VCU news

By Jeff Kelley

Momentum.

That, a leading Virginia Commonwealth University hand surgeon said, is what it takes to successfully move research from the lab into the real world.

Jonathan Issacs, M.D., professor in the Department of Orthopaedic Surgery in the School of Medicine and chair of VCU Health’s Division of Hand Surgery, is the surgeon-scientist behind Nerve Tape, a tiny biologic wrap used to repair severed peripheral nerves. Like a piece of high-tech tape with tiny, flexible embedded hooks, the wrap loops around and self-seals the nerve’s outer connective tissues — improving nerve alignment and promoting regeneration.

This year, the device received clearance from the U.S. Food and Drug Administration. It is a critical milestone in anticipation of the team’s first human use in 2023.

“All these major, big medical centers are, like, ‘This thing is so cool. I wish we’d thought of that. We can't wait to use it,’” said Isaacs, recipient of the 2022 Billy R. Martin VCU Innovator of the Year Award, announced by P. Srirama Rao, Ph.D., vice president for research and innovation, at a ceremony on Nov. 17. “We’ve got good-looking data, we’ve got surgeon buy-in, we’ve got patents and we’ve got FDA clearance. We’ve maintained momentum.”

That drive began more than a decade ago. Isaacs recognized that even for experienced surgeons like him, repairing peripheral nerves isn’t easy. When a nerve is cut due to injury, proper repair requires precision alignment of the tiny, severed circuitry through what are known as micro-sutures (tiny, microscopic stitches).

Less than half of all patients fully recover from injuries where nerves are cut, or transacted, Isaacs said.

And beyond the skills required, the instruments and tools needed to perform such microsurgery are expensive, and the procedures time-intensive.

Isaacs, who is internationally recognized in the relatively niche field of nerve repair, knew there had to be a better way. “As a surgeon-scientist, I’m committed to figuring out how we can do things better,” he said.

His idea was the concept of a tape with tiny, embedded hooks that could be used to secure nerves back together. Initial experiments began in 2012 with one-millimeter fishing hooks used in jewelry design, which he would specially order online for $10 per hook. Executing the concept wasn’t easy. Fishing hooks would fall on the floor, never to be found again. “I would joke with my research assistant that a day in the lab for us is to walk in, light ten $10 bills on fire and leave,” he said.

Through a friend in the nerve-repair world, Isaacs was introduced to Axion, a company based in Atlanta, which had created a metal disc with tiny micro-needles used for measuring electrical signals in muscles.

“It was about the size of what we needed,” Isaacs said. He received a disc from Axion, placed a severed 5-millimeter cadaver nerve on it, and tried pulling it off the disc. “We couldn’t move it. The nerve stayed in place, completely secured,” Isaacs recalled. “It was a total ‘aha’ moment.”

From there, he and the Axion engineers began tweaking and adjusting the product, almost daily. “I knew that if I let the Axion engineers lose momentum on this, I’d never get them back,” he said. So he’d operate during the day, hit the lab in the evening, tussle with the nerves and latest device iteration, and send results and pictures to the Atlanta team, who would update the prototype and send him a new version.

Dozens of device versions were built. Isaacs and Axion landed a grant from the National Institutes of Health to enlarge his lab, and the team co-patented the designs with the help of VCU’s office that assists in tech transfer and faculty ventures. Seeing the rocketing potential of the product, in 2016 Axion spun out a company, BioCircuit Technologies, focused on Isaacs’ work and other fixes to the body’s nerves, its biological circuitry.

The team developed a prototype, which was tested on animal models, and, with enough data in hand, froze the design. Whereas the initial prototype was rigid stainless steel, the final uses the more forgiving nitinol metal alloy attached to the tape material derived from pig intestines, called small-intestine submucosa, which also helps human tissue heal.

They called the product Nerve Tape.

“It was years and years of me believing in the idea a lot more than anybody else believed in it,” Isaacs said. “All of a sudden, in the last year, it has just exploded with BioCircuit now being completely focused on it, with VCU being focused on it. It’s surreal, and it’s coming very, very quickly.”

Ivelina Metcheva, Ph.D., assistant vice‌ president‌ ‌for‌ ‌innovation‌ at VCU TechTransfer and Ventures (formerly Innovation Gateway), said Isaacs is an excellent example of a surgeon-scientist.

“Most of the innovations we receive are from faculty researchers, but he's a practicing surgeon,” said Metcheva, whose office bestows the Innovator of the Year Award. “Because physicians or surgeons are practicing, they know best what the needs are and what the pain in the market is. And they can come up with something really useful to address unmet needs in clinical care.”

Isaacs and Dawson Reimer, who oversees commercial and business development at BioCircuit, say there is even greater potential for Nerve Tape as a platform for other uses.

“One of the beautiful things about Nerve Tape is that the product could open up nerve repair to fields that don’t traditionally repair nerves,” Reimer said. “There’s a clinical burden of people out there who have had an injury or a tumor removed and are told to just deal with the paralysis or numbness in a part of their body that comes along with those surgeries. There is an untapped clinical opportunity in extending nerve repair capabilities beyond microsurgeons. That’s the long-term opportunity that could become the biggest legacy of Nerve Tape.”

Isaacs, along with senior orthopaedic research scientist Geetanjali Bendale, Ph.D., continues to explore new uses for Nerve Tape but also other aspects of improving patient outcomes following nerve injury. They are looking at methods of reversing the loss of function in denervated muscles, for example.

VCU also protects Issacs’ time to dedicate to the lab. “But I really enjoy research. It’s part of my job, but it’s also my hobby,” Isaacs said.

“Jonathan is more engaged than the average clinical scientist who has founded a company,” Reimer said. “He loves the product and treats it like his baby.”

And if in doubt of Issacs’ passion for his research, the license plates on his car read “NRVTPE.”