Self-Healing Polymeric Puerarin Hydrogel Dressing Promotes Diabetic Wound Healing Through Synergistic Immunomodulation and Tissue-Regenerative Remodeling

Chronic wound healing is a significant challenge in diabetes. Puerarin is an active compound extracted from the traditional Chinese medicine <i>Pueraria lobata</i>. Puerarin has been used in the treatment of diabetes and derives benefits from its antioxidant, anti-inflammatory, antibacterial, and pro-angiogenesis properties, but its efficacy is hampered by poor water solubility and bioavailability. In this study, we designed a polyvinyl alcohol (PVA)-borax-puerarin (BP) hydrogel system that self-assembled via boronic ester bonds. The BP hydrogel exhibited exceptional physical characteristics, including adaptability, injectability, plasticity, self-healing capabilities, and robust compressive strength, as well as good biocompatibility. In the chronic wound diabetic rats model, the BP hydrogel significantly accelerated wound healing, as evidenced by hematoxylin and eosin (HE) staining, as well as Masson and picrosirius red (PSR) staining. RNA-sequencing and multiple immunohistochemistry (mIHC) analyses revealed that the BP hydrogel exerts a therapeutic effect by modulating macrophage polarization, promoting angiogenesis, and regulating collagen remodeling. Our findings suggest that the BP hydrogel represents a promising wound dressing and holds great potential for clinical applications in acute and chronic wound management.