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FINAL PROGRAM<br />
BOOK OF ABSTRACTS<br />
ORGANIZED BY<br />
Croatian Academy of Sciences and Arts - Department of Medical Sciences<br />
IN COOPERATION WITH<br />
University of Rijeka - Department of Biotechnology<br />
GUEST SOCIETIES<br />
Croatian Society for Rheumatology<br />
International Society for Applied Biological Sciences<br />
Croatian Society for Allergology and Clinical Immunology
Knee Preservation System <br />
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INTERFERENCE SCREW<br />
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LOAD-TO-FAILURE AFTER 500 CYCLES<br />
( N )<br />
1 Data on file. 1 Mehta, Vishal, et al. Cyclic Testing of 3 All-Inside Meniscal Repair Devices:<br />
A Biomechanical Analysis. The American Journal of Sports Medicine, 2009.<br />
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Hospitalija trgovina d.o.o.<br />
Vojvodici 25<br />
10431 Sv. Nedelja<br />
Telefon: +385 (0)1 3322-526<br />
E-Mail: mario.musa@htrg.hr<br />
www.hospitalija-trgovina.hr<br />
Linvatec Austria GmbH<br />
Eduard-Bodem-Gasse 5-7<br />
6020 Innsbruck<br />
Telefon: +43(0)512 34 24 35<br />
Fax: +43(0)512 34 24 35 20<br />
E-Mail: info@linvatec.at<br />
©2012 ConMed Linvatec All rights reserved. M2012284
CONTENTS<br />
20 - 22 September 2012, Opatija, Croatia<br />
Welcome to the 2 st International Conference on Regenerative Orthopedics and Tissue Engineering........................ 2<br />
Sponsors ........................................................................................................................................................................................................ 4<br />
Final Program ............................................................................................................................................................................................... 5<br />
General Information .................................................................................................................................................................................. 8<br />
Book of Abstracts ....................................................................................................................................................................................... 11<br />
Lecturers’ Resumes .................................................................................................................................................................................... 47<br />
Poster Presentations ................................................................................................................................................................................. 77<br />
Index of Authors ......................................................................................................................................................................................... 91<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Dear Colleagues and Friends,<br />
The Department of Medical Sciences of The Croatian Academy of Sciences and Arts in cooperation with the Department<br />
of Biotechnology University of Rijeka is proud to announce the 2nd edition of the “International Conference<br />
on Regenerative Orthopedics and Tissue Engineering”, to be held in Opatija, Croatia on September 20-22,<br />
2012.<br />
In line with the spirit of the successful first edition, that was held in July 2010, this Conference’s goal is to present<br />
the latest scientific and clinical innovations in the field of bone and cartilage regeneration, osteoporosis treatment<br />
and stem cell research and application. We also propose a new topic that aims to cover novel treatment options<br />
in rheumatology, including biological and gene therapy. Once more, the Conference will be a multidisciplinary<br />
program of research and practice, giving the opportunity to interact and share clinical and research experiences<br />
with colleagues from the orthopaedic and musculoskeletal community. Prominent domestic and international<br />
speakers will provide comprehensive, up-to-date, research-based answers to the most frequent questions that<br />
arise in this rapidly evolving field of medicine.<br />
We would like to strongly encourage you to submit your abstracts and to attend in order to share your achievements<br />
in the fields of musculoskeletal regeneration and tissue engineering.<br />
The Conference will take place in the unique city of Opatija that radiates with quiet elegance and sumptuous<br />
beauty. Here, where the Adriatic Sea softly kisses the shore and the romantic spirit pervades every corner, buildings<br />
that still evoke the beauty of the old aristocracy (who visited them lovingly) were erected. Even today, many<br />
years later, Opatija, like a beautiful lady, enjoys her riches and fullness of life.<br />
Once again, on behalf of your Croatian hosts, we welcome you with the conviction that our Conference will prove<br />
to be the place to revive old and form new friendships, and with the hope that you will find it stimulating, informative<br />
and a pleasure.<br />
Sincerely yours,<br />
Christopher H. Evans<br />
Marko Pećina<br />
Krešimir Pavelić<br />
Presidents of the Conference<br />
Alan Ivković<br />
General Secretary of the Conference
Organized by:<br />
Croatian Academy of Sciences and Arts<br />
Department of Medical Sciences<br />
In cooperation with:<br />
University of Rijeka<br />
The Department of Biotechnology<br />
Guest societies:<br />
Croatian Society for Rheumatology<br />
International Society for Applied Biological Sciences<br />
Croatian Society for Allergology and Clinical Immunology<br />
Organizing Committee<br />
Presidents<br />
Christopher H. Evans (USA)<br />
Marko Pećina (Croatia)<br />
Krešimir Pavelić (Croatia)<br />
Vice Presidents<br />
Miroslav Hašpl (Croatia)<br />
Ivan Martin (Switzerland)<br />
Secretary General<br />
Alan Ivković (Croatia)<br />
Members<br />
Đurđica Babić-Naglić (Croatia)<br />
Tamas Bardos (UK)<br />
Matej Drobnič (Slovenia)<br />
Simeon Grazio (Croatia)<br />
Damir Hudetz (Croatia)<br />
Mislav Jelić (Croatia)<br />
Dražen Matičić (Croatia)<br />
Ryan M. Porter (USA)<br />
Gian M. Salzmann (Germany)<br />
Martin Stoddart (Switzerland)<br />
Andre Terzic (USA)<br />
Gamze Torun Kose (Turkey)<br />
Matjaž Vogrin (Slovenia)<br />
Stanimir Vuk-Pavlović (USA)<br />
Slobodan Vukičević (Croatia)<br />
Local Organizing Committee<br />
Roberto Antolović<br />
Nikica Daraboš<br />
Miljenko Franić<br />
Željko Jeleč<br />
Petar Kostešić<br />
Inga Marijanović<br />
Radovan Mihelić<br />
Tomislav Vlahović<br />
Andreja Vukasović<br />
Topics:<br />
Cartilage Regeneration<br />
Bone Regeneration<br />
Osteoporosis<br />
Stem Cells<br />
Rheumatology<br />
20 - 22 September 2012, Opatija, Croatia<br />
Language:<br />
The official language of the Conference is English.<br />
Scientific Committee<br />
Full members of the Department of Medical Sciences<br />
of the Croatian Academy of Sciences and Arts<br />
Slavko Cvetnić<br />
Ivo Čikeš<br />
Dragan Dekaris<br />
Vida Demarin<br />
Vladimir Goldner<br />
Drago Ikić<br />
Ivica Kostović<br />
Zvonko Kusić<br />
Josip Madić<br />
Davor Miličić<br />
Marko Pećina<br />
Ivan Prpić<br />
Željko Reiner<br />
Daniel Rukavina<br />
Marko Šarić<br />
Zdenko Škrabalo<br />
Eugen Topolnik<br />
Teodor Wikerhauser<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Exhibitors and Sponsors<br />
Endorsed by:
CONFERENCE PROGRAMME: September 21 st and 22 nd 2012.<br />
Friday September 21 st<br />
09:00 - 09:20 Welcome Address<br />
09:00 - 09:05 Marko Pećina, President of the 2nd ICRO<br />
09:05 - 09:10 Pero Lučin, Dean Univesity of Rijeka<br />
09:10 - 09:15 Alan Ivković, Secretary General of the 2nd ICRO<br />
09:20 - 10:35 Bone Regeneration and Tissue Engineering<br />
Chairmen: Ivan Martin, Gamze Torun Kose, Alan Ivković<br />
20 - 22 September 2012, Opatija, Croatia<br />
09:20 - 09:35 “Evolution of Bone Tissue Engineering Strategies”<br />
Ivan Martin, Institute for Surgical Research and Hospital Management, University Hospital Basel, Switzerland<br />
09:35 - 09:50 “Use of Biodegradable Materials and Stem Cells in the Treatment of Bone Defects”<br />
Gamze Torun Köse, Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey<br />
09:50 - 10:00 “Fibrin-encapsulated, Genetically Modified Adipose-derived Stem Cells for Use in Bone Repair”<br />
Martina Shinhan, Medical University of Vienna, Austria<br />
10:00 - 10:10 “Non-nion Treatment with New Bone-regeneration Solving by FIXAs”<br />
Nedžad Šabić, Poliklinika dr. Šabić, Zenica, Bosnia and Herzegovina<br />
10:10 - 10:20 Discussion<br />
10:20 - 10:50 “Durolane Mini Symposium by Smith&Nephew: Single Injection Treatment for Osteoarthritis”<br />
Mislav Jelić, Dept. of Orthopaedic Surgery, Clinical Hospital Center Zagreb and School of Medicine University of Zagreb,<br />
Croatia<br />
10:50 - 11:05 Coffee Break<br />
11:05 - 12:50 Cartilage Repair and Regeneration<br />
Organized by Arthroscopy and Sports Traumatology Section Croatian Society for Sports Medicine<br />
Chairmen: Marko Pećina, Mahmut Nedim Doral, Mislav Jelić<br />
11:05 - 11:20 “Autologous Chondrocyte Transplantation Today and Tomorrow”<br />
Giann M. Salzman, Dept. of Orthopaedic and Trauma Surgery, University Medical Center, Albert-Ludwigs University,<br />
Freiburg, Germany<br />
11:20 - 11:35 “Characterized Chondrocyte Implantation Versus Microfracture for Symptomatic Cartilage Defects<br />
of the Knee”<br />
Mislav Jelić, Dept. of Orthopaedic Surgery, Clinical Hospital Center Zagreb and School of Medicine University of Zagreb,<br />
Croatia<br />
11:35 - 11:50 “Biological vs. Non-Biological Joint Reconstruction”<br />
Tahsin Beyzadeoglu, Dept. of Orthopaedic Surgery, Yeditepe University Hospital, Istanbul, Turkey<br />
11:50 - 12:05 “The Biological Tropism Between Synovial and Chondral Tissues”<br />
Mahmut Nedim Doral, Hacettepe University, Faculty of Medicine, Department of Orthopaedics and Traumatology, Ankara,<br />
Turkey<br />
12:05 - 12:20 “Cadaveric Models for Cartilage Repair Studies”<br />
Matej Drobnič, Department of Orthopedic Surgery, Medical School University of Ljubljana, Slovenia<br />
12:20 - 12:30 “Incidence of Cartilage Lesions During Knee Arthroscopy”<br />
Miroslav Hašpl, Denis Tršek, Nenad Medančić, Special Hospital for Orthopaedic Surgery and Traumatology Akromion,<br />
Krapinske toplice, Croatia<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
12:30 - 12:40 “Sequentially Programmed Magnetic Field (SPMF) Therapy, an Effective Treatment for Knee Osteoarthritis”<br />
Vishwanath Gopalakrishna Vasishta, SBF Healthcare and Research Centre Pvt Ltd, Bangalore, India<br />
12:40 - 12:50 Discussion<br />
12:50 - 13:50 Lunch<br />
13:50 - 15:20 Stem Cells in Regenerative Medicine and Tissue Engineering<br />
Chairmen: Andre Terzic, Krešimir Pavelić, Stanimir Vuk-Pavlović<br />
13:50 - 14:05 “Stem Cells for the Curious”<br />
Stanimir Vuk-Pavlović, Stem Cell Laboratory, Mayo Clinic, Rochester, USA<br />
14:05 - 14:20 “Human Stem Cell Research and Regenerative Medicine – A European Perspective on Scientific,<br />
Ethical and Legal Issues”<br />
Krešimir Pavelić, Department of Biotechnology, University of Rijeka, Croatia<br />
14:20 - 14:35 “Stem Cells and Prediction of Phenotype Through Transcriptome Deconvolution”<br />
Carmen M. Terzic, Department Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, USA<br />
14:35 -14:50 “Mechanoregulation of Stem Cell Fate”<br />
Martin Stoddart, Musculoskeletal Regeneration Program, AO Research Institute Davos, Switzerland<br />
14:50 - 15:00 “Human Tendon Perivascular Cells Are Multipotent and Express Embryonic Stem Cell Associated<br />
Markers”<br />
Herbert Tempfer, Paracelsus Medical University, Salzburg, Austria<br />
15:00 - 15:10 “Tendon Stem/Progenitor Cells: Nutrition Matters!”<br />
Christine Lehner, University Hospital Salzburg, Austria<br />
15:10 - 15:20 Discussion<br />
15:20 - 16:00 Mini Symposium by Linvatec: “Sequent - Meniscal Repair with an All-Inside and Stay Inside System”<br />
Patrick Weninger, The Knee Institute,Vienna, Austria<br />
16:00 - 16:15 Coffee Break<br />
16:15 – 16:30 Spotlight Lecture: „Current Concepts in Osteogenesis Imperfecta“<br />
Dragan Primorac, University of Split, Split, University of Osijek, Osijek, Croatia, The Pennsylvania State University, USA,<br />
University of New Haven, USA<br />
16:30 - 17:25 Platelet-rich Plasma in Orthopedics and Sports Medicine<br />
Chairmen: Miroslav Hašpl, Matjaž Vogrin, Damir Hudetz<br />
16:30 - 16:45 “The Role of Platelet Rich Plasma in Sports Medicine”<br />
Matjaž Vogrin, Department of Orthopaedic Surgery, University Clinical Center Maribor, Slovenia<br />
16:45 - 16:55 “Double Bundle Technique Combined with a Biologic Regenerative Treatment Give the Best Result<br />
of ACL Surgery”<br />
Nikica Daraboš, Department of Traumatology, Clinical Hospital Center “Sestre milosrdnice”, Zagreb, Croatia<br />
16:55 - 17:05 “Platelet-rich Plasma Derived Growth Factors and TGF-β Antagonists Promote Muscle Regeneration<br />
in Vitro”<br />
Robi Kelc, Department of Anatomy, Faculty of Medicine Maribor, Slovenia<br />
17:05 - 17:15 “Significant Pain Reduction in Osteoarthritis of the Knee by ACP Administration”<br />
Michael Borsky, Etzelclinic, Pfaffikon, Switzerland
17:15 - 17:25 Discussion<br />
20:00 Social Dinner<br />
Saturday September 22 nd<br />
9:00 - 9:30 Spotlight Lecture: Regenerative Medicine - Transforming healthcare solutions<br />
Andre Terzic, Dept. of Regenerative Medicine, Mayo Clinic, Rochester, USA<br />
9:30 - 13:00 Emerging New Biological Therapies for Rheumatoid Arthritis<br />
Chairmen: Christopher H. Evans , Asja Stipić Marković, Srđan Novak<br />
9:30 - 9:45 “Update on the Pathogenesis and Treatment of Rheumatoid Arthritis”<br />
Asja Stipić Marković, Dept. of Internal Medicine, University Hospital Sveti Duh, Zagreb, Croatia<br />
20 - 22 September 2012, Opatija, Croatia<br />
9:45 - 10:30 “Gene Therapy for Rheumatoid Arthritis”<br />
Christopher H. Evans, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical<br />
School, Boston, MA<br />
10:30 - 10:45 Coffee Break<br />
10:45 - 11:00 “Biological Agents in Rheumatoid Arthritis”<br />
Srđan Novak, Dept. of Iternal Medicine, Clinical Hospital Center Rijeka, Croatia<br />
11:00 - 11:15 “The Future of Rheumatoid Arthtritis Treatment - Combining Pharmacology and Surgery”<br />
Duška Kaliterna, Dept. of Iternal Medicine, Clinical Hospital Center Split, Croatia<br />
11:15 - 11:25 “Enhanced Osteoclastogenesis in Arthritis is Paralleled with the Increased Expression of Proinflammatory<br />
Mediators CCL2, IL-17 and IL-18”<br />
Marina Ikić, Dept. of Internal Medicine, University Hospital Sveti Duh, Zagreb, Croatia<br />
11:25 - 12:00 Mini Symposium by BioTissue AG: “Cell-based and Cell-free Joint Implants for Cartilage Repair”<br />
Michaela Endres, TransTissue Technologies GmbH - RD Department of BioTissue AG., Berlin, Germany<br />
12:00 – 12:15 Spotlight Lecture: “SPECT/CT a Novel Diagnostic Tool for Evaluation of Loading Pattern of the Knee”<br />
Michael T. Hirschmann, Department of Orthopedics and Traumatology, Kantonspittal Bruderholz, Basel, Switzerland<br />
12:15 - 13:05 Emerging Concepts in Osteoporosis Treatment<br />
Chairmen: Danka Grčević, Željko Jeleč<br />
12:15 - 12:30 “Osteoporosis: Common Feature Underlined by Different Pathogenetic Mechanisms”<br />
Danka Grčević, Dept. of Physiology and Immunology, School of Medicine, University of Zagreb<br />
12.30 - 12:45 “Effect of Quercetin on Osteoporosis Caused by Retinoic Acid in Rats”<br />
Željko Jeleč, Department of Orthopaedic Surgery, General Hospital Sisak, Croatia<br />
12:45 – 12:55 “The Treatment of the Proximal Femoral Fractures in County Hospital Dubrovnik in a Period April<br />
2011 - April 2012”<br />
Marijo Bekić, County Hospital Dubrovnik, Croatia<br />
12:55 - 13:05 Discussion<br />
13:05 End of the Conference<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Conference venue:<br />
Grand hotel Adriatic, Opatija - Croatia<br />
Registration Fee<br />
Early registration fee Late registration fee<br />
(before June 5st 2012) (after June 5st 2012)<br />
Participants 1.250 HRK/ 175 EUR 1.400 HRK/ 195 EUR<br />
Residents* 650 HRK/ 90 EUR 750 HRK/ 105 EUR<br />
Sponsors 750 HRK/105 EUR 750 HRK/105 EUR<br />
Undergraduate students 350 HRK/ 50 EUR 350 HRK/50 EUR<br />
Accompanying persons 750 HRK/105 EUR 750 HRK/105 EUR<br />
*PhD students and Post Doc students are welcome to register for subsidized registration fee.<br />
Registration fee covers:<br />
Admission to all lectures and access to the exhibition area<br />
Conference bag with conference materials<br />
Admission to the Welcome Drink on Thursday Sep 20 st<br />
Coffee Breaks, Lunch on Friday, Sept. 21 st and Social Dinner on Friday Sep 21 st<br />
Certificate of Attendance<br />
REGISTRATION DESK<br />
From Thursday 20 th September from 15:00 till Saturday 22 nd September 14:00<br />
SPEAKER PREVIEW ROOM<br />
The Speaker Preview Room, located close to the entrance of the conference room in hotel Adriatic, will bi open<br />
from Thursday 20 th September from 15:00 till Saturday 22 nd September till 14:00<br />
Presenters are asked to check their MS Power Point presentations to the Speaker Preview Room at least two<br />
hours before the session. Posters will be presented at the exhibition area.<br />
LANGUAGE<br />
The official language of the meeting is English.<br />
About Croatia<br />
Despite the hype, Croatia’s pleasures are more timeless than trendy. Along its 1778 km coastline, a glistening sea<br />
winds around rocky coves, lapping at pine-fringed beaches. Istrian ports bustle with f ishermen while children<br />
dive into the sparkling water. In Dalmatia, cities throb with nightlife amid ancient Roman ruins. Yachts glide up the<br />
coast, movie stars discreetly arrange to buy one of Croatia’s 1185 islands and no Mediterranean cruise is complete<br />
without a stop in Dubrovnik. The interior landscape is as beguiling, even though less visited. Soak in a thermal<br />
spa at Istarske Toplice in Istria. Hike through pristine forests watered by mountain streams in the west. Let the<br />
waterfalls of Plitvice moisten your face. And then there’s the culture. The country that endured Roman, Venetian,<br />
Italian and Austro-Hungarian rule has a unique and slightly schizoid identity. You’ll find a strong central European<br />
flavour in the baroque architecture of Zagreb, and Italian devotion to the good life percolates up from the coast,<br />
permeating Croatian food and style. During holidays and festivals the country’s Slavic soul emerges, as colourfully<br />
costumed dancers whirl about to traditional folk melodies.
