By William J. Cromie

Gazette Staff

Custom-tailored synthetic fibers are being used to regenerate damaged nerves, offering the possibilities of bringing smiles to immovable faces and movement to paralyzed arms and legs. Developed by Medical School researchers, the hollow reeds coax the ends of severed nerves to hook up to each other.

"We know that nerve fibers have the capability to regenerate, but we have not been able to guide them to do so in a manner that results in useful return of function or sensation," says Professor of Surgery Joseph Vacanti, who works at Children's Hospital. "Work that we've done so far on animals makes us hopeful and enthusiastic about being successful with humans."

Vacanti even hopes that someday surgeons will be able to regenerate circuits in the brain which have been damaged by disease or birth defects.

In the more immediate future lies the possibility that people will grow their own nerves into transplanted organs and tissues.

"A heart, liver, or kidney will function once it has been connected to a patient's blood vessels," notes research fellow Tessa Hadlock. "But with innervation, transplanted organs should become more integrated with a person's body and could work more effectively."

Getting the Right Connections

Nerves that move our muscles and activate our senses consist of bundles of individual fibers as thin as hairs. When such a bundle becomes severed, it is extremely difficult to get each fiber to reattach to its mate on the other side of the cut.

Hadlock, who is also a resident in head and neck surgery at Massachusetts Eye and Ear Infirmary, knows the situation well. She tries to restore faces to normalcy after facial nerve injuries.

"At present, we remove a nerve from another part of the body and graft it to the face," she explains. "But the injured nerve contains fibers going to the neck, forehead, eye, cheek, and mouth. All we can do is hope that the right connections will be made naturally, but often they are not. Fibers intended for the eye may grow down to the mouth, so when the person closes her eye, her lip twitches. Or when she smiles, her eye closes."

In addition, the place from which the nerve graft was removed becomes numb and less functional.

To solve the problems, Vacanti and Hadlock custom-tailor artificial grafts from synthetic fibers, or polymers, the same materials used for operating-room sutures. Hadlock pours the melted material into a mold containing hundreds of extremely thin, carefully positioned wires. After the polymer solidifies, the wires are removed, leaving patterns of channels that simulate the native nerve fibers.

She can make nerve conduits less than a 10th-of-an-inch in diameter that contain as many as 250 channels. In a facial nerve, such devices can be fashioned with subgroups of channels, each intended for a different destination, such as an eye, cheek, or mouth.

"Right now, getting a nerve to grow to its target is like putting a plant stem inside one end of the Holland or Callahan tunnel and expecting it to grow to a target the size of a pencil lead at the other end," says Vacanti. "With this new device, stems fill the entire tunnel and are guided straight to their destinations."

In addition, hormones and other natural factors that promote nerve growth can be impregnated into the synthetic material.

"Not only do we customize the shape of the polymer to guide the direction of nerve growth, we impregnate it with substances that release slowly and enhance growth," Hadlock notes. "Each group of nerves can be bathed in a factor that best promotes its growth."

She and Vacanti have used these polymers to regenerate sciatic nerves in 80 rats. The largest nerve in a rat or human, it runs from the pelvis to the back of the knee. Most new nerve-repair methods are first tested on rat sciatic nerves before being tried on humans.

Several weeks after treatment, the rats respond to heat applied to their feet, indicating successful regeneration and function. Inert and degradable, like operating room stitches, polymers cause no rejection and disappear completely in several months.

Asked when such experiments might be done in humans, Hadlock answers, "Within five years."

More cautious, Vacanti replies, "It's too soon to know."

Spinal Repairs

For a long time, surgeons have been aware that sciatic, facial, and other peripheral nerves that control arms and legs will regenerate themselves. But nerves in the spinal cord, leading to and from the brain, were considered impossible to restore.

In the past 10 years, however, researchers found that the spinal cord could be brought back to life with so-called Schwann cells. These cells form protective, insulating sheaths around nerves, thereby increasing the efficiency by which they conduct impulses of sensation and movement.

Recent experiments have revealed that Schwann cells from peripheral nerves promote regeneration of spinal cord nerves. "Schwann cells seem to work like little factories of growth factors," Hadlock comments. "Our plan is to coat the inside of our polymer channels with them."

"We think that natural substances inhibit growth of spinal, optic, and other nerves of the central nervous system," says Vacanti. "Schwann cells evidently make compounds that check the activity of these inhibitors. Preliminary attempts to regenerate spinal nerves with the help of these cells look very promising. It puts the goal of restoring movement to the limbs of paraplegics and quadriplegics into the realm of scientific possibility."

Electric Stimulation

The idea of plastic nerve conduits is also being explored in the laboratory of Professor Robert Langer of the Massachusetts Institute of Technology. Taking advantage of the fact that minute electrical currents enhance the growth of nerves, he and his colleagues experiment with plastic nerves that conduct electricity.

"But the plastic is not biodegradable and that can create a problem," notes Hadlock, who received her M.D. degree from the Harvard-M.I.T. Division of Health Sciences and Technology. "Growing nerve fibers will eventually be compressed by the plastic, interfering with their function."

Hadlock builds the nerve regenerators she uses manually. Later, she plans to take advantage of electrical stimulation by surrounding her devices with a biodegradable conducting substance.

"One of my goals is to innervate flaps of tissue grafted from other parts of the body to the head and neck," Hadlock says. "We now attach such grafts and organ transplants to a patient's blood vessels. Restoring sensation to these flaps and organs could greatly improve their function."

Once peripheral and spinal nerves can be regenerated, the next goal will be to restore lost capacity in the brain. "I think the work now under way is going to be fundamentally important to finding ways for us to do this," Vacanti says. "We see no technical limitation to using our technique in the brain once we isolate connections that need to be repaired to effect a cure."