REGENERATION OF INJURED SPINAL CORD BY APPLYING SUBDURAL ELECTRO PULSED STIMULATION AND STEM CELL BIO-HYBRID APPROACH

Spinal cord injury (SCI) affects 14.5 million people globally and lacks curative therapy (Kim et al., 2025; Varma, Das et al. 2013). The pathophysiology combines primary mechanical trauma with progressive secondary cascades involving neuronal and oligodendrocyte loss, immune activation, and demyelination (Anjum, Yazid et al. 2020; Alizadeh, Karimi-Abdolrezaee 2016). Multifaceted therapeutic strategies combining neuroprotection, cell substitution, and axonal regeneration offer the most promising restoration approach. We present an Electro-Pulsed Biohybrid (EPB) device, an implantable, cell-loaded platform delivering local electrical stimulation and stem cell transplantation for subdural SCI treatment. The EPB applies microsecond pulsed electric fields (µsPEFs) and direct current to regulate cytosolic calcium oscillations (Hanna, Andre et al. 2017), driving neuronal differentiation and neurotrophic factor secretion. A biocompatible scaffold facilitates stem cell engraftment with wireless or wired control. In a rat contusive SCI model, sequential µsPEF (10 days) followed by continuous current (5 days) significantly enhanced mesenchymal stem cell engraftment, reduced microglia reactivity, and did not exacerbate gliosis, fibrosis, or neuropathic pain. Stimulated animals demonstrated markedly improved locomotor running speed compared to controls, with consistent benefits across both configurations. The EPB platform achieves early immunomodulation by suppressing secondary immune cascades while promoting cell homing, providing a versatile foundation for combined cell and electrical therapies in SCI repair.
Funding: European Union's Horizon 2020 FET OPEN (grant N° 964562, RISEUP); FEDER/Ministerio de Ciencia e Innovación PID2021-124359OB-I00 and PID2024-159513OB-I00; CIPROM/2022/25 Prometeo Program GVA—Cell2Spine Project.