20 - 22 September 2012, Opatija, Croatia<br />
About Opatija<br />
Opatija, often called the pearl of the Adriatic, is one of Croatia’s most famous destinations, boasting a tradition of<br />
welcoming visitors dating back more than 160 years. Located at the edge of the Mediterranean, on the slopes of<br />
Mount Učka gently descending towards the coast of Kvarner Bay, Opatija with its local climate, beautiful architecture,<br />
quality hotels and luxurious, well-tended parks and promenades, offers plenty of possibilities for a pleasant<br />
stay throughout the year. The notable person who first discovered the magic of Opatija was Iginio Scarpa, a merchant<br />
from Rijeka who built his holiday home here in 1844 and named it the Villa Angiolina after his late wife. This<br />
event marked the beginning of tourism in Opatija.<br />
After that, Opatija started intensely developing under the supervision of the Austro-Hungarian Empire. Director<br />
of the Austrian Southern Railway Company Friedrich Schüler and its shareholders wanted to improve passenger<br />
traffic to the south. After choosing Opatija as the region’s most promising destination, they started building the<br />
first hotel in this new bathing and climatic health resort, advertising it widely as the “Austrian Nice”.<br />
Several important facilities were built alongside the first hotel: a pavilion with indoor pool for warm sea baths, a<br />
bathing place with separate areas for ladies and gentlemen, and the 12-kilometre-long coastal promenade from<br />
Volosko to Opatija and further to Lovran. The hotel was opened on the 27th March 1884. Its original name was<br />
Hotel Quarnero, and it offered its visitors 60 rooms.<br />
The second hotel that was built in Opatija after the Quarnero was the Hotel Kronprinzessin Stephanie. In 1885,<br />
the Austrian Southern Railway Company organised the first congress of balneologists in Opatija, during which<br />
the decision was made to declare Opatija a climatic health resort, which was officially done in 1889. Some of the<br />
Monarchy’s most eminent physicians opened their sanatoriums in Opatija; numerous promenades and bathing<br />
places were being built. This all turned Opatija into one of Europe’s most important health resorts of the 19th and<br />
the first half of the 20th century, alongside Nice, Karlovy Vary, Cannes and Biarritz. Kings and emperors, writers,<br />
philosophers, poets and composers used to stay here – let us mention some of them: the emperors Franz Joseph<br />
and William II, the queen of Romania Elisabeth who used to publish poems under the pseudonym of Carmen Sylva,<br />
then the empress Sissi, the writers A. P. Chekhov and James Joyce, the ballet dancer Isadora Duncan, and the<br />
composers Gustav Mahler and Giacomo Puccini. To see and be seen – this was the motto for those who came to<br />
Opatija.<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS
BOOK OF<br />
ABSTRACTS<br />
20 - 22 September 2012, Opatija, Croatia<br />
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14<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
EVOLUTION OF BONE TISSUE ENGINEERING STRATEGIES<br />
Ivan Martin, University Hospital Basel, Switzerland<br />
Despite the large clinical needs in bone regeneration and the advances in scaffold production and regulation<br />
of osteoprogenitor cell function, the adoption of cell-based bone graft substitutes in the clinical practice is yet<br />
limited. Indeed no study has yet convincingly demonstrated reproducible clinical performance of tissue engineered<br />
bone graft substitutes and at least equivalent cost-effectiveness as compared to the current treatment<br />
standards. This lecture will describe and discuss three alternative approaches currently pursued by the author’s<br />
team to evolve classical tissue engineering paradigms towards possibly more effective products. The perspective<br />
will address issues related to quality standardization, process control and regulatory compliance in manufacturing<br />
cell-based products and highlight the need not only to automate, but also to streamline and simplify typical production<br />
processes. An alternative strategy based on the intraoperative use of autologous fat-derived cells will be<br />
presented and critically discussed. Finally, as a next generation paradigm, the lecture will propose and exemplify<br />
the concept of engineering regenerative strategies following principles of developmental biology, using the own<br />
body as the in vivo bioreactor.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
USE OF BIODEGRADABLE MATERIALS AND STEM CELLS IN THE<br />
TREATMENT OF BONE DEFECTS<br />
Gamze Torun Kose, Yeditepe University, Faculty of Engineering and Architecture, Department of Genetics<br />
and Bioengineering, Istanbul, Turkey, BIOMATEN, METU Center of Excellence in Biomaterials and Tissue<br />
Engineering, Ankara, Turkey<br />
There are a large number of people suffering from an organ or tissue loss due to injury, infection, or disease. Currently,<br />
major approaches to solve this problem are surgical reconstruction, transplantation or use of prosthesis.<br />
Although these therapies have saved and improved countless lives, they remain imperfect solutions due to occurrence<br />
of infection, chronic irritation, donor shortages, tissue rejection, and longer term complications such as<br />
development of malignant tumor.<br />
Tissue engineering, the development of cell seeded 3D biomaterials for introduction to the defect area is the current<br />
solution for all of the problems mentioned above.<br />
Cell Guidance is a branch of tissue engineering that offers controlled tissue regeneration and allows the repair<br />
of the tissue by mimicking its natural organization to achieve better and faster integration with the native tissue.<br />
Guidance is important especially for constructs for nerve and bone tissues because of their significant levels of<br />
organization and anisotropy.<br />
In one of the study conducted by our research group BIOMATEN on bone tissue engineering, the aim was to<br />
achieve improved attachment and uniform distribution of rat mesenchymal stem cell-derived osteoblasts by introducing<br />
chemical and topographical cues on biopolyester film surfaces. Various patterns such as microgrooves<br />
and micropits were introduced on the film surface by employing micropatterned silicon wafers. Results proved<br />
that microtopographies could improve osseointegration especially when combined with chemical cues, and that<br />
microgrooves and cell adhesive protein lines guided osteoblast adhesion on selective regions and improved alignment.<br />
Oral<br />
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16<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
FIBRIN-ENCAPSULATED, GENETICALLY MODIFIED ADIPOSE-<br />
DERIVED STEM CELLS FOR USE IN BONE REPAIR<br />
Martina Schinhan, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center,<br />
Harvard Medical School, Boston, MA, 2Department of Orthopaedic Surgery, Vienna General Hospital,<br />
Medical University of Vienna, Vienna, Austria<br />
Marc Mueller, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard<br />
Medical School, Boston, MA, Departments of Surgery and of Biomedicine, University Hospital Basel,<br />
Basel, Switzerland<br />
Fangjun Liu, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard<br />
Medical School, Boston, United States<br />
Zhenxin Shen, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard<br />
Medical School, Boston, United States<br />
Ryan Porter, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard<br />
Medical School, Boston, United States<br />
Reinhard Windhager, 2Department of Orthopaedic Surgery, Vienna General Hospital, Medical University<br />
of Vienna, Vienna, Austria<br />
Christopher Evans, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center,<br />
Harvard Medical School, Boston, United States<br />
Elizabete Ferreira, 1Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center,<br />
Harvard Medical School, Boston, United States<br />
Transplantation of stem cells engineered to express Bone Morphogenetic Protein-2 (BMP-2) remains an attractive<br />
approach for bone repair as it provides both BMP and osteoprogenitors. Adipose-derived stem cells (ADSCs) are<br />
of particular interest as they are obtained with lower donor-site morbidity and at greater yields than osteoprogenitors<br />
derived from bone marrow. This study aimed to develop an expedited method, using gene transfer, for<br />
preparing ADSC-loaded fibrin gels to serve as cell and BMP-2 delivery systems.<br />
hADSC suspensions were mixed with recombinant adenovirus carrying hBMP-2 or GFP cDNA. Transduction was<br />
carried out using a centrifugation method (2000g for 15min). The supernatant was removed and the cell pellets<br />
resuspended in media. Subsequently, transduced cells were transferred to fibrinogen solution which then polymerized<br />
into a fibrin gel encapsulating the cells. Cell viability and transgene expression were evaluated over a<br />
3-week study.<br />
Our centrifugation method resulted in at least 70% transduction efficiency. Cell viability and GFP expression within<br />
the scaffolds was maintained for at least 3 weeks. Ad.BMP-2 transduced cells produced ~170 ng BMP-2/24h/106<br />
cells at day 8, after which BMP-2 secretion progressively decreased to basal levels.<br />
These data suggested that ADSCs can be expeditiously engineered and encapsulated in fibrin gels to deliver high<br />
quantities of BMP-2. In vivo studies are underway to evaluate the potential of this system for healing rat segmental<br />
defects.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
NON UNION TREATMENT WITH NEW BONE REGENRATION-<br />
SOLVING BY FixAS<br />
Šabić Nedžad, Poliklinika Dr Šabić, Zenica, Bosnia and Herzegovina<br />
Tarik Kapidžić, Cantonal Hospital, Bosnia and Herzegovina<br />
Enver Šabić, Poliklinika Sunce, Bosnia and Herzegovina<br />
Faruk Hodžić, Cantonal Hospital, Bosnia and Herzegovina<br />
Intraduction:Getting the new-quality bone by distraction of pineal body (epiphysis-growth plate, Ring 1958,<br />
Zivyalov and Plaskin 1968, Ilizarov 1969, Monticelli and Spineli 1981) as well as by distraction calus after corticotomy<br />
and metaphysary lenghtening (Ilizarov 1971, 1988, 1989, Alberty 1990, Terjesen 1984, 1988, Adolphson 1990),<br />
has enabled treatment of larger bone defects without autografted cancellous bone with regenerate which is appropriate<br />
with its width and density. This has been, certainly, made easier with tehnical improvements of fixators<br />
and dynamic possibilities of structures with area, flexible and extrafocal stability. Methods: When solving infected<br />
non-union with bone defects, beside regaining bone continuity and length there is a problem of infection, which<br />
is the heaviest complication in bone-joint surgery..This work presents possibilities of compression – distraction<br />
method by Fix-AS.<br />
1 st GROUP: fixation with shortening of extremities and achieving the length after cover the soft tissue defect.<br />
2 nd GROUP: fixation of the non union with the full length of the extremity and levelling with the nearby joint areas<br />
and treatment of the defect, either by int. or exter. transport<br />
Results: Followed by ways at solving contractures, deformations achieving full length of extremity with simultaneous<br />
infection sanation and non-union consolidation in natural ways. For the last 25 years we*ve successfully<br />
treated 435 non-union, of which 241 infected ones, 185 with bone defect, 51 over 5 cm , which is especially<br />
emphasized in this work. This work analyses and presents infection – defect non-union, after war injuries and<br />
failed treatment by others methods. Conclusion: This way, extremity is saved even in heaviest cases, unlike other<br />
methods (bone grafting, free flap), which were more expensive and unformal, often ended by an amputation.<br />
Oral<br />
17
18<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
CHARACTERIZED CHONDROCYTES IMPLANTATION COMPARED<br />
TO THE MICROFRACTURE IN TREATMENT OF A CHONDRAL<br />
LESION OF THE KNEE: 5 YEAR RESULTS OF A CONTROLLED<br />
RANDOMIZED TRIAL<br />
Mislav Jelić and TIG/ACT/01/2000&EXT Study Group, Department of Orthopaedic Surgery, Clinical<br />
Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia<br />
Characterized chondrocytes are an expanded population of cartilage cells that express a marker profile predictive<br />
for the formation of ectopic hyaline-like cartilage in vivo in a consistent and reproducible manner. A controlled<br />
and consistent manufacturing process was developed to maintain this phenotype stability. Characterized viable<br />
autologous cartilage cells expanded ex vivo expressing specific marker proteins were introduced in clinical practice<br />
in 2004.<br />
A prospective randomized multicenter controlled trial compared characterized chondrocyte implantation (CCI) to<br />
microfracture in the treatment of symptomatic cartilage defects of the femoral condyles. The primary endpoint<br />
was successfully reached at one year, with CCI showing superior tissue regeneration. Clinical outcome at 12 to 18<br />
months measured by the overall Knee injury and Osteoarthritis Outcome Score (KOOS) was comparable for both<br />
treatments. An extension at 3 and 5 years confirmed that a good clinical outcome was maintained over time for<br />
both treatments in the overall patient population. Strikingly, sub analysis of the long-term follow-up data revealed<br />
that early treatment by CCI resulted in statistically significant and most importantly clinically relevant better results<br />
when compared to microfracture, supporting a critical window of opportunity for genuine tissue regeneration.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
AUTOLOGOUS CHONDROCYTE TRANSPLANTATION TODAY<br />
AND TOMORROW<br />
Gian Salzmann, Department of Orthopaedic and Trauma Surgery, University Medical Center, Albert-<br />
Ludwigs University Freiburg, Germany<br />
Following the 1994 pioneer work by Brittberg and colleagues autologous chondrocyte implantation has evolved<br />
significantly until today. The traditional periosteum-covered technique has retrospectively been termed first generation<br />
ACI-P. In order to reduce operating time and as well to avoid graft hypertrophy the second generation<br />
ACI-C has been introduced by replacing the periost by an artificial membrane such as collagen. While the cells are<br />
applied beneath a cover when performing first or second generation ACI, third generation ACI is matrix-assisted<br />
(m-ACI). The chondrocytes are cultured within the matrix for a certain time prior to transplantation. The idea was<br />
to give better primary stability, handling and probably partial cellular redifferentiation. As further alternatives<br />
there are ACI-Cs, where the cells are seeded within the matrix intraoperatively and consecutevily implanted to<br />
have high vitality and mitotic activity. Also bioreactor-assembled implant-ready cartilage products are on the<br />
threshold to clinical implementation, which are sought to present with an already assembled extracellular matrix<br />
at time of implantation. Furthermore one-step cartilage repair techniques are on the rise in order to reduce the<br />
traditional 2-step into a 1-step procedure.<br />
Concerning outcome data, it is now becoming increasingly apparent that ACI gives better tissue quality when<br />
compared to the concurring methods foremost in the long-term and is much better suited for larger cartilage defects.<br />
Literary information on the younger techniques is sparse and one has to await longer-term follow-up among<br />
large patient cohorts to give out treatment suggestions.<br />
Oral<br />
19
20<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
BIOLOGICAL vs. NON-BIOLOGICAL JOINT RECONSTRUCTION<br />
Tahsin Beyzadeoglu, Yeditepe University, School of Medicine, Istanbul - TURKEY, Turkey<br />
Cartilage lesions of the knee joint if left untreated is likely to develop osteoarthrosis. While there are many biological<br />
treatment options in younger patients, focal degenerative cartilage lesions of moderate-to-advanced age are<br />
more difficult to treat due to the low success chance of biological methods. Cartilage lesion size, depth, quality of<br />
the subchondral bone, patient’s age are some of the main determinants for prognosis. The success of biological<br />
procedures depends on the quality of subchondral bone. Total arthroplasty is often considered as the last treatment<br />
option and limited resurfacing arthroplasty is increasingly becoming popular as a new treatment option<br />
with the biggest advantage of preserving the subchondral bone.<br />
In medial gonarthrosis accompanied with varus alignment, resurfacing can be done with simultaneous high tibial<br />
osteotomy. Correct alignment can slow the development of arthritis, however, at the presence of patellofemoral<br />
lesions, progression of patellofemoral arthrosis can be seen. At these patients, resufacing of the patellofemoral<br />
joint can relief the symptoms. Limited resurfacing fills the gap between biological methods and total knee arthroplasty.<br />
The presence of inflammatory arthritis, body mass index over 35, instability and malignment over 7<br />
degrees, limited resurfacing is relatively contraindicated and simultanous assistive surgeries like ligament reconstruction<br />
or HTO have to be considered. High demand patients with moderate-to-advanced age, yet relatively<br />
preserved joint width, and cannot be treated with existing biological methods are good candidates for limited<br />
surfacing arthroplasty. However, the implant as well as a new one needs long-term clinical follow-up studies.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
THE BIOLOGICAL TROPISM BETWEEN SYNOVIAL AND<br />
CHONDRAL TISSUES<br />
Mahmut Nedim Doral, Hacettepe University Dept. of Orthopaedics & Traumatology, Dept. of Sports<br />
Medicine, Ankara, Turkey<br />
The importance of articular cartilage lesions was first described by William Hunter in 1743. Ever since, the efforts<br />
to repair the damaged joint cartilage have been accelerating intensively through basic and clinical investigations.<br />
Arthroscopic debridement with or without intra-articular injections, perichondrial or periosteal covering, abrasion<br />
arthroplasty, microfracture, transplantation of chondrocytes, meniscal allografts, osteochondral allografts/<br />
otografts, autologous chondrocyte transplantation, tissue engineering and gene therapies are some methods to<br />
treat cartilage lesions. However, any treatment modality has enabled full restoration of the injured articular cartilage<br />
to its original phenotype yet.<br />
In recent years, mesenchymal stem cells (MSCs) have been recommended as a cell therapy to regenerate chondrocytes.<br />
MSCs are known to be present in the bone marrow and other tissues such as skeletal muscle, tendon, fatty<br />
tissue, neural tissue, hepatic tissue, periosteum and synovium. Morphological and functional characteristics of<br />
the chondral tissue formed from MSCs that are originated from various tissue types show some differences. MSCs<br />
derived from the synovium have been shown to be highly potential for chondrogenesis that presents them as an<br />
attractive source for the treatment of the damaged cartilage tissue. Intra-articular loose bodies are described as<br />
cartilaginous, osseous or osteochondral fragments located within the joint cavity and are known to be produced<br />
by the synovium. Free or pediculated ‘‘chondroosteophytes’’ that are frequently seen in arthroscopic observations<br />
and their close biological relationship with the synovial tissue formed the basis of our study, in which the hypothesis<br />
was that ‘‘the synovial tissue might have a pivotal role in the formation and growth of intra-articular<br />
chondro-osteophytes and might exert similar growth effects on transplanted cartilaginous tissue grafts’’. So we<br />
aimed to assess the applicability of the use of synovium as an in vivo chondrocyte culture medium and to evaluate<br />
the effects of the synovial tissue on chondrocyte growth in a rabbit model study. We tried to determine the<br />
effects of synovium on cartilage proliferation as “in-vivo” culture medium and to anticipate a new, biological and<br />
cheap treatment method for the articular cartilage pathologies. In our study, 12 New Zealand rabbits were used<br />
and standardized cartilage samples were taken from both knees. Two groups were formed: In group I (synovium<br />
group), the cartilage samples were placed into the synovial tissue on the supracondylar groove, and in group II (intraarticular<br />
group), behind the patellar tendon. After 4 months, we sized and analyzed samples histologically with<br />
the camera lucida method to count the chondrocyte numbers (Mann-Whitney U-Test and regression analysis).<br />
The chondrocyte numbers in the osteochondral samples were found to be higher than chondral samples (p
22<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
HUMAN CADAVERIC MODELS FOR CARTILAGE REPAIR STUDIES<br />
Matej Drobnic, Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Slovenia<br />
Armin Alibegovic, Institute of Forensic Medicine, Medical Faculty, University of Ljubljana, Slovenia<br />
Marjana Hribernik, Institute of Anatomy, Medical Faculty, University of Ljubljana, Slovenia<br />
The research in the field of cartilage repair has been growing increasingly for the last two decade. The preclinical<br />
studies require an appropriate model to simulate the intra-articular milieu to which the graft or the repair tissue<br />
will be exposed in the clinical application. Cell cultures and experimental animals are most commonly used, but<br />
they are unable to stimulate the conditions in human joints entirely. Human cadaveric cartilage, which can be<br />
used as fresh or preserved, represents an additional spectrum of preclinical testings. Fresh cadaveric chondral<br />
samples provide a high number of viable chondrocytes as they are protected from the autolysis in the abundant<br />
chondral matrix. The duration of viability of such samples is long enough to study the impact of external physical<br />
or chemical stimuli and also to isolate viable chondrocytes for the research of cell cultures. The preserved, non-viable<br />
human material can be applied in the studies of biomechanics and surgical techniques. However, ethical<br />
approval has to be granted before any research on human cadaveric material is to be performed.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
PREVALENCEOF THE CHONDRAL DEFECTS: A RETROSPECTIVE<br />
STUDY OF 1000 KNEE ARTHROSCOPIES<br />
Miroslav Hašpl, Special Hospital for Orthopaedic Surgery AKROMION, Krap inske Toplice, Croatia<br />
Denis Tršek, Special Hospital for Orthopaedic Surgery AKROMION, Krap inske Toplice, Croatia<br />
Borna Strahonja, Special Hospital for Orthopaedic Surgery AKROMION, Krap inske Toplice, Croatia<br />
PURPOSE: To determine the prevalence of chondral defects during knee arthroscopy.<br />
METHODS: We performed retrospective analysis of cartilage lesions in 1000 knee joints treated at our institution<br />
during 2010 and 2011 year.In all cases was performed arthroscopy for various indications. Age of our patients was<br />
44 (13-80) years. Males 629 (62.9%) and females 371 (37.1%). Chondral lesions are analyzed by location and classification<br />
according to ICRS (International Cartilage Repair Society).<br />
RESULTS: One or more chondral lesions had 679 (67.9%) knees. Chondral lesions were most often associated with<br />
other disease and were not primary indication for arthroscopy. Rupture of the medial meniscus we found at 645<br />
knees, lateral meniscusat 260, anterior cruciate ligament rupture at 286, parapatellarplicasyndroms in 58, patellofemoral<br />
instability in 26 patients, different etiology of synovitis at 33, stiff knee at 24, and of patellar enthesitis<br />
(jumpre’s knee) at 10 and other diseases and injuries at 24 knees (intrarticular tumors, intraarticular fractures,<br />
osteochondriotisdissecans etc.)<br />
Chondral patellar lesions were found in 436 knees (9.4% I; 25.7% II; 6.6% III; 1.9% IV degree ), at trochlear femoral<br />
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;<br />
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<br />
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%<br />
II;2.1% II; 1.9% IV degree).<br />
In 498 (49.8%) knees underwent one or more surgical procedures on chondral lesions at one or more locations.<br />
Chondral debridemente was done on 437 (43.7.0%) knees, microfracture in 151 (15.1%) knees, mozaikplasty on 4<br />
(0.4%) and on 9 (0.9%) knees intraarticular osteosynthesis for osteochondral lesions.<br />
CONCLUSION: The present study shows that cartilage lesion is the most common finding during knee arthroscopy.<br />
Mostcartilagedamagewas found on medialcondyleof the femurandthepatella. Fourth degree of damageismost<br />
commonon themedialfemoralcondyle. In many cases surgery is required in such a damaged cartilage, especially<br />
the fourth grade.<br />
Oral<br />
23
24<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
SEQUENTIALLY PROGRAMMED MAGNETIC FIELD<br />
(SPMF) THERAPY, AN EFFECTIVE TREATMENT FOR KNEE<br />
OSTEOARTHRITIS<br />
Vishwanath Gopalakrishna Vasishta, SBF Healthcare and Research Centre Pvt Ltd, India<br />
Background: Sequentially Programmed Magnetic Field (SPMF) therapy utilizes magnetic fields of specific strength<br />
and frequencies which are generated from Magnetic Field Generators (MFG) that can be focused on the affected<br />
tissues. These are non-thermal, non-ionizing and has no known side effects. The efficacy of SPMF therapy in knee<br />
osteoarthritis was first published in the Scientific Medicine Journal in 2009. The current study is to evaluate the<br />
long term efficacy of SPMF Therapy in knee Osteoarthritis.<br />
Methods: 300 patients were enrolled for this follow up study to evaluate the long term results of SPMF therapy after<br />
12months of the treatment. All the patients underwent SPMF for 21consecutive days and were evaluated with<br />
Total Knee Score (TKS), Total Functional Score (TFS) and MRI to measure Cartilage thickness pre treatment, Post<br />
treatment at 21days, 3months and 12months.<br />
Result: Statistical analysis demonstrated that an improvement in TFS scores from 39.64 (SD=21.53) pre-treatment<br />
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<br />
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<br />
21days, 3 months and 12months respectively. The cartilage thickness was 0.64mm (±0.02mm) at pre-treatment,<br />
which increased to 0.88mm (±0.07mm) at 3months and 1.24(±0.03mm).<br />
Conclusion: The results confirm significant improvement in the strength, stability and significant reduction of pain<br />
as shown in the TKS and TFS value. The result also shows significant regeneration of cartilage and progressive increase<br />
in the cartilage thickness in MRI, to show that SPMF being non invasive and without any side effect should<br />
be used as a first line of treatment for knee Osteoarthritis.<br />
Oral
STEM CELLS FOR THE CURIOUS<br />
Stanimir Vuk-Pavlović, College of Medicine, Mayo Clinic, Rochester, United States<br />
20 - 22 September 2012, Opatija, Croatia<br />
Recent evidence for induction of stem cell characteristics in somatic cells by epithelial–mesenchymal transition,<br />
by induced activation of a small number of transcription factors, or by modification of microenvironment has<br />
invalidated the once held notion of differentiation as a strictly unidirectional deterministic process. Together with<br />
the broad interest elicited by current clinical trials testing different cellular preparations dubbed “stem cells,” this<br />
necessitates reconsideration of the very definition of the stem cell. As a result, the focus has shifted from consideration<br />
of “stem cells” as a class of cells to “stemness” as a property that can be acquired, conferred and/or retained<br />
by cells. What is stemness that allows a cell (population) to divide, maintain the size of its pool and differentiatiate<br />
at the same time? How is it defined, induced, maintained? A recent view posits “stemness as a cell default state”<br />
(cf. Casanova, EMBO Reports, 13: 396, 2012). It is based on experimental evidence compatible with a deterministic<br />
model of stemness maintained as long as maintained is the intrinsic/inherent inhibition to differentiation. Another<br />
model invokes stochastic gene and protein expression that drives transitions among deterministic attractors<br />
characterizing stemness and the possible differentiation states (MacArthur et al., Nature Rev. Mol. Cell Biol. 10: 672,<br />
