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Z Orthop Ihre Grenzgeb 2004; 142(5): 540-545
DOI: 10.1055/s-2004-832362
Knorpelersatz

© Georg Thieme Verlag Stuttgart · New York

Meniskusersatz: Aktuelle Aspekte auf dem Gebiet des Tissue engineering

Meniscus Replacement: Current Aspects in Tissue EngineeringR. Müller-Rath1 , T. Mumme1 , O. Miltner1 , S. Andereya1 , U. Schneider1
  • 1Orthopädische Klinik, Universitätsklinikum Aachen
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Publication History

Publication Date:
07 October 2004 (online)

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Zusammenfassung

Tissue engineering eröffnet neue Möglichkeiten für die Meniskusheilung und den Meniskusersatz. Auf diesem Gebiet werden verschiedene Ansätze verfolgt, um ein Implantat für den Meniskusersatz durch die Kombination aus einem Matrixgerüst, Zellen und spezifischen Stimuli zu generieren. Meniskusersatz durch azelluläre Matrizes: Eine Matrix für den Meniskusersatz muss hohen biomechanischen Ansprüchen gerecht werden. Hierbei stellen neben der Implantatgeometrie die Materialeigenschaften und eine sichere intraartikuläre Fixation die Voraussetzung für die Implantatfunktion dar. Ein azelluläres Kollagen-Gerüst wird als partieller Meniskusersatz bereits klinisch eingesetzt. Außerdem sind resorbierbare Polymere sowie ein Implantat aus Dünndarmsubmukosa im Tierversuch erprobt worden. Nach Implantation werden diese Matrizes von Zellen besiedelt und unterliegen einem Remodeling. Die Bildung eines fibrokartilaginären Regeneratgewebes wurde beobachtet. Die biomechanische Qualität von Implantaten und deren Auswirkungen auf den Knorpelschutz müssen noch weiter untersucht werden. Zelluläre Besiedelung von Matrizes für den Meniskusersatz: Eine zelluläre Besiedelung von Matrizes in vitro könnte zu einer Verbesserung der biologischen und biomechanischen Implantateigenschaften führen. Allerdings ist der hierfür ideale Zelltyp noch nicht definiert. Autologe Meniskuszellen, artikuläre Chondrozyten und mesenchymale Stammzellen stellen mögliche zelluläre Quellen dar. Zusätzliche Stimuli, wie Zytokine und mechanische Kräfte, sowie gentechnische Verfahren bieten Möglichkeiten, die Qualität eines Ersatzgewebes weiter zu steigern.

Abstract

Tissue engineering offers new opportunities for meniscus repair and replacement. In this field different approaches are being studied to genererate a meniscus subsitute by a combination of a matrix scaffold, cells and specific stimuli. Meniscus replacement by acelluar matrices: For meniscus replacement the matrix material has to meet high biomechanical demands. Besides implant geometry, the material properties and a secure intraarticular attachment are important preconditions for implant function. A collagen scaffold has already been applied clinically for partial meniscus replacement. Scaffolds made of synthetic, bioabsorbable polymers and small intestine submucosa have been employed in animal studies. Following implantation, matrices are invaded by cells and undergo a process of remodeling. Formation of fibrocartilage repair tissue has been observerd. The biomechanical quality of implants and their effect on cartilage preservation have to be studied further. Cellular seeding of matrices for mensicus replacement: Advanced biological and biomechanical implant quality might be achieved by seeding matrices with cells in vitro. However, the ideal type of cell for this purpose has not yet been identified. Autologous mensicus cells, articular chondrocytes and mesenchymal stem cells represent possible cellular sources. Additional stimuli, such as cytokines and mechanical forces, and techniques of genetic engineering might further contribute to enhance the quality of engineered tissue.

Schlüsselwörter

Meniskus - Tissue engineering - Meniskusersatz - Matrix - Zelle

Key words

Meniscus - tissue engineering - meniscus replacement - matrix scaffold - cell

Literatur

  • 1 Shoemaker S C, Markolf K L. The role of the meniscus in the anterior-posterior stability of the loaded anterior cruciate deficient knee: effects of partial versus total excision.  J Bone Joint Surg [Am]. 1986;  26 71-79
    PubMedGoogle Scholar
  • 2 Hoshino A, Wallace W A. Impact-absorbing properties of the human knee.  J Bone Joint Surg [Br]. 1987;  69 807-811
    PubMedGoogle Scholar
  • 3 Fukuda Y, Takai S, Yoshino N, Murase K, Tsutsumi S, Ikeuchi K, Hirasawa Y. Impact load transmission of the knee joint-influence of leg alignment and the role of meniscus and articular cartilage.  Clin Biomech. 2000;  15 516-521
    CrossrefPubMedGoogle Scholar
  • 4 Wilson W, von Rietbergen B, van Donkelaar C C, Huiskes R. Pathways of load-induced cartilage damage causing cartilage degeneration in the knee after meniscectomy.  Journal Biomech. 2003;  36 845-851
    PubMedGoogle Scholar
  • 5 Elliott D M, Guilak F, Vail T P, Wang J Y, Setton L A. Tensile properties of articular cartilage are altered by meniscectomy in a canine model of osteoarthritis.  J Orthop Res. 1999;  17 503-508
    CrossrefPubMedGoogle Scholar
  • 6 Wyland D J, Guilak F, Elliot D M, Setton L A, Vail T P. Chondropathy after meniscal tear or partial meniscectomy in a canine model.  J Orthop Res. 2002;  20 996-1002
    CrossrefPubMedGoogle Scholar
  • 7 Cicuttini F M, Forbes A, Yunyuan W, Rush G, Stuckley S L. Rate of knee cartilage loss after partial meniscectomy.  J Rheumatol. 2002;  39 1954-1956
    PubMedGoogle Scholar
  • 8 Cox J S, Nye C E, Schaefer W W. The degenerative effects of partial and total resection of the medial meniscus in the dogs knees.  Clin Orthop. 1975;  109 178-183
    PubMedGoogle Scholar
  • 9 Allen P R, Denham R A, Swan A V. Late degenerative changes after meniscectomy. Factors affecting the knee after operation.  J Bone Joint Surg [Br]. 1984;  66 121-128
    PubMedGoogle Scholar
  • 10 McCarty E C, Marx R G, DeHaven K E. Meniscus Repair - Considerations in treatment and update of clinical result.  Clin Orthop. 2002;  402 122-134
    PubMedGoogle Scholar
  • 11 Messner K. The concept of a permanent synthetic meniscus prosthesis: a critical discussion after 5 years of experimental investigations using dacron and teflon implants.  Biomaterials. 1994;  15 243-250
    CrossrefPubMedGoogle Scholar
  • 12 Bruns J, Kahrs J, Kampen J, Behrens P, Plitz W. Autologous perichondral tissue for meniscal replacement.  J Bone Joint Surg [Br]. 1998;  80 918-923
    PubMedGoogle Scholar
  • 13 Kohn D, Rudert M, Wirth C J, Plitz W, Reiss G, Maschek H. Medial meniscus replacement by a fat pad autograft.  Int Orthop. 1997;  21 232-238
    CrossrefPubMedGoogle Scholar
  • 14 Kohn D, Wirth C J, Reiss G, Plitz W, Maschek H, Erhardt W, Wülker N. Medial meniscus replacement by a tendon autograft. Experiments in sheep.  J Bone Joint Surg [Br]. 1992;  74 910-917
    PubMedGoogle Scholar
  • 15 Metak G, Scherer M A. Development of replacement meniscus of autogenous tissue.  Unfallchirurg. 1996;  99 477-486
    PubMedGoogle Scholar
  • 16 Johnson L L, Feagin J A. Autogenous tendon graft substitution for absent knee joint meniscus: a pilot study.  Arthroscopy. 2000;  16 191-196
    PubMedGoogle Scholar
  • 17 Goble E M, Kohn D, Verdonk R, Kane S M. Meniscal substitutes - human experience.  Scand J Med Sci Sports. 1999;  9 146-157
    PubMedGoogle Scholar
