Orthopädie und Unfallchirurgie up2date 2009; 4(5): 339-354
DOI: 10.1055/s-0029-1215105
Grundlagen

© Georg Thieme Verlag KG Stuttgart · New York

Regenerative Medizin zur Behandlung von Knorpelschäden

B.  Rolauffs1 , W.  K.  Aicher1 , B.  G.  Ochs1 , C.  Bahrs1 , D.  Albrecht1 , K.  Weise1
  • 1Berufsgenossenschaftliche Unfallklinik Tübingen
Further Information

Publication History

Publication Date:
09 October 2009 (online)

Die Regenerative Medizin ist ein relativ neues Gebiet der Biomedizin, deren Name dem lateinischen Wort regeneratio entstammt und Neuentstehung bedeutet. Sie befasst sich mit der Anregung endogener Regenerations- und Reparaturprozesse zur körpereigenen Wiederherstellung funktionsgestörter Zellen, Gewebe und Organe und, wenn die eigenen Reparaturmechanismen versagen, mit dem biologischen Ersatz dieser Strukturen. Im Fachgebiet der Orthopädie und Unfallchirurgie kommt den Erkrankungen und Verletzungen des muskuloskelettalen Systems eine große Bedeutung zu. Besonders degenerative Erkrankungen der großen Gelenke und der Wirbelsäule, aber auch traumatische, entzündliche, tumor- oder operationsbedingte Weichteil- oder Knochendefekte sind Gegenstand der Forschung in der Regenerativen Medizin. Vor allem der hyaline Gelenkknorpel, der Bandscheibenknorpel und der Knochen werden in der Regenerativen Medizin als klinisch relevante und wissenschaftlich zukunftsorientierte Strukturen betrachtet. Wichtige Forschungsgebiete umfassen Strategien der In-situ-Regeneration, das Tissue Engineering, die Stammzelldifferenzierung und auch die Gentherapie.

