Recent Advances in Cartilage Repair (ICL 3)

  • Giuseppe M. PerettiEmail author
  • Peter Angele
  • Giuseppe Filardo
  • Elizaveta Kon
  • Laura Mangiavini
  • Antongiulio Marmotti
  • Silvia Mattia
  • Konrad Slynarski
  • Francesc Soler
  • Dieter Van Assche
  • Henning MadryEmail author


Articular cartilage possesses low intrinsic healing property due to its lack of vascularity and progenitor cells. Thus, damage to the hyaline cartilage may lead to a progressive degeneration of the joint and eventually to osteoarthritis (OA). In the last years, different surgical techniques have been introduced in the clinical practice to overcome this issue. Bone marrow stimulation, for example, is a widely known method to allow cell invasion from the bloodstream to the site of damage. However, the reparative tissue has different morphological and biomechanical properties when compared to the native cartilage. In particular, the newly formed fibrocartilage has a low amount of proteoglycans and a higher concentration of type I collagen. This different matrix composition leads to a decrease in the mechanical strength and to a poor integration of the reparative tissue with the native cartilage.


Mesenchymal Stem Cell Subchondral Bone Cartilage Defect Cartilage Repair Autologous Chondrocyte Implantation 
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.


  1. 1.
    Bekkers JE, Tsuchida AI, van Rijen MH, Vonk LA, Dhert WJ, Creemers LB, Saris DB. Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Am J Sports Med. 2013;41(9):2158–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Berruto M, Delcogliano M, de Caro F, Carimati G, Uboldi F, Ferrua P, Ziveri G, De Biase CF. Treatment of large knee osteochondral lesions with a biomimetic scaffold: results of a multicenter study of 49 patients at 2-year follow-up. Am J Sports Med. 2014;42(7):1607–17.CrossRefPubMedGoogle Scholar
  3. 3.
    Carmont MR, Carey-Smith R, Saithna A, Dhillon M, Thompson P, Spalding T. Delayed incorporation of a TruFit plug: perseverance is recommended. Arthroscopy. 2009;25(7):810–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Delcogliano M, de Caro F, Scaravella E, Ziveri G, De Biase CF, Marotta D, Marenghi P, Delcogliano A. Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc. 2014;22(6):1260–9.PubMedGoogle Scholar
  5. 5.
    Dhollander AA, Liekens K, Almqvist KF, Verdonk R, Lambrecht S, Elewaut D, Verbruggen G, Verdonk PC. A pilot study of the use of an osteochondral scaffold plug for cartilage repair in the knee and how to deal with early clinical failures. Arthroscopy. 2012;28(2):225–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Drobnic M, Radosavljevic D, Cor A, Brittberg M, Strazar K. Debridement of cartilage lesions before autologous chondrocyte implantation by open or transarthroscopic techniques: a comparative study using post-mortem materials. J Bone Joint Surg Br. 2010;92(4):602–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Eldracher M, Orth P, Cucchiarini M, Pape D, Madry H. Small subchondral drill holes improve marrow stimulation of articular cartilage defects. Am J Sports Med. 2014;42(11):2741–50.CrossRefPubMedGoogle Scholar
  8. 8.
    Filardo G, Kon E, Berruto M, Di Martino A, Patella S, Marcheggiani Muccioli GM, Zaffagnini S, Marcacci M. Arthroscopic second generation autologous chondrocytes implantation associated with bone grafting for the treatment of knee osteochondritis dissecans: results at 6 years. Knee. 2012;19(5):658–63.CrossRefPubMedGoogle Scholar
  9. 9.
    Filardo G, Kon E, Di Martino A, Busacca M, Altadonna G, Marcacci M. Treatment of knee osteochondritis dissecans with a cell-free biomimetic osteochondral scaffold: clinical and imaging evaluation at 2-year follow-up. Am J Sports Med. 2013;41(8):1786–93.CrossRefPubMedGoogle Scholar
  10. 10.
