A Paintable Small-Molecule Hydrogel with Antimicrobial and ROS Scavenging Activities for Burn Wound Healing

Delayed wound healing induced by bacterial infection and a persistent inflammatory response remains a great clinical challenge. Herein, we reported a paintable, anti-bacterial, and anti-inflammatory Nap-F3K-CA (Nap-Phe-Phe-Phe-Lys-Caffeic Acid) hydrogel for burn wound management based on caffeic acid (CA)-functionalized short peptides (Nap-Phe-Phe-Phe-Lys). Hydrogels are assembled by non-covalent interactions between gelators, and the incorporation of CA promotes the self-assembly of the hydrogel. After being applied to burn wounds, the hydrogel effectively adapted to irregular wound beds and maintained a moist protective environment at the wound. The Nap-F3K-CA hydrogel can scavenge ROS to relieve oxidative damage and downregulate proinflammatory levels. The Nap-F3K-CA hydrogel also displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria, which reduced the incidence of wound infections. Moreover, the hydrogel exhibited good biocompatibility and hemostatic function. In vivo experiments demonstrated that the Nap-F3K-CA hydrogel significantly accelerated the repair of the skin structure including promoting collagen deposition, vascular regeneration, and hair follicle formation. These findings proved the clinical application potential of the Nap-F3K-CA hydrogel as a promising burn wound dressing.