pH-Responsive and Self-Adaptive Hydrogel Dressing Based on a TA/PVA Network Co-Loaded with Cannabidiol and Mupirocin for Synergistic Infected Wound Healing

Background The development of advanced wound dressings capable of dynamically adapting to the complex wound microenvironment represents a critical unmet need in the management of infected and chronic wounds. Methods A novel multifunctional hydrogel dressing was fabricated through a green, physical crosslinking strategy based on hydrogen bonding between tannic acid (TA) and polyvinyl alcohol (PVA). The network was co-loaded with cannabidiol (CBD) and mupirocin (MUP) to achieve synergistic therapeutic effects. The hydrogel was characterized for its microstructure, mechanical properties, swelling capacity, and pH-responsive behavior. In vitro evaluations included antibacterial activity, antioxidant capacity, biocompatibility, and fibroblast migration assays. In vivo efficacy was assessed using a murine full-thickness wound model. Results The optimized hydrogel exhibited a uniform porous structure, suitable mechanical properties, and excellent swelling capacity. It demonstrated intelligent pH-responsive degradation and drug release, with accelerated release under alkaline conditions and sustained release under acidic conditions. In vitro, the hydrogel showed potent broad-spectrum antibacterial activity, pH-modulated antioxidant capacity, excellent biocompatibility, and promoted fibroblast migration. In vivo, it significantly accelerated wound closure (72.80% by day 7) and enhanced tissue regeneration through improved re-epithelialization, collagen deposition, and angiogenesis, with histopathological analysis confirming excellent biosafety. Conclusions This study provides an innovative, responsive hydrogel platform that intelligently coordinates antibacterial, antioxidant, and pro-healing functions. The work offers a promising strategy for managing infected and chronic wounds through a dynamically adaptive and synergistic therapeutic approach.