Multimodal Energy Conversion‐Enhanced Microneedle System Combats Bacterial Biofilm via Defense Disruption and Neutrophil Activation

ABSTRACT Strategies that manipulate redox homeostasis and activate host immunity have shown great promise in combating bacterial infections. However, precisely regulating these processes remains a formidable challenge. This study reports a multimodal energy conversion strategy for effectively disrupting bacterial defense while precisely activating and modulating neutrophil immune functions. Specifically, a flexible hydrogel microneedle (MN) patch containing FPS@BTO nanocomposites based on photothermal FePS 3 nanosheets (FPS NSs) and pyroelectric BaTiO 3 nanoparticles (BTO NPs) is created for enhanced biofilm eradication and tissue regeneration. The MNs efficiently penetrate biofilms, enabling wound‐responsive release of nanocomposites that undergo a multimodal photonic‐to‐thermal‐to‐electric‐to‐chemical energy conversion under 1064 nm laser irradiation to autonomously generate sufficient reactive oxygen species (ROS). Simultaneously, Fe 3+ depletes overexpressed glutathione (GSH) in the microenvironment. The combined ROS storm and GSH depletion can disrupt bacterial redox homeostasis, sensitizing bacteria to immune clearance. Notably, this multifaceted nanoplatform enhances neutrophil phagocytosis and bactericidal activity while curbing overactivation and aberrant neutrophil extracellular traps (NETs) formation, enabling precise immunomodulation. Coupled with enhanced angiogenesis and bioactive anions‐mediated anti‐inflammation, this work proposes a revolutionary strategy to overcome antibiotic‐resistant infections and accelerate wound healing, thus establishing a new paradigm for intelligent energy conversion therapy.