Literatur

  • 1 Kuettner K E, Aydelotte M B, Thonar E J. Articular cartilage matrix and structure: a minireview.  J Rheumatol. 1991;  27 (Suppl.) 46-48
  • 2 Jadin K D. et al . Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis.  J Histochem Cytochem. 2005;  53 1109-1119
  • 3 Aydelotte M B, Kuettner K E. Differences between sub-populations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production.  Connect Tissue Res. 1988;  18 205-222
  • 4 Venn M, Maroudas A. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. Chemical composition.  Ann Rheum Dis. 1977;  36 121-129
  • 5 Nieminen M T. et al . T2 relaxation reveals spatial collagen architecture in articular cartilage: a comparative quantitative MRI and polarized light microscopic study.  Magn Reson Med. 2001;  46 487-493
  • 6 Maroudas A, Venn M. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. II. Swelling.  Ann Rheum Dis. 1977;  36 399-406
  • 7 Burr D B. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis.  Osteoarthritis Cartilage. 2004;  12 (Suppl. A) S20-S30
  • 8 Mow V C, Holmes M H, Lai W M. Fluid transport and mechanical properties of articular cartilage: a review.  J Biomech. 1984;  17 377-394
  • 9 Chen A C. et al . Depth- and strain-dependent mechanical and electromechanical properties of full-thickness bovine articular cartilage in confined compression.  J Biomech. 2001;  34 1-12
  • 10 Krishnan R. et al . Inhomogeneous cartilage properties enhance superficial interstitial fluid support and frictional properties, but do not provide a homogeneous state of stress.  J Biomech Eng. 2003;  125 569-577
  • 11 Schinagl R M. et al . Depth-dependent confined compression modulus of full-thickness bovine articular cartilage.  J Orthop Res. 1997;  15 499-506
  • 12 Klein T J. et al . Depth-dependent biomechanical and biochemical properties of fetal, newborn, and tissue-engineered articular cartilage.  J Biomech. 2007;  40 182-190
  • 13 Hunziker E B, Quinn T M, Hauselmann H J. Quantitative structural organization of normal adult human articular cartilage.  Osteoarthritis Cartilage. 2002;  10 564-572
  • 14 Poole C A. Articular cartilage chondrons: form, function and failure.  J Anat. 1997;  191 1-13
  • 15 Lu X L, Mow V C. Biomechanics of articular cartilage and determination of material properties.  Med Sci Sports Exerc. 2008;  40 193-199
  • 16 Lu X L. et al . The generalized triphasic correspondence principle for simultaneous determination of the mechanical properties and proteoglycan content of articular cartilage by indentation.  J Biomech. 2007;  40 2434-2441
  • 17 Buschmann M D, Grodzinsky A J. A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics.  J Biomech Eng. 1995;  117 179-192
  • 18 Meachim G, Stockwell R. The matrix. In: Freeman MAR, ed Adult Articular Cartilage. Tunbridge Wells; Pitman Medical 1979: 1-67
  • 19 Jay G D. et al . Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25.  J Orthop Res. 2001;  19 677-687
  • 20 Schumacher B L. et al . A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage.  Arch Biochem Biophys. 1994;  311 144-152
  • 21 Lee D A. et al . Response of chondrocyte subpopulations cultured within unloaded and loaded agarose.  J Orthop Res. 1998;  16 726-733
  • 22 Tallheden T. et al . Human articular chondrocytes – plasticity and differentiation potential.  Cells Tissues Organs. 2006;  184 55-67
  • 23 Bywaters E. The metabolism of joint tissues.  J Path Bact. 1937;  44 247-268
  • 24 Quinn T M, Hunziker E B, Hauselmann H J. Variation of cell and matrix morphologies in articular cartilage among locations in the adult human knee.  Osteoarthritis Cartilage. 2005;  13 672-678
  • 25 Stockwell R A. The interrelationship of cell density and cartilage thickness in mammalian articular cartilage.  J Anat. 1971;  109 411-421
  • 26 Kim A C, Spector M. Distribution of chondrocytes containing alpha-smooth muscle actin in human articular cartilage.  J Orthop Res. 2000;  18 749-755
  • 27 Jurvelin J S. et al . Surface and subsurface morphology of bovine humeral articular cartilage as assessed by atomic force and transmission electron microscopy.  J Struct Biol. 1996;  117 45-54
  • 28 Darling E M, Hu J C, Athanasiou K A. Zonal and topographical differences in articular cartilage gene expression.  J Orthop Res. 2004;  22 1182-1187
