Cell-Free Scaffolds for the Treatment of Chondral and Osteochondral Lesions

  • Iacopo Romandini
  • Francesco Perdisa
  • Giuseppe Filardo
  • Elizaveta KonEmail author


In the last two decades, the achievements of tissue engineering provided the surgeons with a pool of new and promising options for the treatment of cartilage defects. Cell-based regenerative techniques, also in combination with various biomaterials, were proposed to improve the tissue quality and the clinical outcomes. Despite several investigations that showed satisfactory clinical results in the long term, the need for two surgical procedures and the related costs limited their use. Thus, the possibility to avoid any cell augmentation by implanting biomaterials able to exploit the patient self-regenerative potential in situ was explored. Since then, several matrices were successfully introduced in the clinical use, and their intrinsic ability to promote tissue regeneration produced positive results in terms of clinical improvement. Also, some biomaterials were combined to reproduce the requirements of both bone and cartilage, in order to address osteochondral defects. This narrative review aims at resuming the state of the art concerning the clinical use of acellular scaffolds for the treatment of cartilage conditions.


Chondral scaffold Osteochondral scaffold Cartilage regeneration Cell-free 


  1. 1.
    Madry H, Kon E, Condello V, et al. Early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2016;24(6):1753–62.CrossRefPubMedGoogle Scholar
  2. 2.
    Andrade R, Vasta S, Pereira R, et al. Knee donor-site morbidity after mosaicplasty – a systematic review. J Exp Orthop. 2016;3(1):31.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331(14):889–95.CrossRefPubMedGoogle Scholar
  4. 4.
    Goyal D, Goyal A, Keyhani S, et al. Evidence-based status of second- and third-generation autologous chondrocyte implantation over first generation: a systematic review of level I and II studies. Arthroscopy. 2013;29(11):1872–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Peterson L, Vasiliadis HS, Brittberg M, et al. Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med. 2010;38(6):1117–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Aldrian S, Zak L, Wondrasch B, et al. Clinical and radiological long-term outcomes after matrix-induced autologous chondrocyte transplantation: a prospective follow-up at a minimum of 10 years. Am J Sports Med. 2014;42(11):2680–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Gille J, Behrens P, Schulz AP, et al. Matrix-associated autologous chondrocyte implantation: a clinical follow-up at 15 years. Cartilage. 2016;7(4):309–15.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gille J, Kunow J, Boisch L, et al. Cell-laden and cell-free matrix-induced chondrogenesis versus microfracture for the treatment of articular cartilage defects: a histological and biomechanical study in sheep. Cartilage. 2010;1(1):29–42.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pape D, Filardo G, Kon E, et al. Disease-specific clinical problems associated with the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):448–62.CrossRefPubMedGoogle Scholar
  10. 10.
    Kon E, Filardo G, Perdisa F, et al. 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
  11. 11.
    Kusano T, Jakob RP, Gautier E, et al. Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg Sports Traumatol Arthrosc. 2012;20(10):2109–15.CrossRefPubMedGoogle Scholar
  12. 12.
    Schiavone Panni A, Cerciello S, Vasso M. The manangement of knee cartilage defects with modified amic technique: preliminary results. Int J Immunopathol Pharmacol. 2011;24(1 Suppl 2):149–52.CrossRefPubMedGoogle Scholar
  13. 13.
    Gille J, Schuseil E, Wimmer J, et al. Mid-term results of autologous matrix-induced chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc. 2010;18(11):1456–64.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Gille J, Behrens P, Volpi P, et al. Outcome of Autologous Matrix Induced Chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC registry. Arch Orthop Trauma Surg. 2013;133(1):87–93.CrossRefPubMedGoogle Scholar
  15. 15.
    Stanish WD, McCormack R, Forriol F, et al. Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J Bone Joint Surg Am. 2013;95(18):1640–50.CrossRefPubMedGoogle Scholar