    Filardo G, Kon E, Perdisa F, Di Matteo B, Di Martino A, Iacono F, Zaffagnini S, Balboni F, Vaccari V, Marcacci M. Osteochondral scaffold reconstruction for complex knee lesions: a comparative evaluation. Knee. 2013;20(6):570–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Filardo G, Kon E, Di Matteo B, Di Martino A, Marcacci M. Single-plug autologous osteochondral transplantation: results at minimum 16 years’ follow-up. Orthopedics. 2014;37(9):e761–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Filardo G, Kon E, Perdisa F, Balboni F, Marcacci M. Autologous osteochondral transplantation for the treatment of knee lesions: results and limitations at two years’ follow-up. Int Orthop. 2014;38(9):1905–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015;43(7):1575–82.CrossRefPubMedGoogle Scholar
  14. 14.
    Filardo G, Kon E, Roffi A, Di Matteo B, Merli ML, Marcacci M. Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2459–74.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gomoll AH, Madry H, Knutsen G, van Dijk N, Seil R, Brittberg M, Kon E. The subchondral bone in articular cartilage repair: current problems in the surgical management. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):434–47.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Gomoll AH, Farr J, Gillogly SD, Kercher JS, Minas T. Surgical management of articular cartilage defects of the knee. Instr Course Lect. 2011;60:461–83.PubMedGoogle Scholar
  17. 17.
    Görmeli G, Görmeli CA, Ataoglu B, Çolak C, Aslantürk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2015;2:1–8.Google Scholar
  18. 18.
    Ha C-W, Park Y-B, Chung J-Y, Park Y-G. Cartilage repair using composites of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel in a minipig model. Stem Cells Transl Med. 2015;4:1044–51.CrossRefPubMedGoogle Scholar
  19. 19.
    Hangody L, Dobos J, Baló E, Pánics G, Hangody LR, Berkes I. Clinical experiences with autologous osteochondral mosaicplasty in an athletic population: a 17-year prospective multicenter study. Am J Sports Med. 2010;38(6):1125–33.CrossRefPubMedGoogle Scholar
  20. 20.
    Hindle P, Hendry JL, Keating JF, Biant LC. Autologous osteochondral mosaicplasty or TruFit plugs for cartilage repair. Knee Surg Sports Traumatol Arthrosc. 2014;22(6):1235–40.CrossRefPubMedGoogle Scholar
  21. 21.
    Hui AY, McCarty WJ, Masuda K, Firestein GS, Sah RL. A systems biology approach to synovial joint lubrication in health, injury, and disease. Wiley Interdiscip Rev Syst Biol Med. 2012;4(1):15–37.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Johnson LL. Arthroscopic abrasion arthroplasty historical and pathologic perspective: present status. Arthroscopy. 1986;2(1):54–69.CrossRefPubMedGoogle Scholar
  23. 23.
    Joshi N, Reverte-Vinaixa M, Díaz-Ferreiro EW, Domínguez-Oronoz R. Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation. Am J Sports Med. 2012;40(6):1289–95.CrossRefPubMedGoogle Scholar
  24. 24.
    Kim YS, Park EH, Lee HJ, Koh YG, Lee JW. Clinical comparison of the osteochondral autograft transfer system and subchondral drilling in osteochondral defects of the first metatarsal head. Am J Sports Med. 2012;40(8):1824–33.CrossRefPubMedGoogle Scholar
  25. 25.
    Kon E, Delcogliano M, Filardo G, Fini M, Giavaresi G, Francioli S, Martin I, Pressato D, Arcangeli E, Quarto R, Sandri M, Marcacci M. Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial. J Orthop Res. 2010;28(1):116–24.PubMedGoogle Scholar
  26. 26.
    Kon E, Drobnic M, Davidson PA, Levy A, Zaslav KR, Robinson D. Chronic post-traumatic cartilage lesion of the knee treated with an acellular osteochondral regenerating implant – case history with rehabilitation guidelines. J Sport Rehabil. 2013;23(3):270–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Kon E, Filardo G, Di Matteo B, Marcacci M. PRP for the treatment of cartilage pathology. Open Orthop J. 2013;7:120–8.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kon E, Filardo G, Di Martino A, Busacca M, Moio A, Perdisa F, Marcacci M. Clinical results and MRI evolution of a nano-composite multilayered biomaterial for osteochondral regeneration at 5 years. Am J Sports Med. 2014;42(1):158–65.CrossRefPubMedGoogle Scholar
  29. 29.
    Kon E, Filardo G, Perdisa F, Di Martino A, Busacca M, Balboni F, Sessa A, Marcacci M. A one-step treatment for chondral and osteochondral knee defects: clinical results of a biomimetic scaffold implantation at 2 years of follow-up. J Mater Sci Mater Med. 2014;25(10):2437–44.CrossRefPubMedGoogle Scholar
