Microfluidic hollow fiber with improved stiffness repairs peripheral nerve injury through non-invasive electromagnetic induction and controlled release of NGF

Peripheral nerve injury can lead to paralysis, chronic pain, muscle atrophy and disability due to interrupted bioelectric signal communications between spinal cord and the innervated bodies. Bioelectric materials, particularly conductive hydrogels, have shown the increasing potentials in neural engineering because they serve as tissue scaffolds that can support cell growth and differentiation, and restore functional electric conduction. In this work, we fabricated size-tunable microfluidic hollow fibers (HF) with improved stiffness and elasticity based on a triple network called SCPAPPy, which was composed of sodium alginate/Ca2+ (SC), polyacrylamide (PA), and polypyrrole (PPy). This HF showed a higher conductivity of 0.32 S/m than that of native sciatic nerve. Based on finite element analysis and digital oscilloscope measurement, the conductive HF was demonstrated to generate electromotive forces through electromagnetic induction by using a figure-eight coil. This creative approach could non-invasively facilitate myelination by improving Schwann cell's growth and migration. Meanwhile, the electromotive forces drove the secretion of endogenous nerve growth factor (NGF) from Schwann cells. Moreover, exogenous nerve growth factor-75 (NGF-75) was loaded in the HF, which was released gradually and promoted the differentiation of neurons in a controlled manner. By applying the pulsed magnetic field (MF) and NGF-75 together, it was found that the rats with 5-mm sciatic nerve defects achieved a more rapid nerve regeneration and functional recovery. In a word, our study demonstrated the practical role of electromagnetic induction on nerve repair, and opened the window of synergistic therapy combining the bioelectricity and neurotrophic factors towards peripheral nerve injury.