A tissue engineering strategy for integrative cartilage repair

Abstract

Tissue engineering for cartilage repair is a promising approach for improving the healing of articular defects, as biomaterials and growth factors can be supplied directly to a focal lesion. However, integrating neo-tissue with native cartilage to provide mechanical and biological continuity at the interface remains a challenge due to the limited regenerative capacity of the tissue. In an effort to improve integration, enzyme treatments were investigated as a means of functionally grafting engineered tissue to native tissue. Using an in vitro model of defect repair, this study develops a repair strategy that employs both a hydrogel (KLD) functionalized with HB-IGF-1 and an enzyme pre-treatment of the cartilage surrounding a defect to provide local delivery of the pro-anabolic factor and allow for functional integration of cartilage neo-tissue. Results indicate that the rate of proteoglycan synthesis was elevated in cartilage explants into which KLD pre-mixed with HB-IGF-1 had been cast; both the explants that had received the enzyme pre-treatment and those that were left untreated had a two-fold increase compared to the explants exposed to non-functionalized KLD. Similarly, GAG content was favorably elevated in the chondrocyte-seeded gels exposed to the growth factor. While GAG was depleted selectively within the inner annulus of the explants receiving the pre-treatment, no negative effect was observed on the rate of proteoglycan synthesis or GAG content compared to that in explants left untreated. Further, mechanical tests suggest that the combination of KLD functionalized with HB-IGF- 1 together with an enzyme pre-treatment is able to increase interfacial strength between engineered tissue and native matrix. Taken together, a repair strategy combining an enzyme pre-treatment of a defect with a peptide hydrogel functionalized with pro-anabolic HB-IGF-1, as developed in this study, is a promising approach for enhancing integration. Stimulating the surrounding tissue with the growth factor and allowing for functional integration of newly synthesized matrix promotes continuity at the interface between new and native tissue, ultimately improving the overall quality of repair.