Stage-Adaptive Therapy for Infected Diabetic Wound Through Photothermal-Enhanced Sonocatalytic Antibacterial and Repair Activation.

Abstract

Diabetic chronic wounds remain nonhealing largely due to persistent bacterial infection, reactive oxygen species (ROS) accumulation, and impaired tissue remodeling. Although nanozyme-based wound healing strategies have been widely explored, most of them rely on multiple components to overcome multi-stage healing barriers, which often makes the system complex and difficult to achieve stage-adaptive functions. Here, we developed a simple and stage-adaptive platform (MF127) by integrating a thermosensitive hydrogel with high-content 1T phase-engineered MoSe₂ nanosheets (1T-MoSe₂) as the only active nanozyme component. The MF127 hydrogel exhibits injectability, sprayability, and rapid sol-gel transition, enabling conformal coverage of irregular wounds. Under near-infrared (NIR) and ultrasound (US) stimulation, MF127 acts as a sonosensitizer for ROS generation through photothermal-enhanced sonocatalytic effects, eliminating both planktonic bacteria and biofilms. Under non-stimulated conditions, MF127 exhibits antioxidant enzyme-like activity, reducing excessive oxidative stress and promoting M2-like macrophage phenotype modulation. Furthermore, MF127 also actively promotes wound healing through fibroblast activation and extracellular matrix (ECM) remodeling in vivo. This work presents a simplified, stage-adaptive platform that integrates antibacterial action, antioxidation, and regeneration to meet the needs of infected diabetic wound management.