PEG-based hydrogels as chondrocyte carriers for tissue engineered cartilage: Controlling extracellular matrix evolution and integration with native cartilage

Mature articular cartilage is an avascular tissue with limited ability for self-repair. Tissue engineering techniques have the potential to improve the outcome of surgical repair procedures on damaged or diseased cartilage. We are particularly interested in controlled degradation of poly(ethylene glycol) (PEG) hydrogels, and its effects on the distribution of matrix molecules, maintenance of encapsulated chondrocyte morphology, and mechanical functionality in the bulk of regenerated cartilaginous matrix and at interfaces with native cartilage tissue. These effects have been investigated by careful examination of degradation profiles in PEG gels with a variety of macromonomer chemistries, and chondrocyte encapsulation studies in which the evolution of cartilaginous matrix was monitored with culture time. Gels with bimodal degradation profiles were synthesized by copolymerizing a slow degrading PEG dimethacrylate (PEG-DM) and a PEG macromonomer with fast degrading, hydrolytically cleavable poly(lactic acid) blocks. Degradation studies investigated a range of copolymer ratios that resulted in nearly complete gel degradation, maximizing diffusion of matrix molecules while maintaining a minimum number of crosslinks to maintain the swollen gel network. Copolymer gels showed better maintenance of proper chondrocyte morphology and function than fast degrading homopolymer gels, and facilitated better matrix distribution than slow degrading homopolymer gels. Understanding the important differences between copolymer gels and slow degrading homopolymer gels enabled experiments to investigate the effects of matrix accumulation and distribution on nondestructive ultrasonic propagation and interfacial integration of regenerated matrix with native cartilage tissue.; Control over hydrogel degradation was further improved by characterization studies of an exogenously triggerable, enzymatically degradable PEG gel with short polycaprolactone blocks. The mass loss in these gels was described with a bulk degradation model incorporating enzyme kinetics and a statistical interpretation of structural changes upon degradation. This model was found to be applicable for caprolactone reaction rates that are relatively lower than enzyme diffusion rates, and was applied in the design of cell encapsulation studies to investigate the effects of triggered degradation on matrix evolution.; This thesis presents new understanding of PEG gel degradation and the consequential effects on characterizations of cartilaginous matrix evolution, providing background for a wide range of future studies of cartilage regeneration.