Photothermal and immunomodulatory chitosan composite hydrogel remodels the pathological microenvironment to...

The recalcitrant nature of chronic diabetic wounds stems from a complex pathological microenvironment characterized by bacterial biofilm formation, elevated reactive oxygen species (ROS) levels, and persistent inflammation. To address this challenge, we developed an L-arginine/ferrocene dual-functionalized chitosan hydrogel architecture (CLF@MZ) integrated with Ti₃C₂ MXene quantum dots (QDs) and ZIF-8 nanoparticles. This system aims to remodel the wound microenvironment through a multi-synergistic photothermal-biochemical strategy. Upon near-infrared irradiation, the MXene QDs generate localized hyperthermia to physically eradicate Staphylococcus aureus biofilms. Targeting the pathological microenvironment, CLF@MZ exhibits pH/ROS dual-responsive characteristics. In the acidic environment, ZIF-8 decomposes to release Zn²⁺; meanwhile, excessive ROS at the wound site is utilized to drive ferrocene-mediated conversion of L-arginine into NO. This cascade reaction not only consumes endogenous ROS to alleviate oxidative stress but also leverages the synergistic effects of the generated NO and Zn²⁺ to induce macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype. Subsequently, the anti-inflammatory microenvironment significantly promotes the neoformation of a mature vascular network and drives ordered collagen deposition. This synergistic system effectively overcomes the healing barriers of chronic diabetic wounds and achieves high-quality skin tissue repair, offering a novel microenvironment remodeling strategy for the treatment of complex chronic wounds.