Enzymatically crosslinked hydrogels based on linear poly(ethylene glycol) polymer: performance and mechanism

Abstract

In the present work, a horseradish peroxidase (HRP)-catalyzed hydrogel based on a double-end tyramine conjugated linear poly(ethylene glycol) (TA-PEG-TA) polymer is developed. The TA-PEG-TA is designed to act as not only a substrate of HRP, but also a macromonomer. We find that, the linear structure is sufficient to form robust hydrogels, and therefore it greatly simplifies the polymer architecture applicable to HRP-catalyzed hydrogels, which are always based on graft or branched polymers. The gelation time and strength of the TA-PEG-TA hydrogels can be well tuned by varying the concentrations of the polymer and HRP as well as the molar ratios of H₂O₂ to TA groups. The gelation mechanism is clarified by exploring the HRP-catalyzed reaction of a single-end tyramine conjugated poly(ethylene glycol) monomethyl ether (mPEG-TA). The multiple active hydrogen atoms (in the hydroxyl group and the o-position) of phenol moieties can be oxidized by H₂O₂via HRP catalysis, which should be responsible for the generation of mPEG-TA oligomers and the gelation of TA-PEG-TA. This study provides a new strategy for the design of injectable enzymatically crosslinked hydrogels.