Our bodies have evolved to be pretty good at dealing with incursions by foreign objects and bacteria. Usually, that's a positive thing, but it can spell trouble for medical devices, such as replacement joints, cardiac implants and dialysis machines, which increase the risk of blood clots and bacterial infection. Now researchers at Harvard University have developed a surface coating that smooths the way for medical devices to do their job inside the human body.
The new surface coating is the latest evolution of the SLIPS (Slippery Liquid-Infused Porous Surfaces) surface technology that we first came across in 2012 when it was preventing ice forming on metal surfaces. In 2013 it played a role in a spleen-on-a-chip blood filtration device, before being made transparent and more durable a few months later.
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Inspired by the carnivorous pitcher plant, which features a slippery rim that causes insects to fall into its trap, SLIPS places a liquid layer on a surface that provides a barrier to repel just about any material. In this latest development, the technology was modified to make it compatible with medical devices.
"Traditional 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 Joanna Aizenberg, Ph.D., who led the Harvard research team responsible for SLIPS. "This is yet another incarnation of the highly customizable SLIPS platform that can be designed to create slippery, non–adhesive surfaces on any material."
The coating was developed from materials already approved by the US Food and Drug Administration (FDA), with the team claiming it repelled blood from more than 20 different substrates made from materials commonly used in medical devices, such as plastic, glass and metal. The coating also repelled bacteria and suppressed the formation of biofilm.
Scanning Electron Microscope (SEM) image showing how red blood cells coagulate to form a blood clot (Image: James Weaver, Harvard’s Wyss Institute)
Furthermore, the team found that medical-grade tubing and catheters coated with the material and implanted in large blood vessels in pigs prevented blood from clotting for at least eight hours without the use of blood thinners, such as heparin. Although necessary in medical treatments where blood clotting is a risk and included on the World Health Organization's List of Essential Medicines, heparin can often have potentially lethal side effects, such as excessive bleeding.
"Devising a way to prevent blood clotting without using anticoagulants is one of the holy grails in medicine," says Don Ingber, M.D., Ph.D., Founding Director of Harvard's Wyss Institute for Biologically Inspired Engineering and senior author of the team's study.
Adhering the super-repellent coating to existing, approved medical devices is a two-step process that begins with chemically attaching a monolayer of perfluorocarbon, a material similar to Teflon. Then, a layer of liquid perfluorocarbon, which has a variety of medical applications, is added to form a tethered perfluorocarbon and a liquid layer. The team call this a Tethered-Liquid Perfluorocarbon surface, or TLP.
In addition to its aforementioned capabilities, the researchers found that TLP produced a number of other impressive results. Medical tubing treated with TLP still prevented clot formation after being stored for a year under normal temperature and humidity conditions, and the TLP surface remained stable when subjected to the shear stresses resulting from blood flow in catheters, central lines and dialysis machines. The surface coating repelled fibrin and platelets, the components of the blood that cause clotting.
Also, less than one in a billion of Pseudomonas aeruginosa bacteria grown in TLP-coated medical tubing for more than six weeks were able to adhere to the surface, with central lines coated in TLP found to significantly reduce sepsis from Central-Line Mediated Bloodstream Infections (CLABSI). In an experiment purely to satisfy their own curiosity, the TLP coating was even able to undo the gecko's famous sticking power.
"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., referring to the relatively simple catheters and perfusion tubing setups used to demonstrate the technology, not the gecko. Leslie will now look to test the TLP coating 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 project was funded by DARPA and the Wyss Institute for Biologically Inspired Engineering at Harvard University, with the team's paper appearing in the journal Nature Biotechnology.
The coating is detailed in the video below.
Source: Wyss Institute