Chemically triggered rapid degradation of tetraPEG gels crosslinked with a diacylhydrazine-containing cross-linker

Abstract

Controlling the degradability of cross-linked polymer materials is essential for designing soft materials that combine structural stability during use with on-demand disassembly at the desired time. Herein, we report a chemically degradable tetra-armed poly(ethylene glycol) (tetraPEG) hydrogel cross-linked with a newly designed diacylhydrazine-containing crosslinker. The cross-linker incorporates cysteine residues as reactive sites and a diacylhydrazine moiety as a chemically cleavable unit that undergoes rapid scission in response to sodium hypochlorite (NaClO). The cross-linker exhibited efficient reactivity toward maleimide compounds through thiol-maleimide click chemistry, enabling the formation of a stable tetraPEG network from tetraPEG bearing maleimide end groups. Upon treatment with NaClO, the tetraPEG gel underwent rapid degradation in a concentration-dependent manner. Microscopic analysis further revealed that the squared diameter decreased nearly linearly with time, consistent with a diffusion-limited surface erosion process. The degraded polymer component was almost identical to the original tetraPEG precursor, indicating that network cleavage occurred selectively at the diacylhydrazine units to release soluble tetraPEG chains. These results demonstrate that diacylhydrazine-based cross-linking provides an effective strategy for constructing robust yet chemically degradable hydrogel networks with controllable degradation behavior.