  16. 16.
    Shive MS, Stanish WD, McCormack R, et al. BST-CarGel(R) treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage. 2015;6(2):62–72.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Benthien JP, Behrens P. Autologous matrix-induced chondrogenesis (AMIC). A one-step procedure for retropatellar articular resurfacing. Acta Orthop Belg. 2010;76(2):260–3.PubMedGoogle Scholar
  18. 18.
    Benthien JP, Behrens P. The treatment of chondral and osteochondral defects of the knee with autologous matrix-induced chondrogenesis (AMIC): method description and recent developments. Knee Surg Sports Traumatol Arthrosc. 2011;19(8):1316–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Piontek T, Ciemniewska-Gorzela K, Szulc A, et al. All-arthroscopic AMIC procedure for repair of cartilage defects of the knee. Knee Surg Sports Traumatol Arthrosc. 2012;20(5):922–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Gobbi A, Scotti C, Karnatzikos G, et al. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surg Sports Traumatol Arthrosc. 2017;25(8):2494–501.CrossRefPubMedGoogle Scholar
  21. 21.
    Gobbi A, Whyte GP. One-stage cartilage repair using a hyaluronic acid-based scaffold with activated bone marrow-derived mesenchymal stem cells compared with microfracture: five-year follow-up. Am J Sports Med. 2016;44(11):2846–54.CrossRefPubMedGoogle Scholar
  22. 22.
    Rodriguez-Vazquez M, Vega-Ruiz B, Ramos-Zuniga R et al. Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine. Biomed Res Int. 2015;2015:821279.CrossRefGoogle Scholar
  23. 23.
    Steinwachs MR, Waibl B, Mumme M. Arthroscopic treatment of cartilage lesions with microfracture and BST-CarGel. Arthrosc Tech. 2014;3(3):e399–402.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Methot S, Changoor A, Tran-Khanh N, et al. Osteochondral biopsy analysis demonstrates that BST-CarGel treatment improves structural and cellular characteristics of cartilage repair tissue compared with microfracture. Cartilage. 2016;7(1):16–28.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Trattnig S, Ohel K, Mlynarik V, et al. Morphological and compositional monitoring of a new cell-free cartilage repair hydrogel technology – GelrinC by MR using semi-quantitative MOCART scoring and quantitative T2 index and new zonal T2 index calculation. Osteoarthr Cartil. 2015;23(12):2224–32.CrossRefPubMedGoogle Scholar
  26. 26.
    Fortier LA, Chapman HS, Pownder SL, et al. BioCartilage improves cartilage repair compared with microfracture alone in an equine model of full-thickness cartilage loss. Am J Sports Med. 2016;44(9):2366–74.CrossRefPubMedGoogle Scholar
  27. 27.
    Niederauer GG, Slivka MA, Leatherbury NC, et al. Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials. 2000;21(24):2561–74.CrossRefPubMedGoogle Scholar
  28. 28.
    Gelber PE, Batista J, Millan-Billi A, et al. 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. 2014;21(4):827–32.CrossRefPubMedGoogle Scholar
  29. 29.
    Bekkers JE, Bartels LW, Vincken KL, et al. Articular cartilage evaluation after TruFit plug implantation analyzed by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Am J Sports Med. 2013;41(6):1290–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Quarch VM, Enderle E, Lotz J, et al. Fate of large donor site defects in osteochondral transfer procedures in the knee joint with and without TruFit plugs. Arch Orthop Trauma Surg. 2014;134(5):657–66.CrossRefPubMedGoogle Scholar
  31. 31.
    Dhollander AA, Liekens K, Almqvist KF, et al. 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
  32. 32.
    Slivka MA, Leatherbury NC, Kieswetter K, et al. Porous, resorbable, fiber-reinforced scaffolds tailored for articular cartilage repair. Tissue Eng. 2001;7(6):767–80.CrossRefPubMedGoogle Scholar
  33. 33.
    Barber FA, Dockery WD. A computed tomography scan assessment of synthetic multiphase polymer scaffolds used for osteochondral defect repair. Arthroscopy. 2011;27(1):60–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Carmont MR, Carey-Smith R, Saithna A, et al. Delayed incorporation of a TruFit plug: perseverance is recommended. Arthroscopy. 2009;25(7):810–4.CrossRefPubMedGoogle Scholar
  35. 35.
