A biomedical engineering team from Michigan Technical University is planning to drop the healing time by amplifying what the body already does naturally: build layers of new tissue pumped up by nitric oxide. In patients with diabetes, impaired nitric oxide production lessens the healing power of skin cells. The long-term plan of researchers is to create nitric oxide-laden bandages that adjust the chemical release depending on the cell conditions.

Assessing nitric oxide under diabetic and normal conditions in human dermal fibroblast cells is the focus of the team's latest paper, published this week in Medical Sciences. The corresponding author of the study, Dr. Megan Frost, the interim chair of the Department of Kinesiology and Integrative Physiology, in addition to her biomedical engineering team leading activities, runs a polymeric biomaterials lab at Michigan Tech where she works on nitric oxide-releasing technology. "Nitric oxide is a powerful healing chemical, but it's not meant to be heavy-handed," Frost says. "We're looking at the profiles of healthy and diabetic cells to find a more nuanced way to recover wound function." As a wound heals, three types of skin cells step in. Macrophages are the first responders -- and the most widely studied cells -- that arrive within 24 hours of damage. Next, fibroblasts arrive, which are like the body's engineers. They help lay down the extracellular matrix that makes it possible for the next cells, keratinocytes, to come in and do the heavy-lifting and rebuilding.

"Wound healing is a complex, cell-mediated symphony of events, progressing through a series of predictable and overlapping stages," Frost and her team write in their Medical Sciences paper. When any part of that orchestra is out of tune, the whole process falls flat. Fibroblasts, which are not as well studied as macrophages in the healing process, are a key instrument and past studies have shown their delayed response in patients with diabetes may be a major factor in slow healing time. That's where nitric oxide steps in, a kind of chemical metronome to get the process back into the right rhythm. But the body's dermal orchestra is not so simple -- just as playing a metronome louder and louder isn't necessarily going to make a musician's timing improve, flooding a wound with nitric oxide isn't a cure all.

"The old approach is to add nitric oxide and sit back to see if it works," Frost says. "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." A big problem that Frost and her team address is how nitric oxide is measured in the first place. While stable nitrite is easier to measure, by itself it cannot relay the real-time healing status like nitric oxide levels can. So, Frost's lab built a nitric oxide-measuring device for their study by hand. Now they are exploring ways to streamline the building process and produce commercial nitric oxide measurement devices that would improve their research. In a few years, they plan to have a working bandage prototype, one that leaves off the clunky nitrite proxies and nitric oxide dumps. Instead, patients dealing with diabetic foot ulcers will see a light at the end of the tunnel much sooner than half a year or more -- the nitric oxide-releasing bandage could help heal one of healthcare's toughest diseases in less than a month.

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