A drug-free hyaluronic acid and modified carboxymethyl cellulose double cross-linked multifunctional hydrogel wound...

Damaged skin barriers create a vulnerable interface for pathogen colonization, and subsequent pathogen invasion significantly delays tissue repair. Hydrogel dressings have been widely applied in clinical wound management as an effective treatment modality. However, prolonged reliance on antibiotics can induce allergic reactions and exacerbate the risk of drug resistance. Therefore, the development of natural hydrogel dressings that are biocompatible, mechanically robust, and antibiotic-free remains a critical technological challenge. In this study, OHA/PVA/HCMC@NaHCO₃ composite hydrogels were prepared using oxidized hyaluronic acid (OHA), hydrazine-containing carboxymethylcellulose (HCMC), polyvinyl alcohol (PVA), and sodium bicarbonate (NaHCO₃) as the primary components. The high aldehyde content of OHA chemically crosslinked with hydrazine-containing HCMC formed acylhydrazine bonds, while physical crosslinking with PVA and NaHCO₃ formed hydrogen bonds. The incorporation of PVA enhanced the mechanical strength of the hydrogel without compromising its high liquid absorption capacity. NaHCO₃ imparts notable antibacterial and antioxidant properties to the composite hydrogel. These effects act synergistically with HA, promoting wound healing while preserving HA's intrinsic skin repair functionality. It exhibited potent antibacterial activity against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In vitro analyses confirmed good biocompatibility and the ability to promote fibroblast proliferation and migration. In a rat full-thickness skin wound model, the OHA/PVA/HCMC@NaHCO₃ hydrogel significantly accelerated wound closure, promoted epidermal regeneration, reduced inflammation, and enhanced collagen deposition and tissue remodeling. The drug-free, readily prepared OHA/PVA/HCMC@NaHCO₃ composite hydrogels demonstrate promising potential for clinical application in the treatment of infected wounds.