Matrix turnover in human cartilage repair tissue in autologous chondrocyteimplantation

Objective. Autologous chondrocyte implantation (ACI) is a form of tissue en gineering that is being used increasingly to treat damaged articular cartil age. What happens at the graft site subsequent to the transplantation of ch ondrocytes beneath a periosteal flap has largely remained a matter of conje cture. We examined biopsy samples from the graft site using a panel of spec ific antibodies to investigate the cellular mechanisms involved and to dete rmine whether remodeling of the matrix occurs. Methods. Ten full-depth core biopsy samples were obtained from patients who had undergone ACI 9-30 months previously (ages 28-53 years), in addition t o 6 "control" biopsy samples. Cryosections were evaluated by standard histo logic examination using polarized light and immunohistochemistry. Antibodie s specific for type II collagen (ClIC1) were used, as well as antibodies ag ainst the C-propeptide of type II collagen (R160) and its denaturation prod uct (Col2-3/4m), as indicators of anabolism or catabolism. In addition, ant ibodies to the matrix proteinase-generated neoepitopes of the aggrecan core protein were used to demonstrate either aggrecanase (BC-3 and BC-13) or ma trix metalloproteinase (MMP) (BC-4 and BC-14) activity. Results. All biopsy samples stained for type II collagen, even in areas of fibrocartilaginous morphology. There was evidence of newly synthesized type II collagen in addition to denatured collagen. MMP and aggrecanase activit y on the proteoglycan population was evident, with aggrecanase being more a ctive in fibrocartilaginous areas. Conclusion. The findings of this study indicate that ACI is capable of not only cartilage repair but, in some cases, regeneration. This may be achieve d by the turnover and remodeling of an initial fibrocartilaginous matrix vi a enzymatic degradation and synthesis of newly formed type II collagen.