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In a lab at the University of Pennsylvania, a plastic dish holds two rows of tiny black dots, pairs of them connected by dozens of thin, hairlike filaments. Each dot is a cluster of thousands of neurons, explains Douglas Smith, who is a professor of neurosurgery and the director of Penn’s Center for Brain Injury and Repair. The fibers that stretch between them actually comprise thousands of axons, long, slender projections that conduct electrical impulses away from each neuron’s central body. These bundles–each one a lab-engineered nerve–represent physical bridges that Smith hopes will help researchers like him mend previously irreparable injuries.

When sections of nerves in the body are severed or crushed, they die. Although the nerves can regenerate, they do it at the glacial pace of about one millimeter a day. And there’s another catch: as new axons grow, they need the original nerve sheath–a protective membrane made up of several different kinds of cells–to guide them to the area that has lost function. That sheath begins to dis­integrate after about three months without a living nerve in it. “It’s a race against time,” says Smith. A nerve severed in, say, the wrist can span the short distance to the hand and heal in time to restore function. If the same nerve were cut near the shoulder, however, the person would almost certainly lose full use of that hand, since the new growth would not reach the hand before the sheath died.

Not even the most advanced experimental techniques have been able to restore nerve function to sites far from an injury. Smith thought he might facilitate fast nerve re­generation by using lab-grown nerve­s as a kind of scaffold that doctors could place where a patient’s nerve has died. Though the implanted nerve would not transmit signals itself, the presence of the living tissue could guide the body’s regenerating nerve back to the injury site while keeping the detached nerve sheath intact.

To get the engineered nerves to grow long enough to span the injured area by the time they were transplanted, he applied slight, gradually increasing physical tension; this process, he found, encouraged nerves to grow almost 100 times as fast as scientists had believed possible. And the nerves grew not just longer but also thicker, apparently because additional proteins form in response to the tension. Smith and his team introduced these engineered nerves into rats that had part of their leg nerves cut out. Within four months, as the natural nerves began to regenerate in the rats’ bodies, the transplants had helped guide those nerves across the chasms, successfully restoring function to the rats’ legs.

Stretching It
To make the long nerve transplants, Smith and his team first collect sensory neurons–­cells that transmit information to the brain–from the spinal cords of fetal rats. Research technician Kevin Browne then pipettes a gelatinous pink protein called collagen onto two adjacent films in a specially built chamber. About the size of a shoebox, it houses a stretching apparatus made up of a vertical block attached to metal rods. One of the small, clear films, called the towing membrane, is suspended at one end by the block and curves down almost to the base of the chamber, where it overlaps the second membrane. Browne places one set of neurons in the collagen on the towing membrane and another on the bottom membrane. At this point, the two groups are less than 100 micrometers–two hairs’ width–apart. He puts the whole setup into a humming incubator that runs at 37 °C, mimicking the internal temperature of a rat.

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Credit: Porter Gifford
Video by Kristina Grifantini, edited by Brittany Sauser

Tagged: Biomedicine

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