2012). As a further development, one can interrogate the factors that define all levels of cell differentiation (i.e.,<br />
attractors) as properties emergent within complex biological systems.<br />
Oral<br />
25
26<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
HUMAN STEM CELL RESEARCH AND REGENERATIVE MEDICINE<br />
- EUROPEAN PERSPECTIVES ON SCIENTIFIC, ETHICAL AND<br />
LEGAL ISSUESS<br />
Krešimir Pavelić, University of Rijeka, Department of Biotechnology, Rijeka, Croatia<br />
The concept of using stem cells for therapeutic purposes has much in common with the now conventional principle<br />
of organ transplantation. Today several applications of stem cell in therapies are recognized in humans: from<br />
bone marrow transplants through to more recent advances in skin and cornea repair. The cells used in these cases<br />
are adult stem cells. They exist in several adult tissues and they are usually rare. Primordial progenitor cells derived<br />
from the earliest stages of embryonic development are capable of producing all tissue types of the adult.<br />
Embryonic stem cells are very potent but difficult to control at the present time of knowledge. Research on both<br />
embryonic stem cells and adult stem cells is providing prospects of therapies for a variety of tissue-specific diseases,<br />
including major illnesses as type I diabetes, Parkinson’s disease as well as cancer. There are few obstacles in advancing<br />
stem cell research in Europe. Currently there is relatively little commercial support for, or industry engagement<br />
in, stem cell research and development in Europe. One of the major inhibitory factors is the European Patent<br />
Office’s interpretation of the morality clause in the European Biotechnology Directive (adopted into the European<br />
Patent Convention). European Patent Office is to exclude from patentability all inventions or claims relating to human<br />
embryonic stem cells. This position has its roots in rule 23d(c) of the European Patent Convention which stipulates<br />
that „European patents may not be granted in respect to biotechnological inventions which, in particular,<br />
concern uses of human embryos for industrial or commercial purposes according to current EPO interpretation,<br />
that excludes from patentability all claims to associated products necessitating the direct and unavoidable use<br />
of human embryo – including claims on cells derived from an embryo.” European stem cell research is concerned<br />
with the protection of intellectual property relating to the manipulation of established human embryonic stem<br />
cell research and differentiated derivatives. This situation renders the European biotechnology sector at a serious<br />
disadvantage compared with global competitors. The disparate national regulations governing stem cell research<br />
in Europe inhibit the field from benefiting from the internationality of approach inherent to scientific advance.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
STEM CELLS AND PREDICTION OF PHENOTYPE THROUGH<br />
TRANSCRIPTOME DECONVOLUTION<br />
Carmen Terzic, Mayo Clinic, Rochester, United States<br />
Genomic perturbations that challenge normal signaling at the pluripotent stage may trigger unforeseen ontogenic<br />
aberrancies. Anticipatory systems biology identification of transcriptome landscapes that underlie latent<br />
phenotypes would offer molecular diagnosis before the onset of symptoms. Bioinformatic surveillance of calreticulin-null<br />
stem cells, a monogenic insult model, diagnosed a disruption in transcriptome dynamics, which re-prioritized<br />
essential cellular functions. Calreticulin-calibrated signaling axes were uncovered, and network-wide cartography<br />
of undifferentiated stem cell transcripts suggested cardiac manifestations. Calreticulin-deficient stem<br />
cell-derived cardiac cells verified disorganized sarcomerogenesis, mitochondrial paucity, and cytoarchitectural<br />
aberrations to validate calreticulin-dependent network forecasts. Furthermore, magnetic resonance imaging and<br />
histopathology detected a ventricular septal defect, revealing organogenic manifestation of calreticulin deletion.<br />
Thus, bioinformatic deciphering of a primordial calreticulin-deficient transcriptome decoded at the pluripotent<br />
stem cell stage a reconfigured multifunctional molecular registry to anticipate predifferentiation susceptibility<br />
toward abnormal cardiophenotype.<br />
Oral<br />
27
28<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
MECHANOREGULATION OF STEM CELL FATE<br />
Martin Stoddart, AO Research Institute Davos, Davos, Switzerland<br />
Bone marrow derived mesenchymal stem cells (MSCs) offer great promise in the repair of defects of the musculoskeletal<br />
system. Classical tissue engineering incorporates a source of cells, a scaffold to retain them, and biochemical<br />
cues. Increasingly mechanical force is being shown to regulate the phenotypic fate decisions in these cells.<br />
Mechanical stimuli are of crucial importance for the development and maintenance of articular cartilage. While a<br />
number of studies have shown a beneficial effect of load for chondrogenesis of MSCs there is some controversy<br />
as other studies have indicated an inhibitory effect. For conditioning of cartilaginous tissues, various bioreactor<br />
systems have been developed that have mainly aimed to produce cartilaginous grafts for tissue engineering applications.<br />
Emphasis has been on in vitro preconditioning, whereas the same devices could be used to attempt<br />
to predict the response of the cells in vivo or as a prescreening method before animal studies. As a result of the<br />
complexity of the load and motion patterns within an articulating joint, no bioreactor can completely recreate the<br />
in vivo situation. Using a custom built loading device, it is possible to apply compression, shear or a combination<br />
of both stimuli onto fibrin/polyurethane composites in which human mesenchymal stem cells were embedded.<br />
To simplify the system, and more accurately mimic the in vivo situation it is possible to perform studies where no<br />
exogenous growth-factors are added to the culture medium. Thus any chondrogenic induction is purely as a result<br />
of the loading protocol applied. Recent data would suggest that under these conditions, shear is a critical component<br />
when inducing chondrogenesis in human mesenchymal stem cells by mechanical means. In agreement with<br />
other groups, uniaxial load in isolation does not appear sufficient to induce chondrogenic differentiation. This may<br />
play a role in natural healing within the musculoskeletal system, whereby the same cell type (MSCs) initiates bone<br />
repair (uniaxial load) and cartilage repair (multiaxial load) resulting from different mechanical cues.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
HUMAN TENDON PERIVASCULAR CELLS ARE MULTIPOTENT<br />
AND EXPRESS EMBRYONIC STEM CELL ASSOCIATED MARKERS<br />
Herbert Tempfer, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria<br />
Renate Gehwolf, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria<br />
Christine Lehner, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria<br />
Andrea Wagner, Paracelsus Medical University, University of Salzburg, Salzburg, Austria<br />
Hans-Christian Bauer, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria<br />
Tendon-derived stem cells are commonly considered to be of mesenchymal origin, having the capacity to differentiate<br />
into adipocytes, chondrocytes, osteoblasts and tendon cells. Earlier on we have shown that human tendon<br />
perivascular cells express markers associated with neural stem cells such as Nestin and Musashi1.<br />
Here we describe a so far unrecognized type of human tendon perivascular stem cells (hTPSC) expressing markers<br />
commonly associated with embryonic stem cells (ESC). By immunohistochemistry and single cell PCR on human<br />
tendon tissue we demonstrate that hTPSCs express Oct4, Nanog, Klf4, Cmyc and Sox2 in vivo. In cell culture, these<br />
cells give rise to clonal spheroid cell aggregates harbouring cells expressing the stem cell markers mentioned and<br />
markers associated with all three embryonic germ layers, such as Insulin and Glucagon, Collagens type 1 and 3 and<br />
GFAP and Galactosyl ceramidase. In differentiation experiments, hTPSC can give rise to adipocytes, osteoblasts,<br />
oligodendrocytes, astrocytes and insulin producing cells.<br />
Despite their ESC-like marker expression, these cells do not form tumors upon injection into immunodeficient<br />
mice.<br />
These findings suggest that TPSC represent a more undifferentiated cell type than mesenchymal stem cells.<br />
hTPSC may be a valuable source for future applications in tissue engineering and cell therapy.<br />
Oral<br />
29
30<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
TENDON STEM/ PROGENITOR CELLS: NUTRITION MATTERS!<br />
Renate Gehwolf, Paracelsus Medical University, Salzburg, Austria<br />
Christine Lehner, University Hospital Salzburg, Salzburg, Austria<br />
Andrea Wagner, Paracelsus Medical University, University of Salzburg, Salzburg, Austria<br />
Corinna Hirzinger, University Hospital Salzburg, Salzburg, Austria<br />
Verena Heu, University Hospital Salzburg, Salzburg, Austria<br />
Peter Augat, Trauma Center Murnau, Murnau, Germany<br />
Daniel Stephan, Trauma Center Murnau, Murnau, Germany<br />
Hans-Christian Bauer, Paracelsus Medical University, Salzburg, Austria<br />
Herbert Tempfer, Paracelsus Medical University, Salzburg, Austria<br />
Diabetes and obesity are known to be risk factors for tendinopathy, tendon injury and impaired tendon healing.<br />
Earlier on we described a so far unrecognized, insulin producing tendon cell type in humans and rats. These cells<br />
are responsive to glucose stimulation and their depletion leads to mechanical impairment in a rat model.<br />
We now hypothesize that dietary glucose levels influence the properties of human and rat tendons and test this<br />
hypothesis both by in vivo and in vitro experiments.<br />
We therefore fed healthy rats with either high glucose diet (HGD), low carbohydrate diet (LCD) and control diet<br />
(CD) for one month. Achilles tendons were then tested for their maximum tensile load and for the expression of<br />
Insulin and matrix degrading enzymes.<br />
Both HGD and LCD lead to an increased load to failure in rat Achilles tendons by 26% and 34%, respectively<br />
(p
20 - 22 September 2012, Opatija, Croatia<br />
CURRENT CONCEPTS OF OSTEOGENESIS IMPERFECTA<br />
Dragan Primorac, Penn State University, USA; University of Split, University of Osijek, Croatia<br />
Osteogenesis imperfecta (OI) or brittle bone disease is a heritable disorder of connective tissue that is associated<br />
with osteoporosis and variable amount of skeletal deformities. During the last years molecular concept of<br />
OI changed from a single gene disorder to multigenes disorder. Dominant negative mutations including glycin<br />
substitution mutations in COL1A1 or COL1A2 genes (the most common defect), helical splicing mutations (mainly<br />
mutations within donor or acceptor of either gene has been associated with exon skipping) produce abnormalities<br />
in the sequence of different regions of the type I collagen gene and result in expression of a mutant protein<br />
that drastically affects the normal triple-helix configuration. On the other hand, null allelic mutations may result<br />
in a 50% reduction of total collagen mRNA, creating a mild clinical phenotype of OI. Recent findings showed that<br />
mutations on CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1 and SP7 are responsible for autosomal recessive OI while<br />
dominant inheritance of OI is linked with mutations in COL1A1 or COL1A2 genes. Since bisphosphonates cannot<br />
correct the primary cause of OI, and their long-term use and effectiveness are still uncertain, new treatment options<br />
including mesenchymal stem cells and gene therapy are being developed by different group of scientists<br />
and clinicians.<br />
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32<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
THE ROLE OF PLATELET RICH PLASMA IN SPORTS MEDICINE<br />
Matjaz Vogrin, Department for orthopaedic surgery, Universtiy Medical Center Maribor, Maribor, Slovenia<br />
Robi Kelc, Department for orthopaedic surgery, Universtiy Medical Center Maribor, Maribor, Slovenia<br />
Among new therapeutical options for achieving more efficient healing, autologous thrombocytes have a very<br />
important place. Although there is no randomized prospective study confirming its value, platelet-rich plasma<br />
(PrP) as a source of autologous growth factors is speculated to be used by many sports physicians for treating<br />
muscle injuries. The use of platelet-derived preparations was prohibited by WADA until 2011 but was removed<br />
from the list after considering the lack of current evidence concerning the use of the method for the purposes of<br />
performance enhancement as current studies did not reveal a potential for performance enhancement beyond<br />
a therapeutic effect.PrP is today being widely used in therapy of tendinopathies and ligament injuries. Its place is<br />
being extensively investigated in case of muscle injuries, where the use seems to be more problematic due to the<br />
fibrotic scarring issue.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
DOUBLE BUNDLE TECHNIQUE COMBINED WITH A BIOLOGIC<br />
REGENERATIVE TREATMENT GIVE THE BEST RESULT OF ACL<br />
SURGERY<br />
Nikica Daraboš, University Clinic for Traumatology, Clinical Hospital Center Sisters of Mercy, Zagreb, Croatia<br />
Miroslav Hašpl, Special Hospital Acromion, Krapinske Toplice, Croatia<br />
Denis Tršek, Special Hospital Acromion, Krapinske Toplice, Croatia<br />
Carsten Moser, Institute for Microtherapy, University Witten-Herdecke, Bochum, Germany<br />
The bone tunnel widening appear after knee anterior cruciate ligament (ACL) single bundle technique (SB) reconstruction<br />
and could result in a ligament laxity or lead to increased failure rates. It could be affected on the<br />
biomechanical and biomolecular base. This research was carried out to establish whether a double bundle technique<br />
(DB) in a combination with.biologic regenerative treatment of intra-articular application of Autologous Conditioned<br />
Serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and several growth<br />
factors, could enhance a result of ACL surgery.<br />
In a prospective, randomized, double-blind trial with four parallel groups, 124 patients were treated. We compared<br />
a tibial bone tunnel width measured by CT-scans in three different post-operative periods. The clinical efficacy was<br />
assessed by patient administered outcome instruments (IKDC 2000, LYSHOLM, TEGNER) up to two years following<br />
the ACL-reconstruction in 4 groups of patients regarding a different combination of treatment: A. SB + Placebo, B.<br />
SB + ACS, C. DB + Placebo, D. DB + ACS.<br />
Postoperative tibial tunnel diameters in all groups were significantly larger than they were directly after surgery.<br />
Bone tunnel enlargement was significantly less in Group D than in the other groups (p
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
PLETELET-RICH PLASMA DERIVED GROWTH FACTORS AND<br />
TGF-β ANTAGONISTS PROMOTE MUSCLE REGENERATION IN<br />
VITRO<br />
Robi Kelc, Department of Orthopaedic Surgery, University Clinical Center Maribor, Maribor, Slovenia<br />
Martin Trapecar, Department of Biochemistry and Nutrition, Faculty of Medicine, University of Maribor,<br />
Maribor, Slovenia<br />
Lidija Gradisnik, Department of Biochemistry and Nutrition, Faculty of Medicine, University of Maribor,<br />
Maribor, Slovenia<br />
Rudi Mlakar, Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia<br />
Marjan Slak Rupnik, Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia<br />
Avrelija Cencic, Department of Biochemistry and Nutrition, Faculty of Medicine, University of Maribor,<br />
Maribor, Slovenia<br />
Matjaz Vogrin, Department of Orthopaedic Surgery, University Clinical Center Maribor, Maribor, Slovenia<br />
Injured skeletal muscle repairs spontaneously via regeneration; however, this process is often incomplete because<br />
of fibrotic tissue formation. Growth factors from platelet-rich plasma (PRP) with proven effects in tendinous and<br />
ligamentous healing have not yet been studied in skeletal muscles mainly due to the concern that exogenous<br />
TGF-β application could lead to even greater fibrosis development in an injured muscle. Therefore, only some<br />
TGF-β antagonists like decorin have shown their positive role in muscle repair so far.<br />
In our study, we have investigated the effects of PRP and decorin on skeletal muscle regeneration. A novel human<br />
myoblast cell culture, defined as CD56 (NCAM)+ and PAX7+ developed in our laboratory, was used for evaluation<br />
of potential bioactivity of PRP and decorin. The influence on the cells mitochondrial activity and expression of<br />
TGF-β was studied in parallel with cell proliferation. Further we have studied the ability of the therapeutic agents<br />
to influence the differential cascade of dormant myoblasts towards fully differentiated myotubes by monitoring<br />
step wise activation of single nuclear factors like PAX7, MyoD and Myogenin via multicolor flow cytometry.<br />
Our results clearly showed that PRP treated myoblasts have a significant increase in the mitochondrial activity and<br />
in the cell proliferation rate as compared to those treated with decorin and control cells. At the same time lower<br />
expression of TGF-β was evident in PRP treated myoblasts. We showed that PRP and decorin influence the activation<br />
of the differential cascade of satellite cells towards myotubes.<br />
Despite concerns about promoting fibrosis developement, PRP inhibits the TGF-β activity. We conclude that PRP<br />
can be a highly potential therapeutic agent for skeletal muscle regeneration and repair.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
SIGNIFICANT PAIN REDUCTION IN OSTEOARTHRITIS OF THE<br />
KNEE BY ACP ADMINISTRATION<br />
Michael Borsky, Etzelclinic, Pfäffikon, Switzerland<br />
Jan Leuzinger, Etzelclinic, Pfäffikon, Switzerland<br />
Alexandro Pellegrino, Etzelclinic, Pfäffikon, Switzerland<br />
We report our experience with ACP administration in osteoarthritic knees. 53 patients were treated by four ACP<br />
injections weekly. Lequesne score and class as well as the VAS score were evaluated before and four weeks after<br />
treatment. 32 patient were scored as extremely or very severe before treatment, whereas only one patient remained<br />
in the very severe class after treatment. The reduction in the Lequesne and VAS score was 68 per cent. We<br />
observed 11 per cent non responders.<br />
In conclusion intraarticular ACP administration in osteoarthritic knees offers a simple and cheap pain reduction for<br />
the patient and prevents a knee arthroplasty in patient up to 3 years.<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
REGENERATIVE MEDICINE: TRANSFORMING HEATLH CARE<br />
SOLUTIONS<br />
Andre Terzic, Center for Regenerative Medicine; Mayo Clinic, Rochester, United States<br />
Regenerative medicine has begun to define a new perspective of future clinical practice. The U.S. Department of Health<br />
and Human Services report “2020: A new Vision” highlights that regenerative medicine is the vanguard of 21st century<br />
healthcare. Patients and society increasingly expect that regenerative medicine will lead to repair of diseased organs,<br />
injured tissues or congenital anomalies. Without the contribution of personalized products and services emerging<br />
from regenerative medicine technology, experts caution that healthcare will face an escalation in inefficient treatments<br />
and a rising global cost. Aimed on functional restoration of damaged tissues, not a mere abatement or moderation of<br />
symptoms, regenerative medicine offers a “disruptive innovation” strategy uniquely poised to add value and transform<br />
healthcare by providing tailored, curative solutions for the unmet needs of our patients. Indeed, the rapidly developing<br />
regenerative medicine armamentarium promises significant human health benefit with tangible outcomes for<br />
increased quality of life and improved patient care building on breakthroughs. Maximizing potential return mandates,<br />
however, an integrated roadmap across the translational continuum of discovery-development-regulation-use to ensure<br />
optimal application of regenerative medicine algorithms in medical and surgical practice.
20 - 22 September 2012, Opatija, Croatia<br />
THE IMMUNOPATHOGENESIS OF RHEUMATOID ARTHRITIS<br />
Asja Stipić Marković, Department of Clinical Immunology, Pulmology and Rheumatology, Clinic for Internal<br />
Medicine, Medical School University of Zagreb, University Hospital Sveti Duh, Zagreb, Croatia<br />
Rheumatoid arthritis (RA) is an autoimmune disease in which the synovial tissue transforms into a destructive pannus<br />
leading to erosions and lost of joint functions.Why the systemic loss of immune tolerance is linked to a localized onset<br />
of inflammation in the joint is still unclear. Distinct disease mechanisms are at play in RA pathology. The heterogeneity<br />
is consequence of the multifactorial nature of the disease and specific combination of environmental factors with polygenetic<br />
background. Environmental factors have a major role in developing RA as it is shown in genetically identical<br />
twins.<br />
Factors that facilitate autoimmunity<br />
Proliferation of synovial, oligoclonal, antigen-specific, autoreactive CD4+T cells is key event in RA pathogenesis. Etiological<br />
antigens are selfproteins, formed, for example, after alterations in citrullination of mucosal proteins upon influence<br />
of environmental stressors on barrier tissues (ie, smoking on pulmonary tissue). Several citrullinated self-proteins with<br />
neoepitopes are recognized, but most of the patients with seropositive RA have antibodies for citrullinated α-enolase<br />
(anticyclic citrullinated peptide antibodies).That is accompanied with strong association with smoking and common<br />
aminoacid motif (QKRAA) in HLA-DRB1*04,PTPN22 genotype. Other citrullinated self-proteins are: keratin, fibrinogen,<br />
collagen, vimetin and fibronectin, all showing similar interactions with smoking and same risk alleles. Altered citrullination<br />
of mucosal proteins also could be induced in periodontal disease by bacteria Porphyromonas gingivalis, microorganism<br />
expressing PADI4 (peptidyl arginine deiminase type IV).<br />
Other important causes facilitating autoimmunity in articular compartment are various microorganisms (bacteria, viruses)<br />
and their products.They induce specific T response which crossreact with human antigens (mechanism named<br />
molecular mimicry). Another mechanism in RA pathophysiology is autoantibody production against Fc portion of human<br />
immunoglobulin, in the course of infection in which immune complexes are produced.<br />
Furthermore, an new mechanism in autoantibody-positive RA is mediated by gastrointestinal microbiome.<br />
Perpetuation of synovial inflammation<br />
Specific,autoreactive CD4+Th-1 cells, which infiltrate synovial tissue, migrate from lymph nodes where they got information<br />
about autoantigen from dendritic cells (DC). However, specific antigen induce proliferation of other T cell subsets:<br />
Th-17 (producing IL-17A,IL-17F,TNF-α) and T regulatory cells (Tregs), Foxp3 positive (important arm of the immune<br />
system responsible for suppression of the response). DCs, another key players in immune response, are patrolling and<br />
scanning peripheral tissue. They take antigens and transfer it through lymphatic system to local lymph nodes. In the<br />
lymph nodes, DCs present antigen to naive T cells and act somehow altering the morphology of subcapsular sinus floor<br />
what divert the homing route of T lymphocites, which trafficking through<br />
efferent lymph vessel infiltrate synovial membrane. In synovium, there is no balance (T cell homeostasis) between<br />
Th-17 and T regs, because macrophages and DC provide a milieu supporting Th-17 differentiation. Parallely, Tregs are<br />
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,),<br />
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<br />
persistence of the joint inflammation. Exclusive cytokine expression patterns are characteristic for distinct autoimmune<br />
disease. IFNs, early mediators of the innate immune response, affect initiation and amplification of autoimmunity in<br />
SLE. However, in a subgroup of patients with RA, IFN type I molecular signature is upregulated, but it could mean that<br />
this cytokine profile is patient-specific rather than a disease-specific phenomenon. Further characteristic of this subgroup<br />
of patients is increased activitiy of complement and coagulation cascades. IFN/STAT-1 activation in RA synovium<br />
could be an attempt to limit inflammation. Upregulation of IFN-induced genes has been observed in peripheral blood<br />
cells of patients with other auatoimmune disease as a common hallmark in chronic autoimmunity. Besides T cells, the<br />
synovium in rheumatoid arthritis contains B cells, plasma cells, plasmablasts, macrophages and plasmacytoid dendritic<br />
cells. B cells, localized in T-cell-B-cell aggregates, form humoral part of adaptive autoimmunity.A pathogenic role of B<br />
cells is confirmed by the efficacy of rituximab. The autoantibody level is variably altered after rituximab therapy which,<br />
with the fact that plasma cells are not targeted, suggests that these cells are not only antibody producers but have role<br />
in autoantigen presentation and cytokine production. Plasmacytoid DCs in synovium continue presentation and T cells<br />
activation. Macrophages,(M1 phenotype), represent innate immunity arm along with mast cells (produce vasoactive<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
amines,cytokines,chemokines,proteases) and NK cells, while neutrophils reside mainly in synovial fluid. Macrophages<br />
are the central effectors of synovitis. Their “weapons” are cytokines TNF-α, IL-6,reactive oxygen intermediates, nitrogen<br />
intermediates, product of prostanoids and matrix-degrading enzymes. Macrophages act also as phagocytes and<br />
antigen-presenting cells. Macrophages are activated by Toll-like receptors 2,3,4,8 and by NOD-like receptors. By these<br />
receptors macrophages recognize various microorganisms and antigens deliberate after tissue damage.<br />
Signalling in RA<br />
A network of intercellular signaling cytokines is central controlling mechanism in the pathogenesis of RA.Cytokine<br />
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<br />
has been confirmed by successful therapeutic blockade in clinical settings.Besides intercellular, there are many intracellular<br />
signaling molecules (particulary kinases) that regulate cytokine-receptor-mediated functions. Janus kinase 1<br />
(JAK1) mediate the function of several cytokines, interferons and growth factors what is confirmed in positive clinical<br />
outcomes of JAK1 blockade.<br />
Semiautonomous phenotype of synoviocytes<br />
The normal synovium contains mesenchymal-derived fibroblast-like synoviocytes. In RA this synoviocytes assume a<br />
semiautonomous phenotype characaterized by independence,loss of contact inhibition and expression of high levels<br />
of cytokines, chemokines, adhesion molekules,matrix metalloproteinases and tissue inhibitors of metalloproteinases.<br />
Fibroblast-like synoviocytes contribute directly to local cartilage destruction by adhesion and invasion of the cartilage<br />
surface.A hyperplastic synovium is the major cause of cartilage damage.<br />
Bone erosions<br />
Bone erosions occurs rapidly, within one year after diagnosis. Central effectors of bone destruction are osteoclasts<br />
which have the acidic enzymatic machinery necessary to destroy mineralized cartilage and subhondral bone. Osteoclasts,<br />
activated by network of synovial cytokines, invade periosteal surface adjacent to articular cartilage.”Mechanically<br />
vulnerable” sites such as the second and third metacarpals are prone to erosive changes.Eroded periarticular bone<br />
shows little evidence of repair, unlike bone in other inflammatory arthropathies because differentiation of mesenchymal<br />
precursors into chondroblasts and osteoblasts is inhibited by dickkopf-1 and frizzled-related protein 1, mediators<br />
induced by synovial cytokines.However,mesenchimal stem cells can be detected in the synovium. They have potential<br />
to differentiate into chondrocytes and osteoblasts.<br />
Molecular signature of RA subclases<br />
The heterogeneity of RA patients still remain a challenging problem.By genom-wide expression profiling technologies<br />
