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Sensors such as this one developed at the University of Arkansas contain complex arrays of nanomaterials that are customizable to detect a wide variety of vital signs and transmit them to doctors anywhere in the world.

Some of medicine’s biggest problems are on the cusp of being solved by incredibly small-minded Arkansas scientists. The burgeoning field of nanotechnology is exploding globally, but in many areas affecting the healthcare of the future, University of Arkansas researchers are leading the field. The state’s nanoscience efforts are concentrated in two UA research centers: the Nanotechnology Center at the University of Arkansas at Little Rock (UALR) and the Engineering Research Center (ERC) at the UA in Fayetteville.

Researchers are getting increasingly sophisticated at creating and manipulating stable nanomaterials, durable particles tens and hundreds of thousands times smaller than the diameter of a human hair.

In January, Gov. Mike Beebe announced a $4 million grant to the Fayetteville campus’ engineering program from the state’s General Improvement Fund to further nanoscience and nanotechnology research.

The $4 million from the state follows an additional almost $23 million in research monies leading researchers have brought to the center in recent years. Besides sponsors such as the National Science Foundation (NSF), Department of Energy, National Institutes of Health and U.S. Environmental Protection Agency, a number of governments and science organizations around the globe are contributing to the research being done in Arkansas.

Likewise, the Nanotechnology Center in Little Rock was established in 2005 with a state grant of $5.9 million, and now works with companies, universities and institutions all over the world to further its groundbreaking research.

While both centers’ projects focus on a wide array of nanotechnology applications for defense, chemical and civil engineering, and agricultural engineering projects, a great emphasis is also put on nanomedicine initiatives.
A world-renowned researcher who is both a neurosurgeon and engineer, Dr. Vijay Varadan came to ERC in 2005 for the unique opportunities, facilities and support for research the University of Arkansas system offered him.

Varadan combines his expertise in both engineering and medicine to create unique biomedical technologies. “Less than 3 percent of engineers are also physicians,” he said, “but physicians know the medicine and what is needed, so it’s valuable to have that understanding throughout the process of engineering nanomaterials for medical use.”

Using an NSF presentation for visual aid, Varadan walks visitors through a dizzying number of medical breakthroughs the center’s nanotechnologists have made. Researchers there are working on treatments for diseases and conditions such as Parkinson’s, Alzheimer’s, epilepsy, paralysis, cancer, cardiovascular disease, diabetes, sleep disorders, depression and anxiety disorders, and on nanomechanisms for drug delivery.

Science sans fiction
Much of Varadan’s work centers on sensor arrays. He has developed a number of different wireless sensors using nanomaterials to pick up and transmit precise, real-time patient biometrics and physiological monitoring to physicians anywhere in the world. Some, looking like small transparencies for an overhead projector, can be worn in a patient’s pocket to monitor their condition. The sensors are adaptable with high sensitivity and selectivity to measure many different types of data, including vital signs, brain wave patterns, blood flow, blood oxygen and viscosity, dopamine and glucose levels. They have an almost endless variety of applications.

For example, Varadan has video of patients with Parkinson’s and epilepsy before and after brain surgery to implant a neural probe with nanosensors. Before surgery, the patients demonstrate extreme lack of muscular control including severe palsy, seizures and a shuffling gait. Once the probe, an array of electrodes with nanowire, is in the brain, it can sense the brain’s chemical condition and react to the data for treatment under the direction of the physician. Video of the same patients only hours after surgery shows them walking and moving completely normally. Of one such post-surgical Parkinson’s patient, Varadan said, “She now drives, goes to work … has a normal life.”
Using magnetic nanotubes, Varadan said they are learning to stimulate neurite growth. Eventually, scientists will be able to create an entire new set of neurons for patients with compromised nervous systems, using not stem cells, but nanotechnology that grafts neurites from the patient’s own neurons.

