Advertisement

Basic Science and Clinical Strategies for Articular Cartilage Regeneration/Repair

  • Barry W Oakes
Chapter

Introduction

In the last decade, much has been learnt regarding the regeneration and repair of tissues of the skeleton. Regeneration of tissue readily occurs in the embryo, is almost absent in neonates and is never observed in adults. This may be because of the relatively high proportion of undifferentiated progenitor cells found in embryos and their relative scarcity in adults, that is, 1/10,000 mesenchyme cells in newborn and 1/2 × 106 in an 80 year old adult (Haynesworth et al. 1994). Regeneration is a slow process and seems to recapitulate many steps during embryonic development. In contrast, repair is a much more rapid process probably designed for survival and involves the usual inflammatory cell cascade followed by matrix deposition and then a remodeling process which attempts to partially regenerate damaged tissues in the adult. Repair and remodeling process can take many months to occur in the musculoskeletal system and the resulting repaired tissues, although of inferior...

Keywords

Articular Cartilage Cartilage Repair Autologous Chondrocyte Implantation International Knee Documentation Committee Articular Cartilage Defect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The author would like to thank Ms Maria Kouvalaris from Mercy Tissue Engineering for her great help in the preparation of this manuscript. Also Mrs Sue Connell for preparation and staining of the histology sections. Also Associate Professor Chris Little for the immuno-labeling studies presented here on selected ACI biopsies.

