Jan 31 2005
A plastic that releases nitric oxide could be used to make artificial blood vessels that do not clog.
Plastic tubes can be used to replace blood vessels, for example in coronary-artery bypass surgery. But tubes smaller than about 6 mm across are often gummed up by platelets, the sticky blood cells that make clots. If the clots break free, they can damage the brain and other organs.
Nitric oxide stops platelets sticking together, and stimulates growth in the cells lining blood vessels. Even better, it stunts the growth of smooth muscle that could squeeze an artificial vessel closed.
"That's the remarkable thing about nitric oxide; it has all these beneficial effects on different types of tissue," says bioengineer Jennifer West of Rice University in Houston, one of the plastic's inventors. West's team report their work in the journal Biomacromolecules.
Anticoagulant drugs are often used to keep conventional grafts clear, but this can lead to bleeding elsewhere in the body. Releasing nitric oxide directly from the graft localizes the effect to where it is needed, says West.
"The idea is great; we're working on similar things ourselves," says Larry Keefer, a nitric-oxide researcher at the National Cancer Institute in Frederick, Maryland.
"I hope it will be moved into clinical practice very soon," adds Keefer. There is a lot of commercial interest, he says, but companies are reluctant to be the first into the area. "Someone really needs to get their foot in the door."
Flexible results
West's team used a plastic called polyurethane, modified with a chemical group that decomposes in water to release nitric oxide. The scientists studied the plastic's effects on platelets, and cultures of blood vessel and muscle cells, over two months.
The plastic released nitric oxide in a burst over the first two days, and then more slowly over the remaining time. This stopped platelets sticking together, boosted the number of blood-vessel cells and damped down muscle growth.
The team are sure that nitric oxide, and not the polyurethane, is behind the effect, because they see an increase in cyclic guanosine monophosphate (GMP) in the cell cultures. Nitric oxide triggers the release of cyclic GMP, which then affects enzyme activity and gene expression. Plastic that had shed all its nitric oxide had no effect on the cells.
Polyurethane is more flexible than other plastics used in grafts, so it should also integrate with surrounding tissue better, says West. She has begun studies of the grafts in rabbits, and expects results within a month.
Scientists hope that the new grafts could soon benefit patients. "It's an interesting idea and we look forward to seeing how the system develops from these early results," says Peter Weissberg, medical director of the London-based British Heart Foundation.
For more information on polyurethane, click here.
Source: Nature