Microenvironment-Responsive Hydrogel with Photothermal, Antioxidant, and Neuroregenerative Functions for Diabetic Chronic Infectious Wound Healing

Abstract

Diabetic chronic infectious wounds (DCIW) remain a clinical challenge due to impaired vascularization, persistent infection, and excessive oxidative stress. Here, we report a multifunctional microenvironment-responsive hydrogel constructed via dynamic boronate ester crosslinking of hyaluronic acid derivatives (HA-PBA and HA-DA). The hydrogel incorporates polydopamine-magnesium nanoparticles (Mg@PDA) and mangiferin-loaded micelles (MIC@MF), endowing it with photothermal antibacterial, antioxidative, and neuroregenerative capacities. Mg@PDA exhibits strong photothermal conversion and releases Mg²⁺ to promote nerve repair, while MIC@MF scavenges reactive oxygen species and modulates inflammation. In vitro and in vivo studies demonstrate that this hydrogel effectively eliminates bacterial infection under NIR irradiation, reduces inflammation, enhances angiogenesis, and accelerates wound closure in diabetic rats. This multifunctional hydrogel provides a promising strategy for comprehensive DCIW management and highlights the potential of smart biomaterials in chronic wound therapy.