Bioinspired coating for medical devices avoids clotting and suppresses bacterial infection

Repels blood and bacteria, including biofilms
October 15, 2014

This scanning electron microscope (SEM) image shows how red blood cells coagulate to form a blood clot, which is a common and life-threatening risk associated with the use of implanted medical devices (credit: James Weaver, Harvard’s Wyss Institute)

A team of Harvard scientists and engineers has developed a new surface coating for medical devices that in tests repelled blood from more than 20 medically relevant substrates and also suppressed biofilm formation.

The study was reported in Nature Biotechnology.

Avoiding blood clotting and bacterial infcction

The problem they addressed was that any device implanted in the body (or in contact with flowing blood) could result in blood clotting or bacterial infection.

In a test, the team implanted medical-grade tubing and catheters, coated with the FDA-approved material, in large blood vessels in pigs. That prevented blood from clotting for at least eight hours.

Normally, anticoagulants such as heparin are used for that purpose, but heparin can cause potentially lethal side-effects like excessive bleeding.

“Devising a way to prevent blood clotting without using anticoagulants is one of the holy grails in medicine,” said Don Ingber, M.D., Ph.D., Founding Director of Harvard’s Wyss Institute for Biologically Inspired Engineering and senior author of the study. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, as well as professor of bioengineering at Harvard School of Engineering and Applied Sciences (SEAS).

These glass slides were dipped in blood to demonstrate the effectiveness of the TLP coating. While blood sticks to the untreated slide on the left, the TLP-treated slide on the right emerges entirely clear. (Credit: Harvard’s Wyss Institute)

Inspired by the carnivorous pitcher plant

The idea for the coating evolved from SLIPS (Slippery Liquid–Infused Porous Surfaces)  a pioneering surface technology developed by coauthor Joanna Aizenberg, Ph.D., who is a Wyss Institute Core Faculty member and the Amy Smith Berylson Professor of Materials Science at Harvard SEAS.

Inspired by the slippery surface of the carnivorous pitcher plant, which enables the plant to capture insects, SLIPS repels nearly any material it contacts. The liquid layer on the surface provides a barrier to everything from ice to crude oil and blood.

Tethered-Liquid Perfluorocarbon surface (TLP)

“SLIPS uses porous, textured surface substrates to immobilize the liquid layer, whereas medical surfaces are mostly flat and smooth — so we further adapted our approach by capitalizing on the natural roughness of chemically modified surfaces of medical devices,” said Aizenberg, who leads the Wyss Institute’s Adaptive Materials platform.

The Wyss team developed a super-repellent coating that can be adhered to existing, approved medical devices. In a two-step surface-coating process, they chemically attached a monolayer of perfluorocarbon, which is similar to Teflon. Then they added a layer of liquid perfluorocarbon, which is widely used in medicine for applications such as liquid ventilation for infants with breathing challenges, blood substitution, and eye surgery. The team calls the tethered perfluorocarbon plus the liquid layer a Tethered-Liquid Perfluorocarbon surface (TLP).

The TLP coating achieved the following results:

  • TLP-treated medical tubing was stored for more than a year under normal temperature and humidity conditions and still prevented clot formation
  • The TLP surface remained stable under the full range of clinically relevant physiological shear stresses, or rates of blood flow seen in catheters and central lines, all the way up to dialysis machines
  • It repelled the components of blood that cause clotting (fibrin and platelets)
  • When Pseudomonas aeruginosa bacteria were grown in TLP-coated medical tubing for more than six weeks, less than one in a billion bacteria were able to adhere. Central lines coated with TLP significantly reduced sepsis from Central–Line Mediated Bloodstream Infections (CLABSI). (Sepsis is a life-threatening blood infection caused by bacteria, and a significant risk for patients with implanted medical devices.)

The researchers even tested a TLP-coated surface with a gecko, the superstar of sticking whose footpads contain many thousands of hairlike structures with tremendous adhesive strength. The gecko was unable to hold on.

“We feel this is just the beginning of how we might test this for use in the clinic,” said co-lead author Daniel Leslie, Ph.D., a Wyss Institute Staff Scientist, who aims to test it on more complex systems such as dialysis machines and ECMO, a machine used in the intensive care unit to help critically ill patients breathe.

The cross-disciplinary team included researchers representing the Wyss Institute, SEAS, Harvard Medical School, and Boston Children’s Hospital, with specialties ranging from hematology to immunology, surface chemistry, and materials science.

The project was funded by the Defense Advanced Research Projects Agency (DARPA) and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Harvard’s Wyss Institute | Wyss Institute researchers discuss how they used FDA-approved materials to develop a slippery coating that can be applied to medical devices to prevent blood clotting and bacteria accumulation.