Best of both worlds: Diels–Alder chemistry towards fabrication of redox-responsive degradable hydrogels for protein release

Abstract

Poly(ethylene glycol)-based redox-responsive hydrogels have been prepared via the Diels–Alder reaction between a furan-containing hydrophilic copolymer and a disulfide-containing bis-maleimide based crosslinker. Hydrogels containing varying amounts of the crosslinker were synthesized with 71–82% yield under mild and benign conditions. Variation in the redox-responsive crosslinker density allows tuning of their mechanical properties and their stability under a reducing environment. It was observed that increase in the amount of crosslinker decreases water uptake and reduces porosity of the hydrogels. Using rheological analysis it was deduced that an increase in temperature and crosslinker density speeds the gelation process and the presence of thiol-containing reducing agents leads to their degradation. Notably, the extent of protein release from these hydrogels could be tailored by varying the amount of redox-responsive disulfide moieties incorporated as crosslinkers during their fabrication.