References

  1. Adam C, Eckstein F, Milz S, Putz R. (1998) The distribution of cartilage thickness within joints of the lower limb of elderly individuals. J Anat 193:203–214CrossRefGoogle Scholar
  2. Adams ME, Atkinson MH, Lussier AJ, Schulz JI, Siminovitch KA, Wade JP, et al. (1995) The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cart 3:213–25CrossRefGoogle Scholar
  3. Alford JW, Cole BJ (2005) Cartilage restoration, Part 1 basic science, historical perpspective, patient evaluation, and treatment options. Am J Sports Med 33:295–306CrossRefGoogle Scholar
  4. Aroen A, Loken S, Heir S et al. (2004) Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med 32:211–215CrossRefGoogle Scholar
  5. Barbero A, Grogan SP, Ploegert S, et al. (2002) Age related changes in chondrocyte biology. In: Proceeding of Fourth International Cartilage Repair Society Symposium (ICRS), Toronto, CanadaGoogle Scholar
  6. Barry FP (2003) Mesenchymal stem cell therapy in joint disease. In: Tissue engineering of cartilage and bone. Novartis foundation symposium 249. J Wiley and Sons UK, pp 86–102Google Scholar
  7. Benya PD, Shaffer JD (1982) Dedifferentiated chondrocytes re-express the differentiated phenotype when cultured in agarose gels. Cell 30:215–224CrossRefGoogle Scholar
  8. Benya PD, Padilla SR, Nimni ME (1977) The progeny of rabbit articular chondrocytes synthesize collagen types I and III and type I trimer, but not type II. Verifications by cyanogen bromide peptide analysis. Biochemistry 16:865–872CrossRefGoogle Scholar
  9. Binette F, McQuaid DP, Haudenschild DR et al. (1998) Expression of a stable articular phenotype without evidence of hypertrophy by adult human articular chondrocytes in vitro. J Orthop Res 16:207–216CrossRefGoogle Scholar
  10. Breinan H, Minas T, Hsu H, Nehrer S, Sledge C, Spector M (1997) Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model. J Bone Joint Surg 79A:1439–1451Google Scholar
  11. Briggs TWR, Mahroof S, David LA, Flannelly J, Pringle J, Bayliss M (2003) Histological evaluation of chondral defects after autologous chondrocyte implantation on the knee. J. Bone and Joint Surg 85-B:1077–83CrossRefGoogle Scholar
  12. Brittberg M, Lindhal A, Nilsson et al. (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. NEJM 331:889–895Google Scholar
  13. Brittberg M, Sjogren-Jansson E, Lindahl A, Peterson L (1997) Influence of fibrin sealant (Tisseel) on osteochondral defect repair in the rabbit knee. Biomaterials 18:235–242CrossRefGoogle Scholar
  14. Brown WE, Potter HG, Marx RG, Wickiewicz TL, Warren R (2004) Magnetic resonance imaging appearance of cartilage repair in the knee. Clin Orthop Relat Res, 422:214–223CrossRefGoogle Scholar
  15. Buckwalter JA (1999) Evaluating methods of restoring cartilage articular surfaces. Clin Orthop Rel Research 367S:S224–S238CrossRefGoogle Scholar
  16. Buckwalter JA, Mankin H (1997a) Articular cartilage. Part I: tissue design and chondrocyte-matrix interactions. Instructional course lectures, The American Academy of Orthopaedic Surgeons. J Bone Joint Surg Am 79:600–611Google Scholar
  17. Buckwalter JA, Mankin H (1997b) Articular cartilage. Part II: degeneration and osteoarthrosis, repair, regeneration and transplantation. Instructional course lectures, The American Academy of Orthopaedic Surgeons. J Bone Joint Surg Am 79:612–632Google Scholar
  18. Buckwalter JA, Hunziker E, Rosenberg L et al. (1998) Articular cartilage: composition and structure. In: Woo SLY, Buckwalter JA (eds) Injury and repair of the musculoskeletal tissues. American Academy of Orthopaedic Surgeons, Park Ridge, IL, pp 405–425Google Scholar
  19. Buckwalter JA, Pita JC, Muller FJ, Nessler J (1994) Structural differences between two populations of articular cartilage proteoglycan aggregates. J Orthop Res 12:144–148CrossRefGoogle Scholar
  20. Bugbee W (2005) Fresh osteochondral allografts. Instructional lecture, American Academy Orthopaedic Surgeons, Washington, DC Feb 2005Google Scholar
  21. Bugbee W (2004) Fresh Osteochondral Allografts for the Knee. Tech Knee Surg 3:1–9CrossRefGoogle Scholar
  22. Burstein D, Gray M (2003) New MRI techniques for imaging cartilage. J. Bone Joint Surg Am 85:70–77Google Scholar
  23. Caterson B, Lowther D (1978) Changes in the metabolism of the proteoglycans from sheep articular cartilage in response to mechanical stress. Biochim Biophys Acta 540:412–422CrossRefGoogle Scholar
  24. Chaipinyo K, Oakes BW, van Damme MPI (2002). Effects of growth factors on cell proliferation and matrix synthesis of low-density, primary bovine chondrocytes cultured in collagen I gels. J. Orthopaedic Research 20: 1070–1078.Google Scholar
  25. Chaipinyo K, Oakes BW, van Damme MPI (2004) The use of debrided human articular cartilage for autologous chondrocyte implantation: maintenance of chondrocyte differentiation and proliferation in type I collagen gels. J Orthop Res 22:446–455CrossRefGoogle Scholar
