Abstract
The transplantation of regionally specific spinal neural progenitor cells (sNPCs) has shown promise for functional restoration after spinal cord injury (SCI) by forming connections with host neural circuits. Here, 3D-printed organoid scaffolds for transplantation using clinically relevant human induced pluripotent stem cell-derived regionally specific sNPCs is developed. Scaffolds with microscale channels are printed, and sNPCs are subsequently printed within these channels. The scaffolds direct axonal projections along the channels and guide the cells to simulate in vivo-like conditions, leading to more effective cell maturation and the development of neuronal networks crucial for restoring function after SCI. The scaffolds, with organoids assembled along their lengths, are transplanted into the transected spinal cords of rats. This significantly promotes the functional recovery of the rats. At 12 weeks post-transplantation, the majority of the cells in the scaffolds differentiate into neurons and integrate into the host spinal cord tissue. These results demonstrate their potential to create a relay system along the spinal cord and form synapses in both the rostral and caudal directions relative to the scaffold. It is envisioned that combining sNPCs, organoid assembly, and 3D printing strategies can ultimately lead to a transformative treatment approach for SCI.