Cold Atmospheric Plasma Therapy for Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Aims/hypothesis Diabetic foot ulcers are a common and serious complication of diabetes, frequently resulting in infection, amputation, and increased mortality. Cold atmospheric plasma (CAP) is a new treatment modality that combines antimicrobial activity with promotion of tissue regeneration. We aimed to systematically review and meta-analyse randomized controlled trials to determine whether cold atmospheric plasma therapy, when added to standard wound care, improves healing outcomes and safety in patients with diabetic foot ulcers (DFUs). Methods Following PRISMA 2020 guidelines, we included randomized controlled trials in adults with DFUs comparing adjunctive CAP plus standard care versus standard care. Non-RCTs, non-CAP energy modalities, CAP without concomitant standard care, and studies without a concurrent control were excluded. The primary outcome was final fractional wound area (final/baseline; unitless proportion, 0-1). Secondary outcomes were ≥50% wound-size reduction by week 3, bacterial load, and adverse events. Results Three RCTs (107 participants; 126 ulcers) showed that CAP reduced final fractional wound area (mean difference −0.29 proportion units, 95% CI −0.47 to −0.11; p = 0.002; I 2 = 22%). The proportion achieving ≥50% wound-size reduction by week 3 was higher with CAP (RR 2.39, 95% CI 1.46-3.91; p < 0.001; I 2 = 0%). Bacterial load declined over time in both groups with no sustained between-group difference; immediate post-application reductions were observed with CAP within sessions. No serious treatment-related adverse events were reported. Conclusions/interpretation Adjunctive cold atmospheric plasma improved early healing of diabetic foot ulcers and showed a favourable short-term safety profile, with no sustained advantage in infection control over standard care. Larger, longer randomized trials are warranted to assess complete closure and recurrence outcomes and to define optimal treatment parameters. Registration PROSPERO registration ID CRD4201113940.