of disease-relevant gene coclusters and correlation analysis with clinical parameters, researchers are trying to provide<br />
evidence for molecular signature of the disease. Significant differential gene expression could be detected by web<br />
based tools - bioinformatic analysis using softwares for oligonucleotide microarrays, cDNA microarrays and hierachial<br />
cluster analysis available at web net.<br />
On the basis of proteoglycan 4 (PRG4) genes expression in a group of 66 patients, two RA subpopulations could be<br />
distinguish: PRG4 high and PRG4 low expressors. Low PRG4 expression in synovial fluid is associated with more aggressive<br />
disease stage, which, in accordance with PRG4 loss-of-function mutations, is causing campodactyly-arthropathy-coxavara-pericarditis<br />
syndrome. Level of PRG4 expression is associated with strong synovial stromal activation.<br />
Proteoglycan 4 gene product is major lubricating factor, and with PRG4-coexpressed genes has tissue protection and<br />
regeneration capabilities.<br />
Predictive power to identify seronegative (anti-citrullinated peptide antibody) patients with early arthritis, at risk of<br />
developing RA, belongs to a CD4 T cell gene signature which implicates interleukin 6-mediated STAT3 signalling.<br />
To distinguish between rheumatoid arthritis and other entities (ie. osteoarthritis) upregulation of SPP1-like cluster<br />
genes can serve. Higher level of SPP1 protein can be detected in synovial fluids from RA patients. SPP1 is a secreted<br />
phosphoglycoprotein, functioning as cytokine, DC activator and costimulator of T-cell proliferation.<br />
Conclusion<br />
In recent years there has been great progress towards understanding the molecular basis of RA immunopathophysiology.<br />
However, effective treatment is impeded by a paucity of accurate diagnostic and prognostic tests. There are wide<br />
variations in responsiveness to virtually any treatment in RA consistent with the heterogeneous nature of the disease<br />
why a molecular portrait reflecting the contribution of diverse cellular responses in general, and for classification of the<br />
disease subtypes, is necessary.<br />
Oral
ARTHRITIS GENE THERAPY<br />
Christopher Evans, Harvard Medical School, Boston, United States<br />
20 - 22 September 2012, Opatija, Croatia<br />
Localizing therapeutics to joints in a sustained fashion is extremely difficult because of the rapid rate of egress of<br />
both small and large molecules - intra-articular dwell times are usually measured in hours whereas the diseases are<br />
chronic. Gene transfer to the joint is the only technology that can overcome this limitation in a clinically reasonable<br />
fashion. A variety of vectors and trans-genes have been used in pre-clinical models, establishing unequivocal<br />
proof of principle in both rheumatoid arthritis (RA) and osteoarthritis (OA). There have been four clinical trials for<br />
RA and two for OA. Only one of these has progressed to Phase II.<br />
The first human trial used a retrovirus to deliver the interleukin-1 receptor antagonist (IL-1Ra) cDNA in an ex vivo<br />
fashion into the metacarpophalangeal joints of nine subjects with RA. No safety issues were identified in this<br />
succesful Phase I trial. In a subsequent German study involving just two subjects, there was a remarkable clinical<br />
response in one of the patients. A different approach using adeno-associated virus (AAV) carrying etanercept<br />
cDNA progressed to Phase II, but was marred by the death of one subject; nevertheless, the FDA allowed this trial<br />
to continue to completion. No statistically significant improvement was noted, however.<br />
Phase I trials for the treatment of OA have been completed successfully in the USA and Korea. This protocol uses allografted<br />
chondrocytes that have been transduced with retrovirus to over-express transforming growth factor-β1.<br />
Phase II studies are underway. Our group is trying to initiate a Phase I trial in OA, using AAV to deliver IL-1Ra cDNA.<br />
Although the science and technology behind these studies are sound, progress in clinical implementation is limited<br />
by the high translational costs and the restrictive regulatory environment.<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
BIOLOGICAL AGENTS IN RHEUMATOID ARTHRITIS<br />
Srđan Novak, University Hospital Rijeka, Rijeka, Croatia<br />
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis. If untreated, persistent synovial<br />
inflammation can progress to cartilage and bone destruction. The goal of RA treatment today is to achieve<br />
remission. In clinical practice remission means the presence of one or less swollen and one or less tender joints.<br />
Methotrexate (MTX) is usually the first chosen synthetic disease modifying anti-rheumatic drug (DMARD) and<br />
administered appropriately in some patients it can lead to remission. If remission is not achieved with one or two<br />
DMARDs in six months biologic drugs have to be introduced. The main inflammatory mediators of joint inflammation<br />
and destruction in RA are tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), IL-6, chemokines and proteases.<br />
Advances in our understanding of the key cells and inflammatory cytokines have led to the development of targeted<br />
biologic agents. Among them anti-TNFα drug is usually the frst choice. As of 2012, 5 TNF-alpha inhibitors are<br />
approved for use by the FDA: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol. Etanercept<br />
is a soluble receptor which binds TNF alfa and all others are monoclonal antibodies. In randomized clinical<br />
trials, all these agents have shown to be effective in reducing clinical signs of inflammation in RA patients who<br />
have failed synthetic DMARDs. They are usually given in combination with synthetic DMARD although etanercept<br />
and adalimumab can be given alone. Multiple studies have demonstrated significant benefits of early treatment<br />
with TNF-alpha inhibitors combined with methotrexate. Other FDA-approved biologic agents for treating moderate-to-severe<br />
RA include abatacept which modulates co-stimulation between T lymphocytes, rituximab which<br />
deplets CD20 B cells, and tocilizumab which neutralises IL-6 activity by binding to IL-6 receptors. If ant-TNF drug<br />
fails instead another anti-TNFα drug or tocilizumab or rituximab or abatacept can be given. Generally all biologic<br />
drugs are given in combination with MTX or some other DMARD. If monotherapy is needed tocilizumab is the drug<br />
of choice. All biologic agents carry an increased risk of infections, especially of TB among patients on monoclonal<br />
anti –TNF antibodies although screening to latent TB infection prior to anti TNF therapy significantly reduce the<br />
number of TB cases. All patients being considered for biologic agents should be screened for tuberculosis and<br />
hepatitis B and C. Additional potential side effects include infusion and injection site reactions for intravenous and<br />
subcutaneously administered agents respectively.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
THE FUTURE OF RHEUMATOID ARTHRITIS TREATMENT -<br />
COMBINING PHARMACOLOGY AND SURGERY<br />
Dušanka Martinović Kaliterna, Department of Rheumatology and Clinical Immunology, University<br />
Hospital of Split, Split, Croatia<br />
Rheumatoid arthritis (RA) is widespread and complex multifactorial chronic inflammatory disorder with not always<br />
successful treatment. A great success of RA pharmacotherapy is characterised by novel genetically engineered<br />
biological medicines. The hallmark of RA is chronic synovial inflammation which leads to joint damage and<br />
destruction. The role of cytokines is important not only for local synovial autoimmune response but also for systemic<br />
features. In the last decades the cytokines role is stressed in RA especially tumour necrosis factor alpha and<br />
interleukins. Achievements of molecular biology and genetics promote an individual approach to RA treatment,<br />
with a new concept of personal medicine in the view of genomic sciences. Personalized genomic medicine and<br />
surgery represents a new approach to health care that customised patients’ medical treatment according to their<br />
own genetic information. Genomic information can also indicate the potential risk for certain diseases before the<br />
patient is symptomatic. It is clear that differences in genomes of individuals would likewise affect the effectiveness<br />
of medication.<br />
We are aware that although we have the choice of new biological drugs, it is not always effective. In the beginning<br />
of the disease the bone biopsy is sometimes needed for evaluating the disease, and later the cooperation with<br />
orthopaedist is mostly based in purpose of arthroscopy. Off course in some progressive RA cases surgical reconstruction<br />
and joint replacement may not be avoided.<br />
While the progress in DNA sequencing has been extensive in the last years, it promote the great challenge for<br />
utilizing genomic information for choosing the future more effective pharmacological and surgical therapy in RA.<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
ENHANCED OSTEOCLASTOGENESIS IN ARTHRITIS IS<br />
PARALLELED WITH THE INCREASED EXPRESSION OF<br />
PROINFLAMMATORY MEDIATORS CCL2, IL-17 AND IL-18<br />
Marina Ikić, University Hospital Sveti Duh, Zagreb, Croatia<br />
Zrinka Jajić, University Hospital Sestre Milosrdnice, Zagreb, Croatia<br />
Nataša Kovačić, University of Zagreb, School of Medicine, Department of Anatomy, Zagreb, Croatia<br />
Elvira Lazić, University of Zagreb, School of Medicine, Department of Anatomy, Zagreb, Croatia<br />
Sanja Ivčević, University of Zagreb, School of Medicine, Department of Physiology and Immunology,<br />
Zagreb, Croatia<br />
Frane Grubišić, University Hospital Sestre Milosrdnice, Zagreb, Croatia<br />
Ana Marušić, University of Split, School of Medicine, Department of Anatomy, Zagreb, Croatia<br />
Danka Grčević, University of Zagreb, School of Medicine, Department of Physiology and Immunology,<br />
Zagreb, Croatia<br />
Osteoclasts play a pivotal role in excessive bone destruction of arthritic joints. Many cytokines are involved in the<br />
pathogenesis of arthritis, acting as osteoclastogenic factors, but their effects are not fully revealed. Our aim was to<br />
compare the expression profile of selected proinflammatory factors and osteoclastogenic potential of peripheral-blood<br />
mononuclear cells (PBMC) between control subjects and arthritic patients (including rheumatoid arthritis<br />
(RA) and spondyloarthritis (SpA)). In addition, we assessed osteoclastogenic potential of PBMC and local synovial-fluid<br />
derived mononuclear cells (SFMC) in patients with RA and SpA. PBMC were collected from control subjects<br />
(n=12), whereas PBMC and SFMC were collected from RA patients (n=10) and SpA patients (n=15), either with ankylosing<br />
spondylitis (AS=5) or psoriatic arthritis (PsA=10), after the informed consent. Osteoclasts were stimulated<br />
with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and detected<br />
as tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells. RNA was extracted from PBMC/SFMC<br />
cells, reversely transcribed to cDNA, and amplified by quantitative PCR for the expression of osteoclast differentiation<br />
genes (RANK, cFms, TRAP) and inflammatory mediators (CCL2, VEGF, IL-17, IL-18, TNF-a, and FasL). In addition,<br />
serum and synovial fluid levels of the same mediators were determined by ELISA. Serum levels of inflammatory<br />
mediators CCL2, IL-17 and IL-18 were higher in arthritic patients compared with control subjects, whereas synovial<br />
fluid levels of CCL2, VEGF, TNF-a and IL-18 were higher in RA compared with other patient groups. In addition,<br />
gene expression of inflammatory mediators CCL2, IL-17 and IL18 were higher in PBMC and SFMC of arthritic patients<br />
compared with control subjects. In vitro osteoclastogenesis showed higher osteoclastogenic potential for<br />
PBMC but similar for SFMC in RA compared with AS and PsA patients. In parallel, gene expression of osteoclast<br />
differentiation genes RANK and TRAP was higher in osteoclastogenic cultures derived from PBMC of RA patients.<br />
Our results indicate that patients with RA have greater osteoclastogenic potential compared with control subjects<br />
and SpA patients, which is paralleled with the increased expression of proinflammatory mediators. These findings<br />
may be relevant for the development of therapeutic approaches aimed to modulate proinflammatory as well as<br />
osteoclastogenic effects of those factors.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
CELL-BASED AND CELL-FREE JOINT IMPLANTS FOR CARTILAGE<br />
REPAIR<br />
Michaela Endres, TransTissue Technologies GmbH Berlin/ Germany<br />
For 12 years now, BioTissue has been the pioneer in the field of regenerative cartilage treatment. BioTissue combines<br />
the state of the art in bioengineering industry with the growing demands of the orthopedic market and<br />
the future-oriented visions of science. This is achieved by a high-tech GMP lab, an independent R&D center, and of<br />
course by eager clinical interaction with the physicians.<br />
Articular cartilage cannot regenerate itself. Once damaged, the result is pain and loss of function. Treatment is<br />
absolutely essential to prevent deterioration in conditions such as joint disease. Tissue engineering research had<br />
led to the development of cell-based transplants for bone (BioSeed ® -oral bone) and cartilage repair (BioSeed ® -C).<br />
BioSeed ® -C is an autologous 3-dimensional chondrocyte graft which has been successfully used for many years<br />
to treat articular cartilage defects in the knee, ankle or hip. Therefore, a biopsy of cartilage tissue is taken from<br />
the patient and cells are isolated and expanded. After 3 weeks, these cells are re-transplanted within a no woven<br />
polymer matrix into the cartilage defect by mini-open or arthroscopic procedure. The autologous cell graft replaces<br />
the missing tissue and restores the original function. It provides the chondrocytes (cartilage cells) with an<br />
ideal three-dimensional but stable environment which stimulates them to redifferentiate and thus assume their<br />
original morphology and function.<br />
In contrast to cell-based cartilage repair, chondrotissue ® is a 1-step, CE marked, cell-free implant used to treat articular<br />
cartilage defects in the knee, ankle or hip. It is used after bone-marrow stimulating techniques to repair focal<br />
chondral defects by the possibility of an arthroscopic application. Within the defect it covers the microfractured<br />
area, protects the subchondral bone and insures a stable 3D environment and a chondrogenic cell differentiation<br />
into hyaline-like repair tissue formation. chondrotissue ® provides a unique stable 3D technology ensuring excellent<br />
cell differentiation and allowing for stable fixation. By an easy and fast operation technique and arthroscopic<br />
implantation possibility, cartilage defects can be treated using the cell-free one-step procedure with excellent<br />
clinical outcome.<br />
Oral<br />
43
44<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
SPECT/CT A NOVEL DIAGNOSTIC TOOL FOR EVALUATION OF<br />
LOADING PATTERN OF THE KNEE<br />
Michael T. Hirschmann, Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland,<br />
Bruderholz, Switzerland<br />
Stephan Schoen, Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland,<br />
Bruderholz, Switzerland<br />
Niklaus F. Friederich, Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland,<br />
Bruderholz, Switzerland<br />
SPECT/CT is a promising imaging technology, which promises the combined evaluation of mechanical and biological<br />
information. If the loading pattern and intensity values of the SPECT/CT correlate with the anatomical and<br />
mechanical alignment it could be used for evaluation of postoperative patients after realignment procedures such<br />
as high tibial osteotomies or patellofemoral surgery.<br />
99mTc-HDP-SPECT/CT of 76 patients (mean age 49±17) and 104 knees were analysed using a previously validated<br />
localisation and grading algorithm. The maximum intensity in each femoral, tibial and patellar joint compartment<br />
(medial, lateral, central, superior, inferior) was noted (0-10). In addition, anterior-posterior and lateral weight bearing<br />
radiographs as well as Rosenberg and skyline view were analysed with regards to the Kellgren-Lawrence osteoarthritis<br />
score. Long leg radiographs were used to assess the mechanical and anatomical leg alignment, which<br />
was then classified as varus, valgus or neutral. We correlated the mechanical and antomical alignment with the<br />
intensity of tracer uptake in each area of interest. In addition, the Kellgren Lawrence socre was also correlated. A<br />
sample size calculation was performed. The level of statistical significance was p< 0.05.<br />
The intensity of 99mTc-HDP tracer uptake on the medial compartment significantly correlated with anatomical<br />
and mechanical varus alignment of the knee (p< 0.05). The intensity of 99mTc-HDP tracer uptake on the lateral<br />
compartment significantly correlated with anatomical and mechanical valgus alignment of the knee (p< 0.05). In<br />
patients having higher Kellgren Lawrence scores, which reflects a higher degree of osteoarthritis, higher tracer<br />
uptake values were found in the corresponding joint compartments.<br />
SPECT/CT reflects the loading pattern of the knee joint with regards to the mechanical and anatomical alignment.<br />
SPECT/CT is then a promising imaging technology in particular for follow-up of high tibial osteotomies, deloader<br />
braces treatment and patellofemoral realignment procedures.<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
OSTEOPOROSIS: COMMON FEATURE UNDERLINED BY<br />
DIFFERENT PATHOGENETIC MECHANISMS<br />
Danka Grčević, University of Zagreb School of Medicine, Zagreb, Croatia<br />
The misbalance in the differentiation and activity of principal bone cells, bone forming osteoblasts and bone<br />
resorbing osteoclasts, leads to osteoporosis, characterized by the loss of bone mass and increased risk of fragility<br />
fractures. There are multiple pathogenetic mechanisms underlying osteoporosis, involving not only the osteoblastic<br />
and osteoclastic cell lineages but also other bone-marrow cells, systemic hormones, local cytokines,<br />
and growth factors. The RANKL/RANK interaction is critical for osteoclastogenesis and hence represents a final<br />
common pathway for any pathogenetic factor in osteoporosis that acts by increasing osteoresorption. By using<br />
different mouse models, we investigated several aspects of the disease mechanism, addressing both bone formation<br />
and bone degradation. We used genetic mutation causing the osteogenesis imperfecta murine (OIM),<br />
to confirm that the osteoblastic lineage is under continuous stimulation, but with decreased ability for maturation.<br />
Moreover, immature osteoblasts strongly support osteoclastogenesis, through higher RANKL/OPG ratio and<br />
TNF-alpha expression. In view of the reports that human postmenopausal osteoblasts constitutively express Fas<br />
and our finding that Fas receptor activation directly inhibits osteoblast differentiation, we confirmed that Fas/FasL<br />
system has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and<br />
inhibiting differentiation of osteoblast lineage cells. Inflammatory processes alter the bone microenvironment to<br />
promote irreversible bone destruction. In pathologic states, activated T-lymphocytes produce RANKL and other<br />
proresorptive cytokines playing a role in osteoporosis as well as inflammation-induced bone loss. In the model of<br />
systemic inflammation, by endotoxin administration, and autoimmune reaction, in collagen-induced arthritis, we<br />
confirmed that there is a decrease in total bone mass mediated by increased number of identified bone-marrow<br />
and peripheral osteoclast progenitors and their enhanced activity maintained by proinflammatory factors. Finally,<br />
we hypothesize that cells expressing smooth muscle alpha-actin promoter (aSMA)-directed transgene represent<br />
mesenchymal progenitors of adult bone tissue and confirmed that aSMA+ cells serve as a pool of skeletal progenitors<br />
with a potential for terminal differentiation into mature osteoblasts during fracture healing. Although<br />
we identified a defined population of mesenchymal progenitors with the active role in bone regeneration, many<br />
puzzles are still missing before we would be able to achieve the full therapeutic success in osteoporosis treatment.<br />
Oral<br />
45
46<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
EFFECT OF QUERCETIN ON OSTEOPOROSIS CAUSED BY<br />
RETINOIC ACID IN RATS<br />
Željko Jeleč, General Hospital “Dr. Ivo Pedišić” Sisak, Sisak, Croatia<br />
Nada Oršolić, Faculty of Science, University of Zagreb, Zagreb, Croatia<br />
Osteoporosis is a disease characterised by the loss of bone density and deterioration of bone microarchitecture,<br />
leading to an increased risk of fracture. Several classes of drugs are available for the treatment of osteoporosis: antiresorptive<br />
drugs, oestrogen, selective oestrogen receptor modulators, bisphosphonates, parathyroid hormone,<br />
and strontium ranelate. Due to the adverse effects of these drugs, a natural alternative offered in the form of flavonoids<br />
is of interest.<br />
Research is conducted on rats in whom osteoporosis was induced by means of retinoic acid. Our aim was to assess<br />
the effectiveness of the flavonoid quercetin in the treatment of osteoporosis, as well as to determine whether<br />
flavonoid differ in antiosteoporotic activity from bisphosphonate alendronate, the effectiveness of which has previously<br />
been shown.<br />
We analised changes in masses of experimental animals, masses, length and diameter of femur, calcium and phosphorus<br />
content, as well as some biochemical and haematological variables.<br />
The analysis was carried out in two directions. First observed and analyzed the effect of quercetin in healthy rats,<br />
ie, the experimental animals before getting quercetin are not dealt with retinoic acid. On the other hand, was<br />
monitored and analyzed the effect of quercetin on animals in which the former providing retinoic acid occurred<br />
osteoporosis. We compared the effects of quercetin in relation to the control group and in relation to the bisphosphonate<br />
alendronate.<br />
Quercetin showed good therapeutical potential, and some potential showed in prevention of osteoporosis. Quercetin<br />
was superior to alendronate according to some criteria.<br />
Based on available data from the literature and the results obtained in this study, there is a high probability for<br />
success in the treatment of osteoporosis accounted antioxidant and estrogenic activity of quercetin. Because of<br />
the numerous adverse effects and cost of drugs is now being used on one side, and the proven effectiveness of<br />
quercetin on the other hand, believe that quercetin has a great potential in the treatment of osteoporosis<br />
Oral
20 - 22 September 2012, Opatija, Croatia<br />
THE TREATMENT OF PROXIMAL FEMORAL FRACTURES IN<br />
COUNTY HOSPITAL DUBROVNIK IN PERIOD APRIL 2011-APRIL<br />
2012.<br />
Marijo Bekić, Institute of Surgery, Division of Traumatology, County Hospital Dubrovnik, Dubrovnik,<br />
Croatia<br />
Jakiša Lojpur, Institute of Surgery, Division of Traumatology, County Hospital Dubrovnik, Dubrovnik,<br />
Croatia<br />
Nikša Kojić, Institute of Surgery, Division of Traumatology, County Hospital Dubrovnik, Dubrovnik,<br />
Croatia<br />
Marko Margaritoni, Institute of Surgery, Division of Plastic and Reconstructive Surgery, County Hospital<br />
Dubrovnik, Dubrovnik, Croatia<br />
Fractures of the proximal femur are associated with a greater number of deaths and disabilities and higher medical<br />
expenses than all the other osteoporotic fractures together and therefore represents a great social and economic<br />
problem.<br />
We reported a 65 consecutive patients admitted into the Institute of Surgery, Division of Traumatology, County<br />
Hospital Dubrovnik, Croatia, treated with a different type of implants depending on type of fracture of proximal<br />
femoral region.<br />
Fifteen men and 50 women aged 68 to 92 underwent fixation using an Dinamic Hip Screw (DHS), Short Gamma<br />
Nail, Locking Compression Plate and Partial Endoprothesis (PEP).<br />
All patients with unstable trochanteric femoral fractures were treated operatively using the Gamma Nail. Postoperatively<br />
patients were mobilised early without weight bearing.<br />
A Gamma Nail is useful for the treatment of trochanteric femoral fracture offering an early patient verticalisation<br />
and discharge from Hospital.<br />
Oral<br />
47
LECTURERS’<br />
RESUMES<br />
20 - 22 September 2012, Opatija, Croatia<br />
49
50<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Field of research:<br />
Cartilage, Osteonecrosis, Resurfacing, ACL<br />
Shoulder, Hand Surgery & Microsurgery<br />
Scientific Work<br />
Özler T., Güven M., Kocadal O., Beyzadeoğlu T., Altıntaş F.,<br />
‘Is locked anatomic plate fixation out of problem in adult<br />
displaced clavicle fractures?’<br />
Acta Orthop Traumatol Turc, Accepted, (2012).<br />
Beyzadeoğlu T., Köse G.T., Ekinci I.D., Bekler H., Yılmaz C.,<br />
‘Local anaesthetics are cytotoxic to rats’ articular cartilage<br />
both invivo and invitro: Experimental study’<br />
Acta Orthop Traumatol Turc, Accepted, (2012).<br />
Beyzadeoglu T., Akgun U., Tasdelen N., Karahan M.,<br />
‘Prediction of Semitendinosus and Gracilis autograft sizes<br />
for ACL.’<br />
Knee Surg Sports Traumatol Arthrosc. Nov 25. [Epub<br />
ahead of print] (2011).<br />
Beyzadeoglu T., Gokce A., Bekler H.,<br />
‘Skin and subcutaneous tissue atrophy after corticosteroid<br />
injection for medial epicondylitis.’<br />
Orthopaedics, 34:8, 570 (2011).<br />
Unalan P.C., Akan K., Orhun H., Akgun U., Poyanli O., Baykan<br />
A., Yavuz Y., Beyzadeoglu T., Nuran R., Kocaoglu B., Topsakal<br />
N., Akman M., Karahan M.,<br />
‘A basic arthroscopy course based on motor skill training.’<br />
Knee Surg Sports Traumatol Arthrosc. 18:10, 1395-1399<br />
(2010).<br />
Beyzadeoğlu T., Uluçay Ç.<br />
‘Microsurgical Approach for Acute Dislocations of the<br />
Knee’<br />
Türkiye Klinikleri J Orthop & Traumatol-Special Topics,<br />
2:2, 104-108 (2009).<br />
Gokce A., Beyzadeoglu T., Ozyer F., Bekler H., Erdogan F.,<br />
‘Does bone impaction technique reduce tunnel enlargement<br />
in ACL reconstruction?’<br />
Int Orthop, 33:2 407-412 (2009).<br />
Bekler H., Beyzadeoğlu T., Gökçe A., Servet E.,<br />
‘Aseptic drainage associated with polyglactine sutures<br />
used for repair of Achilles tendon ruptures’<br />
Acta Orthop Traumatol Turc, 42:2, 135-138 (2008).<br />
Tahsin Beyzadeoğlu<br />
M.D., Assoc. Prof. of Orthopaedics & Traumatology<br />
ISTANBUL, TURKEY<br />
tbeyzade@superonline.com<br />
Bekler H., Bulut G., Usta M., Gokce A., Okyar F., Beyzadeoğlu<br />
T.,<br />
‘The contribution of locked screw-plate fixation with varying<br />
angle configurations to stability of osteoporotic fractures:<br />
an experimental study’<br />
Acta Orthop Traumatol Turc, 42:2, 125-129 (2008).<br />
Beyzadeoglu T., Gokce A., Bekler H.,<br />
‘Osteochondritis dissecans of the medial femoral condyle<br />
associated with malformation of the menisci’<br />
Orthopaedics, 31:5, 504 (2008).<br />
Beyzadeoglu T., Inan M., Bekler H., Altintas F.,<br />
‘Arthroscopic excision of an ununited ossicle due to Osgood-Schlatter<br />
disease’<br />
Arthroscopy, 24:9, 1081-1083 (2008).<br />
Bekler H., Beyzadeoglu T., Mercan A.,<br />
‘Groin flap immobilization by axillary brachial plexus block<br />
anesthesia.’<br />
Tech Hand Up Extrem Surg, 12:2, 68-70 (2008).<br />
Bekler H., Beyzadeoğlu T., Gökçe A.,<br />
‘Tibialis posterior tendon transfer for drop foot deformity’<br />
Acta Orthop Traumatol Turc, 41:5, 387-392 (2007).<br />
Gökçe A., Bekler H., Beyzadeoğlu T., Karacaoğlu E., Servet<br />
E.,<br />
‘Our results for open Tibia fractures’<br />
Yeditepe Medical Journal, 1:1, 43-46 (2007).<br />
Beyzadeoğlu T., Gökçe A., Bekler H.,<br />
‘The effectiveness of dorsiflexion night splint added to<br />
conservative treatment for plantar fasciitis’<br />
Acta Orthop Traumatol Turc, 41:3, 220-224 (2007).<br />
Bekler H., Gökçe A., Beyzadeoğlu T.,<br />
‘Dissemination pathways in high-pressure injection injuries<br />
of the hand: an experimental animal model’<br />
Acta Orthop Traumatol Turc, 41:2, 147-151 (2007).<br />
Altıntaş F., Özkut A.T., Beyzadeoğlu T., Eren A., Güven M.,<br />
‘The effect of risedronate treatment on bone turnover<br />
markers in patients with hip fracture’<br />
Acta Orthop Traumatol Turc, 41:2, 132-135 (2007).
