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Better than a diabetic wound that heals But it didn’t work on diabetic wounds.
is one that never happens. Dr. Liechty and At the same time, Dr. Liechty’s research team was
working with microRNAs, non-coding RNAs that
regulate gene expression. They’d been used in
cancer research, but Dr. Liechty’s team was the
first to use them to recreate the inflammatory
conditions of the womb by shutting down pro-
inflammatory interleukins 6 and 8.
his team developed a nanosilk serum that
strengthens the skin.
can’t feel it when you’re injured, and then there’s a
bunch of bacteria sitting around.”
“It creates an environment so inflammatory, so
hostile,” says University of Colorado School of
Medicine regenerative biologist Carlos Zgheib,
PhD, a researcher in Dr. Liechty’s lab, “that cells
are not going to be able to proliferate and close
that wound.”
More than 30 million people in the U.S. have
diabetes, and 20 percent of them have non-healing
wounds. That’s on top of 84 million more with
prediabetes. At last count, the rate of diabetic
amputations was around 73,000 a year.
“So the question is,” says Dr. Liechty, “how do you
fetalize the adult?”
difference in the fetal inflammatory response.
From an evolutionary perspective, that would
make sense.
Once you’re out of
the womb, it’s about
getting the wound
closed before you
die of infection.”
K E N N E T H L I E C H T Y, M D
Pediatric Thoracic and
Fetal Surgeon,
The Sandy Wolf Chair in
Maternal Fetal Surgery
58
A fetus’s priority is to grow and make new tissue.
They don’t need a big, brisk inflammatory response
against the outside world’s many agents of harm.
“Once you’re out of the womb,” he says,
“it’s about getting the wound closed before you
die of infection.”
Good if you’re a hunter-gatherer, not so good if you
have, say, a chronically inflammatory condition.
Even worse if you have one like diabetes, which
also saps the immune system, weakens skin,
damages nerves and, because it often correlates
with obesity, puts extra pressure on feet.
“The bacterial load of diabetic skin is 40 times
higher than healthy skin,” says Dr. Liechty. “So you
have skin that’s weaker and easier to injure, you
A two-pronged approach
to healing
When the skin breaks, macrophages invade the
area and start cranking out reactive oxygen
species, volatile compounds that damage cells
around them by stripping elements of their DNA.
That damages microbes, but it also damages the
surrounding tissue.
Materials engineer and biochemist Sudipta Seal,
PhD, Dr. Liechty’s collaborator at the University
of Central Florida, figured out years ago that a
rare earth metal called cerium oxide could bind
reactive oxygen species. At the time it was used
primarily in catalytic converters and jewelry polish.
Dr. Seal observed that, in the form of nanoparticles
known as nanoceria, it could slow the progression
of macular degeneration. Drs. Liechty and Zgheib
discovered it could promote wound healing.
The problem was that oxidative stress signals
more inflammation. Diabetic wounds were
so persistent that, as soon as the microRNA
wore off, oxidative stress would stoke the
inflammation again.
It was when they combined the two, conjugating
the microRNA to the nanoceria particle, that
everything changed.
“It was like a miracle,” says Dr. Zgheib. “In the
animal model, we corrected diabetic healing to
the normal rate.”
The discovery earned Dr. Zgheib the American
College of Surgeons’ Excellence in Research Award
last year, with publication in that group’s journal.
The research team hopes to start phase 1 clinical
trials this year.
“You’d worry maybe it’s just a superficial closure,
not functionally healed,” adds Dr. Liechty. “We’ve
shown it’s actually better. Diabetic skin at baseline
is weak. When we test our wound closures, they’re
stronger.”
Engineering the delivery
In the meantime, they’re refining how the
combination of nanoceria and microRNA, which
Dr. Zgheib calls “the conjugate,” gets into the wound.
Initially they injected it. That’s fine for animal studies,
but they knew sticking needles into open wounds
would be a tall order for actual patients.
NEW CONSTELLATIONS
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