Clinical Trials and Management of Osteochondral Lesions

  • Carlos A. Vilela
  • Alain da Silva Morais
  • Sandra Pina
  • J. Miguel Oliveira
  • Vitor M. Correlo
  • Rui L. Reis
  • João Espregueira-Mendes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1058)


Osteochondral lesions are frequent and important causes of pain and disability. These lesions are induced by traumatic injuries or by diseases that affect both the cartilage surface and the subchondral bone. Due to the limited cartilage ability to regenerate and self-repair, these lesions tend to gradually worsen and progress towards osteoarthritis. The clinical, social, and economic impact of the osteochondral lesions is impressive and although therapeutic alternatives are under discussion, a consensus is not yet been achieved. Over the previous decade, new strategies based on innovative tissue engineering approaches have been developed with promising results. However, in order those products reach the market and help the actual patient in an effective manner, there is still a lot of work to be done. The current state of the implications, clinical aspects, and available treatments for this pathology, as well as the ongoing preclinical and clinical trials are presented in this chapter.


Musculoskeletal injuries Bone repair Cartilage repair Tissue engineering Osteochondral Clinical studies 



A. da Silva Morais acknowledges ERC-2012-ADG 20120216–321266 (ComplexiTE) for his Postdoc scholarship. Thanks to the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The financial support from the Portuguese Foundation for Science and Technology for the M-ERA-NET/0001/2014 “HierarchiTech” project and for the funds provided under the program Investigador FCT 2012, 2014, and 2015 (IF/00423/2012, IF/01214/2014, and IF/01285/2015) is also greatly acknowledged.


  1. 1.
    Ondrésik M, Oliveira JM, Reis RL (2017) Knee articular cartilage. In: Oliveira JM, Reis RL (eds) Regenerative strategies for the treatment of knee joint disabilities. Springer International, Cham, pp 3–20. CrossRefGoogle Scholar
  2. 2.
    Pearle AD, Warren RF, Rodeo SA Basic science of articular cartilage and osteoarthritis. Clin Sports Med 24(1):1–12. CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Bolog NV, Andreisek G, Ulbrich EJ (2015) Articular cartilage and subchondral bone. In: MRI of the knee: a guide to evaluation and reporting. Springer International, Cham, pp 95–112. CrossRefGoogle Scholar
  4. 4.
    Flik KR, Verma N, Cole BJ, Bach BR (2007) Articular cartilage. In: Williams RJ (ed) Cartilage repair strategies. Humana Press, Totowa, NJ, pp 1–12. CrossRefGoogle Scholar
  5. 5.
    Goldring SR (2012) Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Ther Adv Musculoskelet Dis 4(4):249–258. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Imhof H, Sulzbacher I, Grampp S, Czerny C, Youssefzadeh S, Kainberger F (2000) Subchondral bone and cartilage disease: a rediscovered functional unit. Invest Radiol 35(10):581–588CrossRefPubMedCentralGoogle Scholar
  7. 7.
    Widuchowski W, Widuchowski J, Trzaska T (2007) Articular cartilage defects: study of 25,124 knee arthroscopies. Knee 14(3):177–182. CrossRefPubMedGoogle Scholar
  8. 8.
    Hjelle K, Solheim E, Strand T, Muri R, Brittberg M (2002) Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 18(7):730–734CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Aroen A, Loken S, Heir S, Alvik E, Ekeland A, Granlund OG, Engebretsen L (2004) Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med 32(1):211–215CrossRefGoogle Scholar
  10. 10.
    Farr J, Cole B, Dhawan A, Kercher J, Sherman S (2011) Clinical cartilage restoration: evolution and overview. Clin Orthop Relat Res 469(10):2696–2705. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Vaquero J, Forriol F (2012) Knee chondral injuries: clinical treatment strategies and experimental models. Injury 43(6):694–705. CrossRefPubMedGoogle Scholar
  12. 12.
    Foldager CB (2013) Advances in autologous chondrocyte implantation and related techniques for cartilage repair. Dan Med J 60(4):B4600PubMedGoogle Scholar
  13. 13.
    Hunziker EB (1999) Articular cartilage repair: are the intrinsic biological constraints undermining this process insuperable? Osteoarthritis Cartilage 7(1):15–28. CrossRefPubMedGoogle Scholar
  14. 14.
    Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10(6):432–463. CrossRefPubMedGoogle Scholar
  15. 15.
