Magnetoelectric microrobots for spinal cord injury regeneration

Abstract

Spinal cord injury remains difficult to treat because of the intrinsically limited regenerative capacity of neurons. Although neural progenitor cell (NPC) therapies are promising, inadequate graft survival, uncontrolled differentiation and weak functional integration continue to restrict outcomes. Here we report biohybrid microrobots called NPCbots, fabricated by integrating human-induced pluripotent-stem-cell-derived NPCs with magnetoelectric nanoparticles, enabling wireless magnetic navigation and non-invasive neuronal stimulation. A lab-on-a-chip platform allows scalable fabrication and maintains cell viability and differentiation capacity. In a zebrafish spinal cord injury model, alternating magnetic field stimulation of NPCbots induced rapid in vivo neuronal and astrocytic differentiation, enhanced graft integration at the lesion site, and near-complete recovery of swimming and exploratory behaviours within 3 days. In a non-regenerating murine model of complete spinal cord transection, NPCbots were well tolerated for at least 28 days, localized effectively to the injury site, promoted neural differentiation and resulted in substantial improvements in motor function within 4 weeks. These results demonstrate that magnetically guided NPCbots combined with non-invasive magnetoelectric stimulation promote neural repair and functional recovery in preclinical spinal cord injury models.