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Perfecting the Stent
A new generation gets its groove

October 2002

by Will Sansom

When Health Science Center radiology researcher Julio C. Palmaz, M.D., patented the world’s first stent in 1988, he envisioned a wire-mesh, spring-loaded tube to be threaded with a balloon catheter through clogged blood vessels. At the site of built-up plaque, the balloon would inflate and the compacted stent would spring open, restoring normal blood flow. After balloon deflation and removal, the stent would remain in the vessel as a permanent scaffold to keep the vessel open.

The stent quickly proved to be a spectacular success, eliminating the need for open-heart surgery and other vascular bypasses in thousands of very ill patients. It gained U.S. Food and Drug Administration approval for peripheral vascular procedures in 1990 and for coronary vascular procedures in 1994. Today, 2 million people a year have balloon angioplasty with stents to open diseased vessels in the heart and legs. The invention has returned more licensing revenue, $2 million a year, to the Health Science Center than any other in the university’s history.

Health Science Center researchers are writing new chapters of the stent success story. One key finding indicates that future generations of stents will be, to borrow a ’60s phrase, groovier. Research reveals that endothelial cells, the cells that line our blood vessels, more readily migrate to stents that have tiny grooves etched into them. This migration is crucial for good clinical outcome. Other research shows that endothelial cells tend to migrate in only one direction (with blood flow) at the site of the stent implant. This helps researchers understand the behavior of the blood vessels and how to improve current stents. "We are trying to change the surface of stents to make them more compatible with the surfaces of blood vessels," said Dr. Palmaz, professor of radiology. "We hope to eliminate restenosis ndash; the closing of vessels after balloon angioplasty, which occurs in one-fifth of patients despite improving stent designs."
grooved stent


Scientists use a technique called photo etching to precisely engrave grooves into stents. Endothelial cells migrate more rapidly to the grooved stents than to their smooth counterparts. The faster the cells cover the stent, the less likely a patient will experience blood clots and excess tissue scarring. The grooved stent could eventually prevent the closing of vessels in thousands of patients.


Restenosis occurs when cells, responding to the implant, proliferate as part of the body’s natural inflammatory response. In ongoing research, endothelial cells are placed on a layer of thick gel similar to the arterial wall, said Eugene A. Sprague, Ph.D., who holds the Julio C. Palmaz, M.D., Professorship in Radiology at the Health Science Center. Stent test metals are implanted on the gel sheet and the sheet is placed inside a flow chamber that simulates blood circulation, including its pulses. "For seven to 10 days we observe how rapidly the endothelial cells cover each metal alloy – how quickly they migrate from the edges of the material. This is a key indication of how good a metal is likely to be as a stent in a real blood vessel. We want a stent to cover with endothelial cells quickly, because the stent or graft will stay open longer."

Endothelial cells prevent formation of blood clots on the stent and limit the amount of tissue scarring, both causes of restenosis. "We want to reduce the rate of restenosis to less than 5 percent of patients," Dr. Sprague said. One way, currently in animal testing, might be to make parallel grooves on the stent tube. Current stents are smooth and made of surgical-grade stainless steel. In an early experiment, Dr. Sprague scratched grooves into some stents while roughening the surface of others. "We found that endothelial cells migrated onto the stents with the rough surface at the same rate as they did onto stents with the smooth surface," he said. "But on the grooved surface the migration was four times as fast and always in the direction of the grooves."

Drs. Palmaz and Sprague next had a company make very precise grooves, ranging in size from narrower than the width of an endothelial cell, seven microns, to the width of the largest endothelial cell, about 20 microns. (Twenty-five microns equal one one-thousandth of an inch.) Grooves of 10 to 15 microns were the most effective, the researchers found, because they confined the endothelial cells and dictated their migration. "We implanted the grooved stents into pigs," Dr. Sprague said. "After one week we saw a doubling of endothelial cell migration onto the stent material. After three weeks, the grooved stents were completely covered by endothelial cells. The key is the first-week result. The more rapid the endothelial coverage of the stent and adjacent injured area, the more likely blood clots and excess tissue scarring will be prevented."

The grooved stent is patented but not yet ready for human trials. "We don’t have the manufacturing process perfected and we have other experiments to conduct," Dr. Sprague noted. "It could be ready for widespread use within five years, however. When it does become available, we expect it could benefit thousands of human patients who otherwise would have suffered restenosis. This was a discovery made right here at the Health Science Center and it may save many lives and many repeat procedures."

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