New Constellations 2019 | Page 62

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.” 60 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 61