Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full‐ and partial‐thickness cartilage defects in an equine model

Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on cartilage repair in full‐thickness lesions is scant and no data are available on ACI in partial‐thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial‐ and full‐thickness cartilage defects in the equine model. Paired cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial‐ and full‐thickness cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial‐thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding cartilage improved. DNA and PG content of grafted partial‐thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce cartilage repair. This study indicated implantation of chondrocytes to cartilage defects improved healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall cartilage healing scores. Use of ACI in the more challenging partial‐thickness defects also improved histologic indices and biochemical content. The equine model of cartilage healing closely resembles cartilage repair in man, and results of this study confirm cell persistence and improved early cartilage healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011

[1]  C. Probst,et al.  Use of a Type I/III Bilayer Collagen Membrane Decreases Reoperation Rates for Symptomatic Hypertrophy after Autologous Chondrocyte Implantation , 2009, The American journal of sports medicine.

[2]  A. Gomoll,et al.  Repair of Large Chondral Defects of the Knee with Autologous Chondrocyte Implantation in Patients 45 Years or Older , 2008, The American journal of sports medicine.

[3]  T. Briggs,et al.  Autologous chondrocyte implantation: where do we stand now? , 2008, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[4]  W. Dunn,et al.  Treatment of Focal Articular Cartilage Defects in the Knee , 2008, Clinical orthopaedics and related research.

[5]  Lars Engebretsen,et al.  A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. , 2007, The Journal of bone and joint surgery. American volume.

[6]  A. Nixon,et al.  Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  A J Nixon,et al.  Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model. , 2007, The Journal of bone and joint surgery. British volume.

[8]  P. Lavigne,et al.  Autologous Chondrocyte Implantation: Superior Biologic Properties of Hyaline Cartilage Repairs , 2007, Clinical orthopaedics and related research.

[9]  C. W. Mcllwraith,et al.  Effects of Calcified Cartilage on Healing of Chondral Defects Treated with Microfracture in Horses , 2006, The American journal of sports medicine.

[10]  C. Hidaka,et al.  Biochemical and Biomechanical Properties of Lesion and Adjacent Articular Cartilage after Chondral Defect Repair in an Equine Model , 2005, The American journal of sports medicine.

[11]  U. Windberger,et al.  Marrow stimulation and chondrocyte transplantation using a collagen matrix for cartilage repair. , 2005, Osteoarthritis and cartilage.

[12]  Freddie H. Fu,et al.  Clinical Outcome of Autologous Chondrocyte Implantation at 5 Years in US Subjects , 2005, Clinical orthopaedics and related research.

[13]  C. Archer,et al.  Current strategies for articular cartilage repair. , 2005, European cells & materials.

[14]  J. Buckwalter,et al.  The impact of osteoarthritis: implications for research. , 2004, Clinical orthopaedics and related research.

[15]  M. Brittberg,et al.  Articular Cartilage Engineering with Autologous Chondrocyte Transplantation , 2003 .

[16]  A. Grodzinsky,et al.  Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  F. Luyten,et al.  Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[18]  J. Buckwalter.  Articular cartilage injuries. , 2002, Clinical orthopaedics and related research.

[19]  G. Lust,et al.  Insulin-like growth factor-I enhances cell-based repair of articular cartilage. , 2002, The Journal of bone and joint surgery. British volume.

[20]  M. Brittberg,et al.  Autologous chondrocytes used for articular cartilage repair: an update. , 2001, Clinical orthopaedics and related research.

[21]  M. Spector,et al.  Autologous chondrocyte implantation in a canine model: change in composition of reparative tissue with time , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[22]  E. L. Cain,et al.  Treatment algorithm for osteochondral injuries of the knee. , 2001, Clinics in sports medicine.

[23]  D. W. Jackson,et al.  Cartilage Substitutes: Overview of Basic Science and Treatment Options , 2001, The Journal of the American Academy of Orthopaedic Surgeons.

[24]  D. W. Jackson,et al.  Spontaneous Repair of Full-Thickness Defects of Articular Cartilage in a Goat Model: A Preliminary Study , 2001, The Journal of bone and joint surgery. American volume.

[25]  T. Spector,et al.  Osteoarthritis: New Insights. Part 1: The Disease and Its Risk Factors , 2000, Annals of Internal Medicine.

[26]  M. Brittberg,et al.  Two- to 9-Year Outcome After Autologous Chondrocyte Transplantation of the Knee , 2000, Clinical orthopaedics and related research.

[27]  J. Buckwalter.  Evaluating methods of restoring cartilaginous articular surfaces. , 1999, Clinical orthopaedics and related research.

[28]  S. O’Driscoll,et al.  Articular cartilage regeneration using periosteum. , 1999, Clinical orthopaedics and related research.

[29]  A. Nixon,et al.  Enhanced repair of extensive articular defects by insulin‐like growth factor‐I‐laden fibrin composites , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  C. Helmick,et al.  Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. , 1998, Arthritis and rheumatism.

[31]  A. Nixon,et al.  Chondrocyte-laden collagen scaffolds for resurfacing extensive articular cartilage defects. , 1995, Osteoarthritis and cartilage.

[32]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[33]  R J Todhunter,et al.  Chondrocyte‐fibrin matrix transplants for resurfacing extensive articular cartilage defects , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[34]  G. Lust,et al.  Phenotype and biological activity of neonatal equine chondrocytes cultured in a three-dimensional fibrin matrix. , 1994, American journal of veterinary research.

[35]  R. Salter,et al.  Biological resurfacing of full-thickness defects in patellar articular cartilage of the rabbit. Investigation of autogenous periosteal grafts subjected to continuous passive motion. , 1992, The Journal of bone and joint surgery. British volume.

[36]  A. Grodzinsky,et al.  Fluorometric assay of DNA in cartilage explants using Hoechst 33258. , 1988, Analytical biochemistry.

[37]  D. Buttle,et al.  Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. , 1986, Biochimica et biophysica acta.

[38]  W. Akeson,et al.  The Repair of Large Osteochondral Defects An Experimental Study in Horses , 1972, Clinical orthopaedics and related research.

[39]  David W. Levine,et al.  Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. , 2009, The American journal of sports medicine.

[40]  S. Gabriel,et al.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. , 2008, Arthritis and rheumatism.

[41]  Atlanta,et al.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. , 2008, Arthritis and rheumatism.

[42]  D. Frisbie,et al.  A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee , 2006, Veterinary and Comparative Orthopaedics and Traumatology.

[43]  Albert C. Chen,et al.  Biomechanical assessment of tissue retrieved after in vivo cartilage defect repair: tensile modulus of repair tissue and integration with host cartilage. , 2006, Journal of biomechanics.

[44]  M. Brittberg,et al.  Articular cartilage engineering with autologous chondrocyte transplantation. A review of recent developments. , 2003, The Journal of bone and joint surgery. American volume.

[45]  Michael Sittinger,et al.  The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. , 2003, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[46]  Timothy E. McAlindon,et al.  Osteoarthritis: New Insights , 2002 .

[47]  T. Bryant,et al.  Autologous chondrocyte implantation for chondral defects of the knee: indications and technique. , 2002, The journal of knee surgery.

[48]  M. Spector,et al.  Autologous chondrocyte implantation. , 2001, Clinical privilege white paper.

[49]  M. Hurtig,et al.  Effects of lesion size and location on equine articular cartilage repair. , 1988, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.