280288 Synthesis and Characterization of an Aggrecan-Mimetic Graft Copolymer for Biomedical Applications
Aggrecan is an important component of articular cartilage due to its contribution to the high compressive modulus of cartilage and to joint lubrication. These contributions are a result of aggrecan’s nanoscale organization and the biochemical behavior of the structural components. Aggrecan is a bottlebrush structure comprised of a core protein and highly-charged glycosaminoglycan (GAG) side chains. The GAG side chains are hydrophilic and able to bind and stabilize growth factors. Osteoarthritis is associated with an imbalance in growth factors that maintain metabolic processes within cartilage. This imbalance causes degradation of the natural aggrecan and compromises the structural integrity of cartilage.
Our research group is developing a synthetic aggrecan-mimetic graft copolymer for use as a viscosupplement and as a carrier to stabilize and deliver therapeutic proteins. It is comprised of a dextran backbone with chondroitin sulfate side chains. The dextran is thiolated and then reacted with maleimide-activated chondroitin sulfate. The degree of substitution of dextran with chondroitin sulfate side chains can be adjusted using this strategy, allowing properties such as size, zeta potential, solution dynamics, and biochemical activity of these graft co-polymers to be studied.