Preclinical studies for cartilage repair: Recommendations from the international cartilage repair society

Cartilage

Volumn 2, Issue 2, 2011, Pages 137-152

  Hurtig, Mark B ^a   Buschmann, Michael D ^b   Fortier, Lisa A ^c   Hoemann, Caroline D ^b   Hunziker, Ernst B ^d   Jurvelin, Jukka S ^e   Mainil Varlet, Pierre ^f   McIlwraith, C Wayne ^g   Sah, Robert L ^h   Whiteside, Robert A ⁱ  

^a UNIVERSITY OF GUELPH   (Canada)

^b ÉCOLE POLYTECHNIQUE DE MONTRÉAL   (Canada)

^c Department of Obstetrics Gynecology   (United States)

^d UNIVERSITY OF BERN   (Switzerland)

^e UNIVERSITY OF EASTERN FINLAND   (Finland)

^f Aginko Research AG   (Switzerland)

^g Department of Environmental and Radiological Health Sciences   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ Arthroteq Preclinical Services   (Canada)

Author keywords

Animal models; Cartilage repair; Clinical trial; Outcome measures; Preclinical research

Indexed keywords

EID: 84857127371     PISSN: 19476035     EISSN: 19476043     Source Type: Journal    
DOI: 10.1177/1947603511401905     Document Type: Article

References (128)

