A group of University of Iowa researchers with expertise in neuroscience, pharmaceutical sciences, chemistry, biomedical engineering, and nanofabrication has created a novel solution to prevent blood clots in patients who have suffered a brain aneurysm.
Their solution—a nanometer-thin, protein-infused coating that, when applied to tiny brain stents, reduces the risk of blood clots post-surgery—is a breakthrough they say might not have happened had they not shared expertise across academic departments. And while the new stent-coating has yet to be tested in humans, it has shown promise in a rigorous round of lab tests.
During a recent visit to the Microfabrication Facility, Aju Jugessur and undergraduate electrical engineering student Andrew Textor, a senior from Wilmette, Illinois, demonstrated the coating process. Before anyone enters the cleanroom, they must remove their shoes and put on a lab jumpsuit and booties made from a material that does not release fibers into the environment. Hairnets, surgical masks, and hoods that cover the head and neck also are required. It can take up to 10 minutes to prepare to enter the lab.
“One you’ve done it a couple of times you find ways to make it go faster,” says Textor, a former student of Jugessur’s and the lab’s teaching assistant.
Inside the cleanroom, the lighting is a dull yellow (white light reacts with some lab chemicals), the temperature is maintained at 21 to 23 degrees Celcius, and humidity is constantly monitored. The thin-film deposition machine looks like a giant metal box. It uses intense heat to melt and vaporize materials to create an atomic-level bond of one material to another.
To demonstrate the stent coating process, Textor opens the lid of the deposition machine and places a small aluminum stent inside. When he closes the lid, he must use two hands in order to ensure it is firmly locked and sealed. It takes a few minutes for the machine to finish the coating job—it operates in near silence—and Textor opens the lid and removes the processed stent. To ensure the stent has been coated with the aluminum oxide layer, Textor uses a microscope.
Watching as Textor works, Jugessur talks about the many ways that nanofabrication is now being used in academic research.
“The field of nanofabrication continues to demonstrate that it can offer a common platform that may enable highly innovative interdisciplinary research projects,” he says. “But there is still much to be done to connect the field of micro and nanofabrication to find solutions to real challenges in medicine, science and technology.”
“Compartmentalization of academic disciplines is not a luxury we can afford if we want to advance medicine,” says David Hasan, associate professor of neurosurgery at University of Iowa Hospitals & Clinics, and one of the researchers involved in the stent project. “Innovative products for surgical interventions are most effective when we accommodate perspectives from the fields of biology, chemistry, and mechanics.”
The idea for the improved stent started with Hasan, who was looking for a way to reduce blood clots in aneurysm patients treated with stents without the use of certain anticoagulation medications, drugs that typically are administered before and after a stent is placed in a patient’s brain to guard against aneurysm rupture. Anticoagulants can also thin blood and make it more difficult for patients to heal from cuts, scrapes, and bruises.
Hasan contacted Suresh Raghavan, a professor of biomedical engineering and longtime research partner, and they began looking for solutions. However, they quickly realized they didn’t have the right breadth of expertise, so they sought help elsewhere on campus.
“One day Dr. Hasan just showed up at my door,” says Ned Bowden, professor of chemistry, about the day Hasan paid an unexpected visit to his office to ask him if he’d be interested in working on the stent project.
Bowden agreed, and the research team continued to grow, eventually expanding to five professors and four graduate students, all from various academic backgrounds.
Over many months, the team worked to perfect the nanometer-scale coating process, the initial phase of which was conducted in the UI’s Microfabrication Facility at the Optical Science and Technology Center.
The facility, which is open to researchers from across campus, is home to several cleanroom laboratories, spaces that are sealed off by glass walls to guard against particulate contamination. In one of these labs, team members used a thin-film deposition machine to coat aluminum stents with a fine layer of aluminum oxide. This layer, which measures 30 nanometers in thickness, is about 3,000 times thinner than a human hair.
After the first layer was applied, researchers used equipment in other labs on campus to apply two additional layers, including one with a specific cell protein called human thrombomodulin that can disrupt blood coagulation.
“The first nanometer-scale coating is important because it provides a uniform coating on the stent device that enables subsequent layers to function properly,” says stent team member Aju Jugessur, director of the Microfabrication Facility. “The thin-film deposition machine creates a molecular level bond that covers all nooks and crannies on the stent device.”
As part of the research process that went into its creation, the anti-clot coated stent went through several stages of laboratory testing, the results of which were published recently in the American Chemical Society journal Applied Nano Materials.
“The coating process is really important because it needs to have minimal impact on the stent’s mechanical characteristics,” says Raghavan, a specialist in cardiovascular device biomechanics. “The stent has to be very flexible for effective implantation inside the tortuous arteries of the brain.”
The team is now exploring industry collaborations to further test the stent, and looks forward to new collaborations.
“This collaboration has been one of the most broad and diverse of our careers, and its success has been heartening,” says Raghavan. “We hope to continue to work together on this and other similar projects in the future.”
UI graduate students Anna Schumacher, Chad Gilmer, Keerthi Atluri and Joun Lee participated in the stent device research.