Effects of Cold Atmospheric Plasma Therapy on Chronic Wounds: A Systematic Review and Meta-analysis

Chronic wounds, including diabetic foot ulcers (DFUs) and pressure ulcers (PUs), present major therapeutic challenges due to delayed healing, high recurrence, and persistent microbial colonization. Cold Atmospheric Plasma (CAP) has emerged as a potential adjunctive therapy, but its clinical efficacy has not been comprehensively evaluated. This systematic review and meta-analysis, registered with PROSPERO (CRD42025640913), analyzed randomized controlled trials (RCTs) published from 2010 to 2025. A comprehensive search across PubMed, EMBASE, Cochrane Library, and Web of Science identified studies comparing CAP with standard care. Data synthesis employed random- or fixed-effects models. Risk of bias and certainty of evidence were assessed with the Cochrane Risk of Bias Tool and the GRADE framework. Subgroup analyses were conducted based on plasma generation technology, treatment frequency, and study quality. 12 RCTs (477 participants) were included. CAP significantly reduced wound area (MD = –1.36; 95% CI: –2.09 to –0.62; p = 0.0011) and DFU area (MD = –1.48; 95% CI: –2.81 to –0.15; p = 0.0296). CAP also improved healing rates (RR = 2.90; 95% CI: 1.45 to 5.80; p = 0.0052) and reduced bacterial load (MD = –0.36; 95% CI: –0.64 to –0.08; p = 0.0126). Subgroup analysis revealed variability by plasma technology (Dielectric Barrier Discharge vs Plasma Jet) and methodological quality. CAP therapy significantly improves wound healing and bacterial load reduction in chronic wounds, particularly DFUs. However, significant heterogeneity and limitations in study quality underscore the need for larger, high-quality trials with standardized protocols to validate long-term benefits. • CAP boosts chronic ulcer healing, especially for diabetic foot ulcers (DFU). • CAP’s reactive species reduce bacterial load and modulate wound inflammation. • Meta-analysis shows CAP outperforms standard dressings for wound closure.