Abstract
Fibrin, a homologous polymer, is the natural scaffold of wound healing and therefore a candidate as a carrier for cell transplantation. We explored a novel matrix-based implant cartilage repair composed of both fibrin and hyaluronan in a defined ratio that takes advantage of the biological and mechanical properties of these two elements. The matrix was seeded with autologous chondrocytes expanded in the presence of a proprietary growth factor variant designed to preserve their chondrogenic potential. We prospectively followed eight patients with symptomatic-chronic cartilage defects treated with this carrier. Patients had arthroscopy to harvest autologous chondrocytes then grown in autologous serum. Chondrocytes were cultured in the presence of the FGF variant and then seeded on the fibrin-hyaluronan matrix. About 4 weeks following biopsy, the patients underwent implantation of the constructs by miniarthrotomy. Three of the eight patients had transient effusion. Clinical performance was measured by Lysholm and IKDC scores, MRI, and the need for secondary surgery. The clinical outcome of a 1-year followup demonstrated increase of clinical scores. The MRI followup showed good filling of the defect with tissue having the imaging appearance of cartilage in all patients. Apart from the transient effusion in three patients we observed no other adverse events during the followup.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Similar content being viewed by others
References
Bartlett W, Skinner JA, Gooding CR, Carrington RW, Flanagan AM, Briggs TW, Bentley G. Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br. 2005;87:640–645.
Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI) - 5-year follow-up. Knee. 2006;13:194–202.
Bobic V. Autologous osteo-chondral grafts in the management of articular cartilage lesions [in German]. Orthopade. 1999;28:19–25.
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889–895.
Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998;47:487–504.
Chu CR, Coutts RD, Yoshioka M, Harwood FL, Monosov AZ, Amiel D. Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res. 1995;29:1147–1154.
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;13:655–664.
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;26:3617–3629.
Gobbi A, Kon E, Berruto M, Francisco R, Filardo G, Marcacci M. Patellofemoral full-thickness chondral defects treated with Hyalograft-C: a clinical, arthroscopic, and histologic review. Am J Sports Med. 2006;34:1763–1773.
Grigolo B, Roseti L, Fiorini M, Fini M, Giavaresi G, Aldini NN, Giardino R, Facchini A. Transplantation of chondrocytes seeded on a hyaluronan derivative (hyaff-11) into cartilage defects in rabbits. Biomaterials. 2001;22:2417–2424.
Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, Duca M, Pavesio A, Facchini A. Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAff 11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002;23:1187–1195.
Hangody L, Feczko P, Bartha L, Bodo G, Kish G. Mosaicplasty for the treatment of articular defects of the knee and ankle. Clin Orthop Relat Res. 2001;391(Suppl):S328–336.
Hefti F, Muller W, Jakob RP, Staubli HU. Evaluation of knee ligament injuries with the IKDC form. Knee Surg Sports Traumatol Arthrosc. 1993;1:226–234.
Homminga GN, Bulstra SK, Bouwmeester PS, van der Linden AJ. Perichondral grafting for cartilage lesions of the knee. J Bone Joint Surg Br. 1990;72:1003–1007.
Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002;10:432–463.
Jakob RP, Franz T, Gautier E, Mainil-Varlet P. Autologous osteochondral grafting in the knee: indication, results, and reflections. Clin Orthop Relat Res. 2002;401:170–184.
Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004;86:455–464.
Kreuz PC, Steinwachs MR, Erggelet C, Krause SJ, Konrad G, Uhl M, Sudkamp N. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthritis Cartilage. 2006;14:1119–1125.
Lysholm J, Gillquist J. Evaluation of knee ligament surgery results with special emphasis on use of a scoring scale. Am J Sports Med. 1982;10:150–154.
Manfredini M, Zerbinati F, Gildone A, Faccini R. Autologous chondrocyte implantation: a comparison between an open periosteal-covered and an arthroscopic matrix-guided technique. Acta Orthop Belg. 2007;73:207–218.
Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Sacchetti GL, Stefani G, Zanasi S. Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res. 2005;435:96–105.
Marlovits S, Singer P, Zeller P, Mandl I, Haller J, Trattnig S. Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol. 2006;57:16–23.
Nehrer S, Breinan HA, Ramappa A, Shortkroff S, Young G, Minas T, Sledge CB, Yannas IV, Spector M. Canine chondrocytes seeded in type I and type II collagen implants investigated in vitro. J Biomed Mater Res. 1997;38:95–104.
Nehrer S, Breinan HA, Ramappa A, Hsu HP, Minas T, Shortkroff S, Sledge CB, Yannas IV, Spector M. Chondrocyte-seeded collagen matrices implanted in a chondral defect in a canine model. Biomaterials. 1998;19:2313–2328.
Nehrer S, Spector M, Minas T. Histologic analysis of tissue after failed cartilage repair procedures. Clin Orthop Relat Res. 1999;365:149–162.
Nehrer S, Minas T. Treatment of articular cartilage defects. Invest Radiol. 2000;35:639–646.
Nehrer S, Domayer S, Dorotka R, Schatz K, Bindreiter U, Kotz R. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair. Eur J Radiol. 2006;57:3–8.
Ossendorf C, Kaps C, Kreuz PC, Burmester GR, Sittinger M, Erggelet C. Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results. Arthritis Res Ther. 2007;9:R41.
Paletta GA, Arnoczky SP, Warren RF. The repair of osteochondral defects using an exogenous fibrin clot. An experimental study in dogs. Am J Sports Med. 1992;20:725–731.
Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000;374:212–234.
Solchaga LA, Dennis JE, Goldberg VM, Caplan AI. Hyaluronic acid-based polymers as cell carriers for tissue-engineered repair of bone and cartilage. J Orthop Res. 1999;17:205–213.
Steadman JR, Rodkey WG, Rodrigo JJ. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001;391(Suppl):S362–369.
Steadman JR, Rodkey WG, Briggs KK. Microfracture to treat full-thickness chondral defects: surgical technique, rehabilitation, and outcomes. J Knee Surg. 2002;15:170–176.
Steinwachs M, Kreuz PC. Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up. Arthroscopy. 2007;23:381–387.
Szerb I, Hangody L, Duska Z, Kaposi NP. Mosaicplasty: long-term follow-up. Bull Hosp Jt Dis. 2005;63:54–62.
Acknowledgments
We thank Roni Wechsler and Ann Avron for critical review of the manuscript. Furthermore we thank Christoph Buchta for preparing the patients’ serum and Siegfried Trattnig for reviewing the MRI studies.
Author information
Authors and Affiliations
Corresponding author
Additional information
One or more of the authors (SN) certifies that he or she has received funding from ProChon to support this project. Two of the authors (AY, HB) are salaried employees of ProChon.
Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.
About this article
Cite this article
Nehrer, S., Chiari, C., Domayer, S. et al. Results of Chondrocyte Implantation with a Fibrin-Hyaluronan Matrix: A Preliminary Study . Clin Orthop Relat Res 466, 1849–1855 (2008). https://doi.org/10.1007/s11999-008-0322-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11999-008-0322-4