Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites

Stem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repai r. Insulin-like growth factor-I facilitates chondrogenesis of bone marrow-d erived stem cells in long-term culture and may enhance chondrogenesis in he aling cartilage lesions in vivo. This study examined the impact of insulin- like growth factor-I, gradually released from fibrin clots polymerized in s itu, on the recruitable stem-cell pool in a full-thickness critical cartila ge defect model. Twelve full-thickness 15-mm cartilage lesions in the femor opatellar articulations of six young mature horses were repaired by an inje ction of autogenous fibrin containing 25 mu g of human recombinant insulin- like growth factor-I or, in control joints, fibrin without the growth facto r. All horses were killed at 6 months, and cartilage repair tissue and surr ounding cartilage were assessed by histology, histochemistry, types I and I I collagen immunohistochemistry, types I and II collagen in situ hybridizat ion, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor-treated defects being more complet ely filled and securely attached to the subchondral bone. A moderately impr oved chondrocyte population, more columnar cellular organization, and bette r attachment to the underlying bone were evident on histological evaluation of growth factor-treated defects. Type-II procollagen mRNA was abundantly present in the deeper half of the treated sections compared with moderate m essage expression in control tissues. Immunolocalization of type-II collage n showed a preponderance of the collagen in growth factor-treated lesions, confirming translation of type-II message to protein. Composite histologic healing scores for treated defects were significantly improved over those f or control defects. DNA content in the cartilage defects was similar in tre ated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surroundin g and re:mote cartilage of the treated and control joints. The proportion o f type-II collagen significantly increased in growth factor-treated tissues . Fibrin polymers laden with insulin-like growth factor-I improved the hist ologic appearance and the proportion of type-II collagen in healing, full-t hickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.