ECM-inspired GHTA@CuS nanocomposite hydrogel for early skin-to-muscle tissue repair under 1064 nm photothermal stimulation

Full-thickness skin-to-muscle injuries remain difficult to repair because restoration of multiple tissue layers requires coordinated control of inflammation and extracellular matrix (ECM) remodeling. In the current study, an ECM-inspired nanocomposite hydrogel (GHTA@CuS) was developed as a localized 1064 nm photothermal interface for early skin-to-muscle tissue repair. The hydrogel consisted of a gelatin–hyaluronic acid matrix containing tannic acid-stabilized Ag nanoparticles and CuS nanoparticles. In vitro testing demonstrated low hemolytic activity and short-term cytocompatibility, and ex vivo photothermal assessment supported the selection of 0.5 W/cm 2 for 1 min for in vivo treatment. In a rat skin-to-muscle wound model, the combined treatment with GHTA@CuS hydrogel and 1064 nm laser irradiation reduced the day-7 wound area to 0.02 ± 0.01 cm 2 compared with the untreated and laser-only groups and decreased neutrophil infiltration. Histological analysis revealed improved early organization and a greater area of muscle-like tissue. At day 7, the combined treatment was associated with increased ERK and AKT phosphorylation and changes in the expression of Ki67, COL1, and COL3. These findings support GHTA@CuS as a localized photothermal biomaterial interface for enhancing early repair of skin-to-muscle injuries.