Dual-Stage Microneedle Patch With Lipid Droplet-Mediated 'Capture-Kill' and Sustained Release for Enhanced Wound...

Chronic wound infections, particularly those complicated by antibiotic-resistant bacteria and biofilm formation, present persistent clinical challenges due to limited drug penetration and unresolved inflammation. Here, we report a lipid-droplet-engineered, gallium-loaded sonodynamic therapeutic platform (LDTG) incorporated into a bilayer microneedle (MN) patch co-delivering all-trans retinoic acid (ATRA), termed LDTG A-MNs, for synergistic antibacterial therapy and accelerated wound repair. The engineered LDTG exhibit strong bacteria-targeting capability by mimicking host lipid droplets and efficiently generate reactive oxygen species (ROS) under ultrasound irradiation to achieve potent sonodynamic bactericidal activity. The bilayer MN design enables rapid release of LDTG for targeted bacterial capture, followed by sustained ATRA release to modulate macrophage polarization and promote tissue regeneration. In vitro, LDTG A-MNs demonstrate robust antibacterial and biofilm-disrupting effects, excellent biocompatibility, and enhanced M2-type macrophage polarization. In vivo, LDTG A-MNs combined with ultrasound effectively eradicate bacterial infection, suppress excessive inflammation, improve collagen deposition, enhance angiogenesis, and significantly accelerate wound closure in infected murine skin wounds. This work presents a minimally invasive and infection-responsive MN system that integrates pathogen targeting, sonodynamic antibacterial therapy, and immune-regulated tissue repair, offering a promising therapeutic strategy for the management of complex and refractory infected wounds.