Plugging Aneurysms with Polymers

By Gene Charleton

Designing advanced polymers to treat potentially deadly cerebral aneurysms — without surgery

Engineers seldom do brain surgery, but some engineers are getting ready to give brain surgeons new tools to help treat potentially deadly defects in blood vessels deep inside the brain.

The defects are aneurysms, balloon-like bulges that can form at weak spots on arteries that carry blood through the brain. If they burst - and they often do - the resulting bleeding causes disabling strokes and other neurological damage.

The unlikely tools are pea-sized foam balls formed from special plastics called shape memory polymers, or SMPs. Inserted into aneurysms, the SMP balls offer an effective way to treat potentially dangerous aneurysms with less risk than surgery or existing nonsurgical approaches, say biomedical engineers at Texas A&M.

Duncan Maitland, an associate professor in Texas A&M's Department of Biomedical Engineering, says the SMP balls offer several improvements over the most commonly used nonsurgical treatment for cerebral aneurysms.

"Shape memory devices reduce the risk or trauma involved in current therapies for these aneurysms," Maitland says.

Understanding aneurysms
Aneurysms are serious business. As many as one person in 15 in the United States will develop a brain, or cerebral, aneurysm during their lifetime. The aneurysms burst, and blood from the leaking artery seeps into the brain in more than 30,000 of these people every year. Between 10 and 15 percent of them die before they get to a hospital, and more than half of the rest die within a month of the rupture. Half the survivors are paralyzed or suffer other neurological damage.

"Shape memory devices reduce the risk or trauma involved in current therapies for these aneurysms."

Brain aneurysms occur in people of every age, but they are most common between the ages of 30 and 60. Women are slightly more likely than men to experience a brain aneurysm.

Medical researchers are uncertain about what causes cerebral aneurysms, but aneurysms are more common in people with inherited diseases, such as connective tissue disorders, some kidney diseases and certain circulatory disorders. Head trauma, some infections, high blood pressure and other circulatory system diseases can also cause aneurysms.

To cut or not to cut

One of the important properties of SMPs is that they can be compressed drastically and still retain their original shape and volume. Here, an SMP cylinder and a compressed cylinder illustrate how much the material can be compressed.

Aneurysms are usually treated either with surgery to expose the aneurysm, which is then closed off with a clip and removed, or nonsurgically, by inserting tiny springlike platinum coils - often a dozen or more - into the aneurysm. The coils interfere with the movement of blood inside the aneurysm and cause the blood to clot and fill the space. Eventually, the cells that form the innermost layer of arteries, endothelial cells, grow over the clot and the aneurysm heals.

Filling an aneurysm with platinum coils can be an effective treatment, but the procedure has potentially serious complications, Maitland says. The risk of the aneurysm bursting increases because the coils put pressure on the walls of the aneurysm and the pressure goes up as additional coils are inserted. Ten coils, for instance, increase the risk by about 20 percent. And sometimes the end of one or more coils works its way back out into the artery, where it increases the likelihood of small clots. These, in turn, increase the risk of other types of strokes elsewhere. If this happens, surgeons must insert another catheter and push the dangling coil back into the aneurysm.

Properties of a proper polymer
Filling the aneurysm with an SMP ball largely avoids both these potential problems, Maitland says. First, the size of the ball can be calibrated to the size of the aneurysm, so that it exerts virtually no pressure on the aneurysm walls and the risk of bursting is greatly reduced. Second, the ball has no parts to shift back into the artery to cause unwanted blood clots there. And because the ball is fabricated from open-celled foam, like a household sponge, blood can fill the aneurysm almost completely and make an effective clot. The clot forms what aneurysm researchers call a scaffold for endothelial cells to grow across and cover the opening into the aneurysm.

"Making foams is literally an art form more than it is a science, although we're starting to get more scientific about it."

SMPs are polymers that can be shaped into one form, changed into another shape and then made to resume the original shape on command, most commonly with heat. Maitland makes the aneurysm-filling polymer balls from a block of spongelike polymer foam. To insert the balls requires pressing into a narrow cylinder that can pass through a catheter, a narrow, steerable tube that is threaded through arteries to the site of the aneurysm. Once through the catheter, the compressed SMP ball can be steered into the aneurysm, where a beam of laser light shone through an optical fiber in the catheter hits the SMP cylinder and causes it to return to its original ball shape, filling the aneurysm.

Maitland and his colleagues have been developing the properties of the SMP foam for eight years and work with the SMP foam at all stages of development: They produce the foam itself, shape the balls that are implanted in aneurysms, and test the balls in laboratories and in animal models.

"Making foams is literally an art form more than it is a science, although we're starting to get more scientific about it," he says. "We are refining how the foam acts, how much surface area there is in the cells and how blood flows through them."

Learning how blood flows through the foam is important to understanding the formation of the clots that will help heal the aneurysm.

"Once we have the ability to measure these things, then we can change the structure of the foam. We're working toward an optimal version of this structure, the scaffold that you implant."

Top-notch testing facilities
Maitland says the Texas A&M Institute for Preclinical Studies (TIPS) is the main reason he brought his aneurysm-related SMP research to the university.
"A lot of researchers who do human diagnostic work need human subjects," he says. "I don't. I need good engineers, good facilities, good veterinarians and good animal facilities. We have that here in the Texas A&M Institute for Preclinical Studies."

TIPS was founded in 2007 to support research in medical device development, facilitate preclinical testing (research that must be conducted prior to introducing devices into people), and provide advanced training for graduate and professional students in science, engineering and veterinary medicine. The institute's facilities include sophisticated imaging equipment, a large-animal hospital, animal housing, surgical laboratories, preoperative preparation and post-op recovery, an interventional catheterization laboratory, and incubator space for startup companies.

"Before I came here, there were only six places in the country that do the kind of work with aneurysms we need," Maitland says. "We brought some of these people in and trained TIPS personnel, and so now TIPS is developing this expertise in an animal model.

"This is good for us, and it's very good for TIPS as well. They're going to have expertise that will make them the seventh facility in the U.S. that can do this kind of work."

From lab to clinic
Getting the results of engineering research from the laboratory to the marketplace is a different process for medical devices from that for the products of most other engineering research.

"The medical device industry tends to innovate through acquisition of startup companies, not through putting a lot of money into research and development," he says. "This means you have to push and champion your work farther than most academics do or would be comfortable with.

"It's a lot like doing the venture-capital road show, where you're giving 10-minute presentations, trying to get people interested in the business potential of what you're doing."

"Before I came here, there were only six places in the country that do the kind of work with aneurysms we need. And now TIPS is developing this expertise in an animal model."

To move the process along more smoothly, Maitland has organized a company, Shape Memory Therapeutics, to further develop and market the foam aneurysm treatment.

"Most of the stuff that the company is doing is intellectual property, regulatory plan, manufacturing plan, all that kind of stuff that I need to show mid- size to large-size medical device companies that this technology can work with their technology and it will be better than current devices."

That's not all. Maitland says that clinical problems of all sorts still fascinate him.

"I take on diseases or clinical problems as my driving motivation. Sometimes the potential solutions require innovation in materials. Sometimes they require altogether new solutions,
which may or may not use the materials that I'm currently working with.

"I try to let the problem define the solution, as opposed to having hammers and screwdrivers and looking around to see where they fit."