1. US Food and Drug Administration. Guidance for industry: Preparation of IDEs and INDs for products intended to repair or replace knee cartilage. Rockville, MD: US Food and Drug Administration, Center for Biologics Evaluation and Research; 2007. www.fda.gov/downloads/BiologicsBloodVaccines/ucm078710.pdf
2. Levine DW, Mondano L, Halpin M. FDA regulatory pathways for knee cartilage repair products. Sports Med Arthrosc Rev. 2008;16:202-207.
3. ASTM International. Standard guide for in vivo assessment of implantable devices intended to repair or regenerate articular cartilage. ASTM International F2451-07(2010). www.astm.org/Standards/medical-device-and-implant-standards.html
4. Fretz PB, Cymbaluk NF, Pharr JW. Quantitative analysis of long-bone growth in the horse. Am J Vet Res. 1984;45:1602-9.
5. Hunziker EB, Kapfinger E, Geiss J. The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthritis Cartilage. 2007;15:403-13.
6. Rieppo J, Hyttinen MM, Halmesmaki E, Ruotsalainen H, Vasara A, Kiviranta I, et al. Changes in spatial collagen content and collagen network architecture in porcine articular cartilage during growth and maturation. Osteoarthritis Cartilage. 2009;17:448-55.
7. Malina RM. Physical growth and biological maturation of young athletes. Exerc Sport Sci Rev. 1994;22:389-433.
8. Muller-Gerbl M. The subchondral bone plate. Adv Anat Embryol Cell Biol. 1998;141:III-XI, 1-134.
9. Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18:419-33.
10. Gilmore RS, Palfrey AJ. A histological study of human femoral condylar articular cartilage. J Anat. 1987;155:77-85.
11. Brommer H, Brama PA, Laasanen MS, Helminen HJ, van Weeren PR, Jurvelin JS. Functional adaptation of articular cartilage from birth to maturity under the influence of loading: a biomechanical analysis. Equine Vet J. 2005;37:148-54.
12. Dell'accio F, Vincent TL. Joint surface defects: clinical course and cellular response in spontaneous and experimental lesions. Eur Cell Mater. 2010;20:210-7.
13. Wagner W, Reichl J, Wehrmann M, Zenner HP. Neonatal rat cartilage has the capacity for tissue regeneration. Wound Repair Regen. 2001;9:531-6.
14. Wei X, Messner K. Maturation-dependent durability of spontaneous cartilage repair in rabbit knee joint. J Biomed Mater Res. 1999;46:539-48.
15. Wei XC, Gao JZ, Messner K. Maturation-dependent repair of untreated osteochondral defects in the rabbit knee joint. J Biomed Mater Res. 1997;34:63-72.
16. Jiang CC, Chiang H, Liao CJ, Lin YJ, Kuo TF, Shieh CS, et al. Repair of porcine articular cartilage defect with a biphasic osteochondral composite. J Orthop Res. 2007; 25:1277-90.
17. Blanke M, Carl HD, Klinger P, Swoboda B, Hennig F, Gelse K. Transplanted chondrocytes inhibit endochondral ossification within cartilage repair tissue. Calcif Tissue Int. 2009;85: 421-33.
18. Carlson CS, Hilley HD, Meuten DJ, Hagan JM, Moser RL. Effect of reduced growth rate on the prevalence and severity of osteochondrosis in gilts. Am J Vet Res. 1988;49:396-402.
19. Fortier LA, Kornatowski MA, Mohammed HO, Jordan MT, O'Cain LC, Stevens WB. Age-related changes in serum insulin-like growth factor-I, insulin-like growth factor-I binding protein-3 and articular cartilage structure in Thoroughbred horses. Equine Vet J. 2005;37:37-42.
20. Henry JL. Molecular events of chronic pain: from neuron to whole animal in an animal model of osteoarthritis. Novartis Found Symp. 2004;260:139-45. discussion 145-53, 277-9.
21. Ghadially FN, Thomas I, Oryschak AF, Lalonde JM. Longterm results of superficial defects in articular cartilage: a scanning electron-microscope study. J Pathol. 1977;121:213-7.
22. Firth EC, Klarenbeek A. Transphyseal vessel involvement in repair of metaphyseal retained cartilage. Aust Vet J. 1995;72:452-5.
23. Hoemann CD, Sun J, McKee MD, Chevrier A, Rossomacha E, Rivard GE, et al. Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects. Osteoarthritis Cartilage. 2007;15:78-89.