  26. Cicuttini FM, Forbes A, Yuanyuan W, Rush G, Stuckey SL (2002) Rate of knee cartilage loss after partial menisectomy. J Rheumatol 29:1954–1956Google Scholar
  27. Corpus E, Harman M, Blackman M (1993) Human growth hormone and ageing. Endocr Rev 14:20–39Google Scholar
  28. Curl WW, Krome J, Gordon ES, et al. (1997) Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy 13:456–460CrossRefGoogle Scholar
  29. Derrett S, Stokes ES, James M, Bartlett W, Bentley G (2005) Cost and health analysis after autologous chondrocyte implantation and mosaicplasty: a retrospective comparison. Int J Technol Assess Health Care 21:358–367CrossRefGoogle Scholar
  30. de Witt MT, Handley CJ, Oakes BW, Lowther DA (1984) In vitro response of chondrocytes to mechanical loading. The effect of short term mechanical tension. Connect Tissue Res 12:97–109CrossRefGoogle Scholar
  31. Fu FH, Zurakowski D, Browne JE, Mandelbaum B, Erggelet C, Moseley JB Jr, Anderson AF, Micheli LJ (2005) Autologous chondrocyte implantation versus debridment for treatment of full thickness chondral defects of the knee. An observational cohort with 3-year follow-up. Am J Sports Med 33:1658–1666CrossRefGoogle Scholar
  32. Hangody L, Fules P (2003) Autologous osteochondral mosaicplasty for treatment of full-thickness defects of weight-bearing joints: ten years experimental and clinical experience. J Bone Joint Surg Am 15(Suppl 2):25–32Google Scholar
  33. Hangody L (1998) Mosaicplasty in the treatment of the focal chondral and osteochondral Defects. ICRS Newsletter, Spring, 1998, p11Google Scholar
  34. Handley CJ, Bateman JF, Oakes BW, Lowther DA (1975) Characterization of the collagen synthesizied by cultured cartilage cells. Biochem Biophys Acta 386:444CrossRefGoogle Scholar
  35. Hardingham TE, Oldershaw RA, Tew S (2006) Cartilage, SOX9 and Notch signals in chondrogenesis. J Anat 209:469–480 Google Scholar
  36. Hardingham T (2004) Tissue engineering – view from a small island. Tissue Eng 9:1063–1064CrossRefGoogle Scholar
  37. Haynesworth SE, Goldberg VM, Caplan AI (1994) Diminution of the number of mesenchyme stem cells as a cause for skeletal ageing. In: Buckwalter JA, Goldberg VM, Woo SL-Y (eds) Musculoskeletal soft-tissue ageing: impact on mobility. American Academy of Orthopaedic Surgeons, Rosemont, IL, pp 79–87Google Scholar
  38. Henderson IJP, Tuy B, Connell D, Oakes B, Hettwer WH (2003) Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months. J Bone Joint Surg 85-B:1060–1066CrossRefGoogle Scholar
  39. Henderson IJP, La Valette DP (2005) Subchondral bone overgrowth in the presence of full-thickness cartilage defects in the knee. Knee 12:435–440CrossRefGoogle Scholar
  40. Henderson IJP, Lavigne P, Valenzuela H, Oakes B (2007) Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs. Clin Orthop Relat Res, 455:253–261 Google Scholar
  41. Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil Jun 10:432–63CrossRefGoogle Scholar
  42. Hunziker EB, Driesang MK, Morris EA (2001) Chondrogenesis in Cartilage repair is induced by members of the transforming growth factor-beta superfamily. Clin Orthop Relat Res 391S:S171–S181CrossRefGoogle Scholar
  43. Hunziker EB, Rosenberg LC (1996) Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg 78A:721–733Google Scholar
  44. Hunziker EB (2001a) Growth-factor-induced healing of partial-thickness defects in adult articular cartilage. Osteoarthr Cartil 9:22–32Google Scholar
  45. Hunziker EB (2001b) Growth-factor-induced healing of partial-thickness defects in adult articular cartilage. J Orthop Res 20:1070–1078Google Scholar
  46. Huckle J, Dootson G, Medcalf N, Mc Taggart S, Wright E, Carter A, Schreiber R, Kirby B, Dunkelman N, Stevenson S, Riley S, Davisson T, Ratcliffe A (2003) Differentiated chondrocytes for cartilage tissue engineering. In: Tissue engineering of cartilage and bone. Novartis foundation symposium 249. J Wiley and Sons, UK, pp 103–117Google Scholar
  47. James SLJ, Connell DA, Saifuddin A, Skinner JA, Briggs TWR (2005) MR imaging of autologous chondrocyte implantation of the knee. Eur Radiol 16:1022–1030CrossRefGoogle Scholar
  48. Jones DG, Peterson L (2006) Autologous chondrocyte implantation. Selected instructional course lectures. J Bone Joint Surg Am 88:2501–2501CrossRefGoogle Scholar
  49. Kaab M, Gwyn A, Notzli HP (1998) Collagen fibre arrangement in the tibial plateaux articular cartilage of man and other mammalian species. J Anat 193:23–34CrossRefGoogle Scholar
  50. Kiviranta I, Jurvelin J, Tammi M, Säämänen A-M, Helminen HJ (1987) Weight bearing controls glycosaminoglycan concentration and thickness of articular cartilage in the knee joints of young beagle dogs. Arthritis Rheum 30:801–808Google Scholar
