Plasma-derived hydroxyl radicals in wound healing: A review of mechanisms, therapeutic potential and challenges

The plasma-generated hydroxyl ( OH . ) radicals have emerged as powerful reactive oxidant species (ROS) in advanced wound therapy. This review presents current knowledge on plasma-based OH radical generation, delivery within the wound environment, and their biological impact, highlighting their short lifetime, limited diffusion, and localized reactivity for precise wound microenvironment modulation. The antibacterial mechanisms, redox signaling, and biofilm degradation through a precise oxidative window are discussed, including the involvement of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated β − cells (NF-κB) pathways. The spatiotemporal dynamics of OH . radicals, their interactions with biomolecules and endogenous oxidants, and current detection techniques, including electron spin resonance (ESR) and fluorescence imaging, are critically examined. Challenges related to detection, controlled dosage, long-term biological effects, and differentiation from other ROS are addressed, alongside emerging solutions involving smart biomaterials, ROS-responsive hydrogels, advanced sensing platforms, and artificial intelligence for precision redox medicine are also discussed.