Construction of pH-Sensitive Multifunctional Hydrogel with Synergistic Anti-Inflammatory Effect for Treatment of Diabetic Wounds.

A sustainable inflammatory response is a significant obstacle for diabetic wound care. In this study, the pH-sensitive multifunctional hydrogel ODex/BSA-Zn was fabricated via a Schiff base and coordination force for the first time. The hydrogel consisted of oxidized dextran (ODex), bovine serum albumin (BSA), and zinc ions (Zn) in the absence of an additional crosslinking agent. The hydrogel showed excellent mechanical stability, fast self-healing ability, and significant anti-inflammatory effects, as demonstrated by the formation of dynamic covalent bonds between the aldehyde group (-CHO) of ODex and the amino group (-NH) of BSA via the Schiff base reaction, as well as the metal-ion coordination reaction of Zn with the imidazole ring of BSA. In a diabetic mouse full-thickness cutaneous defect wound model, the ODex/BSA-Zn hydrogel could effectively inhibit the inflammatory response and increase collagen deposition, thereby accelerating the transition of macrophage M1 to M2 and promoting wound closure. This study offers a promising therapeutic approach for managing long-term diabetic ulcers.