Knee Surgery, Sports Traumatology, Arthroscopy

, Volume 20, Issue 12, pp 2590–2601 | Cite as

One-step osteochondral repair with cartilage fragments in a composite scaffold

  • A. Marmotti
  • M. Bruzzone
  • D. E. Bonasia
  • F. Castoldi
  • R. Rossi
  • L. Piras
  • A. Maiello
  • C. Realmuto
  • G. M. Peretti
Experimental Study



This study proposes a single-step therapeutic approach for osteochondral defects using autologous cartilage fragments loaded onto a scaffold composed of a hyaluronic acid (HA) derivative, human fibrin glue (FG) and autologous platelet-rich-plasma (PRP), in a rabbit model. The aim is to demonstrate the in vitro outgrowth of chondrocytes from cartilage fragments and the in vivo formation of a functional repair tissue.


In vitro: minced articular cartilage was loaded onto two different types of scaffold (paste or membrane) according to two different HA preparations (injectable HA-derivative or HA-derivative felt). In vivo: trochlear osteochondral defects were created in 50 adult rabbits, which were then assigned to 5 different treatment groups: cartilage fragments loaded onto membrane scaffolds with FG (Group 1) or without FG (Group 2); membrane scaffolds alone with FG (Group 3) or without FG (Group 4); empty defects (Group 5). Membrane scaffolds were used “in vivo” for simpler preparation and better adhesive properties. Repair processes were evaluated histologically and by immunohistochemistry at 1, 3, and 6 months.


An in vitro time-dependent cell outgrowth from cartilage fragments was observed with both types of scaffolds. At 6 months, in vivo, cartilage fragment-loaded scaffolds induced significantly better repair tissue than the scaffold alone using histological scoring. Repair in Group 2 was superior to that in any of the control groups (p < 0.05).


Autologous cartilage fragments loaded onto an HA felt/FG/PRP-scaffold provided an efficient cell source, and allowed for an improvement of the repair process of ostechondral defects in a rabbit model. Human FG, however, hampered the rabbit healing process. These results may have clinical relevance as they show the potential of a novel one-stage repair technique for osteochondral defects.


Cartilage repair Minced cartilage fragments Scaffold Hyaluronic acid Platelet-rich-plasma Fibrin glue 



This work was supported by “DJ ESSKA Ortho Grant 2006” and “CRT (Cassa di Risparmio di Torino)–Alfieri project” (independent research fund). Authors are grateful to F.a.b. (Fidia advanced biopolymers) for donation of Hyaff-11 membranes and to Sergio D’Antico MD and Paola Manzini MD for the help in the preparation of the rabbit PRP. We would also like to thank Radhika Srinivasan, PhD, for editing of the manuscript.