  • 29 Khan I M. et al . Expression of clusterin in the superficial zone of bovine articular cartilage.  Arthritis Rheum. 2001;  44 1795-1799
  • 30 Eger W. et al . Human knee and ankle cartilage explants: catabolic differences.  J Orthop Res. 2002;  20 526-534
  • 31 Brighton C T, Kitajima T, Hunt R M. Zonal analysis of cytoplasmic components of articular cartilage chondrocytes.  Arthritis Rheum. 1984;  27 1290-1299
  • 32 Rolauffs B. et al . Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints.  J Struct Biol. 2008;  162 335-344
  • 33 Maroudas A. Physico-chemical properties of articular cartilage. In: Freeman MAR, ed Adult Articular Cartilage. Tunbridge Wells; Pitman Medical 1979: 215-290
  • 34 Hunziker E B. Articular cartilage structure in humans and experimental animals. In: Kuettner KE, Schleyerbach R, Peyron JG, Hascall VC, eds Articular Cartilage and Osteoarthritis. New York; Raven Press 1992: 183-199
  • 35 Repo R U, Finlay J B. Survival of articular cartilage after controlled impact.  J Bone Joint Surg Am. 1977;  59 1068-1076
  • 36 Jeffrey J E, Gregory D W, Aspden R M. Matrix damage and chondrocyte viability following a single impact load on articular cartilage.  Arch Biochem Biophys. 1995;  322 87-96
  • 37 Torzilli P A. et al . Effect of impact load on articular cartilage: cell metabolism and viability, and matrix water content.  J Biomech Eng. 1999;  121 433-441
  • 38 Ewers B J. et al . The extent of matrix damage and chondrocyte death in mechanically traumatized articular cartilage explants depends on rate of loading.  J Orthop Res. 2001;  19 779-784
  • 39 Kerin A J. et al . Propagation of surface fissures in articular cartilage in response to cyclic loading in vitro.  Clin Biomech (Bristol, Avon). 2003;  18 960-968
  • 40 Chen C T. et al . Time, stress, and location dependent chondrocyte death and collagen damage in cyclically loaded articular cartilage.  J Orthop Res. 2003;  21 888-898
  • 41 Kurz B. et al . Biosynthetic response and mechanical properties of articular cartilage after injurious compression.  J Orthop Res. 2001;  19 1140-1146
  • 42 Kurz B. et al . Pathomechanisms of cartilage destruction by mechanical injury.  Ann Anat. 2005;  187 473-485
  • 43 Curl W W. et al . Cartilage injuries: a review of 31,516 knee arthroscopies.  Arthroscopy. 1997;  13 456-460
  • 44 Alford J W, Cole B J. Cartilage restoration, part 1: basic science, historical perspective, patient evaluation, and treatment options.  Am J Sports Med. 2005;  33 295-306
  • 45 Oeppen R S. et al . Acute injury of the articular cartilage and subchondral bone: a common but unrecognized lesion in the immature knee.  AJR Am J Roentgenol. 2004;  182 111-117
  • 46 Hunter W. Of the structure and disease of articulating cartilages. 1743.  Clin Orthop Relat Res. 1995;  317 3-6
  • 47 Furukawa T. et al . Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee.  J Bone Joint Surg Am. 1980;  62 79-89
  • 48 Nehrer S, Spector M, Minas T. Histologic analysis of tissue after failed cartilage repair procedures.  Clin Orthop Relat Res. 1999;  365 149-162
  • 49 Davis M A. et al . The association of knee injury and obesity with unilateral and bilateral osteoarthritis of the knee.  Am J Epidemiol. 1989;  130 278-288
  • 50 Baumgaertner M R. et al . Arthroscopic debridement of the arthritic knee.  Clin Orthop Relat Res. 1990;  253 197-202
  • 51 Hubbard M J. Articular debridement versus washout for degeneration of the medial femoral condyle. A five-year study.  J Bone Joint Surg Br. 1996;  78 217-219
  • 52 Moseley J B. et al . A controlled trial of arthroscopic surgery for osteoarthritis of the knee.  N Engl J Med. 2002;  347 81-88
  • 53 Insall J N. Intra-articular surgery for degenerative arthritis of the knee. A report of the work of the late K. H. Pridie.  J Bone Joint Surg Br. 1967;  49 211-228
  • 54 Mitchell N, Shepard N. The resurfacing of adult rabbit articular cartilage by multiple perforations through the subchondral bone.  J Bone Joint Surg Am. 1976;  58 230-233
  • 55 Johnson L L. Arthroscopic abrasion arthroplasty historical and pathologic perspective: present status.  Arthroscopy. 1986;  2 54-69
  • 56 Steadman J R. et al . [The microfracture technic in the management of complete cartilage defects in the knee joint].  Orthopäde. 1999;  28 26-32