Similarly, though there are many biomedical nanotechnologies being researched in Little Rock at the Nanotechnology Center, the most advanced and sensational project thus far is bone tissue regeneration, said Chief Scientist Alex Biris. Biris and other researchers work closely with local surgeons and physicians. In at least 33 clinical cases with 100 percent success and no tissue rejection, inflammation or other side effects, Nanotechnology Center researchers have been able to regenerate bone tissue within about six weeks using bio-functionalized, three-dimensional nanostructure scaffolding. Patients with bone cancer, crushed or otherwise damaged bones can grow healthy new tissue.

“Imagine the capabilities of regenerating the limbs of soldiers or people who have horrible damages, patients dying form bone cancer,” Biris said, adding that the researchers are certain this platform technology can be extended to skin, arteries and other systems. “We’ll be able to extend this technology to create artificial skin for burn victims, for instance, and to deliver drugs and antibiotics through it. It’s unbelievably powerful research.”

The unique properties of nanomaterials have hope for cancer patients as well, as researchers at both institutions are working on safe ways to use nanoscience to detect and kill cancerous cells without damaging surrounding tissue. Biris said the Nanotechnology Center recently has made significant progress working with the UAMS radiology researchers and has been able kill cancer cells in a “very, very short time,” about 10 or 15 minutes. In another advanced project with UAMS, Biris said they have been able to visualize in real time in vivo biological processes by using nanoparticles and are able to see how these nanoparticles travel in real time through a living tissue.

Multiple cardiology treatments are under development in the University system, including arterial stents filled with nanotubes for myocardium ischemia monitoring. The nanomaterials inside the stent can sense and report exact data to the physician such as blood flow, viscosity and oxygen levels and can predict silent heart attacks before they occur.

Another project involves developing a feedback loop control with an implantable defibrillator and ion sensors measuring the cardiac dynamics at a nearby location. University of Arkansas researchers are working on creating protein-based nanobatteries to act as organic, long-term power supplies for such defibrillators and similar internal devices.

The research also has public health implications. Varadan said Beebe expressed particular interest in some nanofiltration technologies when he visited. Much of rural Arkansas has high levels of mercury and arsenic in the water supply, he said. But filters using nano-scaffolding can filter out not only the kind of sediments removed by currently available commercial filters like Brita, but also mercury, arsenic, viruses and other impurities. The same kinds of filters could also be used for hospital air systems, greatly decreasing the chance of hospital-acquired infections.

Caution and commercialization
Most of the technologies are at least several years from commercialization, though a few are already starting to be produced, such as a watch that senses blood glucose levels through the skin and uses nano-sized needles to inject the appropriate amount of insulin directly into the patient.

Biris said that commercialization of technologies is a high priority for the Nanotechnology Center and that promoting Arkansas economic development is an explicit part of its mission.

“We want to do research that can be translated into economic development, particularly for the state of Arkansas,” he said. “Every piece of research, we try to turn into companies or to work very, very closely with local companies to improve their products.”

He said the promising results and the portfolio of patents for the bone tissue regeneration nanotechnology have already been spun off into a new Arkansas-based company called Orlumet. Varadan said a number of other biotechnology companies are now associated with the research in Fayetteville.

“This is cutting-edge research with strong potential for short-term and long-term dividends in economic development,” Beebe said in Fayetteville on Jan. 15 when he announced the $4 million grant. “The world is watching these Arkansas scientists, and this research can lead to high-quality, knowledge-based jobs for Arkansans.”

The world is entering a new age, but although there is a global race for patents as scientists make new discoveries in nanoscience, the realization of their findings in the marketplace cannot be rushed. “We have to be very thorough because we are working at the edge of a new science,” he said. “We don’t want to make mistakes.”

For that reason, another UALR project underway with the Arkansas Department of Health and the UAMS Department of Public Health is researching the cytotoxicity of these nanoparticles to understand their effects on the living body in the short and long terms. Once scientists are confident in the long-term safety and efficacy of man-made nanostructures, he said, the healthcare industry would see enormous changes.

“I strongly, strongly believe that nanotechnology will play a major role in medical science in the next 15 to 20 years, but as far as one to three years, it’s difficult to predict,” Biris said. “I know for sure that soon every aspect of our lives will be impacted by nanotechnology. I’m sure of it.”



March 2008

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