Three-in-one bilayer microneedle patch for ultrasound-activated antibacterial therapy and immune modulation in wound healing

Reactive oxygen species (ROS)-based therapies have emerged as promising non-antibiotic strategies for treating infected wounds due to their broad-spectrum antimicrobial activity and low risk of resistance development. However, their clinical translation remains limited by low delivery efficiency, poor bacterial targeting, and uncontrolled post-treatment inflammation. To address these challenges, we reported a multifunctional bilayer microneedle patch (LFT/S-MN) designed for efficient bacterial eradication and enhanced wound healing. The patch integrates positively charged lactoferrin-based nanoparticles (LFT NPs) conjugated with a porphyrin sonosensitizer (TAPPFe) in the dissolvable base layer, and a pH-responsive tip layer loaded with the anti-inflammatory agent spermidine (SPD). Upon insertion into infected tissue, the released LFT NPs efficiently target and aggregate negatively charged bacteria, enabling robust ROS generation through synergistic chemodynamic and sonodynamic therapy (CDT/SDT) under ultrasound stimulation. Concurrently, the acidic wound microenvironment triggers the gradual degradation of the tip layer, allowing controlled SPD release for immunomodulation. In a murine P. aeruginosa -infected wound model, the LFT/S-MN patch significantly reduced bacterial load, suppressed inflammation, promoted collagen deposition and neovascularization, and accelerated wound closure. This work presents a promising non-antibiotic strategy for wound disinfection and regeneration through synergistic CDT/SDT and inflammation modulation.