    Bedi A, Foo LF, Williams RJ 3rd, et al. The maturation of synthetic scaffolds for osteochondral donor sites of the knee: an MRI and T2-mapping analysis. Cartilage. 2010;1(1):20–8.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Hindle P, Hendry JL, Keating JF, et al. Autologous osteochondral mosaicplasty or TruFit plugs for cartilage repair. Knee Surg Sports Traumatol Arthrosc. 2014;22(6):1235–40.CrossRefPubMedGoogle Scholar
  37. 37.
    Tampieri A, Sandri M, Landi E, et al. Design of graded biomimetic osteochondral composite scaffolds. Biomaterials. 2008;29(26):3539–46.CrossRefPubMedGoogle Scholar
  38. 38.
    Delcogliano M, de Caro F, Scaravella E, et al. 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
  39. 39.
    Kon E, Filardo G, Di Martino A, et al. 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
  40. 40.
    Marcacci M, Zaffagnini S, Kon E, et al. 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
  41. 41.
    Filardo G, Kon E, Perdisa F, et al. Osteochondral scaffold reconstruction for complex knee lesions: a comparative evaluation. Knee. 2013;20(6):570–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Filardo G, Kon E, Di Martino A, et al. 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
  43. 43.
    Di Martino A, Kon E, Perdisa F et al. Surgical treatment of early knee osteoarthritis with a cell-free osteochondral scaffold: results at 24 months of follow-up. Injury. 2015;46(Suppl 8):S33–S38.CrossRefPubMedGoogle Scholar
  44. 44.
    Kon E, Delcogliano M, Filardo G, et al. Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med. 2011;39(6):1180–90.CrossRefPubMedGoogle Scholar
  45. 45.
    Perdisa F, Filardo G, Sessa A, et al. One-step treatment for patellar cartilage defects with a cell-free osteochondral scaffold: a prospective clinical and MRI evaluation. Am J Sports Med. 2017;45(7):1581–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Berruto M, Delcogliano M, de Caro F, et al. 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
  47. 47.
    Kon E, Filardo G, Perdisa F, et al. Clinical results of multilayered biomaterials for osteochondral regeneration. J Exp Orthop. 2014;1(1):10.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kon E, Filardo G, Shani J, et al. Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model. J Orthop Surg Res. 2015;10:81.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Joshi N, Reverte-Vinaixa M, Diaz-Ferreiro EW, et al. 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
  50. 50.
    Kon E, Delcogliano M, Filardo G, et al. A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions: technique note and an early stability pilot clinical trial. Injury. 2010;41(7):693–701.CrossRefPubMedGoogle Scholar
  51. 51.
    Berruto M, Ferrua P, Uboldi F, et al. Can a biomimetic osteochondral scaffold be a reliable alternative to prosthetic surgery in treating late-stage SPONK? Knee. 2016;23(6):936–41.CrossRefPubMedGoogle Scholar
  52. 52.
    Christensen BB, Foldager CB, Jensen J, et al. Poor osteochondral repair by a biomimetic collagen scaffold: 1- to 3-year clinical and radiological follow-up. Knee Surg Sports Traumatol Arthrosc. 2016;24(7):2380–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Dhollander A, Verdonk P, Almqvist KF, et al. Clinical and MRI outcome of an osteochondral scaffold plug for the treatment of cartilage lesions in the knee. Acta Orthop Belg. 2015;81(4):629–38.PubMedGoogle Scholar
  54. 54.
    Kon E, Drobnic M, Davidson PA, et al. Chronic posttraumatic cartilage lesion of the knee treated with an acellular osteochondral-regenerating implant: case history with rehabilitation guidelines. J Sport Rehabil. 2014;23(3):270–5.CrossRefPubMedGoogle Scholar
  55. 55.
    Kon E, Robinson D, Verdonk P, et al. A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments. Injury. 2016;47(Suppl 6):S27–32.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Iacopo Romandini
    • 1
  • Francesco Perdisa
    • 2
  • Giuseppe Filardo
    • 1
  • Elizaveta Kon
    • 3
    • 4
    Email author
  1. 1.NABI LaboratoryRizzoli Orthopedic Institute IRCCSBolognaItaly
  2. 2.II Orthopedic and Traumatologic ClinicRizzoli Orthopedic Institute IRCCSBolognaItaly
  3. 3.Department of Biomedical SciencesHumanitas UniversityMilanItaly
  4. 4.Humanitas Clinical and Research Center IRCCSMilanItaly

Personalised recommendations