Aligned poly-L-lactic acid nanofibers induce self-assembly of primary cortical neurons into 3D cell clusters

Weir, N., Stevens, B., Wagner, S., Miles, A., Ball, G. ORCID: 0000-0001-5828-7129, Howard, C., Chemmarappally, J., McGinnity, M., Hargreaves, A.J. ORCID: 0000-0001-9754-5477 and Tinsley, C. ORCID: 0000-0002-9369-443X, 2022. Aligned poly-L-lactic acid nanofibers induce self-assembly of primary cortical neurons into 3D cell clusters. ACS Biomaterials Science and Engineering, 8 (2), pp. 765-776. ISSN 2373-9878

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Abstract

Relative to two-dimensional (2D) culture, three-dimensional (3D) culture of primary neurons has yielded increasingly physiological responses from cells. Electrospun nanofiber scaffolds are frequently used as a 3D biomaterial support for primary neurons in neural tissue engineering, while hydrophobic surfaces typically induce aggregation of cells. Poly-l-lactic acid (PLLA) was electrospun as aligned PLLA