  • 57 Rudd R G. et al . The effects of beveling the margins of articular cartilage defects in immature dogs.  Vet Surg. 1987;  16 378-383
  • 58 Alford J W, Cole B J. Cartilage restoration, part 2: techniques, outcomes, and future directions.  Am J Sports Med. 2005;  33 443-460
  • 59 Steadman J R. et al . Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up.  Arthroscopy. 2003;  19 477-484
  • 60 Frisbie D D. et al . Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses.  Vet Surg. 1999;  28 242-255
  • 61 Frisbie D D. et al . Effects of calcified cartilage on healing of chondral defects treated with microfracture in horses.  Am J Sports Med. 2006;  34 1824-1831
  • 62 Steadman J R, Rodkey W G, Rodrigo J J. Microfracture: surgical technique and rehabilitation to treat chondral defects.  Clin Orthop Relat Res. 2001;  391 (Suppl) S362-369
  • 63 Buckwalter J A, Mow V C, Ratcliffe A. Restoration of Injured or Degenerated Articular Cartilage.  J Am Acad Orthop Surg. 1994;  2 192-201
  • 64 Yamashita F. et al . The transplantation of an autogeneic osteochondral fragment for osteochondritis dissecans of the knee.  Clin Orthop Relat Res. 1985;  201 43-50
  • 65 Matsusue Y, Yamamuro T, Hama A. Arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption.  Arthroscopy. 1993;  9 318-321
  • 66 Cain E L, Clancy W G. Treatment algorithm for osteochondral injuries of the knee.  Clin Sports Med. 2001;  20 321-342
  • 67 Pearce S G. et al . An investigation of 2 techniques for optimizing joint surface congruency using multiple cylindrical osteochondral autografts.  Arthroscopy. 2001;  17 50-55
  • 68 Bartz R L. et al . Topographic matching of selected donor and recipient sites for osteochondral autografting of the articular surface of the femoral condyles.  Am J Sports Med. 2001;  29 207-212
  • 69 Hunziker E B, Quinn T M. Surgical removal of articular cartilage leads to loss of chondrocytes from cartilage bordering the wound edge.  J Bone Joint Surg Am. 2003;  85 (Suppl. 2) 85-92
  • 70 Hangody L, Fules P. Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience.  J Bone Joint Surg Am. 2003;  85 (Suppl. 2) 25-32
  • 71 Shasha N. et al . Long-term follow-up of fresh tibial osteochondral allografts for failed tibial plateau fractures.  J Bone Joint Surg Am. 2003;  85 (Suppl. 2) 33-39
  • 72 Williams R J 3rd, Dreese J C, Chen C T. Chondrocyte survival and material properties of hypothermically stored cartilage: an evaluation of tissue used for osteochondral allograft transplantation.  Am J Sports Med. 2004;  32 132-139
  • 73 Williams S K. et al . Prolonged storage effects on the articular cartilage of fresh human osteochondral allografts.  J Bone Joint Surg Am. 2003;  85 2111-2120
  • 74 Ochs B G. et al . [Treatment of osteochondritis dissecans of the knee: one-step procedure with bone grafting and matrix-supported autologous chondrocyte transplantation].  Z Orthop Unfall. 2007;  145 146-151
  • 75 Brittberg M. et al . Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.  N Engl J Med. 1994;  331 889-895
  • 76 Schnabel M. et al . Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture.  Osteoarthritis Cartilage. 2002;  10 62-70
  • 77 Domm C. et al . Redifferentiation of dedifferentiated bovine articular chondrocytes in alginate culture under low oxygen tension.  Osteoarthritis Cartilage. 2002;  10 13-22
  • 78 Ochi M. et al . Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee.  J Bone Joint Surg Br. 2002;  84 571-578
  • 79 Stoop R. Smart biomaterials for tissue engineering of cartilage.  Injury. 2008;  39 (Suppl. 1) S77-87
  • 80 Koay E J, Athanasiou K A. Hypoxic chondrogenic differentiation of human embryonic stem cells enhances cartilage protein synthesis and biomechanical functionality.  Osteoarthritis Cartilage. 2008;  16 1450-1456
  • 81 Kisiday J D. et al . Effects of dynamic compressive loading on chondrocyte biosynthesis in self-assembling peptide scaffolds.  J Biomech. 2004;  37 595-604
  • 82 Vinatier C. et al . Cartilage engineering: a crucial combination of cells, biomaterials and biofactors.  Trends Biotechnol. 2009;  27 307-314
  • 83 Bentley G. et al . A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee.  J Bone Joint Surg Br. 2003;  85 223-230
