A mace-like heterostructural enriched injectable hydrogel composite for on-demand promotion of diabetic wound healing

Wound healing is a multifaceted process that involves hemostasis, inflammation, proliferation, and remodeling stages. Diabetic wounds affect the transition of the organized phases and result in delayed healing due to impaired angiogenesis, chronic inflammation, bacterial infection, and insufficient growth factors. Multifunctional heterostructural nanoparticles enriched minimally invasive hydrogels for on-demand procedural distribution to aid wound healing at various stages has become a promising strategy. Herein, silk fibroin-hyaluronic acid based injectable hydrogels incorporated with mace-like Au-CuS heterostructural nanoparticles (gAu-CuS HSs) were used to cure diabetic wounds. SF-HA and the rough surface of gAu-CuS HSs confer a synergistic hemostatic phase with a nano-bridge effect and rapidly close the wounds. During the inflammation stage, gAu-CuS HSs perform in-space resonance energy transfer under 808 nm laser irradiation which in return produces reactive oxygen species for bacterial destruction. The unusual mace-like rough structure of nanoparticles causes macrophage transfer to the M2 phenotype, regulates cytokine expression (interleukin 6, transforming factor-β1, interferon γ, and interleukin-10), promotes angiogenesis, and promotes cell multiplication and fibroblast emigration to the wound area during the proliferation and remodeling phase. Overall, the gAu-CuS HSs reinforced injectable hydrogel programmatically accelerates wound healing and could represent a versatile strategy for advanced diabetic wound healing.