Glucose-triggered NIR-responsive photothermal antibacterial gelatin/dextran hydrogel simultaneously targeting the high glucose and infection microenvironment in diabetic wound

Abstract

The treatment of diabetic wounds with bacterial infection is a major challenge in the medical field. Microenvironment-responsive hydrogel dressings have shown great advantages, and photothermal antibacterial therapy is a potential antimicrobial strategy to avoid the generation of resistant bacteria. In this work, a glucose-triggered near-infrared (NIR)-responsive photothermal antibacterial hydrogel was designed and named GOGD based on a cascade reaction of glucose oxidation and polyphenol polymerization. The GOGD hydrogel was composed of gelatin and oxidized dextran (Odex), and loaded with a natural plant polyphenol gallic acid (GA) and the dual-biological enzymes (glucose oxidase GOx and horseradish peroxidase HRP). In response to the high glucose environment, GOx in the hydrogel decomposed glucose to produce hydrogen peroxide, which further catalyzed GA polymerization with HRP to produce poly-GA possessing NIR photothermal capability, thus endow GOGD hydrogel with glucose-triggered NIR responsive photothermal antibacterial property simultaneously targeting the high glucose and infection microenvironment in diabetic wounds. Furthermore, the GOGD hydrogel demonstrated good biocompatibility and a strong ability to scavenge reactive oxygen species (ROS), thereby protecting cells from oxidative damage. In a mouse model, this hydrogel not only displayed excellent hemostatic properties but also significantly enhanced the healing of Staphylococcus aureus-infected diabetic wounds by regulating inflammation and promoting angiogenesis. Therefore, the proposed GOGD hydrogel provides a novel approach to diabetic wound treatment by utilizing its unique glucose-responsive mechanism combined with integrated NIR-photothermal bacterial inhibition. This well-designed material holds great promise for significantly improving the healing of infected diabetic wounds and offers new prospects for future advancements in wound therapy.

Keywords: Antibacterial; Diabetic wound; Glucose-triggered; NIR responsive; Photothermal hydrogel.