24. Brittberg M, Nilsson A, Lindahl A, Ohlsson C, Peterson L. Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop Relat Res. 1996:270-83.
25. Menche DS, Frenkel SR, Blair B, Watnik NF, Toolan BC, Yaghoubian RS, et al. A comparison of abrasion burr arthroplasty and subchondral drilling in the treatment of full-thickness cartilage lesions in the rabbit. Arthroscopy. 1996;12:280-6.
26. Mitchell N, Shepard N. The resurfacing of adult rabbit articular cartilage by multiple perforations through the subchondral bone. J Bone Joint Surg Am. 1976;58:230-3.
27. Im GI, Lee JH. Repair of osteochondral defects with adipose stem cells and a dual growth factor-releasing scaffold in rabbits. J Biomed Mater Res B Appl Biomater. 2010;92:552-60.
28. O'Driscoll SW, Keeley FW, Salter RB. The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion: an experimental investigation in the rabbit. J Bone Joint Surg Am. 1986;68:1017-35.
29. O'Driscoll SW, Keeley FW, Salter RB. Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion: a follow-up report at one year. J Bone Joint Surg Am. 1988;70:595-606.
30. Ahern BJ, Parvizi J, Boston R, Schaer TP. Preclinical animal models in single site cartilage defect testing: a systematic review. Osteoarthritis Cartilage. 2009;17:705-13.
31. Brandt KD, Schauwecker DS, Dansereau S, Meyer J, O'Connor B, Myers SL. Bone scintigraphy in the canine cruciate deficiency model of osteoarthritis: comparison of the unstable and contralateral knee. J Rheumatol. 1997;24:140-5.
32. Mrosek EH, Lahm A, Erggelet C, Uhl M, Kurz H, Eissner B, et al. Subchondral bone trauma causes cartilage matrix degeneration: an immunohistochemical analysis in a canine model. Osteoarthritis Cartilage. 2006;14:171-8.
33. Lahm A, Uhl M, Edlich M, Erggelet C, Haberstroh J, Kreuz PC. An experimental canine model for subchondral lesions of the knee joint. Knee. 2005;12:51-5.
34. Cook JL, Fox DB, Malaviya P, Tomlinson JL, Farr J, Kuroki K, et al. Evaluation of small intestinal submucosa grafts for meniscal regeneration in a clinically relevant posterior meniscectomy model in dogs. J Knee Surg. 2006;19:159-67.
35. Nishida M, Higuchi H, Kobayashi Y, Takagishi K. Histological and biochemical changes of experimental meniscus tear in the dog knee. J Orthop Sci. 2005;10:406-13.
36. Breinan HA, Minas T, Hsu HP, Nehrer S, Sledge CB, Spector M. Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model. J Bone Joint Surg Am. 1997;79:1439-51.
37. Cook SD, Patron LP, Salkeld SL, Rueger DC. Repair of articular cartilage defects with osteogenic protein-1 (BMP-7) in dogs. J Bone Joint Surg Am. 2003;85A(suppl 3):116-23.
38. Cook SD, Barrack RL, Patron LP, Salkeld SL. Osteogenic protein-1 in knee arthritis and arthroplasty. Clin Orthop Relat Res. 2004:140-5.
39. Nehrer S, Breinan HA, Ramappa A, Hsu HP, Minas T, Shortkroff S, et al. Chondrocyte-seeded collagen matrices implanted in a chondral defect in a canine model. Biomaterials. 1998;19:2313-28.
40. Budsberg SC, Chambers JN, Lue SL, Foutz TL, Reece L. Prospective evaluation of ground reaction forces in dogs undergoing unilateral total hip replacement. Am J Vet Res. 1996;57:1781-5.
41. Hurtig MB, Novak K, McPherson R, McFadden S, McGann LE, Mul drew K, et al. Osteochondral dowel transplantation for repair of focal defects in the knee: an outcome study using an ovine model. Vet Surg. 1998;27:5-16.
42. Tytherleigh-Strong G, Hurtig M, Miniaci A. Intra-articular hyaluronan following autogenous osteochondral grafting of the knee. Arthroscopy. 2005;21:999-1005.
43. Lane JG, Massie JB, Ball ST, Amiel ME, Chen AC, Bae WC, et al. Follow-up of osteochondral plug transfers in a goat model: a 6-month study. Am J Sports Med. 2004;32:1440-50.
44. Mora G, Alvarez E, Ripalda P, Forriol F. Articular cartilage degeneration after frozen meniscus and Achilles tendon allograft transplantation: experimental study in sheep. Arthroscopy. 2003;19:833-41.
45. Chevrier A, Nelea M, Hurtig MB, Hoemann CD, Buschmann MD. Meniscus structure in human, sheep, and rabbit for animal models of meniscus repair. J Orthop Res. 2009;27:1197-203.
