Nanotechnology meeting focuses on medical advancements

Several Ohio State researchers made presentations, featured on this page, at the BioMEMS and Biomedical Nanotechnology World 2000 meeting, co-sponsored by the University in late September. The meeting was the first-ever comprehensive international conference devoted to two growing disciplines that may revolutionize medicine: micro- and nanotechnology. The conference was led by Mauro Ferrari, director of the Biomedical Engineering Center and associate director of the Heart and Lung Research Institute.

Tiny microchips have big promise in fighting serious diseases

Treatment for life-threatening diseases and relief from disease-related pain may one day be supplied by microscopic chips that could be implanted in the body, according to researchers in the new field of biomedical nanotechnology.

Such chips -- called biological microelectromechanical devices (bioMEMS) -- are less than half the width of a human hair. They could contain drugs, muscle cells or even be equipped to monitor a patient's condition minute-to-minute. And these devices already show therapeutic potential for treating heart disease and diabetes.

"The development of these microscopic chips will let us do a whole host of exciting things in biomedicine,"said Robert Michler, chief of cardiothoracic surgery and co-director of the Heart and Lung Research Institute. Michler and several colleagues discussed the role nanotechnology may play in medicine of the future during their conference presentation on Sept. 26.

Michler said doctors in the future will combine the use of nanotechnology with another revolutionary process -- robotic surgery. Michler led a study using robotic techniques to perform open-heart surgery on 60 patients. Surgeons in the study took arteries from the patients' chest walls and sewed them on to their hearts. Robotic surgery has the advantage of precision, as it "can gain access to very small areas inside the body,"he said.

Michler envisions using robotic surgery to place microchips inside the body, such as on heart tissue or blood vessels. The chips could contain stem cells -- cells that give rise to specific types of cells, such as those comprising muscles, organs, blood and other tissues. They also could contain chemicals that would stimulate the growth of blood vessels, or medication that is slowly released into the body, Michler said.

"The use of microscopic chips will take heart disease treatment to the next level,"he said. "It has the potential to let physicians assess the benefit of their work right in the operating room, rather than waiting to see if symptoms show up.

"We're ready to create the chips and use the robot to insert them into the hearts of lab animals,"Michler said. "We're looking at probably five years before human clinical trials begin."

Joining Michler on the panel were Costantino Benedetti, director of cancer pain, therapy and palliative medicine at the James Cancer Hospital; Michael Caligiuri, the associate director for clinical research at the Comprehensive Cancer Center; and Pascal Goldschmidt, chief of cardiology at Duke University. They offered their perspective on how nanotechnology will affect patient treatment in the future:

• Treating the pain associated with surgery is poorly done in more than 50 percent of patients, even with today's technology, says Benedetti. He hopes for the development of a local anesthetic that could last days -- or even weeks -- and be released inside the body through slow-release technology. Today's strongest local anesthetics last a maximum of eight hours, Benedetti said. "A drug delivery system that would allow a short-acting anesthetic to be released slowly would be advantageous,"he said.

• While the field of cancer vaccines is in its "infancy,"said Caligiuri, there is the potential to develop a vaccine-containing chip or slow-release capsule taken orally that can target specific types of cancer. "Cancer prevention via vaccination is a huge frontier,"he said. Other than developing the appropriate vaccines, obstacles to overcome also include determining the right dose of the vaccine, where in the body to deliver it and the duration of delivery.

Also, a chip could house the tools to relay to physicians information on potentially cancerous tissues. Microchips equipped with sensors could detect mutated genes or dangerous levels of hormones, and enable doctors to determine which tissues to treat.

• Microchips could contain stem cells -- cells that give rise to other specialized cells -- that would grow and proliferate inside the body. This chip technology could even create new tissue on damaged organs. "Instead of transplanting a whole organ, we would do a transplant using stem cells,"Goldschmidt said.

Researchers take steps toward growing replacement blood vessels

Heart attacks may be less deadly in the future, thanks to micro- and nanotechnology research just begun at Ohio State.

Researchers here are investigating ways to re-grow tiny blood vessels to keep damaged heart tissue alive after a heart attack, by a process called therapeutic angio-genesis.

"Our bodies already contain cells that trigger the growth of new blood vessels. We want to use those same cells to create seeds for blood vessels in the laboratory and transplant them into the body,"said Nicanor Moldovan, research scientist and assistant professor in Ohio State's Biomedical Engineering Center and Heart and Lung Research Institute.

He relayed the researchers' initial results in a presentation Sept. 25 at the conference.

Moldovan admits that his plan of growing capillaries in tissue culture and implanting them in the body is very complex, and relies on ideas about blood vessel formation that are just beginning to emerge.

In these earliest results, Moldovan and his colleagues have demonstrated that these "seed"cells, called endothelial cells, will grow in grooves carved in the surface of a soft transparent gel in the laboratory.

The researchers' ultimate plan is to grow endothelial cells inside or on the surface of silicon molds resembling capillaries. If the cells could assume the shape of capillaries under those conditions, they could one day be transplanted -- either alone or with some kind of carrier -- into the heart to start the replacement of blood vessels that died during a heart attack.

Moldovan envisions that one day, capillaries could be carried into the heart tissue by micromachines called "angiochips."Once inside the heart, the implants could begin to undo the damage of a heart attack.

This relates to his other work in the Biomedical Engineering Center, Moldovan said. There, the aim is to stimulate capillary growth by angiogenic drugs released from implantable silicon capsules. "We probably couldn't bring tissue back in its original form, but we could try to re-vascularize, to make a heart beat again. Or, at least, keep the heart tissue from dying by creating new capillaries that would provide blood and oxygen as soon as possible,"he said.

Nanotechnology meets nature in drug delivery

Better ways to deliver drugs to tumors and other targets in the body may come from merging nanotechnology with our body's natural defenses, according to a researcher at Ohio State.

While much nanotechnology research has focused on using silicon for microscopic medical devices, researchers here also are working on hollow plastic capsules that could one day carry drugs to where they are needed in the body. Such capsules would measure only a few micrometers across, smaller than the width of a human hair.

Derek Hansford, assistant professor at Ohio State's Biomedical Engineering Center, discussed efforts to fabricate these plastic capsules on Sept. 24 at the conference.

Hansford explained that most research in this area has focused on either harnessing the body's natural defenses, such as antibodies, to combat cancer and other diseases, or building devices to do the job.

As Hansford describes it, Ohio State's drug delivery research is bringing those two ideas together.

"We don't want to completely reinvent nature with artificial devices," Hansford said. "We want to use what we can get from nature to our advantage."

Hansford and his colleagues plan to use nature to help their tiny capsules find tumors and other targets in the body and stick to them. The body already contains antibodies and other agents that seek out foreign cells and attach to them, Hansford explained.

Plastic capsules coated in antibodies engineered for specific targets could one day enter a person's bloodstream and adhere to the targets before dispensing medication from their hulls, he said.

Plastic is a good choice for a drug delivery material, Hansford said, because researchers can work with it more easily -- and less expensively -- than silicon.

In his presentation, Hansford showed how he and his colleagues are working toward manufacturing hollow box-shaped plastic capsules for drug delivery.

So far, the Ohio State researchers have succeeded in manufacturing small numbers of the capsules by molding the plastic into shape. In the future, Hansford and his colleagues will investigate ways to mass-produce the capsules.

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