Abstract
Background
Matrix-guided autologous chondrocyte transplantation (MACT) has been proposed as an option for treating large full-thickness cartilage defects. However, little is known about the chondrogenic potential of transplants for MACT at the time of implantation, although cell quality and chondrogenic differentiation of the implants are crucial for restoration of function after MACT.
Questions/purposes
We therefore asked: (1) Do MACT implants allow deposition of extracellular cartilage matrix in an in vitro culture model? (2) Are these implants associated with improved knee function 1 year after MACT in large cartilage defects?
Methods
We retrospectively reviewed all 125 patients with large localized cartilage defects (mean defect size 5 cm2) of the knee who were treated with MACT from 2005 to 2010. The mean age was 31 years (range, 16–53 years). Portions of the cell-matrix constructs (n = 50) that were not implanted in the cartilage defects were further cultured and tested for their potential to form articular cartilage. Knee function of all patients was analyzed preoperatively, 3 months, and 1 year postoperatively with the International Knee Documentation Committee (IKDC) score.
Results
In vitro assessment of the cell-matrix implants showed chondrogenic differentiation with positive staining for glycosaminoglycans and collagen II in all cultures. Enzyme-linked immunosorbent assay showed an increase of collagen II production. We observed an improvement in median IKDC score from 41 to 67 points at last followup.
Conclusions
Cartilage extracellular matrix deposition shows adequate implant quality for MACT at the time of implantation and justifies the use for treatment of large cartilage defects.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Similar content being viewed by others
References
Anders S, Lechler P, Grifka J, Schaumburger J. [Repair of local cartilage defects in the patellofemoral joint] [in German]. Orthopade. 2011;40:885–888, 890–895.
Angele P, Kujat R, Nerlich M, Yoo J, Goldberg V, Johnstone B. Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge. Tissue Eng. 1999;5:545–554.
Angele P, Schumann D, Angele M, Kinner B, Englert C, Hente R, Fuchtmeier B, Nerlich M, Neumann C, Kujat R. Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds. Biorheology. 2004;41:335–346.
Angele P, Yoo JU, Smith C, Mansour J, Jepsen KJ, Nerlich M, Johnstone B. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res. 2003;21:451–457.
Basad E, Ishaque B, Bachmann G, Sturz H, Steinmeyer J. Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study. Knee Surg Sports Traumatol Arthrosc. 2010;18:519–527.
Behrens P, Bosch U, Bruns J, Erggelet C, Esenwein SA, Gaissmaier C, Krackhardt T, Lohnert J, Marlovits S, Meenen NM, Mollenhauer J, Nehrer S, Niethard FU, Noth U, Perka C, Richter W, Schafer D, Schneider U, Steinwachs M, Weise K. [Indications and implementation of recommendations of the working group ‘Tissue Regeneration and Tissue Substitutes’ for autologous chondrocyte transplantation (ACT)] [in German]. Z Orthop Ihre Grenzgeb. 2004;142:529–539.
Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br. 2003;85:223–230.
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;331:889–995.
Brown WE, Potter HG, Marx RG, Wickiewicz TL, Warren RF. Magnetic resonance imaging appearance of cartilage repair in the knee. Clin Orthop Relat Res. 2004;422:214–223.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–213.
Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan DC. Failures, re-operations, and complications after autologous chondrocyte implantation—a systematic review. Osteoarthritis Cartilage. 2011;19:779–791.
Harris JD, Siston RA, Pan X, Flanigan DC. Autologous chondrocyte implantation: a systematic review. J Bone Joint Surg Am. 2010;92:2220–2233.
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.
Henderson I, Lavigne P, Valenzuela H, Oakes B. Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs. Clin Orthop Relat Res. 2007;455:253–261.
Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29:577–580.
Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002;10:432–463.
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.
Kon E, Filardo G, Berruto M, Benazzo F, Zanon G, Della Villa S, Marcacci M. Articular cartilage treatment in high-level male soccer players: a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantation versus microfracture. Am J Sports Med. 2011;39:2549–2557.
Kon E, Verdonk P, Condello V, Delcogliano M, Dhollander A, Filardo G, Pignotti E, Marcacci M. Matrix-assisted autologous chondrocyte transplantation for the repair of cartilage defects of the knee: systematic clinical data review and study quality analysis. Am J Sports Med. 2009;37(Suppl 1):156S–166S.
Kujat R, Rose C, Wrobel KH. The innervation of the bovine ductus deferens: comparison of a modified acetylcholinesterase-reaction with immunoreactivities of cholinacetyltransferase and panneuronal markers. Histochemistry. 1993;99:231–239.
LaPrade RF, Bursch LS, Olson EJ, Havlas V, Carlson CS. Histologic and immunohistochemical characteristics of failed articular cartilage resurfacing procedures for osteochondritis of the knee: a case series. Am J Sports Med. 2008;36:360–368.