  51. Knutsen G, Engebretson L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O (2004) Autologous chondrocyte implantation compared with microfracture in the knee: a randomised trial. J. Bone and Joint Surg 86-A:455–464Google Scholar
  52. Knutsen G, Drogset JO, Engebretsen L, et al. (2006) Autologous chondrocyte implantation compared with microfracture in the knee. (Five year follow-up) Proceedings ICRS symposium San Diego (abstract)Google Scholar
  53. Kreuz PC, Steinwachs MR, Ergggelet C et al. (2006) Results after microfracture of full-thickness chondral defects in different compartments of the knee. Osteoarthr Cartil 14:1119–1125CrossRefGoogle Scholar
  54. Leonard CM, Fuld HM, Frenz DA et al. (1991) Role of transforming growth factor – beta in chondrogenic pattern formation in the embryonic limb: stimulation of mesenchymal condensation and fibronectin gene expression by exogenous TGF-beta and evidence for endogenous TGF-beta like activity. Dev Biol 145:99–109CrossRefGoogle Scholar
  55. Lindahl A, Brittberg M, Peterson L (2003) Cartilage repair with chondrocytes : clinical and cellular aspects. In: Tissue engineering of cartilage and bone. Novartis foundation symposium 249. J. Wiley and Sons Ltd. UK, pp 175–189Google Scholar
  56. Lyyra T (1997) Development, validation and clinical application of indentation technique for arthroscopic measurement of cartilage stiffness. University of Kupio, Kuopio, Finland: 1–99Google Scholar
  57. Lyyra T et al. (1999) In vivo charactertiyation of indentation stiffness of articular cartilage in the normal human knee. J Biomed Mater Res. 48:482–487Google Scholar
  58. Mankin HJ (1982) Current concepts review. The response of articular cartilage to mechanical injury. J Bone Joint Surg March 64A:460–466Google Scholar
  59. Marlovits S, Tichy B, Truppe M, Gruber D, Vecsei V (2003) Chondrogenesis of aged human articular cartilage in a scaffold-free bioreactor. Tissue Eng 9:1215–1226CrossRefGoogle Scholar
  60. Marlovits S, Singer P, Zeller P, Mandl I, Haller J, Trattnig S (2006) Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol 57:16–23CrossRefGoogle Scholar
  61. Marlovits S, Striessnig G, Kutscha-Lissberg F, Resinger C, Aldrian SM, Vecsei V, Trattnig S (2005) Early post-operative adherence of matrix-induced autologous chondrocyte implantation for the treatment of full-thickness cartilage defects of the femoral condyle. Knee Surg Sports Traumatol Arthrosc 13:451–457CrossRefGoogle Scholar
  62. Martin JA, Buckwalter J (2003) The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. JBJS 85-A:S106-S110Google Scholar
  63. McQuillan DJ, Handley CJ, Campbell MA, Bolis S, Milway VE, Herington AC (1986) Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage. Biochem J 240:423–430Google Scholar
  64. Mithoefer K et al. (2005a) Articular cartilage repair in soccer players with autologous chondrocyte transplantation. Am J Sports Med 33:1639–1646Google Scholar
  65. Mithoefer K et al. (2005b) Functional outcome of knee articular cartilage repair in adolescent athletes. Am Orthop Soc Sports Med 33:1147–1153Google Scholar
  66. Mithoefer K, Williams RJ III, Warren RF, Potter H, Spock CR, Jones EC, Wickiewics TL, Marx RG (2005c) The microfracture technique for the treatment of articular cartilage lesions of the knee. A prospective cohort study. J Bone Joint Surg Am 87:1911–1920Google Scholar
  67. Nieminen MT, Toyras J, Laasanan MS, Rieppo J, Silvennoinen J, Helminen HJ, Jurvelin JS (2001) MRI quantitation of proteoglycans predicts cartilage stiffness in bovine humeral head. Proceedings American Orthopaedic Society Feb 25–28, San Francisco, California, USAGoogle Scholar
  68. Oakes BW, Connell S, Henderson I (2004) Histological classification of 58 patients with plastic – embedded full thickness core biopsies 2.6–53 months following Autolgous Chondrocyte Implantation (ACI) . Proceedings ICRS meeting Ghent, 2004. (Abstract).Google Scholar
  69. Oakes BW (2003) Tissue healing and repair: tendons and ligaments. In: Frontera WR (ed) Rehabilitation of sports injuries. Scientific basis. The Encylopaedia of Sports Medicine. An IOC Medical Commission Publication. Blackwell Publishing, UK, Australia &Germany. pp 56–98Google Scholar
  70. Oakes BW, Handley CJ, Lisner F, Lowther DA (1977) An ultrastructural and biochemical study of the high density primary culture of embryonic chick chondrocytes. J Embryol Exp Morph 38:239–263Google Scholar
  71. O’Byrne E, Pellas T, Laurent D (2003) Qualitative and quantitative in vivo assessment of articular cartilage using magnetic resonance imaging. In: Tissue engineering of cartilage and bone. Novartis foundation symposium 249. J Wiley and Sons Ltd. UK pp 190–202Google Scholar
  72. Ochi M, Uchio Y, Kawasaki K, Wakitani S, Iwasa J (2002) Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J Bone Joint Surg 84B:571–578CrossRefGoogle Scholar
