Synthesis of an aggrecan mimic for osteoarthritis specific cartilage treatment

A preliminary event in osteoarthritic degradation of cartilage is the cleavage of aggrecan proteoglycan from the cartilage extracellular matrix (ECM). Aggrecan provides the dense negative charges which attract and retain water, providing cartilage with its characteristic compressive strength. In addition, the presence of aggrecan suppresses osteoarthritic degradation of the other main components (type II collagen and hyaluronan) of the cartilage ECM. Due to the importance of aggrecan in healthy cartilage tissue, this research focused on the development of a mimic of aggrecan. The aggrecan mimic was engineered to resist cleavage by the aggrecan degrading enzymes while utilizing natural cartilage components. Specifically, hyaluronan binding peptides were covalently bound to a functionalized form of chondroitin sulfate. In tests, the aggrecan mimic bound strongly to hyaluronan, acting as a crosslinker between multiple hyaluronan chains. The addition of the aggrecan mimic within collagen and hyaluronan gels significantly increased the strength of the gel. Treatment of hyaluronan solutions with the aggrecan mimic protected the hyaluronan from degradation. The results demonstrate the mimic\u27s ability to replicate the important functions of aggrecan, indicating that it is a plausible treatment for osteoarthritis