  • 18 Kohn D. Autograft meniscus replacment: experimental and clinical results.  Knee Surg Sports Traumatol Arthrosc. 1993;  1 123-125
    CrossrefPubMedGoogle Scholar
  • 19 Milachowski K A, Kohn D, Wirth C J. Meniscus replacement using Hoffa's infrapatellar fat body - initial clinical results.  Unfallchirurgie. 1990;  4 190-195
    PubMedGoogle Scholar
  • 20 Verdonk R. Meniscal transplantation.  Acta Orthop Belg. 2002;  68 118-127
    PubMedGoogle Scholar
  • 21 Wirth C J, Peters G, Milachowski K A, Weismeier K G, Kohn D. Long-term Results of Meniscal Allograft Transplantation.  Am J Sports Med. 2002;  2 174-181
    PubMedGoogle Scholar
  • 22 Kohn D. Meniskusersatz.  Orthopäde. 1994;  23 164-170
    PubMedGoogle Scholar
  • 23 Jackson D W, McDevitt C A, Simon T M, Arnoczky S P, Atwell E A. Meniscal transplantation using fresh and cryopreserved allografts. An experimental study in goats.  Am J Sports Med. 1992;  20 644-656
    CrossrefPubMedGoogle Scholar
  • 24 Arnoczky S P, DiCarlo E F, O'Brien S J, Warren R F. Cellular repopulation of deep-frozen meniscsal autografts: An experimental study in the dog.  Arthroscopy. 1992;  8 428-436
    CrossrefPubMedGoogle Scholar
  • 25 Arnoczky S P, Warren R F, McDevitt C A. Meniscal replacement using a cryopreserverd allograft.  Clin Orthop. 1990;  252 121-127
    PubMedGoogle Scholar
  • 26 Shibuya S. Meniscus transplantation using cryopreserved allograft. Histological and ultrastructural study of the transplanted meniscus.  J Orthop Sci. 1999;  4 135-141
    CrossrefPubMedGoogle Scholar
  • 27 Messner K, Kohn D, Verdonk R. Future research in meniscal replacement.  Scand J Med Sci Sports. 1999;  9 181-183
    PubMedGoogle Scholar
  • 28 Milachowski K A, Kohn D, Wirth C J. Transplantation allogener Menisken.  Orthopäde. 1994;  23 160-163
    PubMedGoogle Scholar
  • 29 Rodeo S A, Seneviratne A, Suzuki K, Wickiewicz T L, Warren R F. Histological analysis of human meniscal allografts. A preliminary study.  J Bone Joint Surg [Am]. 2000;  82 1071-1082
    PubMedGoogle Scholar
  • 30 Hamlet W, Liu S H, Yang R. Destruction of a cryopreserved meniscal allograft: a case for acute rejection.  Arthroscopy. 1997;  13 517-521
    PubMedGoogle Scholar
  • 31 Lazovic D, Wirth C J, Sieg A, Gosse F, Maschek H G, Shaffer B. Effect of surgical technique on meniscus transplants. A histological, animal experiment study.  Unfallchirurg. 1997;  100 541-546
    CrossrefPubMedGoogle Scholar
  • 32 Milachowski K A, Weismeier K, Wirth C J, Kohn D. Meniscus transplantation and anterior cruciate ligament replacement - results 2-4 years postoperativ.  Sportverletz Sportschaden. 1990;  4 73-78
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Stollsteimer G T, Shelton W R, Dukes A, Bomboy A L. Meniscal allograft transplantation: A 1- to 5-year follow-up of 22 patients.  Arthroscopy. 2000;  16 343-347
    PubMedGoogle Scholar
  • 34 Arnoczky S P. Building a meniscus.  Clin Orthop. 1999;  367 244-253
    PubMedGoogle Scholar
  • 35 Setton L A, Guilak F, Hsu E W, Vail T P. Biomechanical factors in tissue engineered meniscal repair.  Clin Orthop. 1999;  367 (Suppl) 254-272
    PubMedGoogle Scholar
  • 36 Middleton J C, Tipton A J. Synthetic biodegradable polymers as orthopaedic devices.  Biomaterials. 2000;  21 2335-2346
    CrossrefPubMedGoogle Scholar
  • 37 Claes L, Ignatius A. Development of new, biodegradable implants.  Chirurg. 2002;  73 990-996
    CrossrefPubMedGoogle Scholar
  • 38 De Groot J H, Zijlstra F M, Kuipers H W. Meniscal tissue regeneration in porous 50/50 copoly (L-lacitde/espilon-caprolacotone) implants.  Biomaterials. 1997;  18 613-622
