Self-regulating and photothermal nanozyme enhanced hyaluronic acid/gelatin hydrogel with glucose triggered responsive release for diabetic wound healing.
Healing of diabetic wounds is severely hindered by a persistent vicious cycle of bacterial infection and metabolic disorders. Pathological microenvironments, characterized by high glucose levels and excessive reactive oxygen species (ROS), exacerbate chronic inflammation and impede the transition of macrophages toward a pro-healing phenotype. To address these challenges, we developed a multi-stimuli-responsive composite hydrogel platform (GHFA/Cu@TA) by integrating fulvic acid (FA) and copper-tannic acid nanozymes (Cu@TA NPs) into a dynamic covalent network composed of methacrylated gelatin (GelMA) and phenylboronic acid-modified hyaluronic acid (HA-PBA). This platform implements a self-feedback mechanism to restore metabolic homeostasis: glucose-triggered release of Cu@TA NPs effectively scavenges microenvironmental ROS to drive tissue microenvironment remodeling, thereby decelerating responsive hydrogel degradation upon homeostasis normalization to ensure synchronized on-demand drug delivery. Intelligently released FA promotes M2 macrophage polarization to reshape the immune microenvironment, while Cu@TA NPs achieve photothermal biofilm eradication under near-infrared (NIR) light. This "metabolic sensing-feedback regulation-homeostasis reconstruction" strategy offers a distinct therapeutic framework for addressing diabetic wound and contributes to the rational design of bioactive dressings with stimuli responsiveness.