A dual-network SIS collagen/chitosan hydrogel with integrated antibacterial and regenerative functions for infected wound repair

Abstract

The treatment of infected skin wounds remains a significant clinical challenge due to bacterial infection, delayed healing, and the rise of antibiotic-resistant bacteria. This study aims to develop a dual-crosslinked hydrogel dressing with integrated antibacterial and pro-healing functions to promote the regeneration of infected wounds. A dual-network hydrogel (CC/Cu²⁺ gel) was fabricated through the self-assembly of porcine small intestinal submucosa (SIS) collagen and subsequent ionic crosslinking between chitosan and Cu²⁺. The material’s microstructure, mechanical properties, cytocompatibility, hemocompatibility, and antibacterial activity against S.aureus and E.coli were systematically characterized. The efficacy in promoting infected wound healing was evaluated using a full-thickness skin defect model in Bama miniature pigs. The incorporation of Cu²⁺ formed a denser polymer network, significantly enhancing the compressive modulus and strength of the hydrogel. The CC/Cu²⁺-5 gel formulation demonstrated effective antibacterial activity while maintaining acceptable cytocompatibility and hemocompatibility. In vitro, it facilitated fibroblast proliferation, collagen expression, and angiogenesis. In vivo, it accelerated wound closure, achieving a 98.97% healing rate within 24 days, and promoted well-structured epidermal and dermal regeneration, as confirmed by histological and immunofluorescent analyses. The CC/Cu²⁺ dual-crosslinked hydrogel, leveraging the synergistic effect of SIS collagen and copper ions, represented a promising functional dressing for managing infected wounds.