A ROS-scavenging hydrogel loaded with bacterial quorum sensing inhibitor hyperbranched poly-L-lysine promotes the wound scar-free healing of infected skin in vivo

Staphylococcus aureus (S. aureus) is the most common pathogen causing skin and soft tissue infections. The emergence and spread of methicillin-resistant S. aureus (MRSA) pose a major challenge for the treatment of infected wounds because of its high resistance and enhanced virulence. The overexpression of reactive oxygen species (ROS) at the site of skin wounds also exacerbates inflammation, leading to slower healing and severe scarring. Therefore, comprehensive strategy against MRSA-infected wounds is needed in clinical practice. Interference with quorum sensing (QS), a process of bacterial cell-to-cell chemical communication, has been considered a promising strategy to reduce the virulence and pathogenicity of MRSA. Herein, we designed a ROS-scavenging hydrogel loaded with a type of bacterial QS inhibitor, hyper-branched poly-L-lysine (HBPL), which has efficient bactericidal ability against planktonic and biofilm-embedded MRSA. We found that this multifunction hydrogel showed excellent anti-oxidative effects against different types of ROS, and it could inhibit the QS system, metabolic activity, and bacterial virulence. In vivo, the ROS-scavenging HBPL hydrogel efficiently accelerated the healing of MRSA-infected full-thickness skin defect by blocking QS, killing bacteria, suppressing inflammation, and promoting angiogenesis. Together, our results offer a new insight for scarless healing of MRSA-infected cutaneous wounds.