportmed Institute, Linz, Austria 

Herbert Resch , Universtiy Hospital Salzburg, Traumatology and Sports Injuries, Salzbug, Austria 

Hans-Cjristian Bauer, Paracelsus Medical Universtiy Salzburg, Salzburg, Austria 

Tendons and ligaments are both dense connective tissues which resemble each other in many aspects but exert 

different functions. While the cellular constituents of tendon tissue including tendon progenitor cells have been 

well characterized, less information for ligament cells or progenitor cells in ligaments is available. We explore similarities 

and differences between tendon and ligament cells at a molecular and biochemical level. Therefore we 

used biopsy tissue of semitendinosus tendon (ST) and anterior cruciate ligament (ACL) since ruptured ACL often 

is reconstructed by autologous ST grafts. 

The expression of progenitor cell markers (Nestin, CD133, Scleraxis) in ACL and ST was analysed by immunhistochemistry 

and quantitative RT-PCR. Our analyses revealed differences in the expression levels and expression patterns 

of these marker molecules. We also determined the expression of extracellular matrix components (Collagen 

type 1, Collagen type 3 and Aggrecan), matrix remodelling proteins (MMP-2, MMP-9, Lysyl oxidase) and Substance 

P, a neurotransmitter in pain perception. The mRNA expression of Collagen type 1 and type 3, MMP-2 and Lysyl 

oxidase was significantly higher in ACL than in ST. Substance P was only detectable in ACL, Scleraxis and Nestin 

showed no differences. The ratio of Collagen type 1 to type 3 mRNA was significantly higher in ACL. 

Our results may contribute to the understanding of tendon and ligament nature and origin, and will provide a clue 

towards new therapeutic ways in ligament regeneration or reconstruction. 

Supported: PMU-FFF E-09/09/051-BAH & ABT GmbH

INDEKS OF AUTHORS Abstract/Poster 

Alibegović A. 20 

Augat P. 28 

Bacakova L. 84, 87 

Balen S. 81 

Bauer H. 27, 28, 82, 90 

Bekić M. 45 

Beyzadeoglu T. 18 

Borsky M. 33 

Brkić Š. 83 

Bulić - Jakuš F. 78 

Cencic A. 31 

Cerovecki I. 88, 89 

Daraboš N. 31 

Dembic Z. 81 

Doral M.N. 19 

Douglas T. 84 

Drobnič M. 20 

Endres M. 41 

Essien Etokebe G. 81 

Evans C. 14, 37 

Ferreira E. 14 

Frank O. 87 

Friederich N. F. 42 

Gandhi R. 79 

Garkavenko Y. 80 

Gehwolf R. 27, 28, 82, 90 

Gopalakrishna Vasishta V. 22 

Gradisnik L. 31 

Grčević D. 40, 43 

Grubišić F. 40 

Hašpl M. 21, 31 

Heiland Kaarvatn M. 81 

Heu V. 28 

Himelreich M. 78 

Hirschmann M. T. 42 

Hirzinger C. 28, 90 

Hodžić F. 15 

Hribernik M. 20 

Hudetz D. 88, 89 

Ikić M. 40 

Ivčević S. 40 

Ivković A. 83, 88, 89 



Jajić Z. 40 

Jeleč Ž. 44 

Jelić M. 16 

Ježek D. 88, 89 

Jirka I. 87 

Josipović P. 83 

Jotanović Z. 81 

Jurić - Lekić G. 78 

Kapidzic T. 15 

Karlak I. 83 

Katušić A. 78 

Kelc R. 30, 31 

Kojić N. 45 

Kosović M. 88, 89 

Kostesic P. 88, 89 

Kovačić N. 40 

Lazić E. 40 

Lehner C. 27, 28, 82 

Leuzinger J. 33 

Lisa V. 84 

Liu F. 14 

Lojpur J. 45 

Lončarević J. 78 

Luxbacher T. 87 

Majić Ž. 78 

Margaritoni M. 45 

Marijanović I. 83 

Martin I. 12 

Martinović Kaliterna D. 39, 85 

Marušić A. 40 

Matičić D. 88, 89 

Matić I. 83 

Mihelić R. 81 

Mlakar R. 31 

Moser C. 31 

Mueller M. 14 

Mulac-Jeričević B. 81 

Mužić V. 78 

Novak S. 38 

Novotna K. 84 

Oršolić N. 44 

Parizek M. 83 

93

94 



Pavelić K. 24 

Pećina M. 83, 88, 89 

Pellegrino A. 33 

Petrović T. 88, 89 

Porter R. 14 

Pozdeev A. 80 

Pranić-Kragić A. 85 

Primorac D. 29 

Radić J. 85 

Radić M. 85 

Resch H. 90 

Salzmann G. 17 

Schinhan M. 14 

Schoen S. 42 

Sestan B. 81 

Shen Z. 14 

Sinčić N. 78 

Slak Rupnik M. 31 

Stary V. 87 

Stephan D. 28 

Stipić Marković A. 35 

Stoddart M. 26 

Strahonja B. 21 

Šabic E. 15 

Šabic N. 15, 86 

Šerman Lj. 78 

Tempfer T. 27, 28, 82 

Terzić A. 34 

Terzić K. 25 

Tijanić T. 81 

Tolde Z. 87 

Toljan M. 90 

Torun kose G. 13 

Trapecar M. 31 

Tršek D. 21, 31 

Vandrovcova M. 87 

Vlahović M. 78 

Vogrin M. 30, 31 

Vuk - Pavlović S. 23 

Vukasovic A. 88, 89 

Wagner A. 27, 28, 82, 90 

Windhager R. 14

Profilaksa DVT kod velikih ortopedskih operacija - Depol ...

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