Glucose microenvironment-primed nanocatalytic membranes for rapid bacterial eradication and infected diabetic wound regeneration

Abstract

A hyperglycemic microenvironment providing a favorable niche for bacterial infection and impairing cellular functions, resulting in delayed healing of infected diabetic wounds has become an increasingly severe complication. The prevailing therapeutic strategies primarily focus on the intrinsic antibacterial properties of biomaterials to facilitate subsequent wound healing, without addressing the high-glucose environment. To address this challenge, we developed glucose-responsive heterojunction (HJ) nanocatalytic membranes by integrating poly(lactic-co-glycolic acid) (PLGA) electrospun membranes with GaIn/Ag₂S HJs and glucose oxidase (GOx), aiming to promote the healing of infected diabetic wounds. In this system, GOx continuously consumes glucose to generate hydrogen peroxide (H₂O₂), which both suppresses bacterial metabolism and improves the cellular microenvironment. The GaIn/Ag₂S HJs catalyze the generated H₂O₂ into highly lethal hydroxyl radicals (˙OH) via a Fenton-like reaction, owing to their heterojunction structure, exhibit excellent photothermal effects (ΔT ≈ 25 °C within 10 min) and reactive oxygen species (ROS) production under near-infrared (NIR) irradiation, resulting in rapid synergistic antibacterial action (achieving >98% eradication of S. aureus and E. coli in vitro). Moreover, in vivo experiments demonstrate that the HJ's nanocatalytic membrane remodels chronic stagnant wounds into regenerative ones by eradicating bacteria, reducing inflammation, enhancing collagen deposition and promoting angiogenesis. This work presents a strategy that endows HJ nanocatalytic membranes with a glucose-triggered antibacterial effect, offering a promising avenue for chronic diabetic wound repair.