A glucose-responsive hydrogel delivering gallium-luteolin nanocomplexes for infected diabetic wound repair via antibacterial and oxidative-inflammatory regulation.

Abstract

Diabetic wounds are frequently complicated by persistent bacterial infection, excessive reactive oxygen species (ROS) accumulation, and dysregulated inflammation, which collectively reinforce a hostile microenvironment that delays tissue repair. Herein, we report a glucose-responsive hydrogel platform (GL@PGB) for local delivery of gallium-luteolin nanocomplexes (GL NCs), designed to couple Ga-associated antibacterial metal-homeostasis perturbation with luteolin-associated oxidative-inflammatory regulation. In this system, the PVA/guar gum/borax (PGB) hydrogel functions as a hemostatic and wound-adaptive delivery matrix, enabling local retention and glucose-accelerated release of GL NCs under hyperglycemic conditions. The released GL NCs suppressed bacterial growth and disrupted established biofilms, and transcriptomic analysis suggested perturbation of metal-ion homeostasis and genetic information-processing pathways in S. aureus. Concurrently, GL@PGB reduced intracellular ROS accumulation and promoted macrophage polarization toward a reparative phenotype in vitro. In an S. aureus-infected diabetic full-thickness wound model, GL@PGB reduced bacterial burden, alleviated inflammatory responses, and promoted collagen deposition and angiogenesis, thereby improving wound repair. These results suggest that GL@PGB may serve as a glucose-responsive local delivery system for disrupting bacterial metal homeostasis while reshaping the infection-ROS-inflammation microenvironment.