  30. 30.
    Kon E, Filardo G, Perdisa F, Venieri G, Marcacci M. Clinical results of multilayered biomaterials for osteochondral regeneration. J Exp Orthop. 2014;1:10.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kon E, Filardo G, Robinson D, Eisman JA, Levy A, Zaslav K, Shani J, Altschuler N. Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model. Knee Surg Sports Traumatol Arthrosc. 2014;22(6):1452–64.CrossRefPubMedGoogle Scholar
  32. 32.
    Kon E, Filardo G, Venieri G, Perdisa F, Marcacci M. Tibial plateau lesions. Surface reconstruction with a biomimetic osteochondral scaffold: results at 2 years of follow-up. Injury. 2014;45 Suppl 6:S121–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Könst YE, Benink RJ, Veldstra R, van der Krieke TJ, Helder MN, van Royen BJ. Treatment of severe osteochondral defects of the knee by combined autologous bone grafting and autologous chondrocyte implantation using fibrin gel. Knee Surg Sports Traumatol Arthrosc. 2012;20(11):2263–9.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Liu TM, Martina M, Hutmacher DW, Hui JH, Lee EH, Lim B. Identification of a common pathways mediating differentiation of bone marrow and adipose tissue derived human mesenchymal stem cells into mesenchymal lineages. Stem Cells. 2007;25:750.CrossRefPubMedGoogle Scholar
  35. 35.
    Lv F, Lu M, Cheung KMC, Leung VYL, Zhou G. Intrinsic properties of mesenchymal stem cells from human bone marrow, umbilical cord and umbilical cord blood comparing the different sources of MSC. Curr Stem Cell Res Ther. 2012;7:389–99.CrossRefPubMedGoogle Scholar
  36. 36.
    Marcacci M, Zaffagnini S, Kon E, Marcheggiani Muccioli GM, Di Martino A, Di Matteo B, Bonanzinga T, Iacono F, Filardo G. Unicompartmental osteoarthritis: an integrated biomechanical and biological approach as alternative to metal resurfacing. Knee Surg Sports Traumatol Arthrosc. 2013;21(11):2509–17.CrossRefPubMedGoogle Scholar
  37. 37.
    Marchand C, Chen G, Tran-Khanh N, Sun J, Chen H, Buschmann MD, Hoemann CD. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls. Tissue Eng Part A. 2011;18(5–6):508–19.PubMedGoogle Scholar
  38. 38.
    Marmotti A, et al. e-Poster P133 ICRS 2013 Minced umbilical cord fragments as an effective cell source for cartilage and bone tissue engineering. An in vitro tridimensional study.
  39. 39.
    Menche DS, Frenkel SR, Blair B, Watnik NF, Toolan BC, Yaghoubian RS, Pitman MI. A comparison of abrasion burr arthroplasty and subchondral drilling in the treatment of full-thickness cartilage lesions in the rabbit. Arthroscopy. 1996;12(3):280–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Mithoefer K, Williams 3rd RJ, Warren RF, Potter HG, Spock CR, Jones EC, Wickiewicz TL, Marx RG. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. J Bone Joint Surg Am. 2005;87(9):1911–20.CrossRefPubMedGoogle Scholar
  41. 41.
    Mithoefer K, Williams RJ, Warren RF, Potter HG, Spock CR, Jones EC, Wickiewicz TL, Marx RG. Chondral resurfacing of articular cartilage defects in the knee with the microfracture technique. Surgical technique. J Bone Joint Surg Am. 2006;88(Suppl 1 Pt 2):294–304.PubMedGoogle Scholar
  42. 42.
    Mithoefer K, Williams 3rd RJ, Warren RF, Wickiewicz TL, Marx RG. High-impact athletics after knee articular cartilage repair: a prospective evaluation of the microfracture technique. Am J Sports Med. 2006;34(9):1413–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Mithoefer K, Hambly K, Logerstedt D, Ricci M, Silvers H, Della Villa S. Current concepts for rehabilitation and return to sport after knee articular cartilage repair in the athlete. J Orthop Sports Phys Ther. 2012;42(3):254–73.CrossRefPubMedGoogle Scholar
  44. 44.
    Ochs BG, Müller-Horvat C, Albrecht D, Schewe B, Weise K, Aicher WK, Rolauffs B. Remodeling of articular cartilage and subchondral bone after bone grafting and matrix-associated autologous chondrocyte implantation for osteochondritis dissecans of the knee. Am J Sports Med. 2011;39(4):764–73.CrossRefPubMedGoogle Scholar
  45. 45.
    Orozco L, Munar A, Soler R, Alberca M, Soler F. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013;95:1535.CrossRefPubMedGoogle Scholar