46. Guisasola I, Vaquero J, Forriol F. Knee immobilization on meniscal healing after suture: an experimental study in sheep. Clin Orthop Relat Res. 2002;(395):227-33.
47. Frisbie DD, Cross MW, McIlwraith CW. A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee. Vet Comp Orthop Traum. 2006;19:142-6.
48. Hoemann CD, Sun J, Chrzanowski V, Buschmann MD. A multivalent assay to detect glycosaminoglycan, protein, collagen, RNA, and DNA content in milligram samples of cartilage or hydrogel-based repair cartilage. Anal Biochem. 2002;300:1-10.
49. Melrose J, Smith S, Ghosh P, (2004). Histological and immunohistological studies on Cartilage. In Cartilage and Osteoarthritis, Volume 2, Edited by De Ceuninck F, Sabatini M, and Patoureau P (eds). Humana Press, New Jersey pp 39-63.
50. Archibald M, Runciman J, Dickey J, Hurtig M. Do animal models approximate the subchondral bone and cartilage characteristics of humans? Presented at: 4th International Cartilage Repair Society, June 2002, Toronto, Canada.
51. Jackson DW, Lalor PA, Aberman HM, Simon TM. Spontaneous repair of full-thickness defects of articular cartilage in a goat model: a preliminary study. J Bone Joint Surg Am. 2001;83A:53-64.
52. Simon TM, Jackson DW. Articular cartilage: injury pathways and treatment options. Sports Med Arthrosc Rev. 2006;14:146-54.
53. Hoemann CD, Hurtig M, Rossomacha E, Sun J, Chevrier A, Shive MS, et al. Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Joint Surg Am. 2005;87A:2671-86.
54. Driesang IM, Hunziker EB. Delamination rates of tissue flaps used in articular cartilage repair. J Orthop Res. 2000;18:909-11.
55. Dorotka R, Windberger U, Macfelda K, Bindreiter U, Toma C, Nehrer S. Repair of articular cartilage defects treated by microfracture and a three-dimensional collagen matrix. Biomaterials. 2005;26:3617-29.
56. Dorotka R, Bindreiter U, Macfelda K, Windberger U, Nehrer S. Marrow stimulation and chondrocyte transplantation using a collagen matrix for cartilage repair. Osteoarthritis Cartilage. 2005;13:655-64.
57. Brehm W, Aklin B, Yamashita T, Rieser F, Trub T, Jakob RP, et al. Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results. Osteoarthritis Cartilage. 2006;14:1214-26.
58. Jones CW, Willers C, Keogh A, Smolinski D, Fick D, Yates PJ, et al. Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopy. J Orthop Res. 2008;26:292-303.
59. Kangarlu A, Gahunia HK. Magnetic resonance imaging characterization of osteochondral defect repair in a goat model at 8 T. Osteoarthritis Cartilage. 2006;14:52-62.
60. Lu Y, Markel MD, Swain C, Kaplan LD. Development of partial thickness articular cartilage injury in an ovine model. J Orthop Res. 2006;24:1974-82.
61. van Susante JL, Buma P, Homminga GN, van den Berg WB, Veth RP. Chondrocyte-seeded hydroxyapatite for repair of large articular cartilage defects: a pilot study in the goat. Biomaterials. 1998;19:2367-74.
62. Wong MW, Qin L, Lee KM, Tai KO, Chong WS, Leung KS, et al. Healing of bone-tendon junction in a bone trough: a goat partial patellectomy model. Clin Orthop Relat Res. 2003;1(413):291-302.
63. Hill MA. Causes of degenerative joint disease (osteoarthrosis) and dyschondroplasia (osteochondrosis) in pigs. J Am Vet Med Assoc. 1990;197:107-13.
64. Vasara AI, Hyttinen MM, Pulliainen O, Lammi MJ, Jurvelin JS, Peterson L, et al. Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation. Osteoarthritis Cartilage. 2006;14:1066-74.
65. Jung M, Kaszap B, Redohl A, Steck E, Breusch S, Richter W, et al. Enhanced early tissue regeneration after matrix-assisted autologous mesenchymal stem cell transplantation in full thickness chondral defects in a minipig model. Cell Transplant. 2009;18:923-32.
66. Gotterbarm T, Reitzel T, Schneider U, Voss HJ, Stofft E, Breusch SJ. Integration of periosteum covered autogenous bone grafts with and without autologous chondrocytes: an animal experiment using the Gottinger minipig. Orthopade. 2003;32:65-73.
