An Enzyme-Like Catalyzed Nanosheets for Redox Stress Oscillation Therapy Against Bacterial Infections

The presence of bacterial biofilms creates a physicochemical barrier, as their dense networks and redox homeostasis prevent the penetration of antimicrobial agents, reactive oxygen species, and host immune cells, rendering them highly resistant to antimicrobial treatment and immune-mediated killing and clearance. Here, this study demonstrates that SnSe nanosheets with enzyme-like properties and piezoelectric catalysis can oscillate to regulate bacterial redox homeostasis and improve the lactate-rich immunosuppressive microenvironment of the infection. This strategy enhances innate immune cell responses to infection or inflammation, achieving effective biofilm clearance on implant surfaces and surrounding tissues in a mouse surgical implant infection model. It reshapes the local immune microenvironment, allowing comprehensive infection control and effective restoration of tissue function. Mechanistically, redox stress oscillation therapy reprograms bacterial amino acid metabolism to induce reductive stress, which then generates oxidative stress under piezoelectric catalysis, resulting in continuously oscillating redox stress within the biofilm. Therefore, this study provides an alternative and promising strategy for the treatment of bacterial biofilm infections with recalcitrant redox homeostasis. © 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH.