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.

促进难治性伤口愈合仍然是一个主要的治疗挑战。在这里，开发了一种受疼痛反射启发的对炎症微环境条件有反应的水凝胶，并用于治疗慢性感染的糖尿病伤口。这种材料是通过使具有抗菌特性的 ε-聚赖氨酸与氧化透明质酸反应产生动态席夫碱交联水凝胶，该水凝胶能够响应难治性伤口中发现的较低微环境 pH 值进行触发解离。由于在水凝胶网络中加入了 ε-聚赖氨酸，这种水凝胶表现出内在的抗菌活性。为了使水凝胶具有低 pH 诱导的抗炎和血管生成活性，₂ @DFO）在这个水凝胶骨架上。水凝胶的反射行为使其非常适合促进伤口愈合以应对过度的局部炎症。由此产生的智能水凝胶具有高度的生物相容性，并在体外和体内表现出强大的抗菌、抗炎和促血管生成活性，从而有效促进慢性感染糖尿病伤口的愈合。因此，这种新型水凝胶作为促进难治性伤口愈合的工具具有很大的前景。