Biomedical Engineering Research Offers Creative Options in the Treatment of Deadly Neurological Disorders

By Alice Rhein (BA ’84, MS ’86)

Faced with a scalpel that, figuratively, at least, is a double-edged sword, neurosurgeons must weigh a number of risks and benefits with each patient they treat. But research currently in progress in the College of Engineering has the potential to provide yet another option for treatment using customized polymers that can be targeted to repair neurological lesions.

Daryl Kipke, associate professor, Biomedical Engineering, and David Martin, associate professor, Materials Science and Engineering, and associate professor, Biomedical Engineering, are leading two projects that use novel materials and delivery techniques to overcome limitations associated with invasive brain surgery.

Under Kipke’s direction, the Neural Engineering Laboratory is working on a number of research projects that involve BioMEMS technology, neuroprosthetic systems, and biomaterials and devices for minimally invasive neurovascular surgery.

It was research in the latter area that, late last year, prompted Kipke and research scientist Tim Becker to protect their findings with a patent and launch a spin-off company to guide their technological advancement into the commercial arena.

Sealed with a Polymer

Kipke’s interest in the endovascular surgery project began six years ago after a conversation with a neurosurgeon. “He presented this problem that neurosurgeons have of not being able to effectively occlude vascular lesions like aneurysms or AVMs,” Kipke said, noting that current treatments often introduce solvents that are marginally biocompatible.

With the great advances that researchers have made in developing microcatheters, the surgeon wondered if there was a way in which he could introduce a substance into the brain and effectively seal off the ballooning of an arterial wall—a characteristic of an aneurysm—or lessen the blood flow in the complex network of arteries and veins that develop in an AVM.

Kipke took this challenge and did some ground-level engineering work to identify polymers that might be suitable candidates. There were two criteria. First, a substance had to have a viscosity low enough to flow easily through a microcatheter. Second, the substance needed to have controlled cross-linking to precisely control how the polymer solidified when it reached its target. Using these parameters, Kipke quickly identified the two-component polymer calcium alginate.

Alginate is a natural sugar-based gel that dissolves in water, thereby eliminating the need for organic solvents. Used in endovascular embolization, it is non-adhesive, non-toxic and has tissue-like properties.

Essentially, what the endovascular surgical procedure involves is feeding a microcatheter to the point of the lesion, then injecting the two component polymers during the un-reactive stage and letting them mix and harden within the vessel.

The key factor for treating an aneurysm is to use the right amount of fill. An overfill could block the artery; an underfill could further weaken the vessel wall. Animal testing using a swine model has already shown that the injection and polymerization can be controlled, so Kipke estimates the application would be appropriate for human testing within two years. Ultimately, he would like to see a day when a patient with a neurological lesion is scheduled for an outpatient procedure in which a catheter is inserted and a specialist injects a polymer to block off a ballooned wall or alter the blood flow to an AVM.

“Further down the road,” Kipke said, “we think that the polymer treatment we’re developing could be used for treating cerebral tumors by blocking off the blood supply in a controlled way and perhaps by seeding the polymer with chemotherapeutic drugs to provide a very localized chemotherapy deep within the brain. That’s a bit of conjecture—we have no data to support that—but it’s very possible that it could work.”

While Kipke stresses that making clinical determinations is somewhat out of the realm of biomedical engineers, it’s only through highly collaborative research and creative leadership that his work in minimally invasive endovascular surgery has seen significant progress.

“Working together with neurosurgeons, we provided the engineering and analysis expertise, and they provided their expertise to make progress in this area,” Kipke said. “Whenever you cross disciplines, you have to become sensitive to how others work to develop an effective relationship. It took some creativity to cross that barrier from lab-based biomedical engineering research to almost clinical neurosurgery research.”

It’s because of these substantial collaborations that Kipke and his team has laid the groundwork for providing patients and physicians with fast, effective and cost-effective options for treating life-threatening neurological conditions.

Coats, Soothes, Protects

An uncoated gold electrode provides the medium on which a film of electrically conducting polymer can grow into a fuzzy polymer.

Kipke has also collaborated with Martin to advance the biocompatibility of neural electrodes. While Kipke’s lab designs and fabricates micro-machined electrodes, Martin focuses on coating these with electrically conducting polymers to improve their long-term stability.

These electrodes will be the enabling technology for neural prosthetic systems that can become communication and movement aids for locked-in patients such as those with amyotrophic lateral sclerosis (ALS), severally paralyzed patients and those with significant loss of vision or hearing. Hybrid probes could provide intervention for patients with epilepsy, Parkinson’s and Alzheimer’s disease by combining drug delivery or genetic treatments to the right areas at the right time.

“What we have to do on the engineering side is realize the potential and make better devices and integrated systems that the clinicians can find useful,” Kipke said.

Martin, who has been working with Neural Communication Technology since 1994, likens what he does to finding a fuzzy, comfortable neural environment in which probes feel welcome.

“We’ve developed a method of controlling the way in which polymers are deposited to produce a fuzzy surface morphology. This allows for enhanced electrical connections with the tissue and helps to mediate the big differences in mechanical properties between the substrate and the tissue itself,” Martin said.

The fuzzy surface is key to bio-interaction because it has to be able to facilitate chemical transport in a very small area. “If you think of a surface, you think of it as flat. But natural surfaces aren’t at all flat, and that’s very important,” Martin said. “Understanding and controlling how non-flat it is, is where we’ve been making a lot of progress.”

When a probe is inserted into the brain, quick connections to the neurons are needed to keep other cells away, or they’ll electrically isolate the probe. Current technology, as is used in select Parkinson’s patients, involves inserting an implant deep into the brain. The issue with these implants is that over a long period of time, the ability to communicate with the neurons—to send electrical signals—gets harder because a layer of proteins or molecules or even whole cells tries to electrically isolate the electrode from the brain.

Martin’s research is closing in on creating a more intimate and long-lasting connection that will help to resolve the issue of incapability.

“Imagine a steel needle wiggling around in your brain,” Martin said, “and there’s a coating that goes on the surface that is soft and fuzzy, and the brain is more comfortable interacting with it, since it has mechanical properties that are more like the brain itself.”

What’s been a very attractive aspect of this experimentation is that researchers can reproduce results so consistently. “We can control how thick the surface is and the morphology and structure by controlling the time, current density and other characteristics of the deposition,” Martin said.

Certainly this approach could be important to other applications such as cardiac electrodes and pacemakers. Martin is quick to note that his area of attention is the material, but he’s constantly collaborating with other disciplines and laboratories to enhance his research.

“Our primary focus has been on neural implants because of the Center for Neural Communication Technology and because of the experts here,” Martin said.

And while biomedical engineering is, by definition, an integrated field where collaboration is imperative, creative leaders initiating more cross-disciplinary studies are what will take current research to the next level. And perhaps, one day, make more treatment options available to those in need. —E

Alice Rhein (BA ’84, MS ’86) is a freelance writer and former newspaper editor. Her cover story on “Protective Measures: College of Engineering Research is Making the World a Safer Place to Live” appeared in the Spring/Summer 2002 issue of Michigan Engineer.