Plasma-Activated Water Improve Wound Healing in Diabetic Rats by Influencing the Inflammatory and Remodelling Phase

Diabetic foot ulcers have an enormous impact on patients' quality of life and represent a major economic burden. The cause is delayed and incomplete wound healing due to hyperglycemia, reduced blood flow, infections, oxidative stress and chronic inflammation. Plasma-activated water (PAW) is emerging as a new therapeutic approach in wound treatment, as it has many of the advantages of cold atmospheric plasma but is easier to apply, thus allowing for widespread use. The aim of this study was to investigate the potential of PAW to improve wound healing in diabetic rats, with a focus on uncovering the underlying mechanisms. Two full-thickness wounds in control and diabetic animals were treated with PAW, and healing was monitored for 15 days at five time points. PAW improved wound healing in diabetic rats and mainly affected the inflammatory phase of wound healing. Application of PAW decreased the number of inflammatory cells, myeloperoxidase (MPO) and N-acetyl-b-D-glycosaminidase (NAG) activity, as well as the mRNA expression of proinflammatory genes in diabetic rats. Ten days after injury, PAW treatment increased collagen deposition in the diabetic animals by almost 10% without affecting collagen mRNA expression, and this is in correlation with a decrease in the Mmp-9/Timp-1 ratio. In conclusion, PAW treatment affects wound healing by reducing the inflammatory response and influencing extracellular matrix turnover, suggesting that it has great potential to accelerate the healing of diabetic wounds.