    Johnson VL, Hunter DJ (2014) The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol 28(1):5–15. CrossRefPubMedGoogle Scholar
  16. 16.
    Jackson DW, Simon TM, Aberman HM (2001) Symptomatic articular cartilage degeneration: the impact in the new millennium. Clin Orthop Relat Res (391 Suppl):S14–25CrossRefGoogle Scholar
  17. 17.
    Nukavarapu SP, Dorcemus DL (2013) Osteochondral tissue engineering: current strategies and challenges. Biotechnol Adv 31(5):706–721. CrossRefGoogle Scholar
  18. 18.
    Batty L, Dance S, Bajaj S, Cole BJ (2011) Autologous chondrocyte implantation: an overview of technique and outcomes. ANZ J Surg 81(1–2):18–25. CrossRefPubMedGoogle Scholar
  19. 19.
    Durur-Subasi I, Durur-Karakaya A, Yildirim OS (2015) Osteochondral lesions of major joints. Eur J Med 47(2):138–144. CrossRefGoogle Scholar
  20. 20.
    Lewandrowski KU, Muller J, Schollmeier G (1997) Concomitant meniscal and articular cartilage lesions in the femorotibial joint. Am J Sports Med 25(4):486–494CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Vilela CA, Correia C, Oliveira JM, Sousa RA, Reis RL, Espregueira-Mendes J (2017) Clinical management of articular cartilage lesions. In: Oliveira JM, Reis RL (eds) Regenerative strategies for the treatment of knee joint disabilities. Springer International, Cham, pp 29–53. CrossRefGoogle Scholar
  22. 22.
    Resnick D, Vint V (1980) The “Tunnel” view in assessment of cartilage loss in osteoarthritis of the knee. Radiology 137(2):547–548. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Rosenberg TD, Paulos LE, Parker RD, Coward DB, Scott SM (1988) The forty-five-degree posteroanterior flexion weight-bearing radiograph of the knee. J Bone Joint Surg Am 70(10):1479–1483CrossRefPubMedCentralGoogle Scholar
  24. 24.
    Casula V, Hirvasniemi J, Lehenkari P, Ojala R, Haapea M, Saarakkala S, Lammentausta E, Nieminen MT (2016) Association between quantitative MRI and ICRS arthroscopic grading of articular cartilage. Knee Surg Sports Traumatol Arthrosc 24(6):2046–2054. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chan DD, Neu CP (2013) Probing articular cartilage damage and disease by quantitative magnetic resonance imaging. J R Soc Interface 10(78):20120608. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Vilela CA, Correia C, Oliveira JM, Sousa RA, Espregueira-Mendes J, Reis RL (2015) Cartilage repair using hydrogels: a critical review of in vivo experimental designs. ACS Biomater Sci Eng 1(9):726–739. CrossRefGoogle Scholar
  27. 27.
    Outerbridge RE (1961) The etiology of chondromalacia patellae. J Bone Joint Surg Br 43-B:752–757CrossRefPubMedCentralGoogle Scholar
  28. 28.
    Casscells SW (1990) Outerbridge’s ridges. Arthroscopy 6(4):253CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Brittberg M, Winalski CS (2003) Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 85-A(Suppl 2):58–69CrossRefGoogle Scholar
  30. 30.
    Chen CH, Liu YS, Chou PH, Hsieh CC, Wang CK (2013) MR grading system of osteochondritis dissecans lesions: comparison with arthroscopy. Eur J Radiol 82(3):518–525. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ellermann JM, Donald B, Rohr S, Takahashi T, Tompkins M, Nelson B, Crawford A, Rud C, Macalena J (2016) Magnetic resonance imaging of osteochondritis dissecans: validation study for the ICRS Classification System. Acad Radiol 23(6):724–729. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lazic S, Boughton O, Hing C, Bernard J (2014) Arthroscopic washout of the knee: a procedure in decline. Knee 21(2):631–634. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Katz JN, Brownlee SA, Jones MH (2014) The role of arthroscopy in the management of knee osteoarthritis. Best Pract Res Clin Rheumatol 28(1):143–156. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Marcacci M, Filardo G, Kon E (2013) Treatment of cartilage lesions: what works and why? Injury 44(Suppl 1):S11–S15. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Bentley G, Bhamra JS, Gikas PD, Skinner JA, Carrington R, Briggs TW (2013) Repair of osteochondral defects in joints—how to achieve success. Injury 44(Suppl 1):S3–10. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19(5):477–484. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Versier G, Dubrana F, French Arthroscopy S (2011) Treatment of knee cartilage defect in 2010. Orthop Traumatol Surg Res 97(8 Suppl):S140–S153. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lee GW, Son JH, Kim JD, Jung GH (2013) Is platelet-rich plasma able to enhance the results of arthroscopic microfracture in early osteoarthritis and cartilage lesion over 40 years of age? Eur J Orthopaed Surg Traumatol 23(5):581–587. CrossRefGoogle Scholar
  39. 39.
