Gene Therapy Improves Outcomes of Nerve Graft Surgery in Mice

Researchers from Ohio State University have developed a gene therapy that promotes blood vessel growth following nerve graft surgery. A study published today in Science Advances reports a significant improvement in both nerve growth and muscle strength in treated mice. 

Peripheral nerve injury can cause long-term disability, weakness, numbness, or loss of function. While nerve grafts can help repair some of these injuries by regrowing damaged nerves and reconnecting any gaps left by the original injury, many patients still can’t fully recover mobility or feeling. 

The new approach developed at Ohio State combines traditional nerve graft surgery with a gene therapy delivered using quick electrical pulses to the nerve drafts. This technique, known as tissue nanotransfection (TNT) is used to introduce three genes (Etv2, Fli1 and Foxc2) into graft cells that promote the formation of new blood vessels. 

“This study is the first to combine TNT with nerve graft surgery,” said Daniel Gallego-Perez, PhD, professor of biomedical engineering at Ohio State and senior author of the study. “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.”

In a mouse model of peripheral nerve injury, mice treated with the gene therapy grew more blood vessels than those only receiving a conventional nerve graft surgery. The treatment did not just help nerves regrow and reconnect, but also improved function and general health outcomes in mice. 

“We saw improvements not just under the microscope, but in real function like stronger muscle contractions and better grip strength,” said Amy Moore, MD, chair of Ohio State’s Department of Plastic and Reconstructive Surgery and interim dean of the university’s College of Medicine. “The findings from this study advance our ability to reconstruct long nerve gaps and restore function to limbs with devastating nerve injuries.” 

Moore noted that this approach could make a significant difference when treating severe, complex nerve injuries common among military services injured in training or combat. The treatment is being developed as part of the Military Medicine Program at Ohio State, which focuses on offering surgical reconstruction and pain management care for wounded service members.  

Development of the gene therapy will continue with studies in larger animals before human trials can begin. Next, the research team plans to investigate how long the benefits of the treatment last.

This novel approach could one day become part of routine nerve graft surgery, adding a simple short step to significantly improve the outcomes of a well-established procedure. Salazar-Puerta added: “This is designed to fit into the operating room and is a single treatment that could have lasting benefits.” 

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