67. Petersen JP, Ueblacker P, Goepfert C, Adamietz P, Baumbach K, Stork A, et al. Long term results after implantation of tissue engineered cartilage for the treatment of osteochondral lesions in a minipig model. J Mater Sci Mater Med. 2008;19:2029-38.
68. Jung M, Breusch S, Daecke W, Gotterbarm T. The effect of defect localization on spontaneous repair of osteochondral defects in a Gottingen minipig model: a retrospective analysis of the medial patellar groove versus the medial femoral condyle. Lab Anim. 2009;43:191-7.
69. Frisbie DD, Trotter GW, Powers BE, Rodkey WG, Steadman JR, Howard RD, 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;28:242-55.
70. Hurtig MB, Fretz PB, Doige CE, Schnurr DL. Effects of lesion size and location on equine articular cartilage repair. Can J Vet Res. 1988;52:137-46.
71. Nixon AJ, Fortier LA, Williams J, Mohammed H. Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites. J Orthop Res. 1999;17:475-87.
72. Masri M, Lombardero G, Velasquillo C, Martinez V, Neri R, Villegas H, et al. Matrix-encapsulation cell-seeding technique to prevent cell detachment during arthroscopic implantation of matrix-induced autologous chondrocytes. Arthroscopy. 2007;23:877-83.
73. Bodo G, Hangody L, Modis L, Hurtig M. Autologous osteochondral grafting (mosaic arthroplasty) for treatment of subchondral cystic lesions in the equine stifle and fetlock joints. Vet Surg. 2004;33:588-96.
74. Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H, et al. Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. J Orthop Res. 1994;12:485-97.
75. Frisbie DD, Oxford JT, Southwood L, Trotter GW, Rodkey WG, Steadman JR, et al. Early events in cartilage repair after subchondral bone microfracture. Clin Orthop Relat Res. 2003;(407):215-227.
76. Fortier LA, Nixon AJ, Lust G. Phenotypic expression of equine articular chondrocytes grown in three-dimensional cultures supplemented with supraphysiologic concentrations of insulin-like growth factor-1. Am J Vet Res. 2002;63:301-5.
77. Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, et al. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am. 2010;92:1927-37.
78. Martinelli MJ, Eurell J, Les CM, Fyhrie D, Bennett D. Agerelated morphometry of equine calcified cartilage. Equine Vet J. 2002;34:274-8.
79. Lowerison M, Allendorf S, Bell A, White L, Whiteside R, Marks P, et al. Subchondral bone plate characteristics in human and animal bone: implications for cartilage repair. Presented at the 9th World Congress of the International Cartilage Repair Society, September 26-29, 2010, Sitges, Barcelona, Spain.
80. Frisbie DD, Lu Y, Kawcak CE, DiCarlo EF, Binette F, McIlwraith CW. In vivo evaluation of autologous cartilage fragment-loaded scaffolds implanted into equine articular defects and compared with autologous chondrocyte implantation. Am J Sports Med. 2009;37(suppl 1):71S-80S.
81. Frisbie DD, Bowman SM, Colhoun HA, DiCarlo EF, Kawcak CE, McIlwraith CW. Evaluation of autologous chondrocyte transplantation via a collagen membrane in equine articular defects: results at 12 and 18 months. Osteoarthritis Cartilage. 2008;16:667-79.
82. Barnewitz D, Endres M, Kruger I, Becker A, Zimmermann J, Wilke I, et al. Treatment of articular cartilage defects in horses with polymer-based cartilage tissue engineering grafts. Biomaterials. 2006;27:2882-9.
83. von Rechenberg B, Guenther H, McIlwraith CW, Leutenegger C, Frisbie DD, Akens MK, et al. Fibrous tissue of subchondral cystic lesions in horses produce local mediators and neutral metalloproteinases and cause bone resorption in vitro. Vet Surg. 2000;29:420-9.
84. Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO. The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev. 2010;16:123-45.
85. Shimomura K, Ando W, Tateishi K, Nansai R, Fujie H, Hart DA, et al. The influence of skeletal maturity on allogenic synovial mesenchymal stem cell-based repair of cartilage in a large animal model. Biomaterials. 2010;31:8004-11.
