Multifunctional carboxymethyl chitosan-based supramolecular-polymeric hydrogel with integrated antibacterial and anti-inflammatory activities for accelerated wound healing

Skin is vulnerable to injuries that can lead to bacterial infection and prolonged inflammation, impeding the healing process. To address this, we developed an antibacterial and anti-inflammatory supramolecular-polymeric composite hydrogel for accelerated wound healing. The hydrogel is formed by integrating paromomycin sulfate-loaded G-quartet (G4) supramolecular nanofibers with a polymeric network of carboxymethyl chitosan grafted with phenylboronic acid (CMCS-PBA). The antibiotic, paromomycin sulfate, was in-situ loaded via dynamic Schiff base linkages with the aldehyde groups on the G4 fibers, enabling a controllable release. While the pure G4 hydrogel is mechanically weak, the introduced CMCS-PBA network significantly enhances the mechanical strength through multi-valent boronate ester bonds and supramolecular co-assembly, making it suitable for wound sites requiring mechanical robustness. The resulting composite hydrogel exhibits excellent tissue adhesion, hemostatic ability, and biocompatibility. It demonstrated potent antibacterial efficacy in vitro and in vivo. In a full-thickness mouse skin wound model, the hydrogel markedly accelerated wound closure and effectively modulated the wound microenvironment by reducing pro-inflammatory cytokines (TNF-α and IL-6) and elevating anti-inflammatory cytokine (IL-10). This work pioneers a synergistic supramolecular-polymeric strategy, yielding a multifunctional platform that surpasses the limitations of traditional single-network hydrogels, offering a versatile therapeutic strategy for managing infected and inflammatory wounds.