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

Theranostics, 2023 · DOI: 10.7150/thno.87288 · Published: August 28, 2023

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injuries (SCI) often lead to permanent sensory and motor function deficits because the body struggles to regenerate damaged neural networks. This study introduces a novel approach using three-dimensional (3D) nanofibrous sponges (NSs) combined with neural stem cell (NSC) transplantation to promote SCI repair. These 3D NSs, created through directional electrospinning and gas-foaming, mimic the natural extracellular matrix, providing an instructive microenvironment for nerve regeneration. The sponges encourage cell infiltration, alignment, and differentiation of NSCs into neurons. In a rat SCI model, NSC-seeded 3D NSs facilitated axon reinnervation and remyelination, leading to the development of new 'neural relays' across the injury site and functional recovery. This suggests a promising tissue-engineered scaffold for SCI repair.

Study Duration

8 Weeks

Participants

Adult female SD rats (220-250 g), n=6 per group

Evidence Level

Not specified

Key Findings

1
The 3D NSs promoted cell infiltration, induced cell alignment, and enhanced neuronal differentiation and maturation of NSCs through cellular adhesion molecule pathways.
2
In vivo experiments showed that NSC-seeded 3D NSs effectively promoted axon reinnervation and remyelination in a rat SCI model, leading to the formation of new neural relays across the lesion gap.
3
Functional recovery in SCI rats was observed, including improved neurological motor scores and decreased sensing time in sensory tests, along with restoration of electrophysiological signaling.

Research Summary

This study introduces a novel three-dimensional (3D) nanofibrous sponge (NS) scaffold, created using directional electrospinning and gas-foaming, to promote neural stem cell (NSC) differentiation and spinal cord injury (SCI) repair. The 3D NSs exhibited aligned nano-architecture, high porosity, hydrophilicity, and mechanical performance, facilitating cell infiltration and neuronal differentiation of NSCs. In vivo, NSC-seeded 3D NSs promoted axon reinnervation and functional recovery in a rat SCI model, suggesting their potential as an ideal tissue-engineered scaffold for SCI repair.

Practical Implications

Therapeutic Strategy

The combination of biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment.

Advanced Scaffold Design

The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.

Clinical Translation Potential

The universal strategy for elevating dimensions dramatically broadens the application boundaries of traditional electrospinning scaffolds, providing a new prospect in the regeneration of CNS and other anisotropic tissues.

Study Limitations

1
The gas-foaming treatment partly reduces the nanofiber orientation of 3D NSs which may have some impact on the directional axon growth
2
It was still challenging to maintain a high NSC survival rate over an extended period of time in vivo because of the deleterious microenvironment at the site of the lesion
3
The spinal cord is not entirely uniformly oriented, which also contains other orientations, complexities, and networks that enable its intricate functions.

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