Parmaksizoglu F., Beyzadeoglu T.,<br />
‘Composite osteocutaneous groin flap combined with<br />
neurovascular island flap for thumb reconstruction’<br />
J Hand Surg (Br), 28:5, 399-404 (2003).<br />
Parmaksizoglu F., Beyzadeoglu T.,<br />
‘Role of side branches in determining suitable arterial segments<br />
for anastomosis in avulsion injuries: Experimental<br />
study’<br />
J Reconstr Microsurg, 19:4, 279-284 (2003).<br />
Parmaksizoglu F., Beyzadeoglu T., Yildirim S.,<br />
‘Hemangioma originating from a tendon sheath at the<br />
wrist as an unusual cause of trigger wrist: Case report’<br />
Handchir Mikrochir Plast Chir, 35:1, 64-65 (2003).<br />
Parmaksizoglu F., Beyzadeoglu T.,<br />
‘Functional latissimus dorsi island pedicle musculocutaneous<br />
flap to restore elbow flexion in replantation or revascularization<br />
of above-elbow amputations’<br />
Handchir Mikrochir Plast Chir, 35:1, 51-56 (2003).<br />
Parmaksızoğlu F., Beyzadeoğlu T.,<br />
‘Surgical approach to the hand injuries with multiple digital<br />
amputations: Case report’<br />
The Journal of Kartal Training and Research Hospital,<br />
14 :1, 44-46 (2003).<br />
Parmaksızoğlu F., Beyzadeoğlu T.,<br />
‘The treatment of bilaeral congenital radioulnar synostosis<br />
with derotation osteotomy: Case report’<br />
Çukurova University Medical Journal, 28:2, 74-80 (2003).<br />
Nişan N., Öğüt T., Erdoğan F., Beyzadeoğlu T.,<br />
‘The fixation of proximal Humerus fractures with modified<br />
tension band wiring’<br />
Joint Diseases and Related Surgery, 13:3, 141-144<br />
(2002).<br />
Parmaksizoglu F., Beyzadeoglu T.,<br />
‘Lengthening of replanted or revascularized lower limbs:<br />
Is length discrepancy a contraindication for limb salvage?’<br />
J Reconstr Microsurg, 18:6, 471-480 (2002).<br />
Parmaksizoglu F., Beyzadeoglu T.,<br />
‘A modified method of microvascular autogenous interposition<br />
vein grafting for vascular reconstruction’<br />
J Reconstr Microsurg, 18:3, 191-194 (2002).<br />
20 - 22 September 2012, Opatija, Croatia<br />
Bilsel N., Beyzadeoglu T., Kafadar A.,<br />
‘Application of Bailey-Dubow rods in the treatment of osteogenesis<br />
imperfecta’<br />
Eur J Orthop Surg Trauma, 10:3, 183-187 (2000).<br />
Membership of Scientific Societies and/or Associations<br />
Since 2006, ICRS, Member of Membership and Bylaws<br />
Committee<br />
Since 2005, ISAKOS, Member of Arthroscopy Committee<br />
Since 2002, AAOS, International Member<br />
Since 2006, ESSKA, Member<br />
51
52<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Matej Drobnič<br />
MD, Ph.D.<br />
Assist Professor<br />
Consultant orthopaedic surgeon<br />
Leading physician for orthopaedic rehabilitation<br />
LJUBLJANA, SLOVENIA<br />
matej.drobnic@mf.uni-lj.si<br />
Institution<br />
University Medical Centre Ljubljana, Department of Orthopaedic Surgery<br />
Field of research<br />
Cartilage repair – basic and clinical research<br />
Knee and ankle reconstructive surgery<br />
Scientific Work<br />
Alibegović A, Balažic J, Petrovič D, Velikonja NK, Blagus R, Suput D, Drobnič M. The Optimal Combination of Cartilage<br />
Source and Apparatus for Long-Term In Vitro Chondrocyte Viability Analysis. J Forensic Sci. 2012<br />
Suhodolčan L, Brojan M, Kosel F, Drobnič M, Alibegović A, Brecelj J Cryopreservation with glycerol improves the<br />
in vitro biomechanical characteristics of human patellar tendon allografts. Knee Surg Sports Traumatol Arthrosc.<br />
2012<br />
Kon E, Filardo G, Drobnič M, Madry H, Jelić M, van Dijk N, Della Villa S. Non-surgical management of early knee<br />
osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):436-49<br />
Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J, Van Dijk CN. Biomechanical considerations<br />
in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):423-<br />
35.<br />
Malicev E, Barlič A, Kregar-Velikonja N, Stražar K, Drobnič M. Cartilage from the edge of a debrided articular defect<br />
is inferior to that from a standard donor site when used for autologous chondrocyte cultivation. J Bone Joint Surg<br />
Br. 2011 Mar;93(3):421-6.<br />
Membership of Scientific Societies and/or Associations<br />
International Cartilage Repair Society (ICRS), member of YSOS committee<br />
European Society of Sports Traumatology Knee Surgery and Arthroscopy (ESSKA), member of cartilage repair<br />
committee<br />
Slovenian Orthopaedic Society (joined member to EFFORT), past secretary<br />
Cell and Tissue Engineering Society of Slovenia, board member
Michaela Endres<br />
MD<br />
Project manager<br />
TransTissue Technologies GmbH, R&D department<br />
BERLIN, GERMANY<br />
michaela.endres@transtissue.com<br />
Institution<br />
TransTissue Technologies GmbH, R&D department<br />
Field of research<br />
Medical and medical products, BioMedical Engineering, Tissue engineering<br />
20 - 22 September 2012, Opatija, Croatia<br />
Scientific Work<br />
Endres M, Andreas K, Kalwitz G, Freymann U, Neumann K, Ringe J, Sittinger M, Haupl T, Kaps C.<br />
Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10<br />
and XCL1 recruit human subchondral mesenchymal progenitor cells.<br />
Osteoarthritis Cartilage. 2010 Nov;18(11):1458-66. Epub 2010 Aug 13.<br />
Endres M, Abbushi A, Thomale UW, Cabraja M, Kroppenstedt SN, Morawietz L, Casalis PA, Zenclussen ML, Lemke<br />
AJ, Horn P, Kaps C, Woiciechowsky C.<br />
Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration<br />
model. Biomaterials. 2010 Aug;31(22):5836-41. Epub 2010 Apr 28.<br />
Endres M, Wenda N, Woehlecke H, Neumann K, Ringe J, Erggelet C, Lerche D, Kaps C. Microencapsulation and<br />
chondrogenic differentiation of human mesenchymal progenitor cells from subchondral bone marrow in Ca-alginate<br />
for cell injection. Acta Biomater. 2009 Jul 19.<br />
Endres M, Neumann K, Schroder SE, Vetterlein S, Morawietz L, Ringe J, Sittinger M, Kaps C.<br />
Human polymer-based cartilage grafts for the regeneration of articular cartilage defects.<br />
Tissue Cell. 2007 Oct;39(5):293-301. Epub 2007 Aug 3.<br />
Endres M, Neumann K, Haupl T, Erggelet C, Ringe J, Sittinger M, Kaps C.<br />
Synovial fluid recruits human mesenchymal progenitors from subchondral spongious bone marrow.<br />
J Orthop Res. 2007 Oct;25(10):1299-307.<br />
Endres M, Leinhase I, Kaps C, Wentges M, Unger M, Olze H, Ringe J, Sittinger M, Rotter N. Changes in the gene<br />
expression pattern of cytokeratins in human respiratory epithelial cells during culture.<br />
Eur Arch Otorhinolaryngol. 2005 May;262(5):390-6. Epub 2004 Nov 11.<br />
Endres M, Hutmacher OW, Salgado AJ, Kaps C, Ringe J, Reis RL, Sittinger M, Brandwood<br />
A, Schantz JT. Osteogenic induction of human bone marrow-derived mesenchymal progenitor cells in novel<br />
synthetic polymer-hydrogel matrices. Tissue Eng. 2003 Aug;9(4):689-702.<br />
Duda GN, Haisch A, Endres M, Gebert C, Schroeder D, Hoffmann JE, Sittinger M. Mechanical quality of tissue<br />
engineered cartilage: results after 6 and 12 weeks in vivo. J Biomed Mater Res. 2000;53(6):673-7.<br />
for more publications please visit http://www.ncbi.nlm.nih.gov/pubmed/<br />
53
54<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Institution<br />
Department of Orthopaedic Surgery<br />
Harvard Medical School<br />
Field of research<br />
Gene Therapy<br />
Biology of Bone and Joint Disease<br />
Christopher Evans<br />
PhD, Maurice Mueller Professor of Orthopaedic Surgery, Center for Advanced<br />
Orthopaedic Studies,Harvard Medical School<br />
Director<br />
BOSTON, USA<br />
cevans@bidmc.harvard.edu<br />
Scientific Work<br />
Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Tarner IH, Robbins PD, Evans CH, Sturz H,<br />
Steinmeyer J, Gay S, Pap T, Muller-Ladner U, Neumann E: Rheumatoid arthritis - evidence for synovial fibroblasts<br />
spreading the disease. Nature Med 15: 1414-1420, 2009<br />
Wehling P, Reinecke J, Baltzer AWA, Granrath M, Schulitz KP, Schultz C, Krauspe R, Whiteside TW, Elder E, Ghivizzani<br />
SC, Robbins PD, Evans CH: Clinical responses to gene therapy in joints of two subjects with rheumatoid<br />
arthritis. Hum Gene Ther 20: 97-101, 2009<br />
Evans CH, Liu FJ, Glatt V, Hoyland JA, Kirker-Head C, Walsh A, Betz O, Wells JW, Betz V, Porter RM, Saad FA, Gerstenfeld<br />
LC, Einhorn TA, Harris MB, Vrahas MS: Use of genetically modified muscle and fat grafts to repair defects<br />
in bone and cartilage. Eur Cells Mater 18: 96-111, 2009<br />
Evans CH, Ghivizzani SC, Robbins PD: Getting arthritis gene therapy into the clinic. Nature Rev Rheumatol 7: 244<br />
- 249, 2011<br />
Liu F, Porter RM, Wells J, Glatt V, Pilapil C, Evans CH: Evaluation of BMP-2 gene-activated muscle grafts for cranial<br />
defect repair. J Orthop Res 30:1095 - 1102, 2012.<br />
Membership of Scientific Societies and/or Associations<br />
1978 – present - Orthopaedic Research Society<br />
Past-President<br />
1981 – present - Royal Society of Chemistry<br />
Fellow<br />
1997 – present - Royal College of Pathologists<br />
Fellow<br />
2009 – present - Hastings Center<br />
Fellow
Danka Grčević<br />
MD, PhD<br />
Associate Professor<br />
ZAGREB, CROATIA<br />
dgrcevic@mef.hr<br />
Institution<br />
Department of Physiology and Immunology, Zagreb University School of Medicine<br />
Field of research<br />
Ostoimmunology, Bone biology<br />
Rheumatology, Hematology<br />
20 - 22 September 2012, Opatija, Croatia<br />
Scientific Work<br />
Cvija H, Kovacic N, Katavic V, Ivcevic S, Aguila HL, Marusic D, Grcevic D. Chemotactic and immunoregulatory<br />
properties of bone cells are modulated by endotoxin-stimulated lymphocytes. Inflammation 2012, accepted.<br />
Grcevic D, Pejda S, Matthews BG, Repic D, Wang L, Li H, Kronenberg MS, Jiang X, Maye P, Adams DJ, Rowe DW,<br />
Aguila HL, Kalajzic I. In vivo fate mapping identifies mesenchymal progenitor cells. Stem Cells 2012, doi: 10.1002/<br />
stem.780.<br />
Li H, Jiang X, Delaney J, Franceschetti T, Bilic-Curcic I, Kalinovsky J, Lorenzo J, Grcevic D, Rowe DW, Kalajzic I.<br />
Immature osteoblast lineage cells increase osteoclastogenesis in osteogenesis imperfecta murine. Am J Pathol<br />
2010;176:2405-13.<br />
Grcevic D, Jajic Z, Kovacic N, Lukic IK, Velagic V, Grubisic F, Ivcevic S, Marusic A. Arthritic patients could be distinguished<br />
by the peripheral blood expression profile of BMPs, tumor-necrosis factor-superfamily molecules and<br />
transcription factor Runx2. J Rheumatol 2010;37:246-56.<br />
Grcevic D, Lee SK, Marusic A, Lorenzo JA. Depletion of CD4 and CD8 T lymphocytes in mice in vivo enhances<br />
1,25OH-D3-stimulated osteoclast-like cell formation in vitro by a mechanism that is dependent on PG synthesis. J<br />
Immunol 2000;165:4231-4238.<br />
Membership of Scientific Societies and/or Associations<br />
European Calcified Tissue Society, since 2008<br />
American Association of Immunologists, since 2001<br />
Croatian Calcified Tissue Society, since 1999<br />
Croatian Immunological Society, since 1998; Vicepresident<br />
55
56<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Miroslav Hašpl<br />
MD, PhD, Full Professor<br />
Consultant Orthopaedic Surgeon and Head of Research<br />
KRAPINSKE TOPLICE, CROATIA<br />
miroslav.haspl@zg.t-com.hr<br />
Institution<br />
Special Hospital for Orthopaedic Surgery AKROMION<br />
Field of research<br />
Cartilage repair<br />
Knee surgery<br />
Scientific Work<br />
Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg<br />
F, Lagae K, van der Bauwhede J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J,<br />
Luyten FP.<br />
Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage<br />
defects of the knee in a randomized controlled trial versus microfracture.<br />
Am J Sports Med. 2008 Feb;36(2):235-46.<br />
Hundrić-Haspl Z, Pecina M, Haspl M, Tomicic M, Jukic I.<br />
Plasma cytokines as markers of aseptic prosthesis loosening.<br />
Clin Orthop Relat Res. 2006 Dec;453:299-304<br />
Haspl M, Bićanić G, Jelić M, Pećina M.<br />
Unicondylar knee arthroplasty with “Repicci” model<br />
Lijec Vjesn. 2005 Jul-Aug;127(7-8):172-6.<br />
Haspl M, Jelić M, Pećina M.<br />
Arthroplasty in treating knee osteoarthritis and proximal tibia stress fracture.<br />
Acta Chir Orthop Traumatol Cech. 2003;70(5):303-5.<br />
Pecina M, Haspl M, Jelic M, Vukicevic S.<br />
Repair of a resistant tibial non-union with a recombinant bone morphogenetic protein-7 (rh-BMP-7).<br />
Int Orthop. 2003;27(5):320-1. Epub 2003 Jun 17.<br />
Membership of Scientific Societies and/or Associations<br />
1995 EFORT (National delegate)<br />
1995 ESSKA<br />
1997 SICOT (National delegate)<br />
2000 UEMS, Section for Orthopaedics and Traumatology (National delegate)
Michael T. Hirschmann<br />
MD, PhD<br />
Consultant Orthopaedic Surgeon and Head of Research<br />
BRUDERHOLZ, SWITZERLAND<br />
Michael.Hirschmann@unibas.ch<br />
Institution<br />
Kantonsspital Baselland, Bruderholz, Department of Orthopaedic Surgery and Traumatology<br />
Field of research<br />
Orthopaedic imaging analysis<br />
Orthobiologic treatment (HTO, meniscal substitution, cartilage repair, deloader)<br />
Knee arthroplasty (UKR; TKR)<br />
Scientific Work<br />
39 Pubmed listed peer-reviewed scientific publications<br />
See pubmed Hirschmann MT<br />
Membership of Scientific Societies and/or Associations<br />
ESSKA<br />
SGOT<br />
AGA<br />
ISAKOS<br />
20 - 22 September 2012, Opatija, Croatia<br />
57
58<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Alan Ivković<br />
MD, PhD, Assistant Professor<br />
Consultant orthopaedic surgeon<br />
ZAGREB, CROATIA<br />
alan.ivkovic@gmail.com<br />
Institution<br />
Department of Orthopaedic Surgery, University Hospital Sveti Duh, Zagreb<br />
Department of Orthopaedic Surgery, St. Catherine’s Hospital, Zabok<br />
Department of Biotechnology, University of Rijeka<br />
Field of research<br />
Regenerative and molecular orthopaedics<br />
Biological joint reconstruction<br />
Scientific Work<br />
Ivković A, Pascher A, Hudetz D, Jelić M, Matičić D, Hašpl M, Windhager R, Pećina M. Articular<br />
Cartilage Repair by Genetically Modified Bone Marrow Aspirate in Sheep. Gene Therapy, 2010.<br />
Miller MA, Ivković A, Porter RM, Harris MB, Estok DM 2nd, Smith RM, Evans CH, Vrahas MS. Autologous bone<br />
grafting on steroids: preliminary clinical results. A novel treatment for nonunions and segmental bone defects.<br />
Int Orthop, 2011.<br />
Ivkovic A, Marijanovic I, Hudetz D, Porter RM, Pecina M, Evans CH. Regenerative medicine and tissue engineering<br />
in orthopaedic surgery. Front Biosci (Elite Ed) 2011<br />
Ivković A, Pascher A, Hudetz D, Jelić M, Hašpl M, Windhager R, Pećina M. Gene therapy of the<br />
musculoskeletal system. Acta Ortho Traum Checosl, 2006.<br />
Beyzadeoglu T, Onal A, Ivkovic A. Matrix-induced autologous chondrocyte implantation (MACI) for a large chondral<br />
defect in a professional football player: a case report. J Med Case Rep, 2012.<br />
Membership of Scientific Societies and/or Associations<br />
2003 – present, Croatian Orthopaedic and Traumatology Association, Member<br />
2007 – present, Orthopaedic Research Society, Junior Member<br />
2007 – present, International Cartilage Repair Society, Junior Member<br />
2007 – present, AO Alumni Organization, Instructor<br />
2007 – present, American Academy of Orthopaedic Surgeons, International Member<br />
2010 – present, Tissue Engineering International Regenerative Medicine Society, Member<br />
2012 - International Society of Orthopaedic Surgery and Traumatology,associate member
Mislav Jelić<br />
M.D.; Ph.D., Assistant Professor<br />
Head of the Biological Reconstruction Unit<br />
ZAGREB, CROATIA<br />
mjelic@mef.hr<br />
20 - 22 September 2012, Opatija, Croatia<br />
Institution<br />
Department of Orthopaedic Surgery, Clincal Hospital Center Zagreb, School of Medicine, University of Zagreb,<br />
Croatia<br />
Field of research<br />
Scaffolds and/or cells in articular cartilage regeneration<br />
Tendon grafts in ACL reconstruction<br />
Scientific Work<br />
Gomoll AH, Filardo G, Almqvist FK, Bugbee WD, Jelic M, Monllau JC, Puddu G, Rodkey WG, Verdonk P, Verdonk R,<br />
Zaffagnini S, Marcacci M. Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures.<br />
Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):468-86.<br />
Kon E, Filardo G, Drobnic M, Madry H, Jelic M, van Dijk N, Della Villa S. Non-surgical management of early knee<br />
osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):436-49.<br />
Vanlauwe J, Saris DB, Victor J, Almqvist KF, Bellemans J, Luyten FP; TIG/ACT/01/2000&EXT Study Group. Fiveyear<br />
outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects<br />
of the knee: early treatment matters. Am J Sports Med. 2011 Dec;39(12):2566-74.<br />
Grgurevic L, Macek B, Mercep M, Jelic M, Smoljanovic T, Erjavec I, Dumic-Cule I, Prgomet S, Durdevic D, Vnuk D,<br />
Lipar M, Stejskal M, Kufner V, Brkljacic J, Maticic D, Vukicevic S. Bone morphogenetic protein (BMP)1-3 enhances<br />
bone repair. Biochem Biophys Res Commun. Apr 29;408(1):25-31. 2011<br />
Ivkovic A, Pascher A, Hudetz D, Maticic D, Jelic M, Dickinson S, Loparic M, Haspl M, Windhager R, Pecina M. Articular<br />
cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther. 2010 Jun;17(6):779-89.<br />
Membership of Scientific Societies and/or Associations<br />
ESSKA cartilage committee, member<br />
ICRS communication committee, member until 2011<br />
YSOS (Young Scientists and Orthopaedic Surgeons Society, founding member (one of 3)<br />
Croatian Calcified Tissue Society, Board member<br />
59
60<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Ivan Martin<br />
PhD, professor<br />
Director of a Research group on Tissue Engineering<br />
BASEL, SWITZERLAND<br />
imartin@uhbs.ch<br />
Institution<br />
IUniversity Hospital Basel, Institute for surgical research and hospital management, Hebelstrasse 20, 4031 Basel<br />
Field of research<br />
Tissue Engineering<br />
3D cell culture<br />
Skeletal Tissue Repair<br />
Scientific Work<br />
Jakob M, Saxer F, Scotti C, Schreiner S, Studer P, Scherberich A, Heberer M, Martin I. Perspective on the evolution of<br />
cell-based bone tissue engineering strategies. Eur Surg Res (In Press)<br />
Martin I, Baldomero H, Bocelli-Tyndall C, Passweg J, Saris D, Tyndall A. The survey on cellular and engineered tissue<br />
therapies in Europe in 2010. Tissue Eng-A (In Press)<br />
Gueven S, Mehrkens A, Saxer F, Schaefer DJ, Martinetti R, Martin I, Scherberich A. Engineering of large osteogenic<br />
grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose<br />
tissue. Biomaterials 32:5801-5809 (2011)<br />
Martin I, Smith T, Wendt D. A roadmap for the bioreactor-based translation of tissue engineering strategies into<br />
clinical products. Trends Biotech 27(9): 495-502 (2009)<br />
Scherberich A, Galli R, Jaquiery C, Farhadi J, Martin I. 3D perfusion culture of human adipose tissue-derived endothelial<br />
and osteoblastic progenitors generates osteogenic constructs with intrinsic vascularization capacity. Stem<br />
Cells 25:1823-1829 (2007)<br />
Membership of Scientific Societies and/or Associations<br />
2010 – present, Journal “Biomaterials”, Editorial Board Member<br />
2008 – 2011, Journal “Tissue Engineering”, Executive Editorial Board Member<br />
2006 – present, Journal “Tissue Engineering and Regenerative Medicine”, Editorial Board Member<br />
2005 – 2011, TERMIS, Member of the Governing Board
20 - 22 September 2012, Opatija, Croatia<br />
Dušanka Martinović Kaliterna<br />
MD,PhD, Assist Professor, spec. of internal medicine, rheumatology and immunology<br />
Assist Professor<br />
Head of department<br />
SPLIT, CROATIA<br />
d.martinovic@inet.hr<br />
Institution<br />
Clinical hospital center of Split, Internal clinic, Department of rheumatology and clinical immunology<br />
Field of research<br />
clinical immunology and rheumatology<br />
rheumatology<br />
immunology<br />
Scientific Work<br />
Author of more than 50 papers, several books, mentor for 7 PhD, faculty member of EUSTAR course, investigator<br />
in two Croatian project and one EULAR project, member of org. comitty of Mediterranian congress of rheumatology.<br />
Nacci F, Righi A, Conforti ML, Miniati O, Fiori G, Martinovic D, Melchiorre D, Sapir T, Blank M, Shoenfeld Y, Moggi<br />
Pignone A, Matucci Cerinic M. Intravenous immunoglobulins (IVIG) improve the function and ameliorate joint<br />
involvement in systemic sclerosis: a pilot study. Ann Rheum Dis. 2007; 66:977-9.<br />
Buća A, Perković D, Martinović-Kaliterna D, Vlastelica M, Titlić M. Neuropsychiatric systemic lupus erythematosus:<br />
diagnostic and clinical features according to revised ACR criteria. Coll Antropol. 2009 Mar;33:281-8.<br />
Martinovic Kaliterna D, Perkovic D, Radic M. Churg-Strauss syndrome associated with montelukast therapy. J<br />
Asthma 2009;46:604-5.<br />
Radic M, Martinovic Kaliterna D, Fabijanic D, Radic J. Prevalence of systemic sclerosis in Split – Dalmatia county<br />
in Southern Croatia. Clin Rheumatol. 2010;29:419-21.<br />
Marasovic-Krstulovic D, Martinovic-Kaliterna D, Fabijanic D, Morovic-Vergles J. Are the anti-cyclic citrullinated<br />
peptide antibodies independent predictors of myocardial involvement in patients with active rheumatoid arthritis?<br />
Rheumatology (Oxford). 2011;50:1505-12.<br />
Membership of Scientific Societies and/or Associations<br />
Croatian ethic committee 1997-2007, member<br />
HLZ- Split, 2007 – vice president<br />
MEF Split, ethic committee member<br />
Immunology association, 2007-member of the board,<br />
61
62<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Mahmut Nedim Doral<br />
MD,PhD, professor<br />
Chairman of Orthopaedics and Traumatology Dept, Chairman of Sports Medicine<br />
Dept.<br />
ANKARA, TURKEY<br />
mndoral@gmail.com, ndoral@hacettepe.edu.tr<br />
Institution<br />
Hacettepe University, Department of Orthopaedics and Traumatology, Department of Sports Medicine<br />
Field of research<br />
Knee Injuries, Arthroscopy<br />
Achilles Tendon Endoscopic Surgery<br />
Scientific Work<br />
Doral MN, Bilge O, Batmaz G, Donmez G, Turhan E, Demirel M, Atay OA, Uzumcugil A, Atesok K, Kaya D. Treatment<br />
of osteochondral lesions of the talus with microfracture technique and postoperative hyaluronan injection. Knee<br />
Surg Sports Traumatol Arthrosc. 2012 Jul;20(7):1398-403<br />
Atesok K, Matsumoto T, Karlsson J, Asahara T, Atala A, Doral MN, Verdonk R, Li R, Schemitsch E. An emerging<br />
cell-based strategy in orthopaedics: endothelial progenitor cells. Knee Surg Sports Traumatol Arthrosc. 2012<br />
Jul;20(7):1366-77<br />
Kaya D, Doral MN, Nyland J, Toprak U, Turhan E, Donmez G, Citaker S, Atay OA, Callaghan MJ. Proprioception level<br />
after endoscopically guided percutaneous Achilles Tendon. Knee Surg Sports Traumatol Arthrosc. 2012 Apr 20.<br />
[Epub ahead of print]<br />
Anoka N, Nyland J, McGinnis M, Lee D, Doral MN, Caborn DN. Consideration of growth factors and bio-scaffolds<br />
for treatment of combined grade II MCL and ACL injury. Knee Surg Sports Traumatol Arthrosc. 2012<br />
May;20(5):878-88<br />
Bilge O, Doral MN, Atesok K, Atay OA, Donmez G, Turhan E, Uzumcugil A, Leblebicioglu G, Kaya D, Bilgili H, Sargon<br />
M. The effects of the synovium on chondrocyte growth: an experimental study. Knee Surg Sports Traumatol<br />
Arthrosc. 2011 Jul;19(7):1214-23<br />
Membership of Scientific Societies and/or Associations<br />
President Turkish Society of Orthopaedics & Traumatology (TOTBID) 2010-2011<br />
President European Federation of Sports Traumatology (EFOST) / 2001-2003<br />
President Asia-Pacific Knee Society (APKS / Knee Section of APOA) / 2004-2006<br />
Program Committee Member and Membership Committee Chairman of International Society of Arthroscopy,<br />
Knee Surgery & Orthopaedic Sports Medicine (ISAKOS) / 2007-2011
Srđan Novak<br />
MD,PhD, professor<br />
Head of Rheumatlogy and Clinical Immunology<br />
RIJEKA, CROATIA<br />
srdan.novak@ri.htnet.hr<br />
Institution<br />
KBC Rijeka, Department for internal medicine<br />
Field of research<br />
Rheumatoid arthritis<br />
Systemic sclerosis, systemic lupus erithematodes, spodyloarthrithis<br />
20 - 22 September 2012, Opatija, Croatia<br />
Scientific Work<br />
Novak S, Anic F, Luke-Vrbanic TS. Extremely high serum ferritin levels as a main diagnostic tool af adult-onset Stil`s<br />
disase. Rheumatol Int 2011: Feb26<br />
Novak S, Anić B, Anić F, Cerovac M, Čikeš N. Clinical significance of autoantibodies induced by infliximab treatment:<br />
two year follow–up after Infliximab discontinuation.Acta Dermatovenelol Croat 2011;19(3):156-160.<br />
Ravlić-Gulan J, Gulan G, Novak S, Duletic-Nacinovic A, Matovinovic D, Rukavina D.A comparison of lymphocyte<br />
subpopulations simultaneously on local and systemic levels in acute rheumatoid arthritis patients. Colll Antropol<br />
2005; 29:661-9<br />
Novak S, Čikeš N. Infliximab-induced lupus or rheumatoid arthriris (RA) overlapping with systemic lupus erythematosus<br />
(SLE) unmasked by infliximab. Clin Exp Rheumatol 2004; 22:268.<br />
Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F C, Bancel PE, Allanore DF, Müller-Ladner Y, Distler U, Iannone O,<br />
Pellerito F, Pileckyte R, Miniati M, Ananieva I, Gurman L, Damjanov AB, Mueller N, Valentini A, Riemekasten G, Tikly<br />
G, Hummers M, Henriques L, Caramaschi MJ, Scheja P, Rozman A, Ton B, Kumánovics E, Coleiro G, Feierl B, Szucs E,<br />
Von Mühlen G, Riccieri CA, Novak S, Chizzolini C, Kotulska A, Denton C, Coelho PC, Kötter I, Simsek I, de la Pena Lefebvre,<br />
Hachulla PG, Seibold E, Rednic JR, Stork S, Morovic-Vergles J, Walker JUA. Causes and risk factors for death<br />
in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis.<br />
2010; 69 (10): 1809-18015.<br />
Membership of Scientific Societies and/or Associations<br />
Croatian Reheumatology Society<br />
Croatian Clinical Immunology Society,<br />
EUSTAR<br />
63
64<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Krešimir Pavelić<br />
MD, PhD, professor<br />
Institution<br />
Department of Biotechnology,University of Rijeka,Croatia<br />
Krešimir Pavelić (1952) medical doctor, professor of molecular biology, Head, Department<br />
of Biotechnology, University of Rijeka, former director and establisher of<br />
Division of Molecular Medicine, Ruder Bošković Institute, Secretary General of the<br />
European Molecular Biology Conference (EMBC), EMBO member, member of Croatian<br />
Academy of Sciences and Arts and many others international scientific organisations, former vice-president of<br />
European Molecular Biology Conference, EMBC, Delegate of Croatian Academy of Sciences and Arts in European<br />
Science Foundation, President of the National Scientific Council, Republic of Croatia, former member of the parliamentarian<br />
committee for national scientific awards, expert for molecular medicine of the Trans radical party in<br />
the European Parliament. Krešimir Pavelić is ex officio member of the EMBO Council and member of the European<br />
Molecular Biology Laboratory. He has published 280 scientific papers in world top scientific journals and several<br />
invited review papers and chapters in prestigious journals and book published by American and European publishers.<br />
He significantly contributed to the understanding of biology of the transformed cell.