    CrossrefPubMedGoogle Scholar
  • 39 Buma P, Ramrattan N N, van Tienen T G, Veth R PH. Tissue engineering of the meniscus.  Biomaterials. 2004;  25 1523-1532
    CrossrefPubMedGoogle Scholar
  • 40 Klompmaker J, Jansen H WB, Veth R PH, de Groot J H, Nijenhuis A J, Pennings A J. Porous polymer implant for repair of meniscal lesions: A prelliminary study in dogs.  Biomaterials. 1991;  12 810-816
    CrossrefPubMedGoogle Scholar
  • 41 De Groot J H, de Vrijer R, Pennings A J, Klompmaker J, Veth R P, Jansen H W. Use of porous polyurethanes for meniscal reconstruction and meniscal prostheses.  Biomaterials. 1996;  17 163-173
    CrossrefPubMedGoogle Scholar
  • 42 Tienen T G, Heijkants R G, Buma P, De Groot J H, Pennings A J, Veth R P. A porous polymer scaffold for meniscal lesion repair - A study in dogs.  Biomaterials. 2003;  24 2541-2548
    CrossrefPubMedGoogle Scholar
  • 43 Klompmaker J, Veth R PH, Jansen H WB, Nielsen H KL, de Groot J H, Pennings A J. Meniscal replacement using a porous polymer prosthesis: a preliminary study in the dog.  Biomaterials. 1996;  17 1169-1175
    CrossrefPubMedGoogle Scholar
  • 44 Kobayashi M, Toguchida J, Oka M. Development of an artificial meniscus using polyvinyl alcohol-hydrogel for early return to, and continuance of athletic life, in sportspersons with severe meniscus injury. I: Mechanical evaluation.  Knee. 2003;  10 47-51
    CrossrefPubMedGoogle Scholar
  • 45 Kobayashi M, Toguchida J, Oka M. Preliminary study of polyvinyl alcohol-hydrogel (PVA-H) artificial meniscus.  Biomaterials. 2003;  24 639-647
    CrossrefPubMedGoogle Scholar
  • 46 Testa Pezzin A P, Cardoso T P, do Carmo Alberto Rincon M, de Carvalho Zavaglia C A, de Rezende Duek E A. Bioreabsorbable polymer scaffold as temporary meniscal prosthesis.  Artif Organs. 2003;  27 428-431
    CrossrefPubMedGoogle Scholar
  • 47 Cook J L, Tomlinson J L, Arnosczky S P, Fox D B, Cook C R, Kreeger J M. Kinetic study of the replacment of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.  Tissue engineering. 2001;  7 321-333
    CrossrefPubMedGoogle Scholar
  • 48 Gastel J A, Muirhead W R, Lifrak J T, Fadale P D, Hulstyn M J, Labrador D P. Meniscal tissue regeneration using a collagenous biomaterial derived from porcine small intestine submucosa.  Arthroscopy. 2001;  17 151-159
    PubMedGoogle Scholar
  • 49 Welch J A, Montgomery R D, Lenz S D, Plouhar P, Shelton W R. Evaluation of small-intestinal submucosa implants for repair of meniscal defects in dogs.  Am J Vet Res. 2002;  63 427-431
    PubMedGoogle Scholar
  • 50 Cook J L, Tomlinson J L, Kreeger J M, Cook C R. Induction of meniscal regeneration in dogs using a novel biomaterial.  Am J Sports Med. 1999;  27 658-665
    CrossrefPubMedGoogle Scholar
  • 51 Stone K R. Meniscus replacement.  Clin Sports Med. 1996;  15 557-571
    PubMedGoogle Scholar
  • 52 Stone K R, Rodkey W G, Webber R, McKinney L, Steadman R J. Meniscal regeneration with copolymeric collagen scaffolds. In vitro an in vivo studies evaluated clinically, histologically and biochemically.  Am J Sports Med. 1992;  20 104-111
    PubMedGoogle Scholar
  • 53 Stone K R, Rodkey W G, Webber R J, McKinney L, Steadman R J. Future directions. Collagen-based prosthesis for meniscal regeneration.  Clin Orthop. 1990;  252 129-135
    PubMedGoogle Scholar
  • 54 Stone K R, Steadman J R, Rodkey W G, Li S T. Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data.  J Bone Joint Surg [Am]. 1997;  79 1770-1777
    PubMedGoogle Scholar
