Engineered biomaterial prevents body’s attack on medical implants

May 16, 2013


These images show differences in collagen buildup (which interferes with implants) in two tissue samples. Collagen is shown in blue. The left image shows a thick collagen wall (arrow) forming in the presence of a poly(2-hydroxyethyl methacrylate), a material that’s currently widely used for implantable devices. In contrast, collagen in the right image is more evenly dispersed in the tissue after the UW-engineered hydrogel has been implanted. (Credit: Lei Zhang/University of Washington)

University of Washington engineers have demonstrated in mice a way to prevent failure of implants and prostheses, using a synthetic hydrogel biomaterial that fully resists the body’s natural attack response to foreign objects.

Medical devices such as artificial heart valves, prostheses and breast implants could be coated with this polymer to prevent the body from rejecting an implanted object.

How medical implants fail

The body’s biological response to implanted devices — medical technologies that often cost millions to develop — has frustrated experts for years. After an implant, the body usually creates a protein wall around the medical device, cutting it off from the rest of the body. Scientists call this barrier a collagen capsule. Collagen is a protein that’s naturally found in our bodies, particularly in connective tissues such as tendons and ligaments.

If a device such as an artificial valve or an electrode sensor is blocked off from the rest of the body, it usually fails to work. Physicians and scientists have tried to minimize this, but they haven’t been able to eliminate it, said Buddy Ratner, co-author and a UW professor of bioengineering and of chemical engineering.

The foreign-body reaction occurs in response to implants made of many materials, including teflon, polyurethane, silicone rubber, polyethylene, poly(methyl methacrylate), poly(ethylene glycol) (PEG), Dacron, gold, titanium and alumina, including other hydrogels, such as poly(2-hydroxyethyl methacrylate) (PHEMA), the authors say in a Nature Biotechnology paper.

Improved hydrogel

Ratner’s collaborator and co-author Shaoyi Jiang, a UW professor of chemical engineering, and his team implanted an improved hydrogel polymer substance, known as poly(carboxybetaine methacrylate)
(PCBMA), into the bodies of mice.

A hydrogel is a flexible biomedical material that swells with water. It’s made from a polymer that deflects all proteins from sticking to its surface. (Scientists have found that proteins appearing on the surface of a medical implant are the first signs that a larger collagen wall will form.)

After three months, Jiang and his team found that collagen was loosely and evenly distributed in the tissue around the polymer, suggesting that the mice bodies didn’t even detect the polymer’s presence.

For humans, the first three weeks after an implant are the most critical, because by then the body will show signs of isolating the implant by building a collagen wall. If this hasn’t happened in the first several weeks, it’s likely the body won’t default to an attack response toward the object.

Human tests

UW researchers and others have worked for nearly 20 years to find a way to help the body accept implants. In 1996, the National Science Foundation-funded UW Engineered Biomaterials (UWEB) research center opened at the UW, with Ratner serving as director. Since that time, researchers have been trying to make a material that is invisible to the body’s immune response and could eliminate the body’s negative reaction to medical implants.

The UW researchers plan to test this material in humans, likely by working with manufacturers to coat an implantable device with the polymer, then measure its ability to ward off protein build-up.

The research was funded by the U.S. Office of Naval Research, UWEB and the UW Department of Chemical Engineering.