86. Gomoll AH, Farr J, Gillogly SD, Kercher J, Minas T. Surgical management of articular cartilage defects of the knee. J Bone Joint Surg Am. 2010;92:2470-90.
87. Grande DA, Pitman MI, Peterson L, Menche D, Klein M. The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res. 1989;7:208-18.
88. Dell'Accio F, Vanlauwe J, Bellemans J, Neys J, De Bari C, Luyten FP. Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J Orthop Res. 2003;21:123-31.
89. Hunziker EB. Articular cartilage structure in human and experimental animal models. In: Kuettner KE, Schleyerbach R, Peyron JG, Hascall VC, editors. Articular cartilage and osteoarthritis. New York: Raven; 1992. p. 183-99.
90. Wang F, Ying Z, Duan X, Tan H, Yang B, Guo L, et al. Histomorphometric analysis of adult articular calcified cartilage zone. J Struct Biol. 2009;168:359-65.
91. Allendorf S, Lowerison M, Bell A, Hoemann C, Bursac P. Interaction of microfracture awl design with subchondral bone in early osteoarthritis. Presented at the 9th World Congress of the International Cartilage Repair Society, September 26-29, 2010, Sitges, Barcelona, Spain.
92. Frisbie DD, Morisset S, Ho CP, Rodkey WG, Steadman JR, McIlwraith CW. Effects of calcified cartilage on healing of chondral defects treated with microfracture in horses. Am J Sports Med. 2006;34:1824-31.
93. Richter W. Mesenchymal stem cells and cartilage in situ regeneration. J Intern Med. 2009;266:390-405.
94. Vasara AI, Hyttinen MM, Lammi MJ, Lammi PE, Langsjo TK, Lindahl A, et al. Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats. Calcif Tissue Int. 2004;74:107-14.
95. Jackson DW, Lalor PA, Aberman HM, Simon TM. Spontaneous repair of full-thickness defects of articular cartilage in a goat model: a preliminary study. J Bone Joint Surg Am. 2001;83A:53-64.
96. von Rechenberg B, Akens MK, Nadler D, Bittmann P, Zlinszky K, Kutter A, et al. Changes in subchondral bone in cartilage resurfacing: an experimental study in sheep using different types of osteochondral grafts. Osteoarthritis Cartilage. 2003;11:265-77.
97. Qi YY, Chen X, Jiang YZ, Cai HX, Wang LL, Song XH, et al. Local delivery of autologous platelet in collagen matrix simulated in situ articular cartilage repair. Cell Transplantation. 2009;18:1161-9.
98. Henderson IJP, La Valette DP. Subchondral bone overgrowth in the presence of full-thickness cartilage defects in the knee. Knee. 2005;12:435-40.
99. Minas T, Gomoll AH, Rosenberger R, Royce RO, Bryant T. Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques. Am J Sports Med. 2009;37:902-8.
100. Fischer BL, Ludders JW, Asakawa M, Fortier LA, Fubini SL, Nixon AJ, et al. A comparison of epidural buprenorphine plus detomidine with morphine plus detomidine in horses undergoing bilateral stifle arthroscopy. Vet Anaesth Analg. 2009;36:67-76.
101. Custers RJ, Saris DB, Dhert WJ, Verbout AJ, van Rijen MH, Mastbergen SC, et al. Articular cartilage degeneration following the treatment of focal cartilage defects with ceramic metal implants and compared with microfracture. J Bone Joint Surg Am. 2009;91:900-10.
102. Hurtig M, Chubinskaya S, Dickey J, Rueger D. BMP-7 protects against progression of cartilage degeneration after impact injury. J Orthop Res. 2009;27:602-11.
103. Hepp P, Osterhoff G, Niederhagen M, Marquass B, Aigner T, Bader A, et al. Perilesional changes of focal osteochondral defects in an ovine model and their relevance to human osteochondral injuries. J Bone Joint Surg Br. 2009;91B:1110-9.
104. Lee KB, Hui JH, Song IC, Ardany L, Lee EH. Injectable mesenchymal stem cell therapy for large cartilage defects: a porcine model. Stem Cells. 2007;25:2964-71.
105. Waddell DD, Bert JM. The use of hyaluronan after arthroscopic surgery of the knee. Arthroscopy. 2010;26:105-11.
106. Ghadially JA, Ghadially R, Ghadially FN. Long-term results of deep defects in articular cartilage: a scanning electron microscope study. Virchows Arch B Cell Pathol. 1977;25:125-36.
