Cur-EGCG-Fe coordination nanoparticle-functionalized gelatin hydrogel biointerfaces for antibacterial and inflammatory microenvironment-regulatory wound repair

Bacterial colonization, oxidative stress, and persistent inflammation jointly impair infected wound healing. Here, curcumin (Cur)-containing epigallocatechin-3-gallate (EGCG)-Fe coordination nanoparticles (CEF NPs) were incorporated into gelatin through Fe3 +-mediated interactions. The resulting hydrogels (Gel/CEF) exhibited injectability, self-healing behavior, a porous structure, and favorable hemocompatibility and cytocompatibility. Under 808 nm near-infrared (NIR) irradiation, Gel/CEF3 generated heat and reduced viable Staphylococcus aureus and Escherichia coli in vitro. Gel/CEF3 extracts decreased intracellular reactive oxygen species and lipid peroxidation in H2O2-challenged fibroblasts. They also preserved superoxide dismutase activity and improved cell migration. In lipopolysaccharide-stimulated macrophages, Gel/CEF3 extracts decreased the proportion of CD86-positive cells and increased CD206-positive cells, supporting a shift toward an M2-like phenotype. Transcriptomic analysis revealed downregulation of TNF and NOD-like receptor signaling-associated gene sets. Protein analyses further showed reduced levels of NLRP3, ASC, IL-1β, and GSDMD, supporting attenuation of an NLRP3-associated inflammatory profile. In S. aureus-infected full-thickness wounds, Gel/CEF3 reduced culturable bacterial burden during the early treatment phase and accelerated wound closure, re-epithelialization, collagen deposition, and angiogenesis. These effects were more pronounced with NIR treatment and were accompanied by improvements in local oxidative stress and inflammatory markers. Major-organ histology and serum biochemical assessments revealed no apparent systemic toxicity at day 14. These findings support Gel/CEF as a metal-phenolic hydrogel platform that combines NIR-responsive antibacterial activity with redox regulation and macrophage-associated inflammatory modulation for S. aureus-infected wound repair.