Tibial cortex transverse transport promotes peripheral nerve regeneration in diabetic neuropathy through an NGF-dependent mechanism

Background Diabetic peripheral neuropathy (DPN) causes progressive peripheral nerve dysfunction with limited recovery. Tibial cortex transverse transport (TTT) is an orthopedic mechanotherapy used in ischemic limb disorders, but its potential for peripheral nerve repair in DPN remains unclear. Methods DPN rats (high-fat diet plus low-dose streptozotocin) were assigned to Control, DPN, Sham, TTT, and TTT plus nerve growth factor (NGF) neutralization groups. Sensory behavior, gait-related function, motor/sensory nerve conduction, and histological outcomes were evaluated. In vitro, serum from each group was applied to Schwann cells, and a Schwann cell–dorsal root ganglion (DRG) neuron co-culture system was used to assess neurite outgrowth. Results TTT improved sensory function and gait performance, increased motor and sensory conduction velocities, and ameliorated structural abnormalities in sciatic nerve and intraepidermal nerve fibers. Sciatic nerve NGF showed a modest increase after TTT, and TTT-derived serum enhanced Schwann cell viability, increased NGF secretion, and promoted DRG neurite extension in vitro. NGF neutralization attenuated multiple TTT-associated benefits in vivo and in vitro. Conclusions TTT confers neurofunctional and structural benefits in experimental DPN, with NGF signaling contributing to its effects, supporting TTT as a promising mechanotherapy for peripheral nerve repair.