  46. 46.
    Orth P, Duffner J, Zurakowski D, Cucchiarini M, Madry H. Small diameter awls improve articular cartilage repair following microfracture treatment in a translational animal model. Am J Sports Med. 2016;44(1):209–19.Google Scholar
  47. 47.
    Pape D, Filardo G, Kon E, van Dijk CN, Madry H. Disease-specific clinical problems associated with the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):448–62.CrossRefPubMedGoogle Scholar
  48. 48.
    Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356–64.CrossRefPubMedGoogle Scholar
  49. 49.
    Peeters CM, Leijs MJ, Reijman M, van Osch GJ, Bos PK. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage. 2013;21:1465.CrossRefPubMedGoogle Scholar
  50. 50.
    Pridie KH. A method of resurfacing osteoarthritic knee joints. Proc Br Orthop Assoc J Bone Joint Surg (Br). 1959;41:618–9.Google Scholar
  51. 51.
    Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, Azma K. Knee osteoarthritis injection choices: platelet- rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:1–8.PubMedPubMedCentralGoogle Scholar
  52. 52.
    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;75(4):532–55.PubMedGoogle Scholar
  53. 53.
    Smillie IS. Treatment of osteochondritis dissecans. J Bone Joint Surg Br. 1957;39(2):248–60.PubMedGoogle Scholar
  54. 54.
    Soler R, Munar A, Soler F, Peirau X, Huguet M, Orozco L. Treatment of knee osteoarthritis with autologous expanded bone marrow mesenchymal cells: 50 cases clinical and MRI results at one year follow-up. J Stem Cell Res Ther. 2015;5:285.Google Scholar
  55. 55.
    Steadman JR, Rodkey WG, Rodrigo JJ. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop. 2001;391(Suppl):S362–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG. Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy. 2003;19(5):477–84.CrossRefPubMedGoogle Scholar
  57. 57.
    Sansone V, de Girolamo L, Pascale W, Melato M, Pascale V. Long-term results of abrasion arthroplasty for full-thickness cartilage lesions of the medial femoral condyle. Arthroscopy. 2015;31(3):396–403.CrossRefPubMedGoogle Scholar
  58. 58.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.CrossRefPubMedGoogle Scholar
  59. 59.
    Tampieri A, Sandri M, Landi E, Pressato D, Francioli S, Quarto R, Martin I. Design of graded biomimetic osteochondral composite scaffolds. Biomaterials. 2008;29(26):3539–46.CrossRefPubMedGoogle Scholar
  60. 60.
    Van Assche D, Staes F, Van Caspel D, Vanlauwe J, Bellemans J, Saris DB, Luyten FP. Autologous chondrocyte implantation versus microfracture for knee cartilage injury: a prospective randomized trial, with 2-year follow-up. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):486–95.CrossRefPubMedGoogle Scholar
  61. 61.
    Vasiliadis HS, Danielson B, Ljungberg M, McKeon B, Lindahl A, Peterson L. Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique. Am J Sports Med. 2010;38(5):943–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Verhaegen J, Clockaerts S, Van Osch GJ, Somville J, Verdonk P, Mertens P. TruFit plug for repair of osteochondral defects-where is the evidence? Syst Rev Lit Cartil. 2015;6(1):12–9.Google Scholar
  63. 63.
    Vijayan S, Bartlett W, Bentley G, Carrington RW, Skinner JA, Pollock RC, Alorjani M, Briggs TW. Autologous chondrocyte implantation for osteochondral lesions in the knee using a bilayer collagen membrane and bone graft: a two- to eight-year follow-up study. J Bone Joint Surg Br. 2012;94(4):488–92.CrossRefPubMedGoogle Scholar
  64. 64.
    Wondrasch B, Arøen A, Røtterud JH, Høysveen T, Bølstad K, Risberg MA. The feasibility of a 3-month active rehabilitation program for patients with knee full-thickness articular cartilage lesions: the Oslo Cartilage Active Rehabilitation and Education Study. J Orthop Sports Phys Ther. 2013;43(5):310–24.CrossRefPubMedGoogle Scholar
  65. 65.
    Zellner J, Mueller M, Krutsch W, Baumann F, Englert C, Nerlich M, Angele P. Arthroscopic three dimensional autologous chondrocyte transplantation with navigation-guided cartilage defect size assessment. Arch Orthop Trauma Surg. 2012;132(6):855–60.CrossRefPubMedGoogle Scholar

