title: Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model.
abstract: This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.
authors.affiliation: Department of Surgery ,University Hospital Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Miot
authors.forename: W
authors.initials: W
authors.lastname: Brehm
authors.forename: S
authors.initials: S
authors.lastname: Dickinson
authors.forename: T
authors.initials: T
authors.lastname: Sims
authors.forename: A
authors.initials: A
authors.lastname: Wixmerten
authors.forename: C
authors.initials: C
authors.lastname: Longinotti
authors.forename: A P
authors.initials: AP
authors.lastname: Hollander
authors.forename: P
authors.initials: P
authors.lastname: Mainil-Varlet
authors.forename: I
authors.initials: I
authors.lastname: Martin
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002358:Cartilage, Articular / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry; D005260:Female; D006041:Goats; D006820:Hyaluronic Acid / Q000737:chemistry; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D016378:Tissue Transplantation / Q000379:methods; D014182:Transplantation, Autologous; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D006820:Hyaluronic Acid; D017886:Durapatite