Healing diabetic ulcers in 21 days instead of 150 days

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 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.

Nitric Oxide vs. Nitrite

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. Current practice substitutes measuring nitrite for nitric oxide—a misleading switch, Frost says, because nitrite is a byproduct with no time signature. 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. That creates a challenge since it means taking measurements is much harder, which limits the dataset size, but Frost has an agreement with Zysense LLC to streamline the building process and produce commercial nitric oxide measurement devices that would improve cell chemistry research.

Next Steps

Collaboration is a key part of the engineering design process. To build a nitric oxide bandage with personalized healing power, the team plans to work next with the UP Portage Health System to gather cell samples from local patients. By expanding their cell samples—and applying the tech to real-world patients—the team will continue to broaden their database while deepening their knowledge of nitric oxide mechanisms.

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 health care’s toughest diseases in less than a month.

Learn more: Diabetic Foot Ulcers Heal Quickly with Nitric Oxide Technology