Thylakoid-Based Photosynthetic Hydrogel for Dual-Phase ROS Regulation in Infected Wounds

Reactive oxygen species (ROS) play a dual-edged role in infected wounds: they are vital for initial pathogen clearance but exacerbate local oxidative stress and delay healing once the infection is contained. Traditional photodynamic therapy (PDT) fails to meet these dynamic needs because its initial bactericidal ROS generation is severely restricted by wound hypoxia, while it simultaneously lacks the ability to scavenge excess ROS in the later stages to relieve oxidative stress. In this work, we developed a self-oxygenating photodynamic hydrogel (denoted GCT) by co-encapsulating spinach-derived isolated thylakoids and Chlorin e6 (Ce6) within a methacrylated gelatin (GelMA) matrix. Under single-wavelength 660 nm irradiation, the embedded thylakoids serve as a photosynthetic oxygen engine, continuously catalyzing water splitting to generate dissolved oxygen in situ, thereby alleviating hypoxia and maximizing Ce6-mediated reactive oxygen species (ROS) production for enhanced antibacterial PDT. Concurrently, the intrinsic antioxidant thylakoids enable robust ROS scavenging without light irradiation, mitigating oxidative stress in host cells and promoting angiogenesis and tissue repair. This photosynthesis-coupled PDT system enables efficient bacterial eradication and promotes a shift from merely sterilization to whole-process wound healing, representing the first thylakoid-based strategy for effective photodynamic management of infected wounds.