Core-Shell Microneedle Patch with Controlled Sequential Release of CuO₂@ZIF-8 Nanoparticles and VEGF for Synergistic...

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 (CuO₂) nanoparticles and vascular endothelial growth factor (VEGF) for synergistic healing. CuO₂ was encapsulated in zeolitic imidazolate framework-8 (CuO₂@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 Cu²⁺, Zn²⁺, and ROS, disrupting biofilms and killing bacteria. Subsequently, the shell swells and degrades to release VEGF, promoting angiogenesis and tissue regeneration. In a Staphylococcus aureus-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.