Design of Hydrolytically Resorbable and Biocompatible Polyethylene Glycol Crosslinkers for Facile Control of Hydrogel Degradation

Hydrogels are increasingly important biomaterials due to their high biocompatibility and ability to mimic soft tissues. Many applications require biodegradable hydrogels, which can control release of encapsulated cells and molecules without requiring device removal from the body afterward. Hydrogels offering tunable, controlled degradability while also preserving cell viability or protein stability are increasingly in demand. Here, we have designed hydrolytically degradable polyethylene glycol (PEG) crosslinkers for use in hydrogels. Degradation is controlled by the crosslinkers' chemical structure, by introducing local hydrophobicity, steric hindrance or electron-withdrawing moieties to the vicinity of a degradable ester bond. Hydrogels made using these crosslinkers had gelation times from 1 to 22 minutes, storage moduli from 3 to 10 kPa, mesh size from 7 to 13 nm, and degradation times from 18 hours to 16 days. When reaction conditions were modified to achieve similar thiol deprotonation rates and gelation time, the differences in hydrogel initial properties were minimized, while differences in degradation rates remained. All crosslinkers were cytocompatible and supported high cell viability upon hydrogel encapsulation and upon cell exposure to hydrogel leachables and degradation products. The developed hydrogels will be useful in applications that require materials of controlled degradation, such as drug delivery or as matrices for cell encapsulation and transplantation.