pH/glucose dual-responsive protein-based hydrogels with enhanced adhesive and antibacterial properties for diabetic wound healing

Designing a wound dressing that offers excellent antibacterial properties while providing dual pH/glucose responsiveness for diabetic wound healing remains a considerable challenge. Herein, a 3D cross-linked native protein hydrogel was constructed through a Schiff base reaction based on -NH₂ in paramyosin (PM) and -CHO in oxidized dextran (ODA) under mild conditions. Within the hydrogel, both amikacin and glucose oxidase were encapsulated during gelation. The resulting hydrogel exhibited favorable rheological properties, featuring self-healing, antibacterial activity, tissue adhesiveness, and excellent biocompatibility. Notably, the hydrogel demonstrated excellent pH/glucose dual-responsive properties. In infected wounds, the Schiff base bonds dissociated due to low pH, while in uninfected wounds with high blood glucose levels, the encapsulated glucose oxidase was functional, which also lowered the local pH level and dissociated the Schiff base bonds. Furthermore, the hydrogel quickly achieved pH/glucose dual responsiveness, leading to increased amikacin release to reduce bacterial invasion, alleviate oxidative stress, promote re-epithelialization and collagen deposition, and eventually accelerate diabetic wound healing. Collectively, the constructed hydrogel offers brand-new viewpoints on glucose-responsive biomaterials for diabetic wound therapy.