A new technique could reduce the risk of blood clots associated with medical implants, making them safer for patients. The technique, which was developed by researchers at the University of Sydney, Australia, involves coating the implants with highly hydrophilic molecules known as zwitterions, thereby inhibiting the build-up of clot-triggering proteins.
Proteins in blood can stick to the surfaces of medical implants such as heart valves and vascular stents. When this happens, it produces a cascade effect in which multiple mechanisms lead to the formation of extensive clots and fibrous networks. These clots and networks can impair the function of implanted medical devices so much that invasive surgery may be required to remove or replace the implant.
To prevent this from happening, the surfaces of implants are often treated with polymeric coatings that resist biofouling. Hydrophilic polymeric coatings such as polyethylene glycol are especially useful, as their water-loving nature allows a thin layer of water to form between them and the surface of the implants, held in place via hydrogen and/or electrostatic bonds. This water layer forms a barrier that prevents proteins from sticking, or adsorbing, to the implant.
An extra layer of zwitterions
Recently, researchers discovered that polymers coated with an extra layer of small molecules called zwitterions provided even more protection against protein adsorption. “Zwitter” means “hybrid” in German; hence, zwitterions are molecules that carry both positive and negative charge, making them neutrally charged overall. These molecules are also very hydrophilic and easily form tight bonds with water molecules. The resulting layer of water has a structure that is similar to that of bulk water, which is energetically stable.
A further attraction of zwitterionic coatings for medical implants is that zwitterions are naturally present in our bodies. In fact, they make up the hydrophilic phospholipid heads of mammalian cell membranes, which play a vital role in regulating interactions between biological cells and the extracellular environment.
Plasma functionalization
In the new work, researchers led by Sina Naficy grafted nanometre-thick zwitterionic coatings onto the surfaces of implant materials using a technique called plasma functionalization. They found that the resulting structures reduce the amount of fibrinogen proteins that adsorb onto the implants by roughly nine-fold and decrease blood clot formation (thrombosis) by almost 75%.
Naficy and colleagues achieved their results by optimizing the density, coverage and thickness of the coating. This was critical for realizing the full potential of these materials, they say, because a coating that is not fully optimized would not reduce clotting.
Naficy tells Physics World that the team’s main goal is to enhance the surface properties of medical devices. “These devices when implanted are in contact with blood and can readily cause thrombosis or infection if the surface initiates certain biological cascade reactions,” he explains. “Most such reactions begin when specific proteins adsorb on the surface and activate the next stage of cascade. Optimizing surface properties with the aid of zwitterions can control / inhibit protein adsorption, hence reducing the severity of adverse body reactions.”
The researchers say they will now be evaluating the long-term stability of the zwitterion-polymer coatings and trying to scale up their grafting process. They report their work in Communications Materials and Cell Biomaterials.
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