Injectable Nanocomposite\nHydrogel with Synergistic\nBiofilm Eradication and Enhanced Re-epithelialization for Accelerated\nDiabetic Wound Healing

Diabetic wounds remain a critical clinical challenge\ndue to their\nharsh microenvironment, which impairs cellular function, hinders re-epithelialization\nand tissue remodeling, and slows healing. Injectable nanocomposite\nhydrogel dressings offer a promising strategy for diabetic wound repair.\nIn this study, we developed an injectable nanocomposite hydrogel dressing\n(HDL@W379) using LAP@W379 nanoparticles and an injectable hyaluronic\nacid-based hydrogel (HA-ADH-ODEX). This dressing provided a sustained,\npH-responsive release of W379 antimicrobial peptides, effectively\nregulating the wound microenvironment to enhance healing. The HDL@W379\nhydrogel featured multifunctional properties, including mechanical\nstability, injectability, self-healing, biocompatibility, and tissue\nadhesion. <i>In vitro</i>, the HDL@W379 hydrogel achieved\nsynergistic biofilm elimination and subsequent activation of basal\ncell migration and endothelial cell tube formation. Pathway analysis\nindicated that the HDL@W379 hydrogel enhances basal cell migration\nthrough MEK/ERK pathway activation. In methicillin-resistant Staphylococcus aureus (<i>MRSA</i>)-infected\ndiabetic wounds, the HDL@W379 hydrogel accelerated wound healing by\ninhibiting bacterial proliferation and promoting re-epithelialization,\nregenerating the granulation tissue, enhancing collagen deposition,\nand facilitating angiogenesis. Overall, this strategy of biofilm elimination\nand basal cell activation to continuously regulate the diabetic wound\nmicroenvironment offers an innovative approach to treating chronic\nwounds.