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

GL@PGB enabled glucose-responsive local delivery of gallium–luteolin nanocomplexes. • GL NCs acted as releasable coordination nanounits for antibacterial and oxidative-inflammatory regulation. • GL@PGB inhibited bacterial growth and disrupted established biofilms. • GL@PGB reduced intracellular ROS accumulation and favored macrophage transition toward a reparative phenotype. • GL@PGB reshaped the infection–ROS–inflammation microenvironment to improve infected diabetic wound repair. 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. Download: Download high-res image (240KB) Download: Download full-size image