20 - 22 September 2012, Opatija, Croatia<br />
Marko Pećina<br />
Academician<br />
Professor emeritus<br />
Secretary of the Department of Medical Sciences – Croatian Academy of Sciencey<br />
and Arts<br />
Editor-in-Chief of the journal “InternationalOrthopaedics”<br />
ZAGREB, CROATIA<br />
marko.pecina@zg.t-com.hr<br />
Institution<br />
Department of Orthopaedic Surgery School of Medicine University of Zagreb<br />
Croatian Academy of Sciences and Arts<br />
SICOT<br />
Field of research:<br />
Orthopaedic surgery – sports traumatology<br />
Reparation/regeneration of musculoskeletal system<br />
Scientific Work<br />
Jelić M, Pećina M, Hašpl M, Kos J, Taylor K, Matičić D, McCartney J, Yin S, Rueger D, Vukičević S. Regeneration of<br />
Articular Cartilage Chondral Defects by Osteogenic Protein-1 (Bone Morphogenetic Protein-7) in Sheep. Growth<br />
factors 19 : 101 - 113, 2001.<br />
Pećina M, Jelić M, Martinović S, Hašpl M, Vukičević S. Articular cartilage repair: the role of bone morphogenetic<br />
proteins, Int Orthop 26 : 131 - 136, 2002.<br />
Pećina M, Bojanić I. Overuse Injuries of the Musculoskeletal System, 2nd Edition, CRC Press, Boca Raton- London<br />
- New York - Washington,DC, 2003.,<br />
Mihelić R, Pećina M, Jelić M, Zoričić S, Kušec V, Simić P, Bobinac D, Lah B, Legović D, Vukičević S. BMP-7 (OP-1)<br />
Promotes Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction in Sheep. Am J Sports Med 32 :<br />
1619 - 1625, 2004.<br />
Hundrić-Hašpl Ž, Pecina M, Haspl M, Tomicic M, Jukic I. Plasma Cytokines as Markers of Aseptic Prosthesis Loosening.<br />
Clin Orthop Relat Res 453 : 299 – 304, 2006.<br />
Membership of Scientific Societies and/or Associations<br />
1964 Croatian Medical Association<br />
1970 Croatian Orthopaedic Society, president 1997-2005<br />
1970 Yougoslav Orthopaedic and Traumatology Association, president 1988-1990<br />
1979 International Society of Orthopaedic Surgery and Traumatology (SICOT) , national delegate 1984-1990 and<br />
1992-2009, Editor from 2008<br />
1980 Societe Francaise de Chirurgie Orthopaedique et Traumatologique (So.F.C.O.T.)<br />
1982 European Spinal Deformity Society (ESDS) founder and vice-president 1989-1992<br />
1983 International Knee Society (IKS)<br />
1984 European Society for Sports Traumatology,Knee Surgery and Arthroscopy (ESSKA)<br />
1986 Hellenic Orthopaedic and Traumatology Society, honoured member<br />
1990 College Europeen de Traumatologie du Sport<br />
1992 Internatiional Association of Olympic Medical Officers<br />
1997 American Academy of Orthopaedic Surgeons, International Affiliate Member<br />
1999 European Calcified Tissue Society<br />
2000 International Federation of Sports Medicine<br />
2004 Czech Society for Orthopaedics and Traumatology, honoured member<br />
2005 Bone and Joint Decade 2000-2010, ambassador and national coordinator<br />
65
66<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Dragan Primorac<br />
MD, Ph.D.<br />
Professor<br />
Office of Dragan Primorac<br />
ZAGREB, CROATIA<br />
office@draganprimroac.org<br />
Institution<br />
Penn State University and University of New Haven USA, University of Split and University of Osijek, Republic of<br />
Croatia<br />
Field of research<br />
Pediatrics, Forensics, Bone Biology, Gene and Cellular Therapy<br />
Pediatrics, Forensic Genetics<br />
Origin of European Man (Y Chromosome Analysis)<br />
Scientific Work<br />
Stover M.L., Primorac D., Liu S.C., McKinstry M.B., and Rowe D.W. Defective Splicing of mRNA from One COL1A<br />
Allele of Type I Collagen in Nondeforming (Type I) Osteogenesis Imperfecta. J. Clin. Invest. 1993;92:1994-2002.<br />
Johnson C.V., Primorac D., Kinstry M.Mc, Rowe D.W, Lawrence J.B.. Tracking COL1A1 RNA in Osteogenesis Imperfecta:<br />
Splice-defective Transcripts Initiate Transport from the Gene but are Retained within the SC35 Domain. J Cell<br />
Biol. 2000; 150: 417-432<br />
Semino O, Passarino G, Oefner JP, Lin AA, Arbuzova S, Beckman EL, De Benedictis G, Francalacci P, Kouvatsi A,<br />
Limborska S, Marcikic M, Mika A, Mika Genetic Legacy of Paleolithic Homo sapiens sapiens in Extant Europeans: A<br />
Y B, Primorac D, Santachiara-Benerecetti AS, Cavalli-Sforza LL, Underhill AP. The Chromosome Perspective. Science<br />
2000; 290: 1155-1159.<br />
Battaglia V, Fornarino S, Al-Zahery N, Olivieri A, Pala M, Myres NM, King RJ, Rootsi S, Marjanovic D, Primorac D,<br />
Hadziselimovic R, Vidovic S, Drobnic K, Durmishi N, Torroni A, Santachiara-Benerecetti AS, Underhill PA, Semino O.<br />
Y-chromosomal evidence of the cultural diffusion of agriculture in southeast Europe. Eur J Hum Genet. 2008;1-11.<br />
Mršić G, Gršković B, Vrdoljak A, Popović M, Valpotić I, Anđelinović Š, Stenzl V, Ehler E, Urban L, Lacković G, Underhill<br />
P, Primorac D. Croatian national reference Y-STR haplotype database. Mol Biol Rep. 2012;39(7):7727-41<br />
Membership of Scientific Societies and/or Associations<br />
International Society of Applied Biological Sciences-ISABS (Founder)<br />
American Academy of Forensic Sciences-AAFS (Fellow)<br />
1997, ISABS, Founder<br />
1997, American Society for Human Genetics, Member<br />
1996, AAFS, Fellow<br />
2000, Hrvatsko društvo za humanu genetiku
Gian M. Salzmann<br />
MD,PhD<br />
Trauma and Knee surgery<br />
FREIBURG, GERMANY<br />
Gian.salzmann@uniklinik-freiburg.de<br />
20 - 22 September 2012, Opatija, Croatia<br />
Institution<br />
DepartmentDepartment of Orthopaedic and Trauma Surgery, University Medical Center, Albert-Ludwigs University<br />
Freiburg, Freiburg, Germany<br />
Field of research<br />
cartilage<br />
Scientific Work<br />
Schriftenverzeichnis<br />
entsprechend den Ausführungsbestimmungen der Habilitationsordnung<br />
(§ 6 Abs. 2 Nr. 5)<br />
(Stand 18.07.2012)<br />
a. Bei kumulativer Habilitationsschrift: Angabe<br />
der in die Habilitationsschrift einfließenden Arbeiten<br />
1. Salzmann GM, Nuernberger B, Schmitz P, Anton M,<br />
Stoddart MJ, Grad S, Milz S, Tischer T, Vogt S, Gansbacher<br />
B, Imhoff AB, Alini M. Physicobiochemical Synergism<br />
Through Gene Therapy and Functional Tissue Engineering<br />
for In Vitro Chondrogenesis. Tissue Eng Part A. 2009<br />
Mar 12.<br />
IF 4.636<br />
2. Salzmann GM, Paul J, Bauer JS, Woertler K, Sauerschnig<br />
M, Landwehr S, Imhoff AB, Schöttle PB. T2 assessment<br />
and clinical outcome following autologous<br />
matrix-assisted chondrocyte and osteochondral autograft<br />
transplantation. Osteoarthritis Cartilage. 2009<br />
Dec;17(12):1576-82. Epub 2009 Sep 1.<br />
IF 3.953<br />
3. Salzmann GM, Niemeyer P, Steinwachs M, Kreuz PC,<br />
Südkamp NP, Mayr HO. Cartilage repair approach and<br />
treatment characteristics across the knee joint: a European<br />
survey. Arch Orthop Trauma Surg. 2010 Jan 16.<br />
IF 1.196<br />
4. Salzmann GM, Buchberger MS, Stoddart MJ, Grad<br />
S, Milz S, Niemyer P, Sudkamp NP, Imhoff AB, Alini M.<br />
Varying regional topology within knee articular chondrocytes<br />
under simulated in vivo conditions. Tissue Eng<br />
Part A. 2011 Feb;17(3-4):451-61. Epub 2010 Oct 12.<br />
IF 4.636<br />
5. Salzmann GM, Sauerschnig M, Berninger MT,<br />
Kaltenhauser T, Schönfelder M, Vogt S, Wexel G, Tischer<br />
T, Sudkamp N, Niemeyer P, Imhoff AB, Schöttle PB. The<br />
dependence of autologous chondrocyte transplanta-<br />
tion on varying cellular passage, yield and culture duration.<br />
Biomaterials. 2011 Sep;32(25):5810-8. Epub 2011<br />
May 17.<br />
IF 7.882<br />
6. Grad S, Salzmann GM. Chondrocytes - one cell type,<br />
different subpopulations: Characteristics and behavior<br />
of different types of chondrocytes and implications for<br />
tissue engineering applications. Orthopade. 2009 Oct 4.<br />
IF 0.583<br />
7. Ueblacker P, Wagner B, Kruger A, Vogt S, DeSantis<br />
G, Kennerknecht E, Brill T, Hillemanns M, Salzmann GM,<br />
Imhoff AB, Plank C, Gansbacher B, Martinek V. Inducible<br />
nonviral gene expression in the treatment of osteochondral<br />
defects. Osteoarthritis and Cartilage. 2004 Sep;12(9)<br />
IF 3.953<br />
8. Ueblacker P, Wagner B, Vogt S, Salzmann G, Wexel G,<br />
Kruger A, Plank C, Brill T, Specht K, Hennig T, Schillinger<br />
U, Imhoff AB, Martinek V, Gansbacher B. In vivo analysis<br />
of retroviral gene transfer to chondrocytes within collagen<br />
scaffolds for the treatment of osteochondral defects.<br />
Biomaterials. 2007 Oct;28(30):4480-7.<br />
IF 7.882<br />
9. Vogt S, Wexel G, Tischer T, Schillinger U, Ueblacker<br />
P, Wagner B, Hensler D, Wilisch J, Geis C, Wübbenhorst<br />
D, Aigner J, Gerg M, Krüger A, Salzmann GM, Martinek<br />
V, Anton M, Plank C, Imhoff AB, Gansbacher B. The influence<br />
of the stable expression of BMP2 in fibrin clots<br />
on the remodelling and repair of osteochondral defects.<br />
Biomaterials. 2009 Apr;30(12):2385-92. Epub 2009 Jan<br />
31.<br />
IF 7.882<br />
10. Schätti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini<br />
M, Stoddart MJ. A combination of shear and dynamic<br />
compression leads to mechanically induced chondrogenesis<br />
of human mesenchymal stem cells. . Eur Cell<br />
Mater. 2011 Oct 11;22:214-25.<br />
IF 9.650<br />
67
68<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
b. als Ersautor<br />
1. Salzmann GM, Naal FD, von Knoch F, Tuebel J;<br />
Gradinger R, Imhoff AB, Schauwecker J. Effects of Cefuroxime<br />
on human osteoblasts in vitro. J Biomed Mater<br />
Res A. 2007 Aug;82(2):462-8.<br />
IF 3.044<br />
2. Salzmann GM, Walz L, Schoettle PB, Imhoff AB. Arthroscopic<br />
anatomical reconstruction of the acromioclavicular<br />
joint. Acta Orthop Belg. 2008 Jun;74(3):397-<br />
400.<br />
IF 0.392<br />
3. Salzmann GM, Paul J, Sandmann GH, Imhoff AB,<br />
Schöttle PB. The Coracoidal Insertion of the Coracoclavicular<br />
Ligaments: An Anatomic Study. Am J Sports Med.<br />
2008 Aug 28.<br />
IF 3.821<br />
4. Salzmann GM, Ahrens P, Spang J, El-Azab H, Imhoff<br />
AB, Lorenz S. Sporting activity after high tibial osteotomy<br />
for the treatment of medial compartment knee osteoarthritis.<br />
Am J Sports Med. 2008 Nov<br />
IF 3.821<br />
5. Salzmann GM, Spang JT, Imhoff AB.Double-bundle<br />
anterior cruciate ligament reconstruction in a skeletally<br />
immature adolescent athlete. Arthroscopy. 2009<br />
Mar;25(3):321-4<br />
IF 3.317<br />
6. Salzmann GM, Nuernberger B, Schmitz P, Anton M,<br />
Stoddart MJ, Grad S, Milz S, Tischer T, Vogt S, Gansbacher<br />
B, Imhoff AB, Alini M. Physicobiochemical Synergism<br />
Through Gene Therapy and Functional Tissue Engineering<br />
for In Vitro Chondrogenesis. Tissue Eng Part A. 2009<br />
Mar 12.<br />
IF 4.636<br />
7. Salzmann GM, Weber TS, Spang JT, Imhoff AB,<br />
Schöttle PB. Comparison of native axial radiographs<br />
with axial MR imaging for determination of the trochlear<br />
morphology in patients with trochlear dysplasia. Arch<br />
Orthop Trauma Surg. 2009 Jun 6.<br />
IF 1.196<br />
8. Salzmann GM, Paul J, Bauer JS, Woertler K, Sauerschnig<br />
M, Landwehr S, Imhoff AB, Schöttle PB. T2 assessment<br />
and clinical outcome following autologous<br />
matrix-assisted chondrocyte and osteochondral autograft<br />
transplantation. Osteoarthritis Cartilage. 2009<br />
Dec;17(12):1576-82. Epub 2009 Sep 1.<br />
IF 3.953<br />
9. Salzmann GM, Niemeyer P, Steinwachs M, Kreuz PC,<br />
Südkamp NP, Mayr HO. Cartilage repair approach and<br />
treatment characteristics across the knee joint: a European<br />
survey. Arch Orthop Trauma Surg. 2010 Jan 16.<br />
IF 1.196<br />
10. Salzmann GM, Buchberger MS, Stoddart MJ, Grad<br />
S, Milz S, Niemyer P, Sudkamp NP, Imhoff AB, Alini M.<br />
Varying regional topology within knee articular chondrocytes<br />
under simulated in vivo conditions. Tissue Eng<br />
Part A. 2011 Feb;17(3-4):451-61. Epub 2010 Oct 12.<br />
IF 4.636<br />
11. Salzmann GM, Walz L, Buchmann S, Glabgly P, Venjakob<br />
A, Imhoff AB. Arthroscopically assisted 2-bundle<br />
anatomical reduction of acute acromioclavicular joint<br />
separations. Am J Sports Med. 2010 Jun;38(6):1179-87.<br />
Epub 2010 May 4.<br />
IF 3.821<br />
12. Salzmann GM, Sauerschnig M, Berninger MT,<br />
Kaltenhauser T, Schönfelder M, Vogt S, Wexel G, Tischer<br />
T, Sudkamp N, Niemeyer P, Imhoff AB, Schöttle PB. The<br />
dependence of autologous chondrocyte transplantation<br />
on varying cellular passage, yield and culture duration.<br />
Biomaterials. 2011 Sep;32(25):5810-8. Epub 2011<br />
May 17.<br />
IF 7.882<br />
13. Salzmann GM, Sah B, Südkamp NP, Niemeyer P.<br />
Reoperative characteristics after microfracture of knee<br />
cartilage lesions in 454 patients. Knee Surg Sports Traumatol<br />
Arthrosc. 2012 Apr 8. [Epub ahead of print]<br />
IF 1.857<br />
14. Salzmann GM, Sah BR, Schmal H, Niemeyer P, Sudkamp<br />
NP. Microfracture for treatment of knee cartilage<br />
defects in children and adolescents. Pediatr Rep. 2012<br />
Apr 2;4(2):e21. Epub 2012 Jun 19.<br />
Noch kein IF, aber Pubmed gelistet<br />
Gesamtsumme Impact Factor als Erstautor: 43.572<br />
Membership of Scientific Societies and/or Associations<br />
AGA, ICRS; DGU
20 - 22 September 2012, Opatija, Croatia<br />
Asja Stipić Marković<br />
MD, PhD, professor of internal medicine, alergologist and clinical immunologist<br />
Head of department<br />
ZAGREB, CROATIA<br />
astipicm@inet.hr<br />
Institution<br />
Department of Clinical Immunology, Pulmology and Rheumatology, School of Medicine University of Zagreb,<br />
University Hospital “Sveti Duh”, Zagreb<br />
Field of research<br />
Allergology and clinical immunology<br />
allergology<br />
clinical immunology<br />
Scientific Work<br />
Pevec B, Radulovic Pevec M, Stipic Markovic A, Batista I, Rijavec M, Silar M, Kosnik M, Korosec P House dust<br />
mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes. Int Arch Allergy<br />
Immunol 2012;159:287-296<br />
Krmpotic D, Luzar-Stiffler V, Rakusic N, Stipic Markovic A, Hrga I, Pavlovic M.Effects of Traffic Air Pollution and<br />
Hornbeam Pollen on Adult Asthma Hospitalizations in Zagreb. Int Arch Allergy Immunol 2011;156:62-68<br />
Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet<br />
J, Braido F, Bruselle G, Canonica GW, Carlsen HK, Chanez P, Fokkens WJ, Garcia-Garcia M, Gjomarkai M, Haahtela<br />
T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska-Polak A, Lødrup-Carlsen K, Mäkelä M,<br />
Malkusova I, Mullol J, Nieto A, Østerberg-Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki I, Rukhadze<br />
M, Stipic-Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, M. Xatzipsalti M,<br />
Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations-A GA2LEN-DARE systematic review.<br />
Allergy 2011; 66(4): 458-68<br />
Pavlisa G, Pavlisa G, Kusec V, Kolonic SO, Markovic AS, Jaksic B. Serum Level of VEGF and bFGF in hypoxic patients<br />
with exacerbation of COPD. Eur Cytokine Network 2010; 21: 92-98<br />
Markovic AS, Pekic P, Schmidt S, Stulhofer-Buzina D. Small and large bowel manifestation of of leukocytoclastic<br />
vasculitis– A Case Report. Wien Klin Wochenschr 2005;115(9):302-308<br />
Membership of Scientific Societies and/or Associations<br />
2004-present, Croatian Society of Allergology and Clinical Immunology, President<br />
2008-present, Croatian Society of Immunology,member of Executive Board<br />
2010-present, Croatian Society of Internal Medicine, Vicepresident<br />
1986-present, European Academy of Allergology and Clinical Immunology, member<br />
69
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Martin James Stoddart<br />
PhD, Principal Investigator<br />
DAVOS PLATZ, SWITZERLAND<br />
Martin.stoddart@aofoundation.org<br />
Institution<br />
AO Research Institute Davos, Musculoskeletal Regeneration Program<br />
Field of research<br />
Mesenchymal stem cells for regenerative medicine treatment of cartilage and bone defects<br />
Mechanoregulation of stem cell fate<br />
Scientific Work<br />
Stoddart MJ, Ettinger L, Hauselmann HJ. Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue<br />
subjected to compression and shear. Biotechnol Bioeng. 95(6):1043-51, 2006<br />
Palmer GD, Stoddart MJ, Gouze E, Gouze J-N , Ghivizzani SC, Porter RM, and Evans CH A simple, lanthanide-based<br />
method to enhance the transduction efficiency of adenovirus vectors. Gene Ther. 15(5):357-63, 2008<br />
Li Z, Kupcsik L, Yao S, Alini M, Stoddart MJ. Chondrogenesis of Human Bone Marrow Mesenchymal Stem Cells in<br />
Fibrin-polyurethane Composites Compared to Pellet Culture. Tissue Eng Part A. 2009 15(7):1729-37.<br />
Li Z, Kupcsik L, Yao SJ, Alini M, Stoddart MJ. Mechanical Load Modulates Chondrogenesis of Human Mesenchymal<br />
Stem Cells through the TGF-β Pathway. J Cell Mol Med. 2010 ;14(6A):1338-46.<br />
O Schätti, S Grad, J Goldhahn, G Salzmann, Z Li, M Alini, MJ Stoddart. A combination of shear and dynamic compression<br />
leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur Cell Mater. 2011<br />
Oct 11;22:214-25.<br />
Membership of Scientific Societies and/or Associations<br />
Since 2001, ICRS, Member<br />
Since 2006, ORS, Member<br />
Since 2010, Faculty of 1000 Medicine- Associate Faculty Member<br />
Since 2011, eCells and Materials Journal, Scientific Editor
20 - 22 September 2012, Opatija, Croatia<br />
Carmen Terzic<br />
MD, PhD, Associate Professor of Medicine and Physical Medicine and Rehabilitation<br />
Chair, Department of Physical Medicine and Rehabilitation<br />
ROCHESTER, MN, USA<br />
terzic.carmen@mayo.edu<br />
Institution<br />
Mayo Clinic; Department of Physical Medicine and Rehabilitation<br />
Field of research<br />
Stem cell regenerative medicine<br />
Cardiovascular rehabilitation<br />
Scientific Work<br />
Faustino RS, Chiriac A, Niederlander N, Nelson TJ, Behfar A, Mishra PK, Macura S, Michalak M, Terzic A, Perez-Terzic<br />
C. Decoded calreticulin-deficient embryonic stem cell transcriptome resolves in latent cardiophenotype, Stem<br />
Cells 2010<br />
Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C, Terzic A. Somatic<br />
oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming.<br />
Cell Metab 2011<br />
Baker DJ, Perez-Terzic C, Jin F, Pitel KS, Niederlander NJ, Jeganathan K, Yamada S, Reyes S, Rowe L, Hiddinga HJ,<br />
Eberhardt NL, Terzic A, van Deursen JM. Opposing roles for p16Ink4a and p19Arf in senescence and aging caused<br />
by BubR1 insufficiency. Nat Cell Biol 2008<br />
Perez-Terzic C, Faustino RS, Boorsma BJ, Arrell DK, Niederlander NJ, Behfar A, Terzic A. Stem cells transform into a<br />
cardiac phenotype with remodeling of the nuclear transport machinery. Nat Clin Pract Cardiovasc Med 2007<br />
Membership of Scientific Societies and/or Associations<br />
2000-present, American Academy of Physical Medicine and Rehabilitation, Diplomate<br />
2000-present, American Board of Physical Medicine and Rehabilitation, Member<br />
2005-present, American Society of Clinical Pharmacology and Therapeutics, Member<br />
1998-present, American Medical Assocation, Member<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Institution<br />
Mayo Clinic<br />
Field of research<br />
Regenerative medicine<br />
Cardiovascular medicine<br />
Stem cell biology<br />
Andre Terzic<br />
MD, PhD, Professor of Medicine and Pharmacology<br />
Director, Center for Regenerative Medicine; Mayo Clinic<br />
ROCHESTER, MN, USA<br />
terzic.andre@mayo.edu<br />
Scientific Work<br />
Behfar A, Terzic A. Derivation of a cardiopoietic population from human mesenchymal stem cells yields functional<br />
cardiac progeny. Nature Clin Pract Cardiovasc Med 2006.<br />
Perez-Terzic C, Faustino RS, Boorsma BJ, Arrell DK, Niederlander NJ, Behfar A, Terzic A. Stem cell transformation<br />
into cardiac phenotype guided by directed remodeling of nuclear transport machinery. Nature Clin Pract Cardiovasc<br />
Med, 2007<br />
Behfar A, Perez-Terzic C, Faustino RS, Arrell DK, Hodgson DM, Yamada S, Puceat M, Niederländer N, Alekseev AE,<br />
Zingman LV, Terzic A. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J Exp Med<br />
2007.<br />
Nelson TJ, Martinez-Fernandez A, Terzic A. Induced pluripotent stem cells: developmental biology to regenerative<br />
medicine. Nature Cardiol Rev, 2010.<br />
Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C, Terzic A. Somatic<br />
oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming.<br />
Cell Metab, 2011<br />
Membership of Scientific Societies and/or Associations<br />
Past President, American Society for Clinical Pharmacology and Therapeutics<br />
Chair, Functional Genomics and Translational Biology Council, American Heart Association<br />
Chair, Scientific Advisory Board, International Society for Cardiovascular Translational Research
Gamze Torun Köse<br />
PhD, professor<br />
Vice Head of Department<br />
ISTAMBUL, TURKEY<br />
gamzekose@yeditepe.edu.tr<br />
20 - 22 September 2012, Opatija, Croatia<br />
Institution<br />
Yeditepe University, Faculty of Engineering and Architecture, Department of Genetics and Bioengineering<br />
Field of research<br />
Cartilage repair – basic and clinical research<br />
Knee and ankle reconstructive surgery<br />
Scientific Work<br />
Ö.Karadas, D.Yücel, H.Kenar, G.T.Köse, V.Hasırcı, Bone Tissue Engineering Using Collagen Calcium Phosphate Composite<br />
Scaffolds And Stem Cells From Wharton’s Jelly And Menstrual Blood, Journal of Tissue Engineering and<br />
Regenerative Medicine, 2012<br />
A.B.Ertan, P.Yılgor, B.Bayyurt, Ayşe Ceren Çalıkoğlu, Ç.Kaspar, F.N.Kök, G.T.Köse*, V.Hasirci, Effect of Double Growth<br />
Factor Release on Cartilage Tissue Engineering, Journal of Tissue Engineering and Regenerative Medicine, DOİ:<br />
10.1002/term.509, 2011<br />
H.Kenar, G.Torun Kose, M.Toner, D.L. Kaplan, V.Hasirci, A 3D Aligned Microfibrous Myocardial Tissue Construct<br />
