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Wednesday, 29 January 2020

New technology allows optimized regeneration of damaged nerves



In many anatomical traumas and diseases, the nerves are often damaged (section, elongation, crushing, degeneration, etc.). The standard procedure is nerve grafting, but the results are not always guaranteed and only between 40 and 60% of the original mobility can be restored. Recently, researchers have developed a polymer tube, coupled with regenerative proteins, which can lead to regeneration of the nerve over long distances with increased mobility greater than that of the graft.



Researchers at the University of Pittsburgh School of Medicine have created a biodegradable nerve guide - a polymer tube - filled with growth-promoting proteins, allowing long sections of damaged nerves to be regenerated without the need for stem cell transplants or a donor nerve. So far, the technology has been tested on monkeys and the results of the experiments have been published in the journal Science Translational Medicine.

“We are the first to show that a cell-free nervous guide was able to fill a large space of 5 cm between the nerve stump and its target muscle. Our guide was comparable and in some ways better than a nervous transplant,” said Kacey Marra, professor of plastic surgery at the McGowan Institute for Regenerative Medicine.



Half of the injured soldiers return home with injuries to their arms and legs, which are not well protected by a bulletproof vest, which often results in damaged nerves and disability. In civilians, car accidents, machine accidents, cancer treatment, diabetes and even birth trauma can cause significant nerve damage.

Better nerve regeneration and increased mobility

The peripheral nerves can grow back up to 0.8 cm on their own, but if the damaged section is longer than that, the nerve cannot find its target. Often the disoriented nerve is knotted in a painful lump called a neuroma. The most common treatment for longer segments of nerve damage is to remove a lean sensory nerve in the back of the leg - which causes numbness in the leg and other complications, but is most likely to be successful.

(Top) Section of the nerve guide surrounded by microspheres observed with a scanning electron microscope. (Bottom) Nerve guide composed of a 5.2 cm polymer tube. Credits: NB Fadia et al. 2020

The nerve is then sectioned in thirds, grouped into pieces and then attached to the end of the damaged motor nerve, usually in the arm. But generally, only about 40 to 60% of the motor function is recovered. Marra's nerve guide restored approximately 80% of the fine motor control in the thumbs of four monkeys, each with a 5 cm nerve gap in the forearm. The guide is made of the same material as the soluble sutures and dotted with a growth-promoting protein - the same as that attached to the brain in a recent trial of Parkinson's, which is released slowly over the months.

Very promising results for future human trials

The experiment had two controls: an empty polymer tube and a nerve graft. Since the legs of monkeys are relatively short, the usual clinical procedure of removing and cutting a nerve from the leg would not work. So the scientists removed a 5 cm segment of nerve from the forearm, turned it over and sewed it in place, fixing a high bar so that the nerve guide matched.

Nervous guide surrounded by protein microspheres. The experimental device enabled optimal nerve regeneration. Credits: NB Fadia et al. 2020

Functional recovery was just as good with Marra's guide as it was with this graft in the best of cases, and the guide surpassed the graft when it came to restoring nerve conduction and regenerating Schwann cells - the layer insulating around the nerves which amplifies electrical signals and supports regeneration.

In both scenarios, it took a year for the nerve to grow back. With these promising results in monkeys, Marra wants to apply her nervous guide to human patients. She is working with the Food and Drug Administration (FDA) on a first clinical trial in humans and is setting up a startup, AxoMax Technologies Inc.




Bibliography:

RESEARCH ARTICLE: NERVE REGENERATION
Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

Neil B. Fadia, Jacqueline M. Bliley, Gabriella A. DiBernard, Donald J. Crammond, Benjamin K. Schilling3, Wesley N. Sivak1,†, Alexander M. Spiess1, Kia M. Washington1,‡, Matthias Waldner1,§, Han-Tsung Liao1,||, Isaac B. James1, Danielle M. Minteer1, Casey Tompkins-Rhoades3, Adam R. Cottrill4, Deok-Yeol Kim1,¶, Riccardo Schweizer, Debra A. Bourne, George E. Panagis5, M. Asher Schusterman II1, Francesco M. Egro1, Insiyah K. Campwala6, Tyler Simpson7, Douglas J. Weber3,7,8, Trent Gause II1, Jack E. Brooker1, Tvisha Josyula3, Astrid A. Guevara1, Alexander J. Repko1, Christopher M. Mahoney3 and Kacey G. Marra

Science Translational Medicine
22 Jan 2020:
Vol. 12, Issue 527, eaav7753

DOI: 10.1126/scitranslmed.aav7753

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