SURGERY • CONTINUED FROM PREVIOUS PAGE
Gels that mimic life
As a general rule, bodies don’t like foreign
substances, so when you deliver an anti-
inflammatory compound into an open wound,
the first rule is to avoid more inflammation.
For this, the zwitterion is ideal.
Monomers with complementary positive and
negative sides, zwitterions link up to form
long polymer chains, chemically slippery and
biologically benign. In fact, they’re not far off from
actual biology. One well-known form of zwitterion:
the amino acid, building block of life.
Dissolved in water, these polymers will evenly
disperse to form a nice gel, the kind Dr. Krebs,
who makes biomimetic hydrogels with a variety of
properties in collaboration with several research
teams at Children’s Colorado (see “Growing a
Growth Plate,” p. 46), likes to work with. As a
drug-delivery system, however, it’s a bit one-
dimensional. The polymer is so evenly dispersed
that the drug pretty much bleeds out right away.
“You make that mix in a freezer, though, and the
polymerization still occurs, but as it’s occurring
the water is freezing, so the ice is clustering, and
that makes the polymer cluster,” says Dr. Krebs. “It
compartmentalizes the ice and the polymer, so you
get a denser polymer structure that can physically
entrap the drugs we’re putting in.”
The natural pressure of daily life then squeezes the
drug out through a kind a labyrinth of polymers for
an impressively even, sustained delivery.
“It keeps the area moist and over time releases
the conjugate into the wound,” says Dr. Liechty.
“We’re seeing healing times along the same lines
as injection.”
Even better, it protects the wound while it heals.
“It keeps in moisture and lets the area knit
together underneath,” says Dr. Krebs. “After a
while, after the tissue heals, our gel will basically
just pop off. It’s like a smart Band-Aid.”
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Better would be a topical application, maybe a
cream or a gel. Something you could do right at
home. For that, they’re partnering with Colorado
School of Mines bioengineer Melissa Krebs, PhD,
who developed a water-based biomimetic gel that
not only to infuses the conjugate into the wound
but acts as a bandage with a time-release.
“We can get up to four months of sustained
protein release,” says Dr. Krebs. “It’s great for
wounds because nothing will stick to it, so you’re
not provoking an inflammation, and it’s acting as
a nice layer of protection.”
But even better than faster healing is a wound
that never occurs. For that the team is developing
another nanoparticle, this one derived from silk.
“You think about silk sutures, they’re strong.
They don’t break,” says Dr. Zgheib. “We found
this nanosilk solution we make in the lab actually
strengthens diabetic skin. The idea is, imagine a
spray bottle. You spray it on, give it a minute to dry
off, that’s it.”
It’s a kind of invisible armor that could protect
skin ulcers of all kinds, from diabetic wounds to
pressure injuries in hospitals or nursing homes.
It’s also effective, coupled with Dr. Krebs’ gel, for
protecting wounds as they heal.
But the implications of their work plumb deeper
than skin. With its dual mechanisms of attack, the
conjugate has potential to revise the mechanism of
healing all over the body, wherever inflammation
exists. Dr. Liechty’s collaborators at the University
of Pennsylvania found it can prevent cardiac
remodeling after a heart attack. Others showed it
can decrease fibrosis and promote lung function.
More studies are in the works.
“Hopefully we’ll have this online by the time I have
heart disease,” Dr. Liechty says, only half-joking.
“It’s really the future.” ●
To see more on wound healing, visit
childrenscolorado.org/Gel.
UROLOGY
Surgery
Like an
Airline
People do things better when they know what they’re doing ahead
of time. That’s the basic philosophy behind ERAS, a set of surgical
care standards first adapted for pediatrics by a group of urologists
at Children’s Colorado.
Now they’re on a mission to spread the word.
“Think about how incredibly safe it is to fly,”
says pediatric urologist Nicholas Cost, MD.
“The strength of the airline industry is checklists
and adherence to protocol. There’s no reason
we shouldn’t do the same thing.”
In the Department of Urology, they’re doing that,
in part, by dismantling and testing every aspect of
conventional surgical procedure. For example, for
most surgeries, the standard is to fast the patient
for a day beforehand and a few days afterward,
using an NG tube to empty the stomach and “rest”
the bowel.
The groundbreaking work of Danish adult
colorectal surgeon Henrik Kehlet, MD, PhD,
showed that’s not only unnecessary, it’s not
even good for the patient.
“Minimizing time where patients get nothing by
mouth actually decreases metabolic stress after
surgery,” says pediatric urologist Kyle Rove, MD.
The strength of the
airline industry
is checklists and
adherence to
protocol. There’s no
reason we shouldn’t
do the same thing.”
N I C H O L A S C O S T, M D
Pediatric Urologist
NEW CONSTELLATIONS
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