Tacrolimus- and Nerve Growth Factor-Treated Allografts for Neural Tissue Regeneration

Treatment of injured peripheral nerves, especially long-distance nerve defects, remains a significant challenge in regenerative medicine due to complex biological conditions and a lack of biomaterials for effective nerve reconstruction. Without proper treatment, nerve injury leads to motor and sensory dysfunction. Here, we have developed an efficacious nerve allograft treated with a dual drug containing acrolimus and nerve growth factor to bridge the nerve gap and achieve rapid neural tissue recovery without immunological rejection. The recovery of the structure, activity, and function of rats treated with the dual drug-treated allograft was investigated by walking track analysis and electrophysiological measurement. The sciatic functional index was measured to be -3.0 after a 12-week treatment. The nerve conduction velocity, peak latency, and peak amplitude of the nerve action potentials demonstrate the functional recovery of the nerve. To study the synergistic effect of the dual drug on the growth of neurites, a neural cell hypoxia model was created. The dual drug exhibited a high efficiency in promoting the growth of nerve cells under the nerve injury-induced hypoxic condition. The dual drug could protect the cells against antioxidative damage from hypoxia by the expression of heat shock protein, hypoxia-inducible factor, β-tubulin, and vimentin.