Water treated by cold plasma helps stubborn wounds heal faster in diabetes

Diabetic wounds, particularly foot ulcers, are among the most serious complications faced by patients with diabetes. These chronic wounds often fail to heal properly due to a combination of poor blood flow, persistent inflammation, and infection. The consequences can be severe, ranging from loss of mobility to amputations, and they place a substantial burden on healthcare systems worldwide. Against this backdrop, researchers have been seeking new treatments that can accelerate wound healing and improve patients’ quality of life.

Led by Dr. Nevena Puač at the University of Belgrade, a team of researchers demonstrated how plasma-activated water can enhance wound healing in diabetic rats. They showed the healing potential of water after plasma treatment, which could provide a more accessible option for patients. Their work is published in the International Journal of Molecular Sciences.

The research showed that plasma-activated water (PAW) treatment significantly improved wound closure in diabetic rats compared to untreated animals. Within the first days of healing, wounds treated with plasma-activated water displayed faster recovery and healthier tissue development. Notably, plasma-activated water did not change blood sugar levels, meaning the observed benefits were specific to the healing process itself. According to Dr. Puač and colleagues, “PAW improved wound healing in diabetic rats and mainly affected the inflammatory phase of wound healing”.

One of the central findings was that plasma-activated water reduced excessive inflammation, a key obstacle in diabetic wound repair. Tissue analysis revealed fewer inflammatory cells in plasma-activated water treated wounds, along with lower activity of enzymes linked to immune cells such as neutrophils, which are the first line of defense against infection, and macrophages, which are cells that clean debris and coordinate healing. These changes brought the healing process in diabetic rats closer to that seen in healthy controls. Dr. Puač explained, “Application of PAW decreased the number of inflammatory cells, myeloperoxidase and N-acetyl-b-D-glycosaminidase activity, and the expression of proinflammatory genes in diabetic rats”.

Beyond inflammation control, the treatment also enhanced tissue remodeling. Collagen, a structural protein vital for wound closure and strength, was deposited in greater amounts—roughly a tenth more—after plasma-activated water therapy. Importantly, this improvement was not due to increased collagen gene expression but rather to a favorable balance between enzymes that break down tissue and those that preserve the wound structure. This suggests plasma-activated water helps stabilize the wound environment, enabling more efficient healing.

Dr. Puač and her colleagues also shed light on how plasma-activated water influences molecular pathways. Levels of key inflammatory genes such as interleukin-1 beta, a molecule that signals inflammation, interleukin-6, another key regulator of the immune response, and tumor necrosis factor, a protein that promotes inflammation, were significantly lower in treated wounds. At the same time, the destructive enzyme matrix metalloproteinase-9, which breaks down connective tissue, was reduced, improving the balance between it and its natural inhibitor. This delicate shift likely explains why more collagen was preserved and integrated into healing tissue. Dr. Puač and the team concluded that plasma-activated water works through a dual mechanism: an early burst of inflammation to clear debris, followed by a rapid calming effect that allows wounds to progress to the proliferative phase, when new tissue forms, and the remodeling phase, when the wound structure strengthens.

In summary, the results suggest that plasma-activated water could offer a practical and effective new therapy for diabetic wounds. Unlike cold atmospheric plasma devices, which are bulky and require specialized equipment, plasma-activated water can be stored and easily applied as a liquid spray, making it more accessible for clinical use. Dr. Puač and her colleagues emphasized that while further studies and clinical trials are necessary, their findings lay the groundwork for developing improved strategies to treat chronic wounds in diabetic patients.