107. Howard RD, McIlwraith CW, Trotter GW, Powers BE, McFadden PR, Harwood FL, et al. Long-term fate and effects of exercise on sternal cartilage autografts used for repair of large osteochondral defects in horses. Am J Vet Res. 1994;55:1158-67.
108. Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1993;75A:532-53.
109. Hunter DJ, Losina E, Guermazi A, Burstein D, Lassere MN, Kraus V. A pathway and approach to biomarker validation and qualification for osteoarthritis clinical trials. Curr Drug Targets. 2010;11:536-45.
110. Park S, Krishnan R, Nicoll SB, Ateshian GA. Cartilage interstitial fluid load support in unconfined compression. J Biomech. 2003;36:1785-96.
111. Buschmann MD, Soulhat J, Shirazi-Adl A, Jurvelin JS, Hunziker EB. Confined compression of articular cartilage: linearity in ramp and sinusoidal tests and the importance of interdigitation and incomplete confinement. J Biomech. 1998;31:171-8.
112. Mow VC, Gibbs MC, Lai WM, Zhu WB, Athanasiou KA. Biphasic indentation of articular cartilage: II. A numerical algorithm and an experimental study. J Biomech. 1989;22:853-61.
113. Roemhildt ML, Coughlin KM, Peura GD, Fleming BC, Beynnon BD. Material properties of articular cartilage in the rabbit tibial plateau. J Biomech. 2006;39:2331-7.
114. Fortin M, Soulhat J, Shirazi-Adl A, Hunziker EB, Buschmann MD. Unconfined compression of articular cartilage: nonlinear behavior and comparison with a fibril-reinforced biphasic model. J Biomech Eng. 2000;122:189-95.
115. Langelier E, Buschmann MD. Increasing strain and strain rate strengthen transient stiffness but weaken the response to subsequent compression for articular cartilage in unconfined compression. J Biomech. 2003;36:853-9.
116. Laasanen MS, Toyras J, Korhonen RK, Rieppo J, Saarakkala S, Nieminen MT, et al. Biomechanical properties of knee articular cartilage. Biorheology. 2003;40:133-40.
117. Bae WC, Temple MM, Amiel D, Coutts RD, Niederauer GG, Sah RL. Indentation testing of human cartilage: sensitivity to articular surface degeneration. Arthritis Rheum. 2003;48:3382-94.
118. Bae WC, Law AW, Amiel D, Sah RL. Sensitivity of indentation testing to step-off edges and interface integrity in cartilage repair. Ann Biomed Eng. 2004;32:360-9.
119. Huang CY, Mow VC, Ateshian GA. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J Biomech Eng. 2001;123:410-7.
120. Soulhat J, Buschmann MD, Shirazi-Adl A. A fibril-networkreinforced biphasic model of cartilage in unconfined compression. J Biomech Eng. 1999;121:340-7.
121. Schmidt TA, Gastelum NS, Nguyen QT, Schumacher BL, Sah RL. Boundary lubrication of articular cartilage: role of synovial fluid constituents. Arthritis Rheum. 2007;56:882-91.
122. Schmidt TA, Sah RL. Effect of synovial fluid on boundary lubrication of articular cartilage. Osteoarthritis Cartilage. 2007;15:35-47.
123. Vasara AI, Nieminen MT, Jurvelin JS, Peterson L, Lindahl A, Kiviranta I. Indentation stiffness of repair tissue after autologous chondrocyte transplantation. Clin Orthop Relat Res. 2005;(433):233-42.
124. Hattori K, Takakura Y, Ohgushi H, Habata T, Uematsu K, Yamauchi J, et al. Quantitative ultrasound can assess the regeneration process of tissue-engineered cartilage using a complex between adherent bone marrow cells and a threedimensional scaffold. Arthritis Res Ther. 2005;7:R552-9.
125. Quenneville Q, Garon G, Legare L, Buschmann MD. Load and streaming potential responses of articular cartilage as a function of compression speed during indentation. Trans Orthop Res Soc. 2003;28:659.
126. Bae WC, Schumacher BL, Sah RL. Indentation probing of human articular cartilage: effects on chondrocyte viability. Osteoarthritis Cartilage. 2007;15:9-18.
127. Trattnig SWinalski CS, Marlovits S, Jurvelin JS. Welsch GH, Potter HG. Magnetic Resonance Imaging of Cartilage Repair-A Review. Cartilage. 2011;2:5-26.
128. Roos EM Engelhart L, Ranstam J, Anderson AF, Irrgang JJ, Marx RG, Tegner Y, Davis AM. ICRS Recommendation Document: Patient-Reported Outcome Instruments for Use in Patients with Articular Cartilage Defects. Cartilage.