Electrified Scaffold Bridges Severed Nerves

With news coming almost daily of dramatic medical advances, one vital area has remained intractable to research. That is the repair of a severed nerve in the spinal column. The fault lies with the nerve cells, themselves, which stubbornly refuse to regenerate.

As one researcher bluntly put it, “To date there are neither workable repairs nor detours that will restore signal flow between the brain and limbs.” In other words, with the severing of the nerves of the spinal cord paralysis is inevitable and is not reversible. Even hope has been in short supply.

Until now.

Treena Arinzeh, Ph.D., M.S.E., director of the New Jersey Institute of Technology’s Tissue Engineering and Applied Biomaterials Laboratory, has proposed a solution. It is a scaffold, made of a polymer, which will coax nerve cells to extend their axons over a spine’s damaged section.

Piezoelectric Polymers

The novel scaffold the team developed won Arinzeh and her lab workers an award from the New Jersey Research and Development Council for their invention of piezoelectric material, which produces an electrical charge in response to a mechanical force. The group’s repair strategy is to build a piezoelectric scaffold with neural cells to try to regenerate nerve tissue in spinal cord injuries.

“Axons—the nerve fibers that transmit messages—can potentially travel long distances if given the right cues to regrow. We knew that an electrical charge could direct this growth," Arinzeh said, adding, "Some tissues in the body are naturally piezoelectric. What we did was to create a fibrous material that is similar, but with a higher charge to stimulate growth."

The Department of Defense, which seeks research into remedies for traumatic battle injuries, learned of the scaffolds. Arinzeh understood and shared the department’s concern. “There is no effective treatment for severe spinal cord injuries, and soldiers can remain completely paralyzed for the rest of their lives,” she noted.

With funding from the agency, the technology is being tested at several locations. One is the University of Miami Miller School of Medicine, where Arinzeh is working with Mary Bunge, Ph.D., a neuroscientist, and her former student.

They are injecting Schwann cells from the peripheral nervous system, which produces the myelin sheath around nerve axons, in combination with the piezoelectric scaffold.

Other testing is examining the efficacy of injecting Schwann cells from the peripheral nervous system, which produce the myelin sheath around nerve axons, in combination with the piezoelectric scaffold, for spinal cord repair. Their hope is that the Schwann cells’ job will be to restore existing cells by stimulating them to extend their axons.

Human Trials Bridge a 5mm Gap

The Miami Project is currently in phase I clinical trials with humans as well. They are testing the use of Schwann cells for spinal cord repair. By combining those cells with piezoelectric scaffolds, "we hope to improve the cells’ survival and their effectiveness when implanted into the spinal cord,” Arinzeh says.

“The nice thing about Schwann cells is that they’re readily accessible from low-risk sites like limbs. I think of them as ‘facilitator cells’ because they provide the signals that prompt axons to grow and reach their targets which are other neurons,” she adds.

In the pre-clinical studies, Arinzeh found that implanted scaffolds with Schwann cells would extend themselves over a 5mm gap in the spinal cord. “The cells survived and were getting good growth—wrapping themselves around the growing axons as the axons extended along the scaffold,” she said

The primary conventional treatment for spinal cord trauma has been to reduce inflammation with drugs. Researchers have also injected cells with growth factors, or growth factors alone, into the spinal cord in the hope of stimulating new growth. So far these have not been successful, Arinzeh says.

“No technology has been effective so far, and so we’re taking it a step further, introducing biomaterials with an electrical charge. We’ve known in the biomedical world that electro stimulation can cause nerve cell growth—we’ve seen this with bone and cartilage tissue—so we set about to identify a polymer with piezoelectric properties. We found it in a material used for sutures, which is biocompatible and promotes nerve growth,” she explained. “We’re looking for some recovery of function. If we can show that, it would be a significant leap.”

Arinzeh has borrowed techniques from engineering sectors to advance tissue regeneration including for bone and cartilage repair. The polymer fibers that compose the framework of her scaffolds are formed by electrospinning, a technique developed by the textile industry.

Arinzeh remains hopeful “We are relying on the scaffold to stimulate the body’s own cells to regrow tissue, but the biological factors driving the formation of neural tissue in the spinal cord appear to be more complex. To induce nervous tissue to not only regrow across the lesion, but to reconnect with the rest of the spinal cord, may require a combination of scaffolds, cells and growth factors.”