Bioinspired glycocalyx-mimetic hydrogel enabling photothermal-amplified therapeutic cascade for chronic wound healing

Regeneration and repair of chronic wounds are still clinical challenges due to the imbalance of the microenvironment caused by biofilm formation by multidrug-resistant bacteria and excessive accumulation of reactive oxygen species. Here, a multifunctional OACPPIh hydrogel is developed using modified dextran (OD-AB), chitosan derivatives (CMCS-PEI), polydopamine (PDA), and iron-hydrated nanoparticles (Ih NPs). The hydrogel not only effectively combats bacterial infections and eradicates biofilms through the bacterial capture capability of OD-AB and the cationic/photothermal synergistic effects of CMCS-PEI/PDA, but also utilizes the photothermal-enhanced nanozyme activity of Ih NPs to simultaneously scavenge reactive oxygen species and generate oxygen, thereby remodeling the hypoxic microenvironment. This multi-mechanism synergistic action provides a comprehensive solution for chronic wound management. In vivo assessment conducted in a diabetic murine model achieved 94.95 % wound closure efficacy within a 15-day therapeutic regimen, with histopathological and immunofluorescence analyses corroborating its marked therapeutic potential in augmenting tissue regeneration and re-epithelialization. This integrated strategy provides a translatable solution for microenvironment-tailored chronic wound therapy materials.