Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulating neural stem cell fate for spinal cord regeneration

Abstract: A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for spinal cord injury (SCI) treatment. In this study, innovative three-dimensional (3D) nanofibrous sponges (NSs) are designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. The as-generated 3D NSs exhibit uniaxially aligned nano-architecture and highly controllable hierarchical structure with high porosity, outstanding hydrophilicity, and reasonable mechanical performance, and they are demonstrated to facilitate cell infiltration, induce cell alignment, promote neuronal differentiation of NSCs, and enhance their maturation by activating the cellular adhesion molecule (CAM) pathways. The in vivo data show that the NSC-seeded 3D NSs efficiently promote axon reinnervation and remyelination in a rat SCI model, with new “neural relays” constructed across the lesion gap. Notably, they significantly increase the neurological motor scores of SCI rats from ~2 to 16 (out of 21) and decrease the sensing time from 140 s to 36 s, accompanied by the restoration of ascending and descending electrophysiological signalling. Overall, the present study indicates that the as-fabricated 3D NSs can effectively regulate the fate of NSCs, and an advanced combination of 3D NS design and transplanted NSCs invites applications as an ideal tissue-engineered scaffold for SCI repair.