    Tuan RS, Chen AF, Klatt BA (2013) Cartilage regeneration. J Am Acad Orthop Surg 21(5):303–311. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Chung JY, Lee DH, Kim TH, Kwack KS, Yoon KH, Min BH (2014) Cartilage extra-cellular matrix biomembrane for the enhancement of microfractured defects. Knee Surg Sports Traumatol Arthrosc 22(6):1249–1259. CrossRefPubMedGoogle Scholar
  41. 41.
    Usuelli FG, de Girolamo L, Grassi M, D'Ambrosi R, Montrasio UA, Boga M All-arthroscopic autologous matrix-induced chondrogenesis for the treatment of osteochondral lesions of the talus. Arthrosc Tech 4(3):e255–e259. CrossRefPubMedCentralGoogle Scholar
  42. 42.
    Cascio BM, Sharma B The future of cartilage repair. Oper Tech Sports Med 16(4):221–224. CrossRefGoogle Scholar
  43. 43.
    Gomoll AH, Filardo G, de Girolamo L, Espregueira-Mendes J, Marcacci M, Rodkey WG, Steadman JR, Zaffagnini S, Kon E (2012) Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc 20(3):450–466. CrossRefPubMedGoogle Scholar
  44. 44.
    Espregueira-Mendes J, Pereira H, Sevivas N, Varanda P, da Silva MV, Monteiro A, Oliveira JM, Reis RL (2012) Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions. Knee Surg Sports Traumatol Arthrosc 20(6):1136–1142. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Robert H (2011) Chondral repair of the knee joint using mosaicplasty. Orthop Traumatol Surg Res 97(4):418–429. CrossRefPubMedGoogle Scholar
  46. 46.
    Farr J, Cole BJ, Sherman S, Karas V (2012) Particulated articular cartilage: CAIS and DeNovo NT. J Knee Surg 25(1):23–29CrossRefGoogle Scholar
  47. 47.
    Stein S, Strauss E, Bosco J 3rd (2013) Advances in the surgical management of articular cartilage defects: autologous chondrocyte implantation techniques in the pipeline. Cartilage 4(1):12–19. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Gomoll AH, Filardo G, Almqvist FK, Bugbee WD, Jelic M, Monllau JC, Puddu G, Rodkey WG, Verdonk P, Verdonk R, Zaffagnini S, Marcacci M (2012) Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures. Knee Surg Sports Traumatol Arthrosc 20(3):468–486. CrossRefPubMedGoogle Scholar
  49. 49.
    Haene R, Qamirani E, Story RA, Pinsker E, Daniels TR (2012) Intermediate outcomes of fresh talar osteochondral allografts for treatment of large osteochondral lesions of the talus. J Bone Joint Surg Am 94(12):1105–1110. CrossRefPubMedGoogle Scholar
  50. 50.
    Giorgini A, Donati D, Cevolani L, Frisoni T, Zambianchi F, Catani F (2013) Fresh osteochondral allograft is a suitable alternative for wide cartilage defect in the knee. Injury 44(Suppl 1):S16–S20. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Pina S, Ribeiro V, Oliveira JM, Reis RL (2017) Pre-clinical and clinical management of osteochondral lesions. In: Oliveira JM, Reis RL (eds) Regenerative strategies for the treatment of knee joint disabilities. Springer International, Cham, pp 147–161. CrossRefGoogle Scholar
  52. 52.
    Barrett I, King AH, Riester S, van Wijnen A, Levy BA, Stuart MJ, Krych AJ (2016) Internal fixation of unstable osteochondritis dissecans in the skeletally mature knee with metal screws. Cartilage 7(2):157–162. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Grimm NL, Ewing CK, Ganley TJ (2014) The knee internal fixation techniques for osteochondritis dissecans. Clin Sports Med 33(2):313–319. CrossRefPubMedGoogle Scholar
  54. 54.
    Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Dhollander AA, Verdonk PC, Lambrecht S, Verdonk R, Elewaut D, Verbruggen G, Almqvist KF (2012) Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee. Knee Surg Sports Traumatol Arthrosc 20(6):1118–1127. CrossRefPubMedGoogle Scholar
  56. 56.
    Zaslav K, Cole B, Brewster R, DeBerardino T, Farr J, Fowler P, Nissen C, Investigators SSP (2009) A prospective study of autologous chondrocyte implantation in patients with failed prior treatment for articular cartilage defect of the knee: results of the Study of the Treatment of Articular Repair (STAR) clinical trial. Am J Sports Med 37(1):42–55. CrossRefPubMedGoogle Scholar
  57. 57.
    D’Ambrosi R, Maccario C, Ursino C, Serra N, Usuelli FG (2017) Combining microfractures, autologous bone graft, and autologous matrix-induced chondrogenesis for the treatment of juvenile osteochondral talar lesions. Foot Ankle Int 38(5):485–495. CrossRefPubMedGoogle Scholar
  58. 58.
    Jacobi M, Villa V, Magnussen RA, Neyret P (2011) MACI—a new era? Sports Med Arthrosc Rehabil Ther Technol 3(1):10. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Kreuz PC, Müller S, Ossendorf C, Kaps C, Erggelet C (2009) Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther 11(2):R33. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Selmi TA, Verdonk P, Chambat P, Dubrana F, Potel JF, Barnouin L, Neyret P (2008) Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years. J Bone Joint Surg Br 90(5):597–604. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Clavé A, Potel J-F, Servien E, Neyret P, Dubrana F, Stindel E (2016) Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial. J Orthop Res 4(4):658–665. CrossRefGoogle Scholar
  62. 62.
    Brix MO, Stelzeneder D, Chiari C, Koller U, Nehrer S, Dorotka R, Windhager R, Domayer SE (2014) Treatment of full-thickness chondral defects with Hyalograft C in the knee. Am J Sports Med 42(6):1426–1432. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Zak L, Albrecht C, Wondrasch B, Widhalm H, Vekszler G, Trattnig S, Marlovits S, Aldrian S (2014) Results 2 years after matrix-associated autologous chondrocyte transplantation using the Novocart 3D scaffold. Am J Sports Med 42(7):1618–1627. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Crawford DC, DeBerardino TM, Williams RJ 3rd (2012) NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years. J Bone Joint Surg Am 94(11):979–989. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Yayon A, Neria E, Blumenstein S, Stern B, Barkai H, Zak R, Yaniv Y (2006) BIOCART™II a novel implant for 3D reconstruction of articular cartilage. J Bone Jt Surg Br 88-B(SUPP II):344Google Scholar
  66. 66.
    Zeifang F, Oberle D, Nierhoff C, Richter W, Moradi B, Schmitt H (2010) Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: a randomized clinical trial. Am J Sports Med 38(5):924–933. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Dewan AK, Gibson MA, Elisseeff JH, Trice ME (2014) Evolution of autologous chondrocyte repair and comparison to other cartilage repair techniques. Biomed Res Int 2014:272481. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    McCormick F, Cole BJ, Nwachukwu B, Harris JD, Adkisson HDIV, Farr J Treatment of focal cartilage defects with a juvenile allogeneic 3-dimensional articular cartilage graft. Oper Tech Sports Med 21(2):95–99. CrossRefGoogle Scholar
  69. 69.
