Articular cartilage normally functions as a low-friction, load-bearing material over the course of a lifetime. The metabolic processes of collagen fibril formation, crosslinking, and matrix degradation maintain the cartilage matrix and allow for normal function. However, when adult cartilage is damaged, these intrinsic processes do not allow for spontaneous repair. Treatment therapies using either biological or synthetic grafts create tissue-host cartilage interfaces at which integration is desirable. However, these interfaces may remain in the long-term, ultimately leading to fibrillation and degeneration of the surrounding tissue. For complete repair, mechanical integration must occur between the host and graft surfaces. Integrative repair of cartilage was previously found to depend on collagen synthesis and maturation. β-aminopropionitrile (BAPN) treatment, which irreversibly blocks lysyl oxidase, inhibited the formation of collagen crosslinks, prevented development of adhesive strength, and caused a buildup of guanidine-extractable collagen crosslink precursors.

This dissertation established that existing matrix and matrix metabolism could be manipulated in order to enhance integrative cartilage repair. Specifically, the buildup of collagen crosslink precursor in the tissue during BAPN treatment may be useful for enhancing subsequent integrative repair. By pre-treating cartilage with BAPN, a quantity of newly-synthesized protein in a guanidine-extractable form was created that was converted to non-extractable form within 3 days of BAPN washout. Integrative repair between cartilage explants was similarly blocked with BAPN and recovered following BAPN removal. Similarly, formation of lysyl oxidase-mediated collagen crosslinks was blocked with BAPN treatment, and after removal of BAPN, crosslink levels recovered to that of non-treated samples within 4 days. Removal of glycasaminoglycans and collagen at the surface of cartilage explants lead to an enhancement of integrative repair. Combining pre-treatment with P-aminopropionitrile and removal of glycasaminoglycans had an additive effect on integrative repair. These results highlight some of the possibilities for enhancing integrative cartilage repair, through manipulation of the cartilage extracellular matrix.