Ohio State scientists say a lab-built “nanochip” that delivers genes in a flash can coax new blood vessels to sprout inside severely injured nerves and help those nerves regrow and reconnect in mice. In head-to-head lab tests, nerve grafts treated with the device showed stronger muscle performance and cleaner-looking nerve wiring than grafts that received standard surgery alone. The work is still squarely in the preclinical stage, and researchers stress that extensive testing is needed before anyone talks about using it in people.
Study used a millisecond nanochip to deliver genes
The findings, published in Science Advances, center on tissue nanotransfection (TNT), described as a millisecond-scale, non-viral technique for pushing genetic material directly into cells at the surface of a nerve graft in mice. In this study, TNT delivered three vasculogenic genes — Etv2, Fli1, and Foxc2, known together as the “EFF” cocktail — to the graft during surgery.
The device applies a rapid electrical pulse that drives the genetic cargo into cells, reprogramming local cells at the graft surface into a blood-vessel-forming state without resorting to viral vectors, according to Science Advances. The authors report that treated animals showed higher axon counts, better myelination, and stronger measures of grip strength and muscle contractility compared with mice that received only graft surgery.
New vessels came mostly from reprogrammed fibroblasts
Investigators also found that the treated nerves developed more blood vessels than controls, and that these new vessels largely originated from fibroblast cells that had been reprogrammed by the EFF factors — a detail local coverage highlighted. As noted in Cleveland.com and summarized by MedicalXpress, this fresh vasculature appeared to act as a guide rail for regenerating axons crossing long nerve grafts and lined up with better functional recovery. In a long-segment defect model, mice that received TNT-treated grafts recovered more quickly than those that underwent graft surgery without the gene treatment.
Why the extra vessels matter
According to Science Advances, blood vessels do double duty in injured nerves. They deliver oxygen and metabolic support, and they also lay down structural cues that help regrowing axons stay on course. The authors argue that this dual role likely underpins the functional gains seen in the TNT-treated mice.
The fact that TNT is non-viral and can be applied right in the operating room is a major selling point for the team. In principle, the technique could be layered onto existing nerve graft procedures without systemic gene delivery. At the same time, the researchers caution that potential off-target effects, long-term safety, and performance in larger animals all need to be nailed down before clinical trials are even on the table.
From the lab toward the OR (and beyond)
This latest work builds on years of TNT research at Ohio State and earlier backing from the Department of Defense. In 2022, a DoD grant awarded millions of dollars to study TNT for traumatic nerve damage, according to Ohio State College of Engineering.
University communications have portrayed TNT as a one-time, millisecond intervention that surgeons could, at least in theory, add at the moment of repair to bolster a nerve graft’s blood supply, Ohio State Wexner Medical Center and an overview from Ohio State College of Engineering note. Peripheral nerve injuries, often caused by car crashes or falls, can leave patients with chronic weakness or numbness, which is why the team frames approaches like TNT as potential add-ons rather than replacements for surgery.
What’s next
Next steps on the research agenda include safety testing in larger animal models, fine-tuning how the genes are delivered, and long-term monitoring for any unintended cell reprogramming or immune system reactions. “This study is the first to combine TNT with nerve graft surgery, and the results are promising,” senior author Daniel Gallego-Perez said in a university statement via Ohio State Wexner Medical Center. If those hurdles can be cleared, the group hopes the approach could eventually be tested in clinical scenarios where long-segment nerve gaps still leave many patients with disappointing recoveries.
