Constructing a Wireless Nerve Electrical Stimulation System to Repair Peripheral Nerve DefectsBo Wang1*, Changfeng Lu1, Xiaojin Luo2, Shuai Han1, Guixi Zhang3, Yue Cui2✉, PeixunZhang1✉1Department of Orthopedics and Trauma, Peking UniversityPeople’s Hospital; Key Laboratory of Trauma and Neural Regeneration (Ministry of Education/Peking University), National Center for Trauma Medicine, Beijing, China.*The first author is now working at Beijing Jishuitan Hospital after graduated from Peking University from July, 2021.2 School of Materials Science and Engineering, Peking University, Beijing, China.3Hongkong University Shenzhen Hospital, Shenzhen,China.Correspondence: [email protected]; [email protected]: This study was supported by the Beijing National Science Foundation (7212121), National Natural Science Foundation of China (22278003, 52072007), Beijing Science and Technology Rising Star Program Foundation (20220484233); Peking University People’s Hospital Research and Development Fund (RDH2020-01); National Center for Trauma Medicine (BMU2020XY005-01, BMU2021XY008-01); Shenzhen City Trauma Sanming Project (SZSM202011001); National Key R&D Program of China (No. 2018YFB1307301).AbstractPurpose: The repair effect of peripheral nerve injury mainly depends on rapid regeneration of proximal axons, accurate docking, and effective nerve re-innervation of target organs. Accordingly, identifying effective methods to protect the functional state of target organs and realize rapid regeneration of proximal nerve fibers is of great significance. The purpose of this study is to build a nervous electrical stimulation system powered by electromagnetic induction and evaluate its repair effect on a rat sciatic nerve defect model.Methods: Biodegradable materials [magnesium (Mg), polylactic acid (PLLA), chitosan, and silk fibroin] were chosen to build thein vivo part of the wireless electrical nerve stimulation system (including a receiving coil, electrode, and Mg-PLLA conductive scaffold) by three-dimensional printing and electrostatic spinning technology. Electromagnetic induction properties of the receiving coil, and mechanical properties and cytotoxicity of the conductive scaffold were studied in vivo . The effects of electric field stimulation of alternating current (AC) on the migration and growth of dorsal root ganglion neurons and secretion of Schwann cells were studied. A rat sciatic nerve defect model of 10 mm was established and repaired with the wireless electrical nerve stimulation system. The repair effects were evaluated by motor function recovery, muscle recovery, electrophysiological detection, morphological analysis of regenerated axons, and quantity analysis of motor end plates.Results: The wireless neural electrical stimulation system generates effective electrical signals through the electromagnetic induction coils in vitro and in vivo , and shows good mechanical properties and biocompatibility. Specific AC stimulation promotes neurotrophic factor secretion by Schwann cells. The effect of 1-h daily electric field stimulation on Schwann cell secretion mainly took effect within 24 h. The effect of the wireless electrical nerve stimulation system in repairing the sciatic nerve defect in rats was significantly better than that of the simple conductive scaffold group and inferior to the group repaired by an autologous nerve graft. However, the degree of myelination of regenerated nerve fibers in the wireless electrical nerve stimulation group was similar to the autologous nerve repair group.Conclusion: An implantable electrical nerve stimulation system without battery implantation was successfully constructed. The system acquired effective electrical signal stimulation through radio magnetic induction, and the conductive nerve scaffold was used as a carrier to accurately stimulate the injury site. The system could effectively promote the repair of rat sciatic nerve defects.KEY WORDS: Peripheral nerve injury, Electrical stimulation, Wireless, Schwann cells, Nerve defect