  • 55 Rodkey W G, Steadman J R, Li S T. A clinical study of collagen meniscus implants to restore the injured meniscus.  Clin Orthop. 1999;  367 (Suppl) 281-292
    PubMedGoogle Scholar
  • 56 Arnoczky S P, Warren R F, Spivak J M. Menicsal repair using an exogenous fibrin clot. An experimental study in dogs.  J Bone Joint Surg [Am]. 1988;  70 1209-1217
    PubMedGoogle Scholar
  • 57 Hunziker E B. Articular cartilage repair: Basic science and clinical progress. A review of the current status and prospects.  Osteoarthritis Cartilage. 2002;  10 432-463
    CrossrefPubMedGoogle Scholar
  • 58 Ghadially F N, Lalonde J M, Wedge J H. Ultrastructure of normal and torn menisci of the human knee joint.  J Anat. 1983;  136 773-791
    PubMedGoogle Scholar
  • 59 Nakata K, Shino K, Hamada M, Mae, T, Miyama T, Shinjo H, Horibe S, Tada K, Ochi T, Yoshikawa H. Human meniscus cell - Characterization of the primary culture and use for tissue engineering.  Clin Orthop. 2001;  391 208-218
    PubMedGoogle Scholar
  • 60 Webber R J, Harris M G, Hough A J. Cell culture of rabbit meniscal fibrochondrocytes: Proliferative and synthetic response to growth factors and ascorbat.  J Orthop Res. 1985;  3 36-42
    CrossrefPubMedGoogle Scholar
  • 61 Webber R J. In vitro culture of meniscal tissue.  Clin Orthop. 1990;  252 114-120
    PubMedGoogle Scholar
  • 62 Webber R J, York J L, Vanderschilden J L, Hough A. An organ culture model for assaying wound repair of the fibrocartilaginous knee joint meniscus.  Am J Sports Med. 1989;  17 393-400
    PubMedGoogle Scholar
  • 63 Isoda K, Saito S. In vitro and in vivo fibrochondrocyte growth behavior in fibrin gel.  Am J Knee Surg. 1998;  11 209-216
    PubMedGoogle Scholar
  • 64 Tanaka T, Fujii K, Kumagae Y. Comparison of biochemical characteristics of cultured fibrochondrocytes isolated from the inner and outer regions of human meniscus.  Knee Surg Sports Traumatol Arthosc. 1999;  7 75-80
    PubMedGoogle Scholar
  • 65 Collier S, Gosh P. Effects of transforming growth factor beta on proteoglycan synthesis by cell and explant cultures derived from the knee joint meniscus.  Osteoarthritis Cartilage. 1995;  3 127-138
    PubMedGoogle Scholar
  • 66 Hidaka C, Ibarra C, Hannafin J A, Torzilli P A, Quitoriano M, Jen S S, Warren R F, Crystal R G. Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering.  Tissue Eng. 2002;  8 93-105
    CrossrefPubMedGoogle Scholar
  • 67 Bhargava M M, Attia E T, Murrell G A, Dolan M M, Warren R F, Hannafin J A. The effect of cytokines on the proliferation and migration of bovine meniscal cells.  Am J Sports Med. 1999;  27 636-643
    PubMedGoogle Scholar
  • 68 Zaleskas J M, Kinner B, Freyman T M, Yannas I V, Gibson L J, Spector M. Growth factor regulation of smooth muscle actin expression and contraction of human articular chondrocytes and meniscal cells in collagen-GAG matrix.  Exp Cell Res. 2001;  270 21-31
    CrossrefPubMedGoogle Scholar
  • 69 Suzuki Y, Takeuchi N, Sagehashi Y, Yamaguchi T, Itoh H, Iwata H. Effects of hyaluronic acid on meniscal injury in rabbits.  Arch Orthop Trauma Surg. 1998;  117 303-306
    CrossrefPubMedGoogle Scholar
  • 70 Ishima M, Wada Y, Sonoda M, Harada Y, Katsumi A, Moriya H. Effects of hyaluronan on the healing of rabbit meniscus injured in the peripheral region.  J Orthop Sci. 2000;  5 579-584
    CrossrefPubMedGoogle Scholar
  • 71 Hashimoto J, Kurosaka M, Yoshiya S, Hirohata K. Meniscal repair using fibrin sealant and endothelial cell growth factor.  Am J Sports Med. 1992;  20 537-541
    PubMedGoogle Scholar