  73. Pavesio A, Abatangelo G, Borrione A, et al. (2003) Hyaluronan-based scaffoids (Hyalogoraft) in the treatment of knee cartilage defects: preliminary clinical findings. In: Tissue Engineering of Cartilage and Bone. Novartis Foundation Symposium 249. J Wiley and Sons Ltd. pp 203–217.Google Scholar
  74. Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A (2000) Two- to – 9 year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 374:212–234Google Scholar
  75. Poole AR (2003) What type of cartilage repair are we attempting to attain. JBJS 85A: 40–44Google Scholar
  76. Poole CA, Ayad S, Gilbert RT (1992) Chondrons from articular cartilage: V. Immunohistochemicql evaluation of type VI collagen in isolated chondrons by light, confocal and electron microscopy. J Cell Sci 103:1101–1110Google Scholar
  77. Ratcliffe A, Mow VC (1996) Articular cartilage. In: Wayne D Comper (ed) Extracellular matrix, volume 1, tissue function, pp 234–302. Harwood Academic Publishers, The Netherlands.Google Scholar
  78. Ratcliffe A, Tyler JA, Hardingham TE (1986) Articuolar cartilage cultured with interleukin-1: increased release of link protein, hyaluronate-binding region, and other proteoglycan fragments. Biochemi J 238:571–580Google Scholar
  79. Roberts S, McCall IW, Darby AJ, Menage J, Evans H, Harrison PE, Richardson JB (2003a) Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology. Arthritis Res Ther 5:R60-R73Google Scholar
  80. Roberts S, Hollander AP, Caterson B, Menage J, Richardson JB (2003b) Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation. Arthritis and Rheum 44:2586–2598Google Scholar
  81. Ruana-Ravina A, Diaz MJ (2006) Autologous chondrocyte implantation: a systematic review. Osteoarthr Cartil 14:47–51CrossRefGoogle Scholar
  82. Samosky JT, Burstein D, Grimson WE, Howe R, Martin S, Gray M (2005) Spatially-loclized correlation of dGEMRIC-measured GAG distribution and mechanical stiffness in the human tibial plateau. J Orthop Res 23:93–101CrossRefGoogle Scholar
  83. Seedhom BB, Hargreaves DJ (1979) Transmission of load in the knee joint with special reference to the role of the menisci, Part II: experimental results, discussions and conclusions. Eng Med 8:220–228CrossRefGoogle Scholar
  84. Shapiro F, Koide S, Glimcher MJ (1993) Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J. Bone Joint Surg Am 75:532–553Google Scholar
  85. Shelbourne KD, Jari S, Gray T (2003) Outcome of untreated articular cartilage defects of the knee. A natural history study. J Bone Joint Surg 85A:S8-S16Google Scholar
  86. Sporn M, Roberts AB, Wakefield LM, Assoian RK (1986) Transforming growth factor-beta: biological function and chemical structure. Science 233:532–534CrossRefGoogle Scholar
  87. Spring BJ, Staudacher HM, Henderson IJP (2001) Biomechanical evaluation of normal articular cartilage in the human knee. (Abstract). Proceedings of the Asia Pacific Orthopaedic Association, Adelaide, April 1–6 p 134Google Scholar
  88. Steadman JR, Rodkey WG, Briggs KK (2002) Microfracture to treat full-thickness chondral defects: surgical technique, rehabilitation, and outcomes. J Knee Surg 15:170–1176Google Scholar
  89. Stockwell R (1971) The interrelationship of cell density and cartilage thickness in mammalian cartilage. J Anat 109:411–421Google Scholar
  90. Takahashi T, Tins B, McCall IW, Richardson JB, Takagi K, Ashton K (2006) MR appearance of autologous chondrocyte implantation in the knee: correlation with the knee features and clinical outcome. Skeletal Radiol 35:16–26CrossRefGoogle Scholar
  91. Tyler JA (1986) Chondrocyte-mediated depletion of articular cartilage proteoglycans in vitro. Biochemi J 225:493–507Google Scholar
  92. Vasara AI, Nieminen MT, Jurvelin JS, Peterson L, Lindahl A, Kivianta I (2005) Indentation stiffness of repair tissue after autologous chondrocyte transplantation. Clin Orthop and Relat Res 433:233–242CrossRefGoogle Scholar
  93. Verdonk R, Steinwachs M, vanlauwe J, Engebretsen L (2006) Trends in cartilage repair. Current opinion of orthopaedic surgeons on cartilage repair: the results of a web-based survey. 3–14. From ICRS web site www.cartilage.org
  94. Vunjak-Novakovic G, Martin I, Obradovich B, Treppo S, Grodzinsky AJ, Langer R, Freed LE (1999) Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage. J Orthop Res 17:130–138CrossRefGoogle Scholar
  95. Walker PS, Erkman MJ (1975) The role of the menisci in force transmission across the knee. Clin Orthop 109:184–192.CrossRefGoogle Scholar
  96. Wen DY (2000) Intra-articular hyaluronic acid injections for knee osteoarthritis. Am Fam Physician 62:565–570, 572Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Mercy Tissue Engineering and Department of Anatomy and Cell BiologyMonash University AustraliaMelbourneAustralia
  2. 2.Australia

Personalised recommendations