Abstract

Diabetic oral ulcers represent a refractory clinical challenge characterized by a distinct pathological microenvironment that severely compromises mucosal regeneration. The healing process in these lesions is frequently stalled by a self-perpetuating cycle of persistent bacterial colonization, excessive reactive oxygen species accumulation, and sustained inflammatory responses. However, conventional hydrogel dressings predominantly offer passive physical protection, lacking the dynamic responsiveness required to actively coordinate infection control with microenvironmental remodeling. Here, we show the design of an injectable and self-healing polysaccharide hydrogel (DAP1) engineered with polydatin-loaded copper-doped zeolitic imidazolate framework-8 nanozymes for infection-responsive wound management. Our results demonstrate that this platform undergoes microenvironment-responsive degradation under simulated pathological conditions, enabling the release of therapeutic components that contribute to antibacterial activity, oxidative stress alleviation, and tissue repair. Furthermore, in a diabetic rat oral ulcer model, the hydrogel significantly accelerates mucosal healing and tissue reconstruction by effectively suppressing inflammatory interleukin-6 expression and promoting robust neovascularization. Collectively, this study presents a microenvironment-responsive therapeutic platform that integrates infection control with regenerative repair, offering a promising strategy for the clinical treatment of refractory diabetic oral wounds.