  • 72 Spindler K P, Mayes C E, Miller R R, Imro A K, Davidson J M. Regional mitogenic response of the meniscus to plateret-derived-growth factor (PDGF-AB).  J Orthop Res. 1995;  13 201-207
    CrossrefPubMedGoogle Scholar
  • 73 Lietman S A, Hobbs W, Inoue N, Reddi A H. Effects of selected growth factors on porcine meniscus in chemically defined medium.  Orthopedics. 2003;  26 799-803
    PubMedGoogle Scholar
  • 74 Tumia N S, Johnstone A J. Promoting the proliferative and synethtic activity of knee meniscal fibrochondrocytes using basic fibroblast growth factor in vitro.  AM J Sports Med. 2004;  4 915-920
    PubMedGoogle Scholar
  • 75 Martinek V, Usas A, Pelinkovic D, Robbins P, Fu H H, Huard J. Genetic engineering of meniscal allografts.  Tissue Eng. 2002;  8 107-117
    CrossrefPubMedGoogle Scholar
  • 76 Evans C H, Robbins P D. Genetically augmented tissue engineering of the musculoskeletal system.  Clin Orthop. 1999;  367 (Suppl) 410-418
    PubMedGoogle Scholar
  • 77 Goto H, Shuler F D, Lamsam D, Moller H D, Niybizi C, Fu F H, Robbins P D, Evans C H. Transfer of LacZ Marker Gene to the meniscus.  J Bone Joint Surg [Am]. 1999;  81 918-925
    PubMedGoogle Scholar
  • 78 Upton M L, Chen J, Guilak F, Setton L A. Differential effects of static and dynamic compresion on meniscal cell gene expression.  J Orthop Res. 2003;  21 963-969
    CrossrefPubMedGoogle Scholar
  • 79 Mueller S M, Shortkoff S, Schneider T O, Breinan H A, Yannas I V, Spector M. Meniscus cells seeded in type 1 and type 2 collagen-GAG matrices in vitro.  Biomaterials. 1999;  20 701-709
    CrossrefPubMedGoogle Scholar
  • 80 Mueller S M, Schneider T O, Shortkoff S, Breinan H A, Spector M. Alpha-smooth muscle actin and contractile behavior of bovine meniscus cells seeded in type 1 and type 2 collagen-GAG matrizes.  J Biomed Mater Res. 1999;  45 157-166
    PubMedGoogle Scholar
  • 81 Ibbara C, Jannetta C, Vacanti C A, Cao Y, Upton J, Vacanti J P. Tissue engineered meniscus: a potential new alternative to allogenic meniscus transplantation.  Transplant Proc. 1997;  29 986-988
    CrossrefPubMedGoogle Scholar
  • 82 Ibarra C, Koski J A, Warren R F. Tissue engineering - Cells and matrix.  Orthop Clin North Am. 2000;  31 411-418
    CrossrefPubMedGoogle Scholar
  • 83 Peretti G M, Gill T J, Xu J W, Randolph M A, Morse K R, Zaleske D J. Cell-therapy for meniscal repair: a large animal study.  Am J Sports Med. 2004;  32 146-158
    CrossrefPubMedGoogle Scholar
  • 84 Peretti G M, Caruso E M, Randolph M A, Zaleske D J. Meniscal repair using engineered tissue.  J Orthop Res. 2001;  19 278-285
    CrossrefPubMedGoogle Scholar
  • 85 Ishimura M, Ohgushi H, Habata T, Tarnai S, Fuhisawa Y. Arthroscopic meniscal repair using fibrin glue. Part I: Experimental study.  Arthroscopy. 1997;  13 551-557
    PubMedGoogle Scholar
  • 86 Walsh C J, Goodmann D, Caplan A I, Goldberg V M. Meniscus regeneration in a partial meniscectomy model.  Tissue Eng. 1999;  5 327-337
    PubMedGoogle Scholar
  • 87 Port J, Jackson D W, Lee T Q, Simon T M. Meniscal repair supplemented with exogenous fibrin clot and autogenous culture marrow cells in the goat model.  Am J Sports Med. 1996;  24 547-555
    PubMedGoogle Scholar
  • 88 Murphy J M, Fink D J, Hunziker E B, Barry F P. Stem cell therapy in a caprine model of osteoarthritis.  Arthritis Rheum. 2003;  48 3464-3474
    CrossrefPubMedGoogle Scholar

Dr. med. Ralf Müller-Rath

Orthopädische Klinik · Universitätsklinikum Aachen

Pauwelsstraße 30

52074 Aachen

Phone: 02 41-80-8 55 85

Fax: 02 41-80-8 25 07

Email: rmueller-rath@ukaachen.de