  1. 1.
    Ahmed TAE, Hincke MT (2010) Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B Rev 16:305–329PubMedCrossRefGoogle Scholar
  2. 2.
    Alford JW, Cole BJ (2005) Cartilage restoration, part 2: techniques, outcomes, and future directions. Am J Sports Med 33:443–460PubMedCrossRefGoogle Scholar
  3. 3.
    Bartlett W, Skinner JA, Gooding CR, Carrington RWJ, Flanagan AM, Briggs TWR, Bentley G (2005) Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br 87:640–645PubMedCrossRefGoogle Scholar
  4. 4.
    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 331:889–895PubMedCrossRefGoogle Scholar
  5. 5.
    Brittberg M, Sjögren-Jansson E, Lindahl A, Peterson L (1997) Influence of fibrin sealant (Tisseel) on osteochondral defect repair in the rabbit knee. Biomaterials 18:235–242PubMedCrossRefGoogle Scholar
  6. 6.
    Buda R, Vannini F, Cavallo M, Grigolo B, Cenacchi A, Giannini S (2010) Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells. J Bone Joint Surg Am 92(Suppl 2):2–11PubMedCrossRefGoogle Scholar
  7. 7.
    Buschmann MD, Gluzband YA, Grodzinsky AJ, Kimura JH, Hunziker EB (1992) Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix. J Orthop Res 10:745–758PubMedCrossRefGoogle Scholar
  8. 8.
    Cavallo C, Desando G, Facchini A, Grigolo B (2010) Chondrocytes from patients with osteoarthritis express typical extracellular matrix molecules once grown onto a three-dimensional hyaluronan-based scaffold. J Biomed Mater Res A 93:86–95PubMedGoogle Scholar
  9. 9.
    Frisbie DD, Lu Y, Kawcak CE, DiCarlo EF, Binette F, McIlwraith CW (2009) In vivo evaluation of autologous cartilage fragment-loaded scaffolds implanted into equine articular defects and compared with autologous chondrocyte implantation. Am J Sports Med 37(Suppl 1):71S–80SPubMedCrossRefGoogle Scholar
  10. 10.
    Giannini S, Buda R, Vannini F, Cavallo M, Grigolo B (2009) One-step bone marrow-derived cell transplantation in talar osteochondral lesions. Clin Orthop Relat Res 467:3307–3320PubMedCrossRefGoogle Scholar
  11. 11.
    Giovannini S, Diaz-Romero J, Aigner T, Heini P, Mainil-Varlet P, Nesic D (2010) Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro. Eur Cell Mater 20:245–259PubMedGoogle Scholar
  12. 12.
    Gomoll AH, Farr J, Gillogly SD, Kercher J, Minas T (2010) Surgical management of articular cartilage defects of the knee. J Bone Joint Surg Am 92:2470–2490PubMedGoogle Scholar
  13. 13.
    Hatic SO 2nd, Berlet GC (2010) Particulated juvenile articular cartilage graft (DeNovo NT Graft) for treatment of osteochondral lesions of the talus. Foot Ankle Spec 3:361–364PubMedCrossRefGoogle Scholar
  14. 14.
    Hjelle K, Solheim E, Strand T, Muri R, Brittberg M (2002) Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 18:730–734PubMedCrossRefGoogle Scholar
  15. 15.
    Johnson KA, Rose DM, Terkeltaub RA (2008) Factor XIIIA mobilizes transglutaminase 2 to induce chondrocyte hypertrophic differentiation. J Cell Sci 121:2256–2264PubMedCrossRefGoogle Scholar
  16. 16.
    Kon E, Filardo G, Delcogliano M, Fini M, Salamanna F, Giavaresi G, Martin I, Marcacci M (2010) Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model. BMC Musculoskelet Disord 11(220):1–12Google Scholar
  17. 17.
    Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M (2011) Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 27:1490–1501PubMedCrossRefGoogle Scholar
  18. 18.
    Lee KBL, Hui JHP, Song IC, Ardany L, Lee EH (2007) Injectable mesenchymal stem cell therapy for large cartilage defects–a porcine model. Stem Cells 25:2964–2971PubMedCrossRefGoogle Scholar
  19. 19.
    Lind M, Larsen A (2008) Equal cartilage repair response between autologous chondrocytes in a collagen scaffold and minced cartilage under a collagen scaffold: an in vivo study in goats. Connect Tissue Res 49:437–442PubMedCrossRefGoogle Scholar
  20. 20.
    Liu Y, Shu XZ, Prestwich GD (2006) Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. Tissue Eng 12:3405–3416PubMedCrossRefGoogle Scholar
  21. 21.
    Lu Y, Dhanaraj S, Wang Z, Bradley DM, Bowman SM, Cole BJ, Binette F (2006) Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair. J Orthop Res 24:1261–1270PubMedCrossRefGoogle Scholar
  22. 22.
    Milano G, Sanna Passino E, Deriu L, Careddu G, Manunta L, Manunta A, Saccomanno MF, Fabbriciani C (2010) The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: an experimental study in a sheep model. Osteoarthr Cartil 18:971–980PubMedCrossRefGoogle Scholar
  23. 23.
    Rudert M, Wirth CJ, Schulze M, Reiss G (1998) Synthesis of articular cartilage-like tissue in vitro. Arch Orthop Trauma Surg 117:141–146PubMedCrossRefGoogle Scholar
  24. 24.
    Saris DBF, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP (2009) Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 37(Suppl 1):10S–19SPubMedCrossRefGoogle Scholar
  25. 25.
    Saris DBF, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, van der Bauwhede J, Vandenneucker H, Yang KGA, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP (2008) Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 36:235–246PubMedCrossRefGoogle Scholar
  26. 26.
    Stone KR, Walgenbach AW, Freyer A, Turek TJ, Speer DP (2006) Articular cartilage paste grafting to full-thickness articular cartilage knee joint lesions: a 2- to 12-year follow-up. Arthroscopy 22:291–299PubMedCrossRefGoogle Scholar
  27. 27.
    Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, Martini L, Giavaresi G, Kon E, Maltarello MC, Nicolini A, Carpi A (2011) Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed) 3:96–107CrossRefGoogle Scholar
  28. 28.
    Widuchowski W, Widuchowski J, Trzaska T (2007) Articular cartilage defects: study of 25,124 knee arthroscopies. Knee 14:177–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • A. Marmotti
    • 1
  • M. Bruzzone
    • 1
  • D. E. Bonasia
    • 1
  • F. Castoldi
    • 1
  • R. Rossi
    • 1
  • L. Piras
    • 2
  • A. Maiello
    • 1
  • C. Realmuto
    • 3
  • G. M. Peretti
    • 4
  1. 1.Department of Orthopaedics and TraumatologyUniversity of TorinoTorinoItaly
  2. 2.Department of Animal Pathology, Surgery SectionUniversity of TorinoTorinoItaly
  3. 3.Molecular Biotechnology CenterUniversity of TorinoTorinoItaly
  4. 4.Department of Sport, Nutrition and Health SciencesUniversity of MilanMilanItaly

Personalised recommendations