Multifunctional Dynamic Hydrogel Based on a Micelle-Cross-Linked Chitosan Network for Infected Wound Healing

Despite significant advancements in the development of hydrogel dressings for wound healing, there remains a highly urgent demand to create multifunctional hydrogels with satisfying biocompatibility, self-healing ability, adhesiveness, appropriate mechanical properties, antibacterial activity, and therapeutic effects. Herein, a versatile hydrogel dressing was prepared through the cross-linking of terminally aldehyde-modified Pluronic-F127 (AF127) micelles with dihydrocaffeic acid-functionalized chitosan (CA) via the formation of a dynamic Schiff base. The cooperation of chitosan grafted with multiple catechol groups and the dynamic nature of the Schiff base imparted the hydrogel with superior antioxidant properties, adhesiveness, rapid self-healing, intrinsic antibacterial activity, and pH-dependent responsiveness. The good adhesiveness and self-healing abilities, derived from the hydrogen bonding interactions of catechol groups and dynamic covalent bonds, enhance hydrogels' resistance to deformation. Moreover, after loading hydrophobic rhein into AF127 micelles, the hydrogel demonstrated potent anti-inflammatory effects and pH-responsive drug release, making it suitable for treating infected and inflammatory skin wounds. In vivo experiments showed that rhein-loaded CA/AF hydrogels significantly accelerated tissue regeneration, with an intact epidermis, enhanced collagen disposition, and increased angiogenesis in a full-thickness skin defect model infected by <i>Staphylococcus aureus</i>. Overall, these versatile chitosan/pluronic hydrogels, possessing intrinsic antibacterial, antioxidant, and anti-inflammatory properties, hold significant potential for treating infected and chronic inflammatory wounds.