Self-Reinforcing Nanozyme-Integrated Microneedles Orchestrate Cascaded Regulation of ROS Homeostasis for Infected Wound Healing

Abstract

Chronic diabetic wounds represent a severe complication of diabetes mellitus and a prototypical form of chronic nonhealing wounds, characterized by biofilm-associated infection, persistent inflammation, and impaired angiogenesis. Herein, a multifunctional microneedle platform incorporating cationic chitosan-coated ruthenium dioxide nanozymes (RuO2@QCS NPs), termed RuO2@QCS-MN, is developed to accelerate diabetic wound healing through microenvironment reprogramming. This integrated system combines photothermal antibacterial activity, reactive oxygen species (ROS) scavenging, and in situ oxygen generation to coordinately regulate the pathological milieu of infected wounds. The microneedles effectively penetrate bacterial biofilms and deliver nanozymes to bacteria-enriched regions, enabling efficient yet mild photothermal antibacterial therapy. Meanwhile, RuO2@QCS NPs exhibit catalase-like activity, catalyzing endogenous hydrogen peroxide into oxygen, thereby enhancing nanozyme diffusion, alleviating oxidative stress, modulating inflammatory responses, and promoting macrophage polarization. Simultaneous oxygen generation may alleviate hypoxia and promote angiogenic responses. Both in vitro and diabetic in vivo models demonstrate efficient bacterial elimination, inflammation suppression, and enhanced re-epithelialization and neovascularization, ultimately accelerating wound repair. This work establishes a highly integrated nanozyme-enabled therapeutic paradigm for the localized treatment of infected diabetic wounds.