Spatiotemporally Orchestrated Microneedle Patch Synergizing Photodynamic Therapy, ROS Scavenging, and Photosynthetic Oxygenation for Chronically Infected Wound Healing.

Abstract

A multistage microneedle (MN) patch was developed to coordinate photodynamic therapy (PDT), oxidative stress reduction, and hypoxia relief for the spatiotemporal treatment of chronically infected wounds. The MN patch uses a hyaluronic acid base loaded with methylene blue (MB), which rapidly releases upon contact with tissue fluid. As the MN penetrates biofilm, it delivers MB effectively, achieving strong antibacterial PDT effects. The needle tips are made of gelatin methacryloyl (GelMA) and contain carbon dots (CDs) and <i>Chlorella pyrenoidosa</i>. During inflammation, CDs scavenge ROS while <i>C. pyrenoidosa</i> generates oxygen via photosynthesis to reduce hypoxia. Importantly, CDs convert light (500-600 nm) into a spectrum (600-700 nm) that can be used by <i>C. pyrenoidosa</i>, boosting oxygen production. The GelMA matrix separates MB and CDs, preventing ROS interference and maintaining PDT effectiveness. This MN platform integrates antibacterial action, inflammation control, angiogenesis, and tissue regeneration, offering a flexible and effective approach for treating chronic wounds.