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Epidural electrical stimulation (EES) has been demonstrated promising for SCI therapy in ways of rehabilitation by facilitating the recovery of lower limb motor abilities. However, EES necessitates a considerable consumption of electrical energy and exhibits large individual differences in treatment. Nanogenerators (NGs) based on a novel power generation technology, are capable of transforming mechanical energy into electrical power. This mechanic\u2010driven electrical stimulation has been reported effective in several types of neuromodulations, but not in EES to enable SCI rehabilitation. This study explores the efficacy of a hybrid\u2010NG (H\u2010NG) to elicit hindlimb locomotion in rats via EES on the spinal cord, in comparison with a commercial stimulus generator (SG). The results reveal that H\u2010NG can activate the spinal cord and induce hindlimb locomotion with much lower electrical parameters and much smaller individual differences than SG. In addition, benefiting from the miniature size of the H\u2010NG, an implantable EES system is constructed in vivo, enabling a self\u2010driven and rational\u2010controlled EES pattern. The proposed H\u2010NG\u2010based EES system provides a new strategy for optimized and personalized treatment for SCI patients.<\/jats:p>","DOI":"10.1002\/advs.202501425","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:40:23Z","timestamp":1747993223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nanogenerator Neuromodulation to Enable Locomotion Rehabilitation for Spinal Cord Injury via Epidural Electrical Stimulation"],"prefix":"10.1002","volume":"12","author":[{"given":"Cong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Second Affiliated Hospital of Xi'an Jiao Tong University  Xi'an Shaanxi 710004 China"},{"name":"Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences  Beijing 101400 China"},{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences  Beijing 100010 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