University of Michigan analytical chemists have developed polymers containing tiny silica particles that release low levels of nitric oxide gas. The U-M polymers are designed to mimic human endothelial cells, which produce nitric oxide to relax blood vessels and inhibit blood coagulation.
"Our goal is to reproduce the body's natural nitric oxide production system, which prevents clots from forming inside blood vessels," said Mark E. Meyerhoff, U-M professor of chemistry.
At the American Chemical Society meeting held here this week, Huiping Zhang, U-M graduate student, presented results of recent studies showing that fumed silica particles incorporated into polyurethane and silicone rubber films can generate levels of nitric oxide comparable to endothelial cells for up to 24 hours.
According to Meyerhoff, polymers that release nitric oxide could help prevent the formation of blood clots on biomedical devices---such as tubing, equipment or plastic bags which come in direct contact with blood during heart by-pass surgery, kidney dialysis or extracorporeal membrane oxygenation (ECMO).
Meyerhoff also hopes to use NO-releasing polymers to coat implantable blood sensors, currently under development at U-M, which could continuously monitor vital electrolytes and blood gases in critically ill patients.
"Ten-nanometer fumed silica particles are chemically derivatized to contain surface diazeniumdiolate functional groups, which release nitric oxide slowly over long periods of time when exposed to water," Zhang explained.
"Our initial studies used nitric oxide release chemistry which contaminated the blood with diamine precursors," Zhang added. To avoid this problem, he has developed and is now testing new silicone rubber and polyurethane materials in which the diazeniumdiolates are covalently linked to the fumed silica filler particles, so leaching cannot occur.
Fabricating polymers with NO-releasing fumed silica particles is not difficult and the materials are inexpensive and readily available, according to Zhang. Additional laboratory and animal tests are currently under way to evaluate the blood compatibility of the NO-generating polymers.
U-M research to develop NO- releasing polymers is funded by the National Institutes of Health and Michigan Critical Care Consultants, Inc. of Ann Arbor, Mich. Kelly A. Mowery and Jeffrey K. Politis, former U-M graduate students, and Melissa Batchelor and Bong Oh, current U-M graduate students, also participated in the research project.
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