September 2001

From University of North Carolina at Chapel Hill

Study: nitric oxide-releasing materials might reduce medical implant infections

CHAPEL HILL – To varying degrees, medical implants such as catheters, artificial organs and sensors placed under the skin are critical to curing illness or making life better for the infirm, but they also raise the risk of serious infection. More than half of all hospital-acquired infections have been linked to implanted medical devices.

Now studies conducted by University of North Carolina at Chapel Hill chemists show it should be possible to cut that risk significantly by a method that mimics the body’s own self-defense mechanisms.

Led by Dr. Mark H. Schoenfisch, assistant professor of chemistry, researchers have found they can store nitric oxide in sol-gel based materials that could be used to coat implants. Nitric oxide, a natural anti-bacterial agent, is slowly released by the coating when placed in watery environments such as blood or tissue and reduces bacteria’s tendency stick to the implants and form living films that lead to infection.

“Efforts to reduce infections related to medical implants using conventional antibiotic treatments suffer from the widespread problem of emerging resistance from the most troublesome bacterial strains,” Schoenfisch said. “However, local nitric oxide release mimics our body’s own self-defense mechanisms against foreign cells.

“During a process called phagocytosis, immune system cells engulf bacteria and release high levels of reactive molecules, including nitric oxide, to destroy these foreign cells,” he said. “Thus, we hypothesized that polymeric nitric oxide release might represent a new approach for reducing bacterial adhesion and possibly the incidence or severity of infection.”

A report on the research will appear in the Journal of the American Chemical Society this fall, but was posted Sept. 6 on the society’s Web site under ASAP Contents http://pubs.acs.org/journals/jacsat/index.html. Graduate student Brian J. Nablo and former postdoctoral fellow Dr. Ta.-Yung Chen also are authors.

The team created compounds known as aminosilane-based sol-gels as thin films on glass slides. They then converted the amino acid groups to nitric oxide “donors” by exposing the films to high pressures of nitric oxide gas.

Later measurements showed that the compounds released nitric oxide gas continuously for days, Schoenfisch said. Varying the amount and type of aminosilane in the sol-gel could change the rate and amount of nitric oxide release.

To test whether the materials prevented bacterial adhesion, the team then exposed both nitric oxide-releasing and untreated control slides to solutions of Pseudomonas aeruginosa, a common infection-causing bacterium. Bacterial adhesion was as much as 70 percent lower on the nitric oxide-releasing slides.

Preventing bacterial adhesion and biofilm formation is vital for reducing infection since biofilms are extremely resistant to immune system defenses once they have formed on an implant, the scientist said. Such films can cause chronic illness with severe and universal symptoms such as headache, nausea, vomiting, abdominal cramps, sore throat, sore eyes and fever, making diagnosis difficult.

Besides its anti-bacterial adhesion properties, nitric oxide plays a role in several other important physiological processes including blood pressure regulation, nerve transmission, platelet adhesion and tumor cell growth. The impotence drug Viagra relies on nitric oxide action to work, he said.

“People in the biomaterial research community have been struggling for years to control bacterial adhesion,” Schoenfisch said. “Despite the many recent advances in medicine, implant-related infection remains a most serious problem. Polymeric nitric oxide release represents a unique strategy, particularly since nitric oxide has a short half-life in blood -- just a few seconds -- and thus would only have an effect on areas near the implant site where it is needed most.”

UNC’s College of Arts and Sciences supported the studies with start-up funding. Note: Schoenfisch can be reached at 919-843-8714 or schoenfi@email.unc.edu.











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