Sprayable sodium alginate/chitosan hydrogel with encapsulated ultrasmall Ga-Fe-cu NPs for synergistic oxidative stress regulation and photothermal therapy of bacteria-infected diabetic wounds

Diabetic ulcer is a common chronic wound, and also one of the typical complications of diabetes. The pathological environment of diabetic ulcer caused by high glucose levels is extremely complex, so the treatment for diabetic ulcers remains a challenge. As a proof of concept, we herein propose to use an ultra-small self-assembled gallic acid (Ga)‑iron (Fe)‑copper-(Cu) metal–phenolic nanoparticles (Ga-Fe-Cu NPs) based sprayable hydrogel for diabetic wound treatment. The Ga-Fe-Cu NPs is synthesized and then incorporated into sprayable hydrogel dressing with sodium alginate/chitosan quaternary ammonium salts to improve therapeutic compliance, culminating in the formulation of Ga-Fe-Cu NPs based sprayable hydrogel. The Ga-Fe-Cu NPs effectively scavenges reactive oxygen species (ROS), reduces oxidative stress, shortening the transition between inflammation and proliferative phase and maintaining redox balance. The Ga-Fe-Cu NPs-based sprayable hydrogel exhibits excellent mechanical properties. The sprayable hydrogel aided in alleviating the hypoxic conditions in bacteria-infected diabetic wound healing, killing bacteria, decreasing inflammation, promoting vascularization, alleviate hypoxia to achieve scarless repair of diabetic infected wound. Ultimately, the Ga-Fe-Cu NPs-based sprayable hydrogel demonstrates superior therapeutic efficacy, achieving 96.6% closure of infected wounds.