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Real-time NO measurement needed in evaluating diabetic ulcer healing

Measuring nitrite is not an accurate way of evaluating nitric oxide (NO) production in skin wounds that are healing, so NO production by the skin should be measured directly, according to new research from Michigan Technological University in Houghton, Mich.

Investigators at the polymeric biomaterials lab at the University have been working to develop wound dressing materials that release NO, with the aim of supporting the regulation of fibroblast activity in diabetic ulcers. “The old approach is to add nitric oxide and sit back to see if it works,” said the paper's senior author Megan C. Frost, PhD, in a press release. “What we’re finding is that it’s not enough to apply and leave; we have to keep tabs on how much nitric oxide is actually needed.”

Dr. Frost is the interim chair of the Department of Kinesiology and Integrative Physiology at Michigan Tech, and an associate professor of biomedical engineering and an affiliated associate professor of materials science and engineering. She runs the polymeric biomaterials lab.

“Nitric oxide is a powerful healing chemical, but it's not meant to be heavy-handed,” said Dr. Frost. “We're looking at the profiles of healthy and diabetic cells to find a more nuanced way to recover wound function.” The current practice to evaluate NO activity in wounds is to measure nitrite, a byproduct of NO, as a proxy, as it is more stable. However that very stability means nitrite does not provide a time signature, so is not useful for measuring NO-related wound healing status in real time, said Dr. Frost.

In the new research paper, published in Medical Sciences (2018; 6(4):99), Dr. Frost and her team describe their findings on NO production in human dermal fibroblasts cultured under both normal and high glucose conditions, compared to levels of nitrite present in the culture media. Using a NO-measuring device they built themselves, the investigators showed that NO production was significantly higher in the cells cultured under normal glucose conditions, compared to those cultured under high glucose conditions. While there was a direct correlation between real-time NO and nitrite observed in the normal-glucose samples, the two measures did not correlate under high glucose conditions. Working with industry partners, Dr. Frost and her team hope to develop practical NO sensing systems as well as as NO-infused bandage prototypes, with the aim of starting human trials within a few years. Their aim is to reduce the healing time of diabetic foot ulcers from as much as 150 days down to as few as 21 days.

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