Novel gene-based therapy helps nerves heal better after severe injury

Peripheral nerve injuries, often caused by traumatic events such as car accidents, falls or battlefield injuries, can leave patients with long-term weakness, numbness or loss of function. Despite surgery and advances in understanding and treating nerve injuries, many patients don’t get all their movement or feeling back.

Researchers at The Ohio State University College of Medicine and College of Engineering developed a new way to improve healing after severe nerve injuries by helping the body grow new blood vessels where the nerve is repairing itself. The new approach combines nerve graft surgery with tissue nanotransfection (TNT), a novel non-viral gene therapy developed at The Ohio State University.

Scientists used TNT to deliver three specific genes (Etv2, Fli1 and Foxc2) that tell cells to help form new blood vessels. These genes were applied via a very quick electrical pulse to nerve grafts used during surgery in mice with severe nerve injuries.

“This study is the first to combine TNT with nerve graft surgery, and the results are promising. While healing nerves do need oxygen and nutrients, blood vessels do much more than just deliver supplies—they help guide and support the repair process. By helping the body quickly grow new blood vessels, our approach creates a healthier environment that allows nerves to heal more effectively,” said study senior author Daniel Gallego-Perez, Ph.D.

Gallego-Perez is a professor and Edgar C. Hendrickson Chair in Biomedical Engineering at Ohio State. Ana Salazar-Puerta, Ph.D., a postdoctoral researcher in Gallego-Perez’s lab, led the research. Results of the study, a collaboration between Ohio State’s Colleges of Medicine and Engineering, are published in the journal Science Advances.

Research results

• Nerves treated with TNT grew more blood vessels than untreated nerves.
• The extra blood vessels helped nerves regrow and reconnect better.
• Treated mice had better health outcomes compared to those that only had surgery.
• The new blood vessels mostly came from fibroblast cells, which play a crucial role in wound healing and tissue repair.

“We saw improvements not just under the microscope, but in real function, like stronger muscle contractions and better grip strength,” said Amy Moore, M.D., chair of Ohio State’s Department of Plastic and Reconstructive Surgery, interim dean of the College of Medicine and the Robert L. Ruberg, M.D. Alumni Endowed Chair.

Researchers said the therapy could one day be applied during surgery, adding only a short step to existing procedures. “This is designed to fit into the operating room and is a single treatment that could have lasting benefits,” Salazar-Puerta said.

Next, researchers will test the method in larger animal models and study how long the benefits last. Ohio State has patented TNT and the gene “cocktail” to make blood vessels.

Moore noted that severe, complex nerve injuries are common among military service members injured in combat or training and can lead to lifelong disability. Ohio State’s Military Medicine Program brings together a team of advanced reconstructive surgeons, military specialists and rehabilitation experts to help restore the health and well-being of severely injured military members.

“The findings from this study are important and advance our ability to reconstruct long nerve gaps and restore function to limbs with devastating nerve injuries,” Moore said.