Strategies and prospects of effective neural circuits reconstruction after spinal cord injury

Due to the disconnection of surviving neural elements after spinal cord injury (SCI), such patients had to suffer irreversible loss of motor or sensory function, and thereafter enormous economic and emotional burdens were brought to society and family. Despite many strategies being dealing with SCI, there is still no effective regenerative therapy. To date, significant progress has been made in studies of SCI repair strategies, including gene regulation of neural regeneration, cell or cell-derived exosomes and growth factors transplantation, repair of biomaterials, and neural signal stimulation. The pathophysiology of SCI is complex and multifaceted, and its mechanisms and processes are incompletely understood. Thus, combinatorial therapies have been demonstrated to be more effective, and lead to better neural circuits reconstruction and functional recovery. Combinations of biomaterials, stem cells, growth factors, drugs, and exosomes have been widely developed. However, simply achieving axon regeneration will not spontaneously lead to meaningful functional recovery. Therefore, the formation and remodeling of functional neural circuits also depend on rehabilitation exercises, such as exercise training, electrical stimulation (ES) and Brain-Computer Interfaces (BCIs). In this review, we summarize the recent progress in biological and engineering strategies for reconstructing neural circuits and promoting functional recovery after SCI, and emphasize current challenges and future directions.