Emerging strategies for spinal cord injury repair: stem cells, extracellular vesicles, biomaterials, and neuromodulation

Abstract

Spinal cord injury (SCI) is a devastating condition that frequently results in permanent disability. Repair and functional recovery after SCI are hindered by the complexity of its pathophysiology and the inherent challenges of neural regeneration within the central nervous system. Despite decades of research aimed at elucidating its pathological mechanisms and developing effective strategies to promote axonal regeneration and circuit rewiring, successful therapeutic outcomes remain limited. Recent advances in bioactive materials and stem cell technology have shifted the research focus from solely stimulating corticospinal tract regeneration toward building intermediate neural networks to facilitate neural repair and circuit reconstruction. Concurrently, emerging technologies that modulate neural activity through physical modalities, such as electrical, magnetic, and ultrasonic stimulation, are rapidly evolving. Among these emerging strategies, several—including stem cell therapy, biomaterial-based interventions, and electromagnetic stimulation—have advanced to clinical trials, with some already entering clinical practice. This review summarizes the major contemporary strategies and research advances in SCI repair. It details the mechanisms and latest developments in stem cell and extracellular vesicle therapy, biomaterial applications, and neuromodulation techniques. Finally, it discusses future therapeutic directions and ongoing challenges in clinical translation.