Pick up a piece of IV tubing (should you happen to have one nearby) and run your hand down the length of it. The surface feels pretty smooth, yes?
From the perspective of bacteria and platelets, that same surface is pockmarked with nooks and crannies where they can stick, aggregate and start to form blood clots (in the case of platelets) or hard-to-combat biofilms (in the case of bacteria).
That’s a problem for hospital care. Contaminated central lines (IV lines threaded into deep veins for long periods of time) cause upwards of 41,000 costly and potentially fatal central line-associated bloodstream infections (CLABSIs) in pediatric and adult patients in U.S. hospitals every year. And blood clots can preclude patients, including premature babies, from receiving new lung-protecting treatments because they can’t tolerate anticoagulants.
Both problems may have a single solution. Clinicians in Boston Children’s Department of Newborn Medicine and engineers at Harvard’s Wyss Institute for Biologically Inspired Engineering have collaborated to develop a coating, inspired by pitcher plants, that makes the surfaces of clinical-grade plastics so slippery that platelets and bacteria can’t get a toehold.
From pitcher plants to SLIPS
The coating is called Slippery Liquid-Infused Porous Surfaces, or SLIPS. Developed by a team led by Wyss faculty member Joanna Aizenberg, PhD, it’s a solid material similar to Teflon infused with a liquid. It’s omniphobic: When fused onto a plastic surface, effectively nothing—blood, bacteria or water—will stick to it.
“SLIPS was originally developed for self-cleaning optics, for transportation of sticky, viscous crude oil and to prevent ice build-up in refrigeration,” says Wyss scientist Michael Super, PhD. “It mimics the surface of Nepenthes pitcher plants, which becomes exceptionally slippery when wet.” (See Aizenberg’s original 2011 Nature paper on SLIPS to learn more.)
Super first became interested in SLIPS when working on a way to keep blood flowing through a device for treating sepsis in soldiers. But a 2012 meeting with Anne Hansen, MD, MPH, medical director of Boston Children’s Neonatal Intensive Care Unit (NICU), turned into an opportunity to use SLIPS to solve to two clinical problems that keep NICU doctors like Hansen up at night—CLABSIs and lung disease in premature babies.
SLIPping the bacteria out of central lines
“About half of all babies in neonatal intensive care have central lines,” says Hansen. “And despite efforts to prevent infection, CLABSIs remain a common occurrence in hospitals across the U.S.”
Looking to reduce CLABSI rates, Super has tested whether bacteria like Pseudomonas aeruginosa could stick to and colonize plastics, IV lines and catheter tips coated with a newer version of SLIPS called Smooth-SLIPS. (“The advantage to Smooth-SLIPS is that we can coat existing, approved medical devices and, should it leach off, the remaining surface is still medical-grade plastic,” Super notes.)
The pair also is testing whether pathogens stick to Smooth-SLIPS-coated central lines in an animal model. So far, all indications say no. Smooth-SLIPS-coated IV lines exposed to Pseudomonas stayed biofilm-free the entire course of a six-week long experiment; in uncoated lines, biofilms formed in just hours.
“We can’t say the bacteria don’t stick at all,” says Super, “but we’ve reached the lowest level of detection of our assays and haven’t found any signs of colonization.”
SLIPpery lines for lung bypass
“Premature infants are born with very under-developed lungs and are often put on ventilators,” Hansen explains. “However, mechanical ventilation itself can lead to chronic lung disease because the babies’ lungs are injured by the pressure, volume and oxygen exposure.”
Neonatologists like Hansen would like to be able to protect the lungs with lung bypass—a life-support system similar to extracorporeal membrane oxygenation (ECMO) or heart-lung bypass.
“With many premature babies, it’s only the lungs that need help because the heart is fine,” Hansen notes. “We want to be able to ‘breathe’ for the babies without them having to use their lungs, protecting them until they develop further.”
To keep the blood flowing, children and adults on ECMO or other kinds of lung bypass must be heavily anticoagulated. But that’s a problem for premature babies: Anticoagulants put them at high risk of bleeding into the brain.
SLIPS mimics the surface of a species of pitcher plant, which becomes exceptionally slippery when wet.
So Super and Hansen have been testing the coating’s ability to keep the blood in IV lines flowing without anticoagulation—both in a laboratory environment and an animal model of an arteriovenous shunt.
Their shunt results are perhaps the most promising and striking. While regular uncoated lines clotted completely within two to four hours, Smooth-SLIPS-coated lines stayed clot-free for more than six hours without any assistance from anticoagulants, and without any signs of microclotting or platelet activation.
As they discussed at a recent Innovators’ Forum, a monthly gathering held by Boston Children’s Innovation Acceleration Program, Hansen and Super know they have many questions to answer before their coated catheters can be inserted into people. How long can a Smooth-SLIPS-coated central line be used without becoming bacterially contaminated? Does Smooth-SLIPS leach from the line’s plastic surface? Will blood clot in Smooth-SLIPS-coated lung bypass machines?
But already the pair has done what many struggle to do: to match a promising technology to a clinical need. “Between Boston Children’s and the Wyss, we have a mix of clinical and engineering expertise that helps match technologies to problems that need to be solved,” Super says. “It’s a great thing.”