Cultured under Transient Perfusion, Biomaterials, 32:23, 5320-5329, 2011<br />
D.Yücel, G.T.Köse, V.Hasırcı, Tissue Engineered, Guided Nerve Tube Consisting of Aligned Neural Stem Cells and<br />
Astrocytes, Biomacromolecules, 11, 3584–3591, 2011.<br />
M.E.Yalvac, M.Ramazanoglu,A.A.Rizvanov, F.Sahin, O.F.Bayrak, U.Salli, A.Palota´s, G.T. Köse, Isolation and characterization<br />
of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization,<br />
osteo-, adipo- and neurogenesis, Pharmacogenomics Journal, 10, 105-113, 2010<br />
Membership of Scientific Societies and/or Associations<br />
2008+, Turkish Biomaterials and Tissue Engineering Society, One of the Founding Members<br />
2007+, Turkish Artificial Organs Society (TUYOD)<br />
2005+, Tissue Engineering and Regenerative Medicine International Society (TERMIS)<br />
2005, European Tissue Engineering Society (ETES)<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Matjaž Vogrin<br />
MD, PhD<br />
Orthopaedic surgeon, Head of Orthopaedic Departement<br />
MARIBOR, SLOVENIA<br />
Matjaz.vogrin@ukc-mb.si<br />
Institution<br />
Department: Orthopaedic Surgery, University Hospital Maribor<br />
Field of research<br />
Sports medicine<br />
Arthroscopic surgery<br />
Scientific Work<br />
VOGRIN, Matjaž, RUPREHT, Mitja, DINEVSKI, Dejan, HAŠPL, Miroslav, KUHTA, Matevž, JEVŠEK, Marko, KNEŽEVIĆ,<br />
Miomir, ROŽMAN, Primož. Effects of a platelet gel on early graft revascularization after anterior cruciate ligament<br />
reconstruction: A prospective, randomized, double-blind, clinical trial. Eur. surg. res., 2010, vol. 45, no. 2, str. 77-85<br />
VOGRIN, Matjaž, RUPREHT, Mitja, CRNJAC, Anton, DINEVSKI, Dejan, KRAJNC, Zmago, REČNIK, Gregor. The effect<br />
of platelet-derived growth factors on knee stability after anterior cruciate ligament reconstruction: a prospective<br />
randomized clinical study. Wien. klin. Wochenschr., Suppl., 2010, vol. 122, suppl. 2, str. 91-95<br />
KRAJNC, Zmago, VOGRIN, Matjaž, REČNIK, Gregor, CRNJAC, Anton, DROBNIČ, Matej, ANTOLIČ, Vane. Increased<br />
risk of knee injuries and osteoarthritis in the non-dominant leg of former professional football players. Wien. klin.<br />
Wochenschr., Suppl., 2010, vol. 122, suppl. 2, str. 40-43<br />
VOGRIN, Matjaž. The role of growth factors in ACL surgery. V: DORAL, Mahmut Nedim (ur.). Sports injuries : prevention,<br />
diagnosis, treatment and rehabilitation. Berlin; Heidelberg: Springer, 2011, cop. 2012, str. 443-447<br />
VOGRIN, Matjaž, KUHTA, Matevž. Anterior ankle impingement. V: DORAL, Mahmut Nedim (ur.). Sports injuries :<br />
prevention, diagnosis, treatment and rehabilitation. Berlin; Heidelberg: Springer, 2011, cop. 2012, str. 635-638<br />
Membership of Scientific Societies and/or Associations<br />
slovenia orthopaedic association<br />
EFOST
Institution<br />
College of Medicine, Mayo Clinic<br />
Field of research<br />
Cancer, immunotherapy, cellular therapy<br />
20 - 22 September 2012, Opatija, Croatia<br />
Stanimir Vuk-Pavlović<br />
Professor of Biochemistry and Molecular Biology<br />
Scientist; Consultant, Division of Hematology, Department of Internal Medicine,<br />
Mayo Clinic<br />
Director Emeritus (1996-2010), Stem Cell Laboratory, Mayo Clinic Cancer Center<br />
ROCHESTER, MINNESOTA, USA<br />
vuk@mayo.edu<br />
Scientific Work<br />
Kogan, Y., Halevi-Tobias, K., Elishmereni, M., Vuk Pavlović, S., Agur, Z.: Reconsidering the paradigm of cancer immunotherapy<br />
by computationally aided real-time personalization.<br />
Cancer Res., 72: 2218-2227, 2012.<br />
Agur, Z., Vuk-Pavlović, S.: Mathematical modeling in immunotherapy of cancer: Personalizing clinical trials. Molecular<br />
Therapy, 20: 1-2, 2012.<br />
Gomez, C.R., Knutson, G.J., Clifton, K.B., Schreiber, C.A., Vuk-Pavlović, S.: Age-dependent response of murine<br />
female bone marrow cells to hyperbaric oxygen. Biogerontology, DOI 10.1007/s10522-012-9373-8, 2012.<br />
Kronik, N., Kogan, Y., Elishmereni, M., Halevi–Tobias, K., Vuk Pavlović, S., Agur, Z.: Predicting outcomes of prostate<br />
cancer immunotherapy by personalized mathematical models. PLoS ONE 5(12), 2010: e15482. doi:10.1371/journal.pone.0015482.<br />
Vuk-Pavlović, S., Bulur, P.A., Lin, Y., Qin, R., Szumlanski, C.L., Zhao, X., Dietz, A.B.: Immunosuppressive CD14+H-<br />
LA-DRlow/– monocytes in prostate cancer. Prostate, 70: 443-455, 2010.<br />
Membership of Scientific Societies and/or Associations<br />
American Association for Cancer Research (1987–)<br />
American Society of Biochemists and Molecular Biologists (1987–)<br />
International Society of Cell Therapy (1996–)<br />
International Society for Applied Biological Sciences (Zagreb; 2004–)<br />
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2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
Institution<br />
Institution full name, Department<br />
Knie&Sport.Wien<br />
Soccerclinic Vienna<br />
Patrick Weninger<br />
Assoc. Professor MD<br />
Consultant orthopaedic sports and trauma surgeon<br />
Chief Medical Officer Austrian Tennis Federation<br />
CMO Austrian Badminton Federation<br />
CMO Austrian Hockey Federation<br />
Team Physician Austrian Soccer Board<br />
VIENNA, AUSTRIA<br />
ordination@dr-weninger.at<br />
Field of research<br />
Arthroscopic meniscal and ACL repair, bioscaffolds, PRP augmentation<br />
Biological ACL repair<br />
Biological meniscus repair<br />
Scientific Work<br />
Weninger et al. Single leg spinal anaesthesia for arthroscopic meniscus and ACL surgery, JBJS Am 2012. (accepted)<br />
Weninger et al. Outpatient meniscal repair: a cost-effectiveness analysis. Am J Sports Surg. 2012 (accepted)<br />
Weninger et al. Perfusion of the pes anserinus. Implcations for biological ACL repair using hamstring tendons. J<br />
Trauma, 2012. (accepted).<br />
Weninger et al. Anterior cruciate ligament reconstruction using autografts and double biodegradable femoral<br />
cross-pin fixation: functional, radiographic and MRI outcome after 2-year minimum follow-up. KSSTA. 2008<br />
Membership of Scientific Societies and/or Associations<br />
Austrian Society of Trauma Surgery<br />
AGA<br />
ESSKA<br />
ISAKOS
20 - 22 September 2012, Opatija, Croatia<br />
77
fondaparinuks<br />
<strong>Profilaksa</strong> <strong>DVT</strong> <strong>kod</strong> <strong>velikih</strong><br />
<strong>ortopedskih</strong> <strong>operacija</strong><br />
ARIXTRA ® (fondaparinuksnatrij) 2,5 mg/0,5 ml otopina za injekciju u napunjenoj štrcaljki. Terapijske indikacije: Prevencija venskih tromboembolijskih događaja (VTD) u bolesnika<br />
koji se podvrgavaju velikom ortopedskom kirurškom zahvatu na donjim ektremitetima poput operacije frakture kuka, velike operacije koljena ili ugradnje umjetnog kuka; Prevencija<br />
venskih tromboembolijskih događaja (VTD) u bolesnika koji se podvrgavaju abdominalnom kirurškom zahvatu, a u kojih postoji visoki rizik nastanka tromboembolijskih komplikacija, npr.<br />
<strong>kod</strong> 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<br />
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<br />
bez elevacije ST-segmenta (UA/NSTEMI) u bolesnika u kojih nije indicirano hitno (
POSTER<br />
PRESENTATIONS<br />
20 - 22 September 2012, Opatija, Croatia<br />
79
80<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
DNA DEMETHYLATING AGENT 5-AZACYTIDINE NEGATIVELY<br />
AFFECTS PROLIFERATION OF MAMMALIAN LIMB BUD CELLS IN<br />
AN ORGAN-CULTURE SYSTEM<br />
Vedrana Mužić, University of Zagreb, School of Medicine, Department of Biology, Department of<br />
Rehabilitation and Orthopaedic Devices, Clinical Hospital Centre Zagreb, Zagreb, Croatia<br />
Gordana Jurić-Lekić, University of Zagreb, School of Medicine, Departmentof Histology and Embryology<br />
Zagreb, Zagreb, Croatia<br />
Marta Himelreich, University of Zagreb, School of Medicine, Department of Histology and Embryology<br />
Zagreb, Croatia<br />
Željka Majić, University of Zagreb, School of Medicine, Department of Biology, Zagreb, Croatia<br />
Nino Sinčić, University of Zagreb, School of Medicine, Department of Biology Zagreb, Croatia<br />
Ana Katušić, University of Zagreb, School of Medicine, Department of Biology Zagreb, Croatia<br />
Maja Vlahović, University of Zagreb, School of Medicine, Department of Biology Zagreb, Croatia<br />
Ljiljana Šerman, University of Zagreb, School of Medicine, Department of Biology, Zagreb, Croatia<br />
Jelena Lončarević, University of Zagreb, School of Medicine, Departmentof Histology and Embryology,<br />
Zagreb, Croatia<br />
Floriana Bulić-Jakuš, University of Zagreb, School of Medicine, Department of Biology, Zagreb, Croatia<br />
Epigenetic drug, DNA demethylating agent 5-azacytidine (5azaC), impairs overall growth of ex vivo cultivated<br />
rat limb buds. The aim of this investigation was to assess proliferative capacity of rat limb buds cultivated with<br />
5azaC at the single cell level. 13-days-old embryos were isolated from pregnant Fisher rat females and limb buds<br />
were microsurgically isolated under the stereomicroscope. They were cultivated in an organ-culture system at the<br />
air-liquid interface in MEM and 50% rat serum. 5-azacytidine (5mmol) was added to the culture medium. During<br />
the second week, explants were processed for immunohistochemistry on Anti-Proliferating Cell Nuclear Antigen<br />
(PCNA). PCNA positive cells were stereologically evaluated using numerical density (Nv) and results were statistically<br />
compared with Student’s t-test. In both fore-limb and hind-limb explants, either treated or controls, differentiation<br />
proceeded in comparison to 13-days-old limb buds. PCNA was expressed in some cells of the cartilage,<br />
stratified squamous epithelium and mesenchyme. Nv values for PCNA were significantly lower (p
20 - 22 September 2012, Opatija, Croatia<br />
RESULTS OF 2 ND GENERATION AUTOLOGOUS CHONDROCYTE<br />
IMPLANTATION IN THE MANAGEMENT OF FOCAL ARTICULAR<br />
CARTILAGE DEFECTS<br />
Rutul Gandhi, B J Medical College, Ahmedabad, India<br />
BACKGROUND: Autologous Chondrocyte Implantation is the most widely used cell based surgical procedure for<br />
the repair of articular cartilage defects. Both short term and long term results are reported to be good or excellent<br />
in 80 to 95 percent of cases. MRI has emerged as the procedure of choice for assessment of graft survival and cartilage<br />
maturation after ACI and for predicting outcome and directing rehabilitation. In this study we intend to assess<br />
the results of ACI in patients with focal articular defects and correlating the MRI findings with clinical outcome.<br />
MATERIALS AND METHODS: Since July 2010, 12 patients with focal articular cartilage defects grade 3 or 4 according<br />
to ICRS grading were treated with ACI. IKDC knee scores were calculated pre operatively and then at 6 months<br />
and then at 12 months. All patients completed subjective knee evaluation forms before and at 6 months and 1<br />
year after surgery. MRI was performed post procedure at 12 weeks and then at 12 months and MOCART scoring<br />
done based on the studies. All adverse events recorded and all data analysed using appropriate tests.<br />
OBSERVATIONS AND RESULTS:<br />
1. Subjective evaluation and functional status: There was a significant improvement in the patients subjective<br />
knee score from a mean of 40.5 points to 88.5 points at the end of 12 months. Before operation only 25%<br />
graded their knee function as level I or II which significantly improved to 75% having grade I or II at 12 months<br />
2. IKDC clinical score: Before operation 75% were classified as A or B using the IKDC objective scoring criteria,<br />
which deteriorated to only 33.3% rated as A or B at 6 months. However again at 12 months there was a significant<br />
clinical recovery with 83.3% rated as A or B.<br />
3. MRI results and MOCART scores: The mean MOCART scores at 6 months were 80 which improved to 90 at 12<br />
months. At 6 months 50% lesions showed normal or nearly normal scores which improved to 83.3% lesions<br />
been graded as normal or nearly normal at 12 months.<br />
CONCLUSIONS: ACI has emerged as one of the leading treatment strategies in management of focal articular<br />
defects. These superior results are attributed to the capacity of ACI to produce hyaline articular cartilage. We recommend<br />
12 months MRI to be a reasonable non invasive means of assessing the maturation of the graft after ACI.<br />
Poster<br />
81
82<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
ARTHROPLASTY BY DEMINERALIZED OSTEOCHONDRAL<br />
ALLOGRAFTS AS AN ALTERNATIVE TO EARLY TOTAL HIP<br />
ARTHROPLASTY IN CHILDREN WITH THE SEQUELAE OF<br />
OSTEOMYELITIS<br />
Yury Garkavenko, The Turner Scientific and Research Institute for Children’s Orthopedics, Saint-Petersburg –<br />
Pushkin, Russian Federation<br />
Alexandr Pozdeev, The Turner Scientific and Research Institute for Children’s Orthopedics, Saint-Petersburg –<br />
Pushkin, Russian Federation<br />
In the period from one to 26 years, the results were studied of the hip arthroplasty by demineralized osteochondral<br />
allografts in 52 patients with sequelae of osteomyelitis of the hip operated at the The Turner Research Institute<br />
for Children’s Orthopedics.<br />
The initial state of the affected hip with destructive hip dislocation was in 56 per cent of patients, in one third of<br />
patients was an ankylosis of the joint in a vicious position, and in 13% of patients was severe flexion-adduction<br />
contracture on the background of coxarthrosis, requiring joint stabilization and restoration of function.<br />
If indicated, the hip arthroplasty with the use of one or two demineralized osteochondral allografts was supplemented<br />
by shortening osteotomy of the femur in its lower third.<br />
The study has shown that in more than a half of the patients, namely in 27 (52%), flexion in the operated hip exceeded<br />
80°, reaching 100° or more in 7 (13.5%) patients.<br />
In the late followup, in all 16 patients with initial ankylosis of the hip the range of motion in at least two planes<br />
has preserved. However, only in four patients (25%) of them the flexion did not exceed 45°, while in the remaining<br />
cases (75%) it exceeded 60°, reaching 100° or more in 9 (56.2%) patients.<br />
Despite the increase in number of patients during later followup with limited range of motion in the operated hip,<br />
the preservation of a sufficient range of flexion beyond 80º was observed in patients even 10-15 years (33.3%), and<br />
even 16-20 years (66, 6%) after performed arthroplasty.<br />
The results presented here provide a basis to consider the arthroplasty with the use of demineralized osteochondral<br />
allografts as an alternative to the early total hip arthroplasty in children with destructive changes in the proximal<br />
femur.<br />
Poster
20 - 22 September 2012, Opatija, Croatia<br />
HIP AND KNEE OSTEOARTHRITIS SUSCEPTIBILITY AND<br />
ASSOCIATION WITH IL1 GENE CLUSTER IN CROATIAN<br />
POPULATION<br />
Zdravko Jotanovic, Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka,<br />
Croatia<br />
Marikken Heiland Kaarvatn, Molecular Genetics Laboratory, Department of Oral Biology, University of<br />
Oslo, Norway<br />
Godfrey Essien Etokebe, Molecular Genetics Laboratory, Department of Oral Biology, University of Oslo,<br />
Norway<br />
Radovan Mihelic, Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka, Croatia<br />
Biserka Mulac-Jericevic, Department of Physiology and Immunology, School of Medicine, University of<br />
Rijeka, Croatia<br />
Tamara Tijanic, Department of Physiology and Immunology, School of Medicine, University of Rijeka,<br />
Croatia<br />
Sanja Balen, Clinical Institute for Transfusion Medicine, Universal Hospital Center Rijeka, School of<br />
Medicine, University of Rijeka, Croatia<br />
Branko Sestan, Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka, Croatia<br />
Zlatko Dembic, Molecular Genetics Laboratory, Department of Oral Biology, University of Oslo, Norway<br />
Osteoarthritis (OA) is a degenerative, chronic, progressive and multifactorial disease of the joints that causes degenerative<br />
changes in articular cartilage, but also causes pathological changes in other parts of the joint. It is<br />
the most common chronic musculoskeletal disease with complex genetic risk, and represents a leading cause of<br />
disability in elderly population worldwide. The risk for primary OA is polygenic in nature, with risk differing among<br />
various human subpopulations. One of the factors involved in the genetic predisposition to both hip OA (HOA)<br />
and knee OA (KOA) is the interleukin-1 (IL-1) gene cluster located on chromosome 2. Using case-control study in<br />
a Croatian Caucasian population with 500 OA patients, of which 240 KOA patients with total knee replacement<br />
(TKR) or partial knee replacement (PKR) and 260 HOA patients with total hip replacement (THR), and 508 healthy<br />
blood donors as controls, we have mapped genetic polymorphisms at 4 loci, comprising three SNPs: IL1A -889<br />
(C>T), IL1B +3594 (C>T) and -511 (G>A), and a VNTR in the IL1RN gene. Further analyses were done by assembling<br />
haplotypes using our previous reports on markers for the same population (the IL1B -511C>T SNP and the IL1RN<br />
VNTR). Our results are consistent with a hypothesis that inflammatory factors like IL-1 are implicated in pathogenesis<br />
of primary OA.<br />
Poster<br />
83
84<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
THE TENDON STEM/ PROGENITOR CELL NICHE: IS THERE A<br />
BLOOD TENDON BARRIER?<br />
Christine Lehner, University Hospital Salzburg, Salzburg, Austria<br />
Renate Gehwolf, Paracelsus Medical Univerity, Salzburg, Austria<br />
Andrea Wagner, Paracelsus Medical Univerity, Salzburg, Austria, University of Salzburg, Austria<br />
Hans-Christian Bauer, Paracelsus Medical Univerity, Salzburg, Austria<br />
Herbert Tempfer, Paracelsus Medical Univerity, Salzburg, Austria<br />
A major challenge for attempts to accelerate tendon healing is to understand the niche that regulates the differentiation<br />
of stem/ progenitor cells towards a tendon cell like phenotype.<br />
Along our attempts to characterize tendon cells we observed a population of perivascular cells expressing tendon-<br />
and neuronal stem cell associated markers. Moreover we observed that tendon endothelial cells express<br />
the tight junction (TJ) associated marker Occludin. We therefore hypothesise that tendon vessels form a barrier<br />
between blood and tendon tissue, establishing a privileged microenvironment.<br />
By immunohistochemistry, Lasermicrodissection, qRT-PCR and transmission electron microscopy we examined<br />
human biceps and semitendinosus tendons and mouse Achilles tendons for TJ associated markers and structures.<br />
Occludin, Claudin5 and ZO1 protein localize at the cell boundaries of tendon endothelial cells, as confirmed by<br />
confocal microscopy of isolated tendon vessels. Besides, these cells express mRNA encoding for the blood-brain<br />
barrier/ blood nerve barrier associated markers Occludin, Claudin1, Claudin5 and Claudin11.<br />
The finding of TJ- like structures in human tendons is confirmed by TEM images published by others.<br />
The finding of TJ- like structures in tendons may shed new light on the composition of the tendon niche. The functional<br />
properties and the role of this barrier in tendon de- and regeneration will have to be addressed by further<br />
studies.<br />
Poster
20 - 22 September 2012, Opatija, Croatia<br />
OSTEOGENIC POTENTIAL AND STEMNESS OF MESENCHYMAL<br />
STEM CELLS AFTER DEXAMETHASONE TREATMENT<br />
Igor Matić, Faculty of Science, University of Zagreb, Zagreb, Croatia<br />
Alan Ivković, Clinical Hospital Sveti Duh, Zagreb, Zagreb, Croatia<br />
Šime Brkić, Faculty of Science, University of Zagreb, Zagreb, Croatia<br />
Pavle Josipović, Faculty of Science, Univeristy of Zagreb, Zagreb, Croatia<br />
Ivan Karlak, Clinic for Traumatology, Zagreb, Zagreb, Croatia<br />
Marko Pećina, School of Medicine, University of Zagreb, Zagreb, Croatia<br />
Inga Marijanović, Faculty of Science, University of Zagreb, Zagreb, Croatia<br />
The purpose of the research was to improve osteogenic differentiation of human bone marrow derived-mesenchymal<br />
stem cells (hMSCs) and to evaluate the level of remaining undifferentiated stem cells in culture. Standard<br />
cell culture protocol includes continuous exposure to the dexamethasone which is not easy to reproduce in human<br />
body. Therefore, our experiment was designed to investigate the possibility of using short-term dexamethasone<br />
exposure in order to induce osteogenic differentiation.<br />
Human bone marrow-derived MSCs were expanded with FGF-2 supplemented media. Afterwards cells were cultured<br />
in osteogenic media (DMEM low glucose, 10% FBS, 10mM β-glycerophosphate, 5µg/ml ascorbic acid, 1mM<br />
piruvat) and treated with different concentrations of dexamethasone, both short-term and continuous. The differentiation<br />
status of the cells was estimated using several osteogenic markers - alkaline phosphatase (AP) activity,<br />
the bone sialoprotein (BSP) and dentin matrix protein 1 (DMP-1) mRNAs. The stemness of the cells was estimated<br />
by the presence of pluripotency markers - SRY (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription<br />
factor 4 (OCT4). The measurements were conducted on the days 7 and 14 after osteogenic conditions<br />
had been introduced.<br />
Our results show that continuous treatment induces the highest level of osteogenesis, but 2 hour exposure also induced<br />
differentiation in comparison with control. Overall, 10-5 M concentration of dexamethasone was the most<br />
