Plasma-activated gas: a new dawn for wound care and infection

FactsPhysical plasma generates reactive oxygen and nitrogen species (RONS), exerting antitumor, anti-infective, and tissue-modulating effects in models.Plasma-derived reactive species act on cell membranes to trigger sustained biological signals.Computational modelling combined with experimental clarify of RONS transport, membrane interactions, and downstream signaling in diseases.Plasma RONS work alone or sensitize other therapies via oxidative stress and tissue remodeling.Plasma modulates immunity: redox signaling, danger-associated molecular pattern release, and immune activation drive durable antitumor responses.Open QuestionsWhich RONS drives beneficial/detrimental effects, and how to precisely control them clinically?How do membrane lipid features affect plasma-cell interactions? Do tumor membranes explain selective plasma sensitivity?What core signaling networks follow plasma-induced membrane oxidation, and how do pathways (mitogen activated protein kinases, nuclear factor-κB, etc.) interact in diseases?Can standardized biomarkers predict response/safety when plasma is combined with other therapies?How to integrate computational modeling with experiments/clinical data for personalized plasma medicine? Plasma-activated gas, an emerging technology derived from non-thermal plasma, demonstrates considerable promise in wound management through its rich repertoire of reactive oxygen and nitrogen species. Plasma-activated gas exerts broad-spectrum antimicrobial activity through multi-target mechanisms, effectively eliminating multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa , as well as disrupting bacterial biofilm architecture. In tissue repair, plasma-activated gas orchestrates the entire wound healing cascade. It accelerates platelet activation and coagulation, enhances proliferation and migration of epithelial cells and fibroblasts by activating vascular endothelial growth factor receptor-extracellular regulated protein kinases 1/2 and transforming growth factor-β/Smad signaling pathways, promotes angiogenesis via the endothelial nitric oxide synthase-vascular endothelial growth factor axis, and optimizes tissue remodeling by fine-tuning the matrix metalloproteinases and their tissue inhibitors balance. Preclinical and early clinical studies confirm that plasma-activated gas significantly shortens healing time, mitigates scar formation, and effectively controls wound infection. Although challenges remain in standardization, safety profiling, and clinical translation, advances in precise dosing strategies and intelligent device design position plasma-activated gas as a transformative approach for managing refractory chronic wounds. The results and cutting-edge advancements summarized in this review are expected to provide a valuable and forward-looking reference for the subsequent research and development upgrading and clinical translational application of plasma-activated gas.