Løken S, Heir S, Holme I, Engebretsen L, Aroen A. 6-year follow-up of 84 patients with cartilage defects in the knee. Knee scores improved but recovery was incomplete. Acta Orthop. 2010;81:611–618.
Mainil-Varlet P, Aigner T, Brittberg M, Bullough P, Hollander A, Hunziker E, Kandel R, Nehrer S, Pritzker K, Roberts S, Stauffer E. Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS). J Bone Joint Surg Am. 2003;85(Suppl 2):45–57.
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.
Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med. 2009;37:2053–2063.
Nehrer S, Spector M, Minas T. Histologic analysis of tissue after failed cartilage repair procedures. Clin Orthop Relat Res. 1999;365:149–162.
Niemeyer P, Koestler W, Sudkamp NP. [Problems and complications of surgical techniques for treatment of full-thickness cartilage defects] [in German]. Z Orthop Unfall. 2011;149:45–51.
Niemeyer P, Salzmann GM, Hirschmuller A, Sudkamp NP. [Factors that influence clinical outcome following autologous chondrocyte implantation for cartilage defects of the knee] [in German]. Z Orthop Unfall. 2012;150:83–88.
Niemeyer P, Steinwachs M, Erggelet C, Kreuz PC, Kraft N, Kostler W, Mehlhorn A, Sudkamp NP. Autologous chondrocyte implantation for the treatment of retropatellar cartilage defects: clinical results referred to defect localisation. Arch Orthop Trauma Surg. 2008;128:1223–1231.
Peterson L, Brittberg M, Kiviranta I, Akerlund EL, Lindahl A. Autologous chondrocyte transplantation. Biomechanics and long-term durability. Am J Sports Med. 2002;30:2–12.
Peterson L, Minas T, Brittberg M, Lindahl A. Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years. J Bone Joint Surg Am. 2003;85(Suppl 2):17–24.
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.
Pietschmann MF, Horng A, Niethammer T, Pagenstert I, Sievers B, Jansson V, Glaser C, Muller PE. Cell quality affects clinical outcome after MACI procedure for cartilage injury of the knee. Knee Surg Sports Traumatol Arthrosc. 2009;17:1305–1311.
Pietschmann MF, Niethammer TR, Horng A, Gulecyuz MF, Feist-Pagenstert I, Jansson V, Muller PE. The incidence and clinical relevance of graft hypertrophy after matrix-based autologous chondrocyte implantation. Am J Sports Med. 2012;40:68–74.
Saris DB, 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 KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP. 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. 2008;36:235–246.
Schewe B, Fritz J, Gaissmaier C, Weise K. [Cartilage cell transplant: surgical technique with matrix-associated chondrocytes] [in German]. Unfallchirurg. 2006;109:577–582.
Taylor KB, Jeffree GM. A new basic metachromatic dye, I:9-dimethyl methylene blue. Histochem J. 1969;1:199–204.
Trattnig S, Mamisch TC, Welsch GH, Glaser C, Szomolanyi P, Gebetsroither S, Stastny O, Horger W, Millington S, Marlovits S. Quantitative T2 mapping of matrix-associated autologous chondrocyte transplantation at 3 Tesla: an in vivo cross-sectional study. Invest Radiol. 2007;42:442–448.
Trattnig S, Millington SA, Szomolanyi P, Marlovits S. MR imaging of osteochondral grafts and autologous chondrocyte implantation. Eur Radiol. 2007;17:103–118.
Vaquero J, Forriol F. Knee chondral injuries: clinical treatment strategies and experimental models. Injury. 2012;43:694–705.
Vasiliadis HS, Lindahl A, Georgoulis AD, Peterson L. Malalignment and cartilage lesions in the patellofemoral joint treated with autologous chondrocyte implantation. Knee Surg Sports Traumatol Arthrosc. 2011;19:452–457.
Vavken P, Samartzis D. Effectiveness of autologous chondrocyte implantation in cartilage repair of the knee: a systematic review of controlled trials. Osteoarthritis Cartilage. 2010;18:857–863.
Acknowledgments
We thank Daniela Drenkard for her technical assistance with histological and enzyme-linked immunosorbent assay analysis.
Author information
Authors and Affiliations
Corresponding author
Additional information
Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.
Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.
This work was performed at the University of Regensburg, Regensburg, Germany, and the Sporthopaedicum Regensburg, Regensburg, Germany.
About this article
Cite this article
Zellner, J., Angele, P., Zeman, F. et al. Is the Transplant Quality at the Time of Surgery Adequate for Matrix-guided Autologous Cartilage Transplantation? A Pilot Study. Clin Orthop Relat Res 471, 2852–2861 (2013). https://doi.org/10.1007/s11999-013-2958-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11999-013-2958-y