    Rodriguez-Merchan EC (2013) Regeneration of articular cartilage of the knee. Rheumatol Int 33(4):837–845. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Schüttler KF, Schenker H, Theisen C, Schofer MD, Getgood A, Roessler PP, Struewer J, Rominger MB, Efe T (2014) Use of cell-free collagen type I matrix implants for the treatment of small cartilage defects in the knee: clinical and magnetic resonance imaging evaluation. Knee Surg Sports Traumatol Arthrosc 22(6):1270–1276. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Perera JR, Gikas PD, Bentley G (2012) The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 94(6):381–387. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Negrin LL, Vecsei V (2013) Do meta-analyses reveal time-dependent differences between the clinical outcomes achieved by microfracture and autologous chondrocyte implantation in the treatment of cartilage defects of the knee? J Orthop Sci 18(6):940–948. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Petri M, Broese M, Simon A, Liodakis E, Ettinger M, Guenther D, Zeichen J, Krettek C, Jagodzinski M, Haasper C (2013) CaReS (MACT) versus microfracture in treating symptomatic patellofemoral cartilage defects: a retrospective matched-pair analysis. J Orthop Sci 18(1):38–44. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Gelber PE, Batista J, Millan-Billi A, Patthauer L, Vera S, Gomez-Masdeu M, Monllau JC (2014) Magnetic resonance evaluation of TruFit(R) plugs for the treatment of osteochondral lesions of the knee shows the poor characteristics of the repair tissue. Knee 21(4):827–832. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Hindle P, Hendry JL, Keating JF, Biant LC (2014) Autologous osteochondral mosaicplasty or TruFit plugs for cartilage repair. Knee Surg Sports Traumatol Arthrosc 22(6):1235–1240. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Delcogliano M, de Caro F, Scaravella E, Ziveri G, De Biase CF, Marotta D, Marenghi P, Delcogliano A (2014) Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 22(6):1260–1269. CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, Shive MS (2013) Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J Bone Joint Surg Am 95(18):1640–1650. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Shive MS, Hoemann CD, Restrepo A, Hurtig MB, Duval N, Ranger P, Stanish W, Buschmann MD (2006) BST-CarGel: in situ chondroinduction for cartilage repair. Oper Tech Orthopaed 16(4):271–278. CrossRefGoogle Scholar
  79. 79.
    Schüettler KF, Struewer J, Rominger MB, Rexin P, Efe T (2013) Repair of a chondral defect using a cell free scaffold in a young patient—a case report of successful scaffold transformation and colonisation. BMC Surg 13(1):11. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Roessler PP, Pfister B, Gesslein M, Figiel J, Heyse TJ, Colcuc C, Lorbach O, Efe T, Schüttler KF (2015) Short-term follow up after implantation of a cell-free collagen type I matrix for the treatment of large cartilage defects of the knee. Int Orthop 39(12):2473–2479. CrossRefPubMedGoogle Scholar
  81. 81.
    Panseri S, Russo A, Cunha C, Bondi A, Di Martino A, Patella S, Kon E (2012) Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration. Knee Surg Sports Traumatol Arthrosc 20(6):1182–1191. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Mall NA, Harris JD, Cole BJ (2015) Clinical evaluation and preoperative planning of articular cartilage lesions of the knee. J Am Acad Orthop Surg 23(10):633–640. CrossRefPubMedGoogle Scholar
  83. 83.
    Agency E-EM (2009) Reflection paper on in-vitro cultured chondrocyte containing products for cartilage repair of the knee—Doc. Ref. EMEA/CAT/CPWP/288934/2009. Acessed Mar 2017
  84. 84.
    Administration F-FD (2011) Guidance for Industry—preparation of IDEs and INDs dor products intended to repair or replace knee cartilage. Accessed Mar 2017
  85. 85.
    Administration F-FD (2017) Learn about clinical studies. Accessed Mar 2017
  86. 86.
    Administratioon F-FD (2017) Clinical trias. Accessed Mar 2017

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Carlos A. Vilela
    • 1
    • 2
    • 3
    • 3
    • 5
  • Alain da Silva Morais
    • 1
    • 2
  • Sandra Pina
    • 4
    • 5
  • J. Miguel Oliveira
    • 4
    • 5
    • 6
  • Vitor M. Correlo
    • 1
    • 2
    • 3
  • Rui L. Reis
    • 1
    • 2
    • 3
  • João Espregueira-Mendes
    • 2
    • 4
    • 5
    • 6
    • 7
  1. 1.Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoBragaPortugal
  2. 2.Orthopedic DepartmentCentro Hospitalar do Alto AveGuimarãesPortugal
  3. 3.Dom Henrique Research CentrePortoPortugal
  4. 4.3B’s Research Group, European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of MinhoGuimarãesPortugal
  5. 5.ICVS/3B’s–PT Government Associate LaboratoryBraga/GuimarãesPortugal
  6. 6.The Discoveries Centre for Regenerative and Precision MedicineUniversity of MinhoBarco/GuimarãesPortugal
  7. 7.Clínica do Dragão—Espregueira-Mendes Sports Centre, FIFA Medical Centre of ExcellencePortoPortugal

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