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Theranostics 2023; 13(14):4762-4780. doi:10.7150/thno.87288 This issue Cite

Research Paper

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

Zhiwei Li1#, Ye Qi2#, Lei Sun3, Zheng Li1, Shaojuan Chen2, Yuqi Zhang1, Yuan Ma1, Jinming Han1, Zide Wang1, Yulin Zhang1, Huimin Geng1, Bin Huang1, Jian Wang1,4, Gang Li1, Xingang Li1, Shaohua Wu2✉, Shilei Ni1✉

1. Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
2. College of Textiles & Clothing, Qingdao University, Qingdao, China.
3. Department of Endocrinology, Qilu Hospital of Shandong University and Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, 250012, China.
4. Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
# These authors contributed equally.

✉ Corresponding authors: E-mail addresses: shaohua.wuedu.cn (S. Wu); nishileiedu.cn (S. Ni).

Citation:
Li Z, Qi Y, Sun L, Li Z, Chen S, Zhang Y, Ma Y, Han J, Wang Z, Zhang Y, Geng H, Huang B, Wang J, Li G, Li X, Wu S, Ni S. Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration. Theranostics 2023; 13(14):4762-4780. doi:10.7150/thno.87288. https://www.thno.org/v13p4762.htm
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Abstract

Graphic abstract

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis. A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment.

Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs.

Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance. They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways. In vivo, the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new “neural relays” developing across the lesion gap. These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s. Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling.

Conclusion: 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.

Keywords: Nanofibrous sponge, Spinal cord injury, Electrospinning, Neural stem cells, Neural tissue engineering.

Citation styles

APA
Li, Z., Qi, Y., Sun, L., Li, Z., Chen, S., Zhang, Y., Ma, Y., Han, J., Wang, Z., Zhang, Y., Geng, H., Huang, B., Wang, J., Li, G., Li, X., Wu, S., Ni, S. (2023). Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration. Theranostics, 13(14), 4762-4780. https://doi.org/10.7150/thno.87288.

ACS
Li, Z.; Qi, Y.; Sun, L.; Li, Z.; Chen, S.; Zhang, Y.; Ma, Y.; Han, J.; Wang, Z.; Zhang, Y.; Geng, H.; Huang, B.; Wang, J.; Li, G.; Li, X.; Wu, S.; Ni, S. Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration. Theranostics 2023, 13 (14), 4762-4780. DOI: 10.7150/thno.87288.

NLM
Li Z, Qi Y, Sun L, Li Z, Chen S, Zhang Y, Ma Y, Han J, Wang Z, Zhang Y, Geng H, Huang B, Wang J, Li G, Li X, Wu S, Ni S. Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration. Theranostics 2023; 13(14):4762-4780. doi:10.7150/thno.87288. https://www.thno.org/v13p4762.htm

CSE
Li Z, Qi Y, Sun L, Li Z, Chen S, Zhang Y, Ma Y, Han J, Wang Z, Zhang Y, Geng H, Huang B, Wang J, Li G, Li X, Wu S, Ni S. 2023. Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration. Theranostics. 13(14):4762-4780.

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