Angela Boahen, Adrian I. Abdo, Neil McMillan, Guilherme Nogueira Pena, Katharina Richter
Globally, approximately 18.6 million individuals develop diabetes-related foot ulcers each year, with 50-60% of these cases subsequently becoming infected. Diabetes-related foot infections (DFI) are a serious complication often resulting in gangrene, lower extremity amputation and death-outcomes exacerbated by multidrug-resistant and biofilm-forming pathogens that render standard antibiotics and antiseptics inadequate, driving up healthcare costs and morbidity. Addressing this challenge necessitates the development of novel, dual-action therapeutic strategies capable of eradicating infection while simultaneously promoting tissue regeneration. Plasma-activated water (PAW) is an emerging solution, produced by treating water with cold plasma; an ionised gas that generates a complex mixture of reactive oxygen and nitrogen species. PAW elicits potent broad-spectrum antimicrobial and antibiofilm activity against a wide range of pathogens implicated in chronic wound infections, including DFI. PAW has also been shown to accelerate wound healing by modulating immune cell activity and promoting epithelial cell proliferation and migration. In this review, we summarise DFI prevalence and recurrence, PAW generation and physicochemical properties, antimicrobial and antibiofilm efficacy against relevant pathogens, effects on cellular responses, therapeutic potential and current limitations. This review positions PAW as a dual-action, resistance-refractory therapeutic strategy for DFIs and other chronic wounds and outlines the translational pathway towards clinical implementation.