  • 84 LaPrade R F. et al . Histologic and immunohistochemical characteristics of failed articular cartilage resurfacing procedures for osteochondritis of the knee: a case series.  Am J Sports Med. 2008;  36 360-368
  • 85 Saris D B. et al . Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture.  Am J Sports Med. 2008;  36 235-246
  • 86 Richter W. Cell-based cartilage repair: illusion or solution for osteoarthritis.  Curr Opin Rheumatol. 2007;  19 451-456
  • 87 Breinan H A. et al . Healing of canine articular cartilage defects treated with microfracture, a type-II collagen matrix, or cultured autologous chondrocytes.  J Orthop Res. 2000;  18 781-789
  • 88 Brittberg M. Autologous chondrocyte implantation–technique and long-term follow-up.  Injury. 2008;  39 (Suppl. 1) S40-49
  • 89 Knutsen G. et al . Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial.  J Bone Joint Surg Am. 2004;  86 455-464
  • 90 Knutsen G. et al . A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years.  J Bone Joint Surg Am. 2007;  89 2105-2112
  • 91 Han E. et al . Shaped, stratified, scaffold-free grafts for articular cartilage defects.  Clin Orthop Relat Res. 2008;  466 1912-1920
  • 92 Tallheden T. et al . Proliferation and differentiation potential of chondrocytes from osteoarthritic patients.  Arthritis Res Ther. 2005;  7 R560-R568
  • 93 Corsi K A. et al . Regenerative medicine in orthopaedic surgery.  J Orthop Res. 2007;  25 1261-1268
  • 94 Conrad S. et al . Generation of pluripotent stem cells from adult human testis.  Nature. 2008;  456 344-349
  • 95 Dominici M. et al . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.  Cytotherapy. 2006;  8 315-317
  • 96 Canalis E, Economides A N, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton.  Endocr Rev. 2003;  24 218-235
  • 97 Grimaud E, Heymann D, Redini F. Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders.  Cytokine Growth Factor Rev. 2002;  13 241-257
  • 98 Fan H. et al . Porous gelatin-chondroitin-hyaluronate tri-copolymer scaffold containing microspheres loaded with TGF-beta1 induces differentiation of mesenchymal stem cells in vivo for enhancing cartilage repair.  J Biomed Mater Res A. 2006;  77 785-794
  • 99 Blaney Davidson E N, van der Kraan P M, van den Berg W B. TGF-beta and osteoarthritis.  Osteoarthritis Cartilage. 2007;  15 597-604
  • 100 Sekiya I. et al . Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma.  Cell Tissue Res. 2005;  320 269-276
  • 101 Grunder T. et al . Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads.  Osteoarthritis Cartilage. 2004;  12 559-567
  • 102 Kuo A C. et al . Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair.  Osteoarthritis Cartilage. 2006;  14 1126-1135
  • 103 Goldring M B, Tsuchimochi K, Ijiri K. The control of chondrogenesis.  J Cell Biochem. 2006;  97 33-44
  • 104 Garrison K R. et al . Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.  Health Technol Assess. 2007;  11 1-150, iii – iv
  • 105 Stewart A A. et al . Effect of fibroblast growth factor-2 on equine mesenchymal stem cell monolayer expansion and chondrogenesis.  Am J Vet Res. 2007;  68 941-945
  • 106 Ellman M B. et al . Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis.  Gene. 2008;  420 82-89
  • 107 Davies L C. et al . The potential of IGF-1 and TGFbeta1 for promoting ”adult” articular cartilage repair: an in vitro study.  Tissue Eng Part A. 2008;  14 1251-1261
  • 108 Uebersax L, Merkle H P, Meinel L. Insulin-like growth factor I releasing silk fibroin scaffolds induce chondrogenic differentiation of human mesenchymal stem cells.  J Control Release. 2008;  127 12-21
  • 109 Schett G. How does joint remodeling work? New insights in the molecular regulation of the architecture of joints.  Cell Adh Migr. 2007;  1 102-103
  • 110 Edwards P C. et al . Sonic hedgehog gene-enhanced tissue engineering for bone regeneration.  Gene Ther. 2005;  12 75-86
  • 111 Richardson S M, Hoyland J A. Stem cell regeneration of degenerated intervertebral discs: current status.  Curr Pain Headache Rep. 2008;  12 83-88
  • 112 Evans C H, Ghivizzani S C, Robbins P D. Orthopedic gene therapy in 2008.  Mol Ther. 2009;  17 231-244

Dr. med. Bernd Rolauffs

Berufsgenossenschaftliche Unfallklinik Tübingen

Schnarrenbergstr. 95
72076 Tübingen

Phone: 07071/253815

Email: berndrolauffs@googlemail.com

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