Tuning Bulk Hydrogel Degradation by Simultaneous Control of Proteolytic Cleavage Kinetics and Hydrogel Network Architecture

摘要

Degradation of three-dimensional hydrogels is known to regulate many cellular behaviors. Accordingly, several elegant approaches have been used to render hydrogels degradable by cell-secreted proteases. However, existing hydrogel systems are limited in their ability to simultaneously and quantitatively tune two aspects of hydrogel degradability: cleavage rate (the rate at which individual chemical bonds are cleaved) and degraded hydrogel architecture (the network structure during degradation). Using standard peptide engineering approaches, we alter the proteolytic kinetics of the polymer cleavage rate to tune gel degradation time from less than 12 h to greater than 9 days. Independently, we vary the cross-linker functionality to achieve network architectures that initially have identical molecular weight between cross-links but upon degradation are designed to release between 5% and 100% of the polymer. Confirming the biological relevance of both parameters, formation of vascular-like structures by endothelial cells is regulated both by bond cleavage rate and by degraded hydrogel architecture. This strategy to fine-tune different aspects of hydrogel degradability has applications in cell culture, regenerative medicine, and drug delivery.