Core-Shell Microneedle Patch with Controlled Sequential Release of CuO@ZIF-8 Nanoparticles and VEGF for Synergistic Treatment of Infected Wounds.

Infected wounds are difficult to treat due to biofilm formation, drug-resistant bacteria, and inefficient localized therapy. To address these challenges, we developed a core-shell microneedle (MN) patch that enables sequential delivery of copper peroxide (CuO) nanoparticles and vascular endothelial growth factor (VEGF) for synergistic healing. CuO was encapsulated in zeolitic imidazolate framework-8 (CuO@ZIF-8) to improve the aqueous stability and regulate reactive oxygen species (ROS) generation. The antibacterial nanocomposite was loaded into a pH-sensitive hyaluronic acid (HA) core layer for rapid release under a weakly acidic wound microenvironment, while VEGF was incorporated into a gelatin methacryloyl (GelMA) shell for sustained delivery. Upon application, the core dissolves to release Cu, Zn, and ROS, disrupting biofilms and killing bacteria. Subsequently, the shell swells and degrades to release VEGF, promoting angiogenesis and tissue regeneration. In a -infected wound model, the MN patch demonstrated potent antibacterial activity, enhanced neovascularization, and accelerated healing. This programmable, dual-functional MN platform offers an effective strategy for treating infected wounds by integrating infection control with tissue regeneration in a temporally coordinated manner.