Treatment of Superbug Infection through a Membrane‐Disruption and Immune‐Regulation Cascade Effect Based on Supramolecular Peptide Hydrogels

Abstract Infections from antimicrobial resistant pathogens have been considered as lethal threats to human health if antibiotic treatments become ineffective. Antimicrobial peptides (AMPs) show broad‐spectrum antimicrobial activity against resistant strains via a membrane disruptive mechanism without developing further resistance and are promising candidates to combat resistant microbes. However, currently developed small molecular AMPs are limited by weak antimicrobial efficacy and potential cytotoxicity. Herein, an antimicrobial AMP hydrogel based on supramolecular self‐assembly is developed. The hydrogel shows strong antimicrobial activity and high potency against antimicrobial resistant microbes. It also possesses high cytocompatibility and immunoregulative activity. The synergistic effects lead to its significant healing of the skin abscess disease induced by the methicillin‐resistant Staphylococcus aureus infection. This study not only sheds light on the design strategies and immune‐related antimicrobial actions of supramolecular AMP hydrogels, but also advances the development of self‐assembly peptide platform to fight against antimicrobial resistant infections.