Carboxymethyl cellulose-collagen XVII composite hydrogel reprograms the immune-oxidative microenvironment for enhanced skin wound repair

. In a murine full-thickness dorsal wound model, topical CMC/COL17 application accelerated wound closure, yielded a thicker and more continuous neoepidermis, improved collagen organization, and induced the early appearance of hair follicle-like structures. RNA sequencing of wound tissue showed suppression of inflammation- and chemotaxis-related pathways, including IL-17 and TNF signaling, with concurrent enrichment of cell-matrix interaction, cytoskeleton, and tissue development pathways. Consistently, at the cellular level, COL17 polarized macrophages toward an M2-like phenotype, suppressed pro-inflammatory cytokine expression, and reduced intracellular reactive oxygen species (ROS) in both fibroblasts and macrophages. Collectively, these results indicate that a simple CMC/COL17 hydrogel can couple a widely used cellulose carrier with a niche-relevant ECM protein to provide both anti-inflammatory and pro-regenerative effects, thus positioning COL17 as an active regulator in wound repair instead of solely a structural basement membrane component.