Dopamine-Substituted Multidomain Peptide Hydrogel with Inherent Antimicrobial Activity and Antioxidant Capability for Infected Wound Healing

Wound infection can cause a delay in wound healing or even wound deterioration, threatening patients' lives. The excessive accumulation of reactive oxygen species (ROS) in infected wounds activates a strong inflammatory response to delay wound healing. Therefore, it is highly desired to develop hydrogels with inherent antimicrobial activity and antioxidant capability for infected wound healing. Herein, a dopamine-substituted multidomain peptide (DAP) with inherent antimicrobial activity, strong skin adhesion, and ROS scavenging has been developed. DAP can form bilayer β-sheets with dopamine residues on the surface of nanofibers. The enhanced rheological properties of DAP-based hydrogel can be achieved not only through UV irradiation but also by incorporation of multivalent ions (e.g., PO₄^3-). Furthermore, the DAP hydrogel shows a broad spectrum of antimicrobial activity due to the high positive charges of lysine residues and the β-sheet formation. When applied to full-thickness dermal wounds in mice, the DAP hydrogel results in a significantly shortened inflammatory stage of the healing process because of its remarkable antimicrobial activity and antioxidant capability. Accelerated wound closure with thick granulation tissue, uniform collagen arrangement, and dense vascularization can be achieved. This work suggests that the DAP hydrogel can serve as antimicrobial coating and ROS-scavenging wound dressing for bacterial-infected wound treatment.