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Defense Department grant spurs nerve regeneration research

May. 30, 2013, 8:59 AM

The study team at Vanderbilt includes (front row, from left) Alonda Pollins, MLI, Nancy Cardwell, Wesley Thayer, M.D., Ph.D., Lillian Nanney, Ph.D., (back row, from left) Colton Riley, Kevin Sexton, M.D., and Richard Boyer. (photo by John Russell)

Vanderbilt investigators led by Wesley Thayer, M.D., Ph.D., assistant professor of Plastic Surgery and Orthopaedic Surgery and Rehabilitation, have been awarded a $1.1 million grant from the Department of Defense to develop a new surgical device that may help repair severed nerves.

The research could help soldiers and cancer patients regain use of a limb and avoid amputations after a catastrophic injury or cancer surgery.

“The real challenge in nerve repair and limb salvage, particularly for our wounded warriors, is that when you have an injury near the spinal cord it takes such a long time for the nerve to regrow from the site of the injury all the way out to the target muscle like the forearm or the hand,” said Thayer, who is also chief of Plastic Surgery at the Veterans Administration Tennessee Valley Healthcare System – Nashville.

Nerves typically grow at a rate of only one millimeter per day and muscles develop permanent atrophy after one year, so restoring limb function is a race against time.

Even when bone and blood vessels can be salvaged after a battlefield wound, many soldiers still undergo amputations because it takes nerves too long to regrow, making the limb unusable.

Vanderbilt investigators have been testing the use of a polyethylene glycol (PEG) solution that is applied to both ends of the severed nerves. PEG is a biologic compound that drives water away from the cells, making the cell membranes sticky. The application of PEG helps the severed nerve stumps stick together and begin to function.

In earlier tests, the researchers found that they must first wash the nerve ends with a calcium-free solution because calcium seals the nerve axons and blocks repair.

In addition to the calcium-free solution and PEG, investigators coat the nerve ends with an antioxidant called methylene blue.

Using this PEG-fusion method, Thayer and his colleagues have been able to restore nerve function and leg movement in animal models.

With funding from the grant award, Vanderbilt engineers and investigators at AxoGen Inc., a private corporation with FDA-approved nerve repair devices, will collaborate with Thayer on the design of a new surgical device that will allow the PEG solution to be delivered to the nerve endings in a uniform and predictable fashion. The device would attach via ports to nerve cuffs that are already commercially available.

The newly designed devices will first be tested in animal models. Thayer said the three-year federal grant supports translational research with real-world applications for patients.

“The hope for this technology is that if we are able to salvage even a portion of the axons that have been severed and keep them alive, we may be able to either regain early function in the limb or preserve just enough enervation to keep those muscles alive until the remainder of the axons can grow out and reach their target. This could potentially become a real game changer for which limbs you might salvage in this setting,” said Thayer.

The PEG solution itself also has shown little toxicity and should prove to be safe for use in humans.

“The buffered solution, the methylene blue and the polyethylene glycol are all commonly used benign substances,” said Thayer. “That’s what’s so special about this technology, because there’s very little toxicity with any of the products involved in the actual fusions.”

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