Seamlessly Melding Man and Machine

A novel implant seeded with muscle cells could better integrate prosthetic limbs with the body, allowing amputees greater control over robotic appendages. The construct, developed at the University of Michigan, consists of tiny cups, made from an electrically conductive polymer, that fit on nerve endings and attract the severed nerves. Electrical signals coming from the nerve can then be translated and used to move the limb.

"This looks like it could be an elegant way to control a prosthetic with fine movement," says Rutledge Ellis-Behnke, a scientist at MIT who was not involved in the research. "Rather than having a big dumb piece of plastic strapped to the arm, you could actually have an integrated tool that feels like it's part of the body."

Living interface: Muscle cells (shown here) are grown on a biological scaffold. Severed nerves remaining from the lost limb connect to the muscle cells in the interface, which transmits electrical signals that can be used to control the artificial arm.

Today, movement of most prostheses is effortful and limited. The limbs are controlled by conscious movement of remaining muscle--the wearer might contract a chest muscle to move the arm in a certain direction, for example. Wiring residual nerves directly to artificial limbs would provide a more intuitive way to control them. But efforts to build peripheral nerve interfaces have been hampered in large part by the growth of scar tissue, which limits the utility and durability of implanted devices.

The most successful method for controlling a prosthesis to date is a surgical procedure in which nerves that were previously attached to muscles in a lost arm and hand are transplanted into the chest. When the wearer thinks about moving the hand, chest muscles contract, and those signals are used to control the limb. While a vast improvement over existing methods, this approach still provides a limited level of control--only about five nerves can be transplanted to the chest.

The new interface, developed by plastic surgeon Paul Cederna and colleagues, builds on this concept, using transplanted muscle cells as targets rather than intact muscle. After a limb is severed, the nerves that originally attached to it continue to sprout, searching for a new muscle with which to connect. (This biological process can sometimes create painful tangles of nerve tissue, called neuromas, at the tip of the severed limb.) "The nerve is constantly sending signals downstream to tell the hand what to do, even if the hand isn't there," says Cederna. "We can interpret those signals and use them to run a prosthesis."

The interface consists of a small cuplike structure about one-tenth of a millimeter in diameter that is surgically implanted at the end of the nerve, relaying both motor and sensory signals from the nerve to the prosthesis. Inside the cup is a scaffold of biological tissue seeded with muscle cells--because motor and sensory nerves make connections onto muscle in healthy tissue, the muscle cells provide a natural target for wandering nerve endings. The severed nerve grows into the cup and connects to the cells, transmitting electrical signals from the brain. Because it is coated with an electrically active polymer, the cup acts as a wire to pick up electrical signals and transmit them to a robotic limb. Cederna's team doesn't develop prostheses themselves, but he says the signals could be transmitted via existing wireless technology.

So far, scientists have tested the interface in rodents with a severed peripheral nerve, showing that the nerve will grow into the cup and make connections with the muscle cells. "If they can keep the end of the neuron intact in that area, that's a major breakthrough," says Ellis-Behnke. The nerves in rats are about the same size as those that would be targeted in humans. The research was presented today at a conference of the American College of Surgeons in Chicago.

The device can also feed sensation back into sensory nerves, which relay heat, pressure, and other information from the skin to the brain. Like motor nerves, sensory nerves make connections onto the muscle cells in the cup. In rodent tests, scientists capped two nerves in a single animal--one motor and one sensory. While the rat did not have a prosthesis, scientists were able to show that the implant could bridge the severed nerve, transmitting neural messages across it; tickling the rat's foot triggered muscle cell activity in the implant.

Sensory capability is a major missing component of today's prostheses--tactile, pressure, and temperature feedback is vital for picking up a fragile egg or a hot pan. Ultimately, prosthetic limbs could be outfitted with heat or pressure sensors that could transmit that information to muscle cells in the interface and allow this information to be sent to the brain.

The research is still in its early stages, and a number of questions remain to be answered. "We need to find out how long it takes for the connections to become functional, and what the durability and robustness will be," says Joseph Pancrazio, a program director at the National Institute for Neurological Disorders and Stroke, who was not involved in the research. "But it looks very exciting." The research is funded by the Department of Defense.

One of the major issues with neural implants to date has been the stability of the devices, because implanted electrodes often become coated in scar tissue and stop working. So far, for the six months that the scientists have been assessing the interfaces in rats, there have been no signs of scarring. While scientists aren't sure why, it may be that the cup protects the implant from the inflammatory reactions that lead to scarring, or that providing a target for the nerve cells dampens these reactions altogether by recreating a more normal environment for the severed nerve. The researchers are now monitoring the implants on a daily basis to determine their durability over time.

One particularly promising early finding, however, is that the tissue surrounding the interface grows new blood vessels to feed the implanted muscle cells, supplying them the nutrients they need to survive.

It's not yet clear how many of these nerve caps patients would need for adequate control over a sophisticated artificial limb. Someone who has lost their arm at shoulder level, for example, would need enough nerve caps to flex and extend the elbow, wrist, and fingers, as well as those for sensory nerves. "The only limit," says Cederna, "is going to be how high-tech they can make the prosthetics."

By Emily Singer


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