Copyright information

© ESSKA 2016

Authors and Affiliations

  • Giuseppe M. Peretti
    • 1
    Email author
  • Peter Angele
    • 2
  • Giuseppe Filardo
    • 3
  • Elizaveta Kon
    • 3
  • Laura Mangiavini
    • 1
  • Antongiulio Marmotti
    • 4
  • Silvia Mattia
    • 5
  • Konrad Slynarski
    • 6
  • Francesc Soler
    • 7
  • Dieter Van Assche
    • 8
  • Henning Madry
    • 9
    Email author
  1. 1.Department of Biomedical Sciences for HealthUniversity of Milan, Milan, Italy, IRCCS Istituto Ortopedico GaleazziMilanItaly
  2. 2.Department of Trauma SurgeryUniversity Medical Center RegensburgRegensburgGermany
  3. 3.Biomechanics Laboratory – II ClinicRizzoli Orthopaedic InstituteBolognaItaly
  4. 4.Department of Orthopaedics and TraumatologyUniversity of TorinoTorinoItaly
  5. 5.Molecular Biotechnology CenterUniversity of TorinoTurinItaly
  6. 6.LEKMEDHospital KartezjuszaWarszawaPoland
  7. 7.ITRTCentro Médico TeknonBarcelonaSpain
  8. 8.Division of RheumatologyUniversity Hospitals LeuvenLeuvenBelgium
  9. 9.Center of Experimental OrthopaedicsSaarland UniversityHomburgGermany

Personalised recommendations