3D nanofibrous frameworks with on-demand engineered gray and white matters for reconstructing the injured spinal cord

Spinal cord injury (SCI) is a disruptive and heterogeneous medical condition affecting millions of patients worldwide. Due to the absence of medical treatments to effectively restore the lost sensorimotor and autonomic functions, there is an ongoing pursuit of scaffolds aiming to bridge the injured spinal area. Herein, a novel electrospinning modality to construct 3D nanofibrous frameworks (NFFs) in accordance with distinct spinal cord microenvironments is used to engineer a biomimetic hemicord. This scaffolding concept gravitates around the possibility of customizing NFFs with on-demand engineered gray and white matters to replicate the native spinal cytoarchitecture. In particular, a 3D reduced graphene oxide-based fibrous-porous system is developed to imitate the gray matter, while a 3D polycaprolactone (PCL)-chitosan nanofibrous network combined with PCL-graphene microfibers intends to mimic the white matter. The scaffolding components are tested in vitro with embryonic neural progenitor cells, integrated into the biomimetic NFF, and then tested in vivo in paralyzed rats with cervical hemisection. After 4 months of implantation, the scaffold generates both neuroprotective (e.g., limited infiltration of vimentin⁺ and ED1⁺ cells) and neuroregenerative (e.g., presence of new blood vessels and neurites) features accompanied with promising signs of forelimb function recovery.