Enzymatic preparation of xanthan gum/polyvinyl alcohol-based nanocomposite hydrogel with antibacterial and immunoregulatory properties for accelerated skin wound healing.

Persistent bacterial infection and inflammation are primary factors impeding skin wound healing. Conventional dressings lack the multifunctionality required to address these challenges effectively. This study therefore developed a novel multifunctional hydrogel dressing using a biocompatible enzymatic strategy to overcome these limitations. The hydrogel is constructed from three key components: (1) methacryloyl and aldehyde groups-modified xanthan gum (MA-XG-CHO), (2) acetoacetyl-grafted polyvinyl alcohol (PVA-ACAC), and (3) a nanoscale complex (SiW@ε-PL) formed by negatively charged silicotungstic acid and positively charged ε-polylysine. Crucially, the hydrogel network is formed through a mild horseradish peroxidase (HRP)/H2O2-mediated enzymatic process: HRP oxidizes the acetoacetyl groups on PVA-ACAC, generating macromolecular radicals that initiate the polymerization and cross-linking of methacryloyl groups on MA-XG-CHO. Simultaneously, dynamic covalent Schiff base linkages form between the aldehyde groups on MA-XG-CHO and amino groups on the SiW@ε-PL nanocomplex. Critically, in a full-thickness skin defect model, the hydrogel demonstrated significant in vivo efficacy: it accelerated wound closure and promoted comprehensive wound regeneration. The healing mechanism involves a dual action: the mannose-containing xanthan gum promotes macrophage polarization toward the pro-healing M2 phenotype to mitigate inflammation and initiate tissue repair, while the SiW@ε-PL nanocomplex provides potent antibacterial activity to eliminate infections due to ε-polylysine could disrupt the bacterial membranes. This study provides a significant strategy for addressing persistent bacterial infection and inflammation in wound care by integrating multifunctional components into a single enzymatically cross-linked hydrogel system. The proposed technology holds promising potential for application in the development of advanced dressings for the treatment of chronic and infected wounds.