Bacteria-responsive hydrogel for on-demand release of antimicrobial peptides that prevent superbug infections and promote wound healing

Various skin infections present a substantial challenge in both patient care and the medical community. A primary obstacle to effective wound healing is the colonization of pathogenic bacteria, which would produce hyaluronidase (HAase). This enzyme degrades hyaluronic acid (HA) at wound sites, facilitating bacterial infection. Herein, we developed a HAase-responsive hydrogel, HA-EPL-PEG, incorporating the antimicrobial peptide ε-Poly-l-lysine (EPL) and Polyethylene glycol diacrylate (PEGDA), chemically crosslinked via a photoinitiator. Following, the in vitro antibacterial and antifouling properties of this hydrogel were evaluated, along with its cytotoxicity to mammalian cells. Subsequently, its bacteria secreted HAase responsive functionality was evaluated. In vivo antibacterial, anti-infectious and wound healing effects were further investigated in a rodent model. All these results demonstrated the multifunctional benefits of HA-EPL-PEG hydrogel, showcasing its HAase-responsive nature, antibacterial and antifouling activities. Importantly, the hydrogel significantly expedited the healing of full-thickness skin wounds, denoting a promising avenue for advancing wound care.