Therapeutic potential of chitosan-based bioadhesive hydrogels in diabetic wound healing.

We describe adhesive and self-healing hydrogels of chitosan functionalized with catechol groups (Chit-Cat) and crosslinked with β-glycerophosphate for the treatment of chronic diabetic wounds. Catechol functionalization enhanced the antibacterial activity of the hydrogels, eliminating both Gram-negative and Gram-positive bacteria while preserving excellent cytocompatibility against human dermal fibroblasts from aged diabetic donors. The efficacy of this therapeutical approach was assessed in vivo in a mice diabetic wound model. The results demonstrated that the treatment with Chit-Cat hydrogels decreased the wound area with no contraction compared to the treatment controls. Additionally, these hydrogels significantly enhanced angiogenesis in the treated wounds, decreased the pro-inflammatory macrophages, and facilitated a controlled transition from the inflammatory to the proliferative phase, characterized by an early prevalence of thick collagen fibers. These data suggest that Chit-Cat hydrogels offer a promising solution for wound dressing and the management of diabetic skin wounds, providing a multifunctional platform that accelerates and improves the healing in challenging clinical scenarios.