Science / Medicine : Two Research Efforts Spark Hope in Repair of Damaged Nerves

Restoring sensation and use to limbs paralyzed by nerve damage has been one of medicine’s greatest challenges.

Although physicians can reattach severed or crushed nerves by using microsurgery techniques, such a damaged limb rarely fully recovers. Scar tissue often blocks the patch of the nerve sensations, and the nerve endings themselves rarely reattach themselves properly.

With 2,000 to 3,000 tiny nerve fibers, or axons, in each nerve, the current practice of suturing a severed nerve is like “taking a 2,000-subscriber telephone trunk line that has been cut in half with a chain saw and pushing it back together again, expecting it to work properly,” said Greg Kovacs, a medical student pursuing a Ph.D. in electrical engineering at Stanford.

But recent breakthroughs at Stanford University and Case Western Reserve University in Cleveland have sparked hope that the problem may be solved within the foreseeable future.

Although the two projects are dissimilar--Stanford researchers are using a combination of microelectronics and microsurgery, while Case Western researchers have developed a ‘living bridge’ of cells--they have a common goal: to reconnect damaged nerve endings so that use can be restored to damaged fingers, hands, arms and legs.

At Stanford researchers are trying to develop a procedure involving a tiny implanted electronic chip that will act like a telephone switchboard, rerouting brain signals past crushed or severed nerves. Scientists hope that the application will be developed for human use within the next decade.

‘Living Bridge’ of Cells

“What we were able to do earlier in 1987 that has never been done before is prove that axons will regenerate individually through holes of an appropriate size in an implanted 1-millimeter-square silicon chip,” explained Kovacs.

The Stanford project was initiated in the early 1980s by Dr. Joseph Rosen and Morton Grosser Ph.D., who are basing their work on earlier findings by Massachusetts Institute of Technology researcher David Edell and others. The nerve chip itself is being designed and implemented by Kovacs.

Coaxing individual axons through the holes in the chip, which are 8 to 10 microns in diameter, is a major step toward allowing researchers to restore electrical communication in the nerve. The chip will pick up the majority of the signals from either side of the nerve. A miniature computer either implanted or worn externally, can transmit the signals past the damaged area.

Last fall Case Western Reserve researchers reported that for the first time they had repaired crushed nerves connecting the extremities to the spinal cord in rats. The rats regained feeling in limbs that had been numbed by the damaged nerve.

The procedure included construction of a ‘living bridge’ of fetal cells over the damaged portion of the nerve. The star-shaped fetal cells, called astrocyctes, help manufacture the substratum needed for nerve cell growth.

Shape of a Pennant

If placed directly on the damaged nerve astrocyctes will move around. But Silver found the astrocyctes will adhere tightly to a porous paper-like material called Millipore. Once the astrocyctes are placed on the material it is cut into the shape of a pennant.

“The pole of the pennant is stuck in the nerve root, and the flag part of the pennant extends into the grey matter of the spinal cord,” explained Silver, who has developed the procedure with Case Western colleague George Smith and Dr. Michel Kliot of the Neurological Institute at Columbia Presbyterian Hospital in New York City. “The pennant then acts as a highway or bridge, across which the nerve endings can grow.” The entire pennant is less than 3 millimeters long.

The fetal cells help guide the regrowth of the damaged nerve cells so they make proper connections with the spinal cord.

“We don’t know what the astrocyctes do exactly,” said Silver. “But we do know they reduce scar formation and they allow the damaged nerves to regenerate over a short distance--two events that are essential for proper nerve restoration.”

Silver has searched for a substitute for fetal cells but has found that other cells have not worked properly. “We are continuing to look, however,” he said.

Silver also stressed that there is no definite timetable for applying his work to humans. “We have had some success with rats, but we still have to do similar studies on primates before considering whether to use it on humans.”

Alternative Method

The latest breakthrough by the Stanford team came Thanksgiving Day, when Kovacs discovered an alternative method of drilling the holes through the silicon chip.

Until then, researchers had to rely on lasers to drill the tiny holes. The problem had been that even the best laser technology scarred the chip’s fragile surface, making it impossible for scientists to attach the microelectronic structures needed to transmit the nerve signals to the computer.

“Right after I finished Thanksgiving dinner,” Kovacs recalled, “I decided to run an experiment on a plasma-etching technique based on three months of prior research by myself and colleagues Chris Storment and Woody Knapp.” He introduced freon gas, from which highly reactive, flourine free radical atoms could be released by electron bombardment onto the chip surface, which was protected except in areas where holes were to be made. The atoms reacted with the silicon, creating the desired holes in the unprotected portion of the chips, while leaving the protected surface undamaged.

“The next step is to put metal on the chips to make an array of electrodes,” Kovacs said. “We will then try to gain information on the nerve and chip interface, including how much current is needed to stimulate the nerve.”

The next phase of the Stanford project will also include modeling the thermodynamics of the nerve-chip connection. Since all electrical circuits generate heat, researchers must know how much heat the nerve can withstand.

“Part of our work will be to study the cooling effects of the body’s normal blood flow,” Kovacs said. “Essentially we are a water-cooled beast so this is a big consideration in determining the thermodynamic model specific for this application.”

‘Playing With Software’

Although the final procedure involving the silicon chip is still “science fiction”, according to Kovacs, in concept it would work this way: Nerve signals from the brain would flow through the trapped axons to the electrodes on the chip. The electrical patterns would be sent to the computer, which would then tell the other end of the nerve what to do.

“Ultimately it all may boil down to playing with software,” Kovacs said. “But there are a lot of obstacles we must overcome before any of this can become a reality. Our next phase should yield truckloads of data when we actually work with implanted chips with the electrodes installed.” Work with the implanted electrodes is to begin this spring.

Silver hopes that application of some of the same principles of the “living bridge” project might eventually lead toward the regeneration of the spinal cord itself.

While scientists have managed to regrow injured nerves within limbs, regeneration of the spinal cord, even in animals, has been a difficult task. “I don’t want to raise false hopes,” he said. “This isn’t something that will happen in the next few years.”

The potential of the human-machine interface being studied by the Stanford researchers could have even more far-reaching implications. For example, it may allow a quadriplegic to operate a wheelchair by manipulating nerves that are working within his or her own body. “It could open an entire world of new possibilities by allowing our own nervous systems to motivate machines,” Kovacs said.