Injectable, self-healing and wound microenvironment responsive hydrogel for photothermal, chemodynamic, and hydrogen sulfide gas synergistic therapy of the infected diabetic wound healing.

Bacteria-infected diabetic wounds represent a significant global healthcare concern. Uncontrolled bacterial infection results in excessive production of reactive oxygen species (ROS), sustained inflammatory responses and immunosuppression, which seriously impede healing processes. Conventional antibiotic treatments are often inadequate for addressing these challenges and concurrently pose the risk of promoting bacterial resistance. Here, an injectable, self-healing, and wound microenvironment-responsive hydrogel (HA-PBA/OAP/FeS@PC) with photothermal effects, chemodynamic therapy, and hydrogen sulfide gas therapy is developed for rapid bacterial eradication and treatment of infected diabetic wounds. Phycocyanin-functionalized FeS NPs (FeS@PC NPs) were introduced into phenylboronic acid (PBA) modified hyaluronic acid (HA-PBA)/oxidized aloe polysaccharide (OAP) Schiff-base double crosslinked hydrogel. This HA-PBA/OAP/FeS@PC hydrogel demonstrated dynamic responsiveness to pH, glucose, and ROS levels, alongside superior injectability, self-healing ability, and tissue adhesion. Furthermore, upon 660 nm laser irradiation, HA-PBA/OAP/FeS@PC hydrogel exhibits a photothermal effect coupled with the generation of hydroxyl radicals through the Fenton reaction and the release of hydrogen sulfide, effectively eradicating bacteria while alleviating inflammatory responses. In a diabetic full-thickness skin defect infection model, HA-PBA/OAP/FeS@PC hydrogel significantly promotes wound repair by modulating inflammatory responses, enhancing collagen matrix deposition, and stimulating neovascularization, thereby accelerating wound closure. Overall, this work presents an innovative bacterial response strategy for achieving in situ multiple antibacterial effects in infected tissues and presents a promising therapeutic approach for treating infected diabetic wounds.