A pain reflex-inspired hydrogel for refractory wound healing

Abstract

Promoting refractory wound healing remains a major therapeutic challenge. Here, a pain reflex-inspired hydrogel responsive to inflammatory microenvironmental conditions was developed and used to treat chronically infected diabetic wounds. This material was produced by reacting ε-Polylysine, which exhibits antibacterial properties, with oxidized hyaluronic acid to yield a dynamic Schiff base-crosslinked hydrogel capable of undergoing triggered dissociation in response to the lower microenvironmental pH found within refractory wounds. This hydrogel exhibited intrinsic antimicrobial activity owing to the incorporation of ε-Polylysine within the hydrogel network. To imbue the hydrogel with low pH-inducible anti-inflammatory and angiogenic activity, Schiff base bonds were used to capture Deferoxamine (DFO)-loaded amino-functionalized mesoporous silica nanoparticles (MSNs-NH2@DFO) on this hydrogel skeleton. The reflexive behaviors of the hydrogel make it ideally suited to facilitating wound healing in response to excessive local inflammation. The resultant intelligent hydrogel was highly biocompatible and exhibited robust antibacterial, anti-inflammatory, and pro-angiogenic activity in vitro and in vivo, thus effectively promoting the healing of chronically infected diabetic wounds. This novel hydrogel therefore holds great promise as a tool to promote refractory wound healing.