powerful in the short-term induction of osteogenesis. SOX2 has not been detected in hMSCs. OCT4 was expressed<br />
in undifferentiated pluripotent hMSCs and its expression subsequently went down, indicating that the differentiation<br />
process is proceeding<br />
Poster<br />
85
86<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
PLGA NANOFIBROUS MEMBRANES LOADED WITH<br />
HYDROXYAPATITE OR DIAMOND NANOPARTICLES AS<br />
SCAFFOLDS FOR BONE TISSUE ENGINEERING<br />
Katarina Novotna, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech<br />
Republic<br />
Martin Parizek, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic<br />
Timothy Douglas, Polymer Chemistry and Biomaterials Group, Ghent University, Ghent, Belgium<br />
Vera Lisa, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic<br />
Lucie Bacakova, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech<br />
Republic<br />
Various types of nanofiber scaffolds have been used in a wide range of tissue engineering applications, mainly<br />
for their ability to mimic the architecture of natural extracellular matrix. Composites of nanofibrous polymers and<br />
hydroxyapatite have been successfully tested for possible enhancement of bone regeneration.<br />
We have evaluated the proliferation of osteoblast-like MG-63 cells on 2 types of poly(lactide-co-glycolide) (PLGA)<br />
nanofibrous membranes, prepared by electrospinning using NanospiderTM device (Elmarco Ltd.). One type of<br />
membranes was loaded with hydroxyapatite nanoparticles (PLGA-HAp), the second with diamond nanoparticles<br />
(PLGA-ND), both about 23 wt% in dry PLGA. Besides the cell growth, we have also tested the possible immune activation<br />
of the cells, manifested by secretion of tumor necrosis factor-alpha (TNF-alpha), measured in the cell culture<br />
medium, and by concentration of intercellular adhesion molecule-1 (ICAM-1), measured in cell homogenates. As a<br />
positive control for TNF-alpha production, the cells stimulated with lipopolysaccharide from Escherichia coli were<br />
used. As MG-63 cells showed only a weak response to the lipopolysaccharide treatment, RAW 264.7 macrophages<br />
were used for the evaluation as well.<br />
The results have showed that both types of PLGA composites, as well as pristine PLGA represent a good support<br />
for attachment and subsequent proliferation of the MG-63 cells. However a notable difference between these<br />
PLGA composites was found in the TNF-alpha production. The concentration of TNF-alpha in the cell culture medium<br />
taken from RAW 264.7 cells grown on PLGA-HAp was significantly higher than on PLGA-ND and pristine PLGA,<br />
which makes PLGA-ND constructs suitable for its use in bone tissue engineering and for further research.<br />
Supported by the Academy of Sciences of the CR (grant No. IAAX00100902) and the Czech Science Foundation<br />
(grants No. P108/11/0794 and P108/12/G108).<br />
Poster
20 - 22 September 2012, Opatija, Croatia<br />
RISKS FACTORS FOR LOW BONE MINERAL DENSITY IN<br />
POST-MENOPAUSAL WOMEN WITH SYSTEMIC SCLEROSIS<br />
Anka Pranić-Kragić, Department of Nuclear Medicine, University Hospital Split, Split, Croatia<br />
Mislav Radić, Department of Rheumatology and Clinical Immunology, University Hospital Split,<br />
Split, Croatia<br />
Dušanka Martinović Kaliterna, University Hospital Split, Split, Croatia<br />
Josipa Radić, Department of Nephrology, University Hospital Split, Split, Croatia<br />
The aim of this study was to determine the prevalence and risk factors for low bone mineral density (BMD) in<br />
women with systemic sclerosis (SSc). A cross-sectional study was conducted among 32 post-menopausal SSc patients.<br />
Patients were evaluated using a questionnaire about the following variables: age, disease duration, disease<br />
activity, Medsger severity score, total skin score and history of fracture. Lumbar spine and hip measurements of<br />
BMD were performed by dual absorptiometry. Univariate and multivariate statistical analyses were used to assess<br />
the relationship between risk factors and BMD. The mean age was 52.8 +/- 10.7 years, and the median duration<br />
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/<br />
cm(2) in the hip. Osteopenia was present in 26.4 % of patients and osteoporosis in 15.6 %. In the multiple regression<br />
analysis, low BMD in the lumbar spine was associated with and low body mass index (BMI). Low BMD in the<br />
hip was associated with cumulative corticosteroid dose Medsger severity score and low BMI. Medsger severity<br />
score, low BMI, and total skin score are risks factors for low BMD in post-menopausal SSc patients. Osteopenia was<br />
found in 26.4 % of patients, while osteoporosis was found in 15.6%. Bone health should receive attention in care<br />
for persons with SSc.<br />
Poster<br />
87
88<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
UNIVERSAL FIXATOR- Fix-AS NEW WAY FOR FULL<br />
STABILITY,REHABILITATION AND MAXIMUM COMFORT FOR<br />
PATIENTS<br />
Šabić Nedžad, Poliklinika Dr Šabić, Zenica, Bosnia and Herzegovina<br />
Question:Could one provide a full stability of the bone sequence, the full flexion and more comfort at heavy war<br />
injuries, big bone defects, and deformity corrections (even at the haviest cases)? Since 1985, compression-distraction<br />
method was successfully used in Cantonal Hospital in Zenica. First six years we only used Illizarov fixator, and<br />
last twenty years we are using our own fixator FixAS.<br />
This work will show advantages of FixAS apparatus at large deformation corrections, simultaneous lengthening by<br />
external or internal transport, and deformation correction, heavy war injuries, non union, big bone defects after<br />
tumor resection, lengthenings and other.<br />
Advantages are especially important for solving hip and femur problems, and knee deformation corrections. Our<br />
method provides full comfort during treatment, as well as easy rehabilitation – until full scope of joint movement.<br />
This way, extremity is saved even in heaviest cases, unlike other methods (bone grafting, free flap), which were<br />
more expensive and unformal, often ended by an amputation. This fully satisfies the principle minimum metal,<br />
maximum stability and comfort. Answer: Yes, indeed, it can be achieved – by using FixAS universal fixator!<br />
Poster
20 - 22 September 2012, Opatija, Croatia<br />
THE ROLE OF Nb IN OXIDIZED SURFACE OF A β-TiNb ALLOY ON<br />
ITS OSTEOINTEGRATION<br />
Marta Vandrovcova, Institute of Physiology AS CR, v.v.i, Prague, Czech Republic<br />
Ivan Jirka, J. Heyrovský Institute of Physical Chemistry AS CR, v.v.i., Prague, Czech Republic<br />
Otakar Frank, J. Heyrovský Institute of Physical Chemistry AS CR, v.v.i., Prague, Czech Republic<br />
Zdenek Tolde, Czech Technical University in Prague, Faculty of Mechanical Engineering, Prague, Czech<br />
Republic<br />
Thomas Luxbacher, Anton Paar GmbH, Graz, Austria<br />
Lucie Bacakova, Institute of Physiology AS CR, v.v.i , Prague, Czech Republic<br />
Vladimir Stary, Czech Technical University in Prague, Faculty of Mechanical Engineerin, Prague, Czech<br />
Republic<br />
The most commonly used Ti-based materials for bone implant fabrication are the alloys composed from titanium,<br />
aluminium and vanadium, particularly Ti6Al4V. These alloys fulfil many requirements for the implant material, i.e.<br />
they are characterized by their beneficial mechanical and chemical properties and high biocompatibility. However,<br />
substantial drawback of the TiAlV materials is the presence of small amounts of highly toxic Al and V oxide<br />
species in their surface region, or release of cytotoxic Al and V ions. Great attention thus has been paid to develop<br />
new materials which do not contain any toxic component. In this context, niobium is prospective as a non-toxic β<br />
stabilizing agent.<br />
In our study, the adhesion, growth and viability of human osteoblast-like MG63 cells on thermally oxidized surface<br />
of titanium (Ti600) and β-titanium-niobium (TiNb600) alloy were investigated. We also compared the influence<br />
-OH-group present on its surface (low concentration of OH-groups was observed after Piranha solution treatment).<br />
The role of sterilization in boiling water on the surface chemistry of the samples and the presence of Nb<br />
on the alloy surface on its interaction with cells was addressed. Sterilization of the samples caused extensive dehydroxylation<br />
of their surfaces. However, the overall acidity of the Ti600 and TiNb600 samples before and after<br />
sterilization is not affected by this treatment.<br />
The differences observed between Ti600 and TiNb600 samples which may participate in higher “osteointegration”<br />
can be summarized as follows: The surface of TiNb600 sample is more acidic. Moreover, the surface of TiNb600<br />
sample is negatively charged at physiological pH (6–7). This charge is, however, smaller than the charge on the<br />
surface of Ti600.<br />
The authors found that TiNb600 alloys showed improved colonization with MG63 cells. This was documented by<br />
significantly higher cell numbers on the TiNb600 (regardless of treatment by Piranha solution) compared with<br />
pure Ti600. In addition cell viability on day 7 after seeding was significantly higher on TiNb600 than on Ti600. Thus,<br />
niobium improves the mechanical properties of stainless steel, and it is suggested that addition of niobium to<br />
metallic alloys (especially to titanium alloys) could be useful for the fabrication of biomedical materials required<br />
definite mechanical features.<br />
Supported by the Grant Agency of the Czech Republic (grant No. P108/10/1858)<br />
Poster<br />
89
90<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
COMPARISON BETWEEN TWO ICRS HISTOLOGY SCORING<br />
SYSTEMS FOR CARTILAGE REPAIR<br />
Andreja Vukasovic, Department of Histology and Embryology, School of Medicine, University of Zagreb,<br />
Zagreb, Croatia<br />
Davor Jezek, Department of Histology and Embryology, School of Medicine, University of Zagreb, Zagreb,<br />
Croatia<br />
Petar Kostesic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine,<br />
University of Zagreb, Zagreb, Croatia<br />
Damir Hudetz, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia<br />
Ivan Cerovecki, School of Medicine, University of Zagreb, Zagreb, Croatia<br />
Marin Kosovic, Department of Physics and Biophysics, School of Medicine, University of Zagreb, Zagreb,<br />
Croatia<br />
Tadija Petrovic, Clinic for Traumatology, Clinical Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia<br />
Drazen Maticic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine,<br />
University of Zagreb, Zagreb, Croatia<br />
Alan Ivkovic, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia<br />
Marko Pecina, School of Medicine, University of Zagreb, Zagreb, Croatia<br />
The histological quality of cartilage is considered to be one of the most important outcome tools to objectify<br />
success of different treatment modalities in regenerative orthopedics and tissue engineering. The aim of this pilot<br />
study was to compare the applicability of two International Cartilage Research Society (ICRS) visual histological assessment<br />
scales, ICRS I and ICRS II in the analysis of cartilage restoration after treatment with genetically modified<br />
autologous bone marrow clots. Chondral defects in 28 skeletally mature sheep which were randomly assigned to<br />
4 different groups; TGF group (TGF-β1 gene transduced bone marrow clot), GFP group (Green fluorescent protein<br />
transduced bone marrow clot), BMC group (untransduced bone marrow clot) and NC group (negative control, no<br />
treatment) were treated accordingly. After 6 months animals were sacrificed and osteochondral explants were<br />
analyzed. For histological assessment, slides were stained with hematoxylin - eosin and Safranin O. Two independent<br />
evaluators examined 112 slides blinded, 4 slides for each specimen using assessment scale ICRS I then ICRS<br />
II. Significant period of time passed between first and second examination, so the possibility of a bias with the<br />
respect to the first examination has been avoided entirely. ICRS I assesses 6 features that are graded with grades<br />
from 0 to 3. With ICRS II 14 features are evaluated on a visual analogue scale. Each parameter is scored on a scale<br />
from 0 to 100%. The ICRS I demonstrated lower inter-reader variability compared with ICRS II. Results yielded with<br />
ICRS I assessment scale were 98.7% coincident between two observers while those obtained with ICRS II assessment<br />
scale varied greatly. Subchondral bone and overall assessment scores had the best correlation coefficients<br />
for inter-reader variability (r = 0.82 and 0.76, respectively). ICRS I score revealed statistical significant difference in<br />
cell distribution between TGF and NC group (p=0.002). ICRS II showed statistical significant difference in surface<br />
and matrix staining score between TGF and NC group (p=0.009 and 0.007, respectively). ICRS II enabled better<br />
discrimination of scoring parameters but it is more suited for evaluators with strong background in cartilage histopathology.<br />
ICRS I remains easy to use for less experienced evaluators.<br />
Poster
20 - 22 September 2012, Opatija, Croatia<br />
OSTEOGENIC POTENTIAL AND STEMNESS OF MESENCHYMAL<br />
STEM CELLS AFTER DEXAMETHASONE TREATMENT<br />
Andreja Vukasovic, Department of Histology and Embryology, School of Medicine, University of Zagreb,<br />
Zagreb, Croatia<br />
Davor Jezek, Department of Histology and Embryology, School of Medicine, University of Zagreb, Zagreb,<br />
Croatia<br />
Petar Kostesic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine,<br />
University of Zagreb, Zagreb, Croatia<br />
Damir Hudetz, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia<br />
Ivan Cerovecki, School of Medicine, University of Zagreb, Zagreb, Croatia<br />
Marin Kosovic, Department of Physics and Biophysics, School of Medicine, University of Zagreb, Zagreb,<br />
Croatia<br />
Tadija Petrovic, Clinic for Traumatology, Clinical Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia<br />
Drazen Maticic, Clinic for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine,<br />
University of Zagreb, Zagreb, Croatia<br />
Alan Ivkovic, Department of Orthopedics, University Hospital Sveti Duh, Zagreb, Croatia<br />
Marko Pecina, School of Medicine, University of Zagreb, Zagreb, Croatia<br />
The purpose of the research was to improve osteogenic differentiation of human bone marrow derived-mesenchymal<br />
stem cells (hMSCs) and to evaluate the level of remaining undifferentiated stem cells in culture. Standard<br />
cell culture protocol includes continuous exposure to the dexamethasone which is not easy to reproduce in human<br />
body. Therefore, our experiment was designed to investigate the possibility of using short-term dexamethasone<br />
exposure in order to induce osteogenic differentiation.<br />
Human bone marrow-derived MSCs were expanded with FGF-2 supplemented media. Afterwards cells were cultured<br />
in osteogenic media (DMEM low glucose, 10% FBS, 10mM β-glycerophosphate, 5µg/ml ascorbic acid, 1mM<br />
piruvat) and treated with different concentrations of dexamethasone, both short-term and continuous. The differentiation<br />
status of the cells was estimated using several osteogenic markers - alkaline phosphatase (AP) activity,<br />
the bone sialoprotein (BSP) and dentin matrix protein 1 (DMP-1) mRNAs. The stemness of the cells was estimated<br />
by the presence of pluripotency markers - SRY (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription<br />
factor 4 (OCT4). The measurements were conducted on the days 7 and 14 after osteogenic conditions<br />
had been introduced.<br />
Our results show that continuous treatment induces the highest level of osteogenesis, but 2 hour exposure also induced<br />
differentiation in comparison with control. Overall, 10-5 M concentration of dexamethasone was the most<br />
powerful in the short-term induction of osteogenesis. SOX2 has not been detected in hMSCs. OCT4 was expressed<br />
in undifferentiated pluripotent hMSCs and its expression subsequently went down, indicating that the differentiation<br />
process is proceeding.<br />
Poster<br />
91
92<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
CELLULAR AND MOLECULAR ARCHITECTURE OF TENDON AND<br />
LIGAMENT<br />
Andrea Wagner, Paracelsus Medical Universtiy Salzburg, Tendon and Bone Regeneration, Salzburg,<br />
Austria<br />
Renate Gehwolf, Paracelsus Medical Universtiy Salzburg, Tendon and Bone Regeneration, Salzburg,<br />
Austria<br />
Corinna Hirzinger, Universtiy Hospital Salzburg, Traumatology and Sports Injuries, Salzbug, Austria<br />
Milan Toljan, Sportmed Institute, Linz, Austria<br />
Herbert Resch , Universtiy Hospital Salzburg, Traumatology and Sports Injuries, Salzbug, Austria<br />
Hans-Cjristian Bauer, Paracelsus Medical Universtiy Salzburg, Salzburg, Austria<br />
Tendons and ligaments are both dense connective tissues which resemble each other in many aspects but exert<br />
different functions. While the cellular constituents of tendon tissue including tendon progenitor cells have been<br />
well characterized, less information for ligament cells or progenitor cells in ligaments is available. We explore similarities<br />
and differences between tendon and ligament cells at a molecular and biochemical level. Therefore we<br />
used biopsy tissue of semitendinosus tendon (ST) and anterior cruciate ligament (ACL) since ruptured ACL often<br />
is reconstructed by autologous ST grafts.<br />
The expression of progenitor cell markers (Nestin, CD133, Scleraxis) in ACL and ST was analysed by immunhistochemistry<br />
and quantitative RT-PCR. Our analyses revealed differences in the expression levels and expression patterns<br />
of these marker molecules. We also determined the expression of extracellular matrix components (Collagen<br />
type 1, Collagen type 3 and Aggrecan), matrix remodelling proteins (MMP-2, MMP-9, Lysyl oxidase) and Substance<br />
P, a neurotransmitter in pain perception. The mRNA expression of Collagen type 1 and type 3, MMP-2 and Lysyl<br />
oxidase was significantly higher in ACL than in ST. Substance P was only detectable in ACL, Scleraxis and Nestin<br />
showed no differences. The ratio of Collagen type 1 to type 3 mRNA was significantly higher in ACL.<br />
Our results may contribute to the understanding of tendon and ligament nature and origin, and will provide a clue<br />
towards new therapeutic ways in ligament regeneration or reconstruction.<br />
Supported: PMU-FFF E-09/09/051-BAH & ABT GmbH
INDEKS OF AUTHORS Abstract/Poster<br />
Alibegović A. 20<br />
Augat P. 28<br />
Bacakova L. 84, 87<br />
Balen S. 81<br />
Bauer H. 27, 28, 82, 90<br />
Bekić M. 45<br />
Beyzadeoglu T. 18<br />
Borsky M. 33<br />
Brkić Š. 83<br />
Bulić - Jakuš F. 78<br />
Cencic A. 31<br />
Cerovecki I. 88, 89<br />
Daraboš N. 31<br />
Dembic Z. 81<br />
Doral M.N. 19<br />
Douglas T. 84<br />
Drobnič M. 20<br />
Endres M. 41<br />
Essien Etokebe G. 81<br />
Evans C. 14, 37<br />
Ferreira E. 14<br />
Frank O. 87<br />
Friederich N. F. 42<br />
Gandhi R. 79<br />
Garkavenko Y. 80<br />
Gehwolf R. 27, 28, 82, 90<br />
Gopalakrishna Vasishta V. 22<br />
Gradisnik L. 31<br />
Grčević D. 40, 43<br />
Grubišić F. 40<br />
Hašpl M. 21, 31<br />
Heiland Kaarvatn M. 81<br />
Heu V. 28<br />
Himelreich M. 78<br />
Hirschmann M. T. 42<br />
Hirzinger C. 28, 90<br />
Hodžić F. 15<br />
Hribernik M. 20<br />
Hudetz D. 88, 89<br />
Ikić M. 40<br />
Ivčević S. 40<br />
Ivković A. 83, 88, 89<br />
20 - 22 September 2012, Opatija, Croatia<br />
INDEKS OF AUTHORS Abstract/Poster<br />
Jajić Z. 40<br />
Jeleč Ž. 44<br />
Jelić M. 16<br />
Ježek D. 88, 89<br />
Jirka I. 87<br />
Josipović P. 83<br />
Jotanović Z. 81<br />
Jurić - Lekić G. 78<br />
Kapidzic T. 15<br />
Karlak I. 83<br />
Katušić A. 78<br />
Kelc R. 30, 31<br />
Kojić N. 45<br />
Kosović M. 88, 89<br />
Kostesic P. 88, 89<br />
Kovačić N. 40<br />
Lazić E. 40<br />
Lehner C. 27, 28, 82<br />
Leuzinger J. 33<br />
Lisa V. 84<br />
Liu F. 14<br />
Lojpur J. 45<br />
Lončarević J. 78<br />
Luxbacher T. 87<br />
Majić Ž. 78<br />
Margaritoni M. 45<br />
Marijanović I. 83<br />
Martin I. 12<br />
Martinović Kaliterna D. 39, 85<br />
Marušić A. 40<br />
Matičić D. 88, 89<br />
Matić I. 83<br />
Mihelić R. 81<br />
Mlakar R. 31<br />
Moser C. 31<br />
Mueller M. 14<br />
Mulac-Jeričević B. 81<br />
Mužić V. 78<br />
Novak S. 38<br />
Novotna K. 84<br />
Oršolić N. 44<br />
Parizek M. 83<br />
93
94<br />
2 st INTERNATIONAL CONFERENCE ON REGENERATIVE ORTHOPAEDICS<br />
INDEKS OF AUTHORS Abstract/Poster<br />
Pavelić K. 24<br />
Pećina M. 83, 88, 89<br />
Pellegrino A. 33<br />
Petrović T. 88, 89<br />
Porter R. 14<br />
Pozdeev A. 80<br />
Pranić-Kragić A. 85<br />
Primorac D. 29<br />
Radić J. 85<br />
Radić M. 85<br />
Resch H. 90<br />
Salzmann G. 17<br />
Schinhan M. 14<br />
Schoen S. 42<br />
Sestan B. 81<br />
Shen Z. 14<br />
Sinčić N. 78<br />
Slak Rupnik M. 31<br />
Stary V. 87<br />
Stephan D. 28<br />
Stipić Marković A. 35<br />
Stoddart M. 26<br />
Strahonja B. 21<br />
Šabic E. 15<br />
Šabic N. 15, 86<br />
Šerman Lj. 78<br />
Tempfer T. 27, 28, 82<br />
Terzić A. 34<br />
Terzić K. 25<br />
Tijanić T. 81<br />
Tolde Z. 87<br />
Toljan M. 90<br />
Torun kose G. 13<br />
Trapecar M. 31<br />
Tršek D. 21, 31<br />
Vandrovcova M. 87<br />
Vlahović M. 78<br />
Vogrin M. 30, 31<br />
Vuk - Pavlović S. 23<br />
Vukasovic A. 88, 89<br />
Wagner A. 27, 28, 82, 90<br />
Windhager R. 14