Injectable and self-healing dual-network chitosan/hyaluronic acid/polypeptide (CHP) antibacterial hydrogels for wound healing

Skin wound healing faces challenges of bacterial infection and environmental stimulation, and hence the design of biocompatible wound dressings with antibacterial and self-healing abilities is promising. Herein, we report the design and synthesis of bioactive composite hydrogels (CHP) with chitosan (CS), hyaluronic acid (HA), and polypeptide (PP). Ascribing to dynamic molecular cross-linking, the fabricated CHP hydrogels exhibit good stability, excellent biocompatibility, injectability, self-healing ability, and antimicrobial activity. Microscopic analysis indicates that the CHP hydrogels maintain a 3D porous dual-network structure, and the porosity of hydrogels is related to the content of PP as the reinforcement. Antimicrobial evaluation of the CHP hydrogels demonstrates significant efficacy against E. coli and S. aureus, with improved performance at higher PP concentration. Furthermore, the hydrogels show enhanced cytocompatibility, minimal hemolysis, and improved in vitro cell proliferation. The tests with wound mouse models indicate that the CHP hydrogels can accelerate wound healing effectively, enhance angiogenesis, and promote tissue regeneration. Histological evaluation confirms complete epidermal regeneration, improved collagen deposition, and increased protein expression. The designed CHP hydrogels present potential clinical applications as a wound dressing material to meet the needs of rapid and effective wound healing.