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Preventing graft rejection.

Damaged human veins and arteries can be repaired with synthetic fabrics, but medical researchers never have solved the problem of rejection caused by clotting or scarring. A new substance being tested at The University of Texas at Austin, however, could "trick" blood vessels into accepting the foreign material. According to chemical engineering professor Jeffery Hubbell, a peptide or synthetic protein fragment some day may be attached to the graft walls to form tiny "hooks" that will attract endothelial cells. These will cover the synthetic graft and prevent unwanted substances from the blood or cell walls from clotting or blocking the vessel.

"Vascular grafts have been used successfully for a couple of decades in treating aneurysms of the aorta. But the problem for smaller vessels in the body is that smooth muscle cells from the connecting vessel grow into the graft, and essentially grow it shut after a few years--or else the blood platelets attach to the synthetic graft material and cause clotting." In effect, this build-up causes a blockage in much the same way that cholesterol can accumulate in a vein or artery and cause clotting. The process by which the accumulation occurs is different, but the effect on the patient's health is the same.

Fortunately for heart patients, the aorta has such a large diameter that the build-up of smooth muscle cells is unlikely to pose a danger in the patient's lifetime. Smaller veins and arteries, however, can become clogged much more quickly, thus causing the graft to fail. This is why heart bypass surgery is performed with grafts of the patient's own veins, Hubbell explains. "What you would like is to have some cells grow into the graft to make it living-biocompatible. That way, you would have living material on the vessel interacting with the blood, rather than non-living material." The answer he has come up with is artificially to enhance the deposition of the body's endothelial cells on the synthetic matter. Such cells normally are found in the blood vessels to prevent the clotting of blood. Thus, an artificial deposit would "tell" the blood that the entire graft was part of the human body, rather than a foreign substance.

The peptide Hubbell is working on is deposited over about one percent of the area of the artificial material, and these hooks serve as an attractor for endothelial cells. In vitro cell cultures have shown that a one percent distribution is about the proper spacing for the effect to occur, and a one-molecule thickness is sufficient. If a sparser distribution of the peptide is used, the endothelial cells do not spread upon the graft material. The hooks are so specific in their design that platelets and muscle cells are not attracted.

Although the peptide is very expensive--about $1,000 for half a gram--it is used in such small quantities that an entire square yard of graft surface could be covered at a cost of one cent.
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Title Annotation:blood vessels
Publication:USA Today (Magazine)
Date:Feb 1, 1993
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