Researchers at the University of Washington Engineered Biomaterials Center (Seattle; 206-616-9718) have developed a technique for coating material surfaces with tiny indentations that bind to specific proteins. The process may be used to create medical implants that trigger normal healing responses rather than the body's typical, and often disruptive, reaction to such devices. This is the first coating process that works on the atomically flat surfaces of artificial implant materials. This is likely to impact a large number of people, as more than 500 million medical devices are implanted in patients every year.
How It Works (Back to Top)
More than 500 million medical devices are implanted in patients every year, ranging from simple catheters to heart valves to artificial hips. While these devices save or improve the lives of millions of people, they often deliver only temporary fixes. The body's natural response to foreign materialwhether it's a medical implant or a bulletis to wall it off with scar-like tissue. Frequently, this reaction disrupts the device's performance and necessitates further medical intervention.
When a patient's body rejects an implant, it is usually because proteins that normally direct the healing process are unable to recognize the artificial materials used to make the implants. The implants are bombarded by a jumble of proteins that confuse the macrophage cells responsible for tissue regeneration and trigger the body's inflammatory reaction to foreign material, according to Buddy Ratner, the research team leader who discovered the new coating process. Ratner directs the UW Engineered Biomaterials Center, a $25 million National Science Foundation initiative to create next-generation medical implants. UW bioengineering graduate student Galen Shi also worked on the research project.
To avoid the scarring process that often accompanies implant surgery, the UW research team devised a complex process for coating artificial materials so their surfaces can attract and bind specific proteins. To begin the process, a layer of the desired protein is spread over a smooth surface like mica. The proteins and mica are then coated with a thin layer of sugar molecules. Next, a Teflon-like fluoropolymer coating is applied to the surface through a gas-phase plasma-deposition process. The coating is then peeled off the mica and dipped into a solution to dissolve the proteins. The remaining material is a Teflon-like polymer coating containing sugar-lined pits in the exact shape of a specific protein.
Laboratory experiments show that coatings prepared in this way have a strong affinity for the protein used to form the pits. This is because of a combination of the proteins recognizing the shape of the pits and the sugar molecules binding to the surface of the proteins, Ratner says. Tests were done using proteins of similar sizes and only the protein with the appropriate shape and chemistry adhered to the UW coating.
Applications (Back to Top)
"The ability to make surfaces that can be recognized by the body is a major step forward in our quest for biomaterials and implants that heal," Ratner says. "This is the first coating process that works on the atomically flat surfaces of artificial materials commonly used in implants and that promotes affinity for specific proteins. Our approach potentially can be used for any kind of implant."
One of the proteins to be tested next is osteopontin. UW bioengineering professor Cecilia Giachelli discovered that osteopontin plays a critical role in preventing calcification of heart valves, but is not typically present in high concentrations on artificial valve implants. Ratner and Giachelli will explore whether valve implants coated using the UW process will bind enough osteopontin to inhibit calcification. This may reduce the need for dangerous and expensive valve replacement surgery in tens of thousands of patients.
"We've achieved with ordinary synthetic materials the highly specific lock-and-key fit we see in natural healing, and that has been one of the toughest hurdles," Ratner says. "The next step is to see if an implant coated using our process actually turns on healing in the body."
The research was reported in the April 15, 1999, issue of Nature. Shi has been recognized by the Society for Biomaterials and the American Vacuum Society for outstanding Ph.D. research in connection with this project. He is supported by the UW Center for Nanotechnology, which along with the UW Engineered Biomaterials Center is a leader in developing nanoscale molecular engineering techniques for precision control of biology.
For more information, call Ratner at 206-616-9718 or e-mail firstname.lastname@example.org.