Low-Temperature Atmospheric Pressure Plasma in Acute Wound Healing: A Multi-Center Randomized Controlled Trial Using Split-Thickness Skin Graft Donor Sites as a Standardized Human Model

Objective: To determine whether low-temperature atmospheric-pressure plasma (LTAPP) improves acute wound healing, using split-thickness skin graft (STSG) donor sites as a standardized clinical model. Materials and Methods: A multi-center randomized controlled trial was conducted across five tertiary hospitals. A total of 111 patients undergoing STSG were randomized to receive standard of care (SOC) with LTAPP or SOC with sham treatment. Primary outcomes included wound healing rates and wound size/volume reduction. Secondary outcomes included exudate clearance, bacterial burden, and cost-effectiveness. Results: Healing rates were comparable between LTAPP and SOC groups (71.2% vs. 75.0%, p=0.652). SOC achieved faster wound closure (median 1.6 vs. 2.3 weeks), while LTAPP demonstrated earlier wound volume reduction without translating into improved clinical healing. Both groups achieved complete bacterial clearance. LTAPP incurred significantly higher costs and was not cost-effective, with ICER analysis showing dominance by SOC. Better scar pigmentation quality was observed in a few patients. Conclusion: Using STSG donor sites as a controlled acute wound model, LTAPP did not improve healing outcomes compared to SOC. These findings suggest that LTAPP may have limited utility in uncomplicated acute wounds but reinforce the value of donor site models for evaluating emerging wound technologies. Future research on LTAPP in wounds should focus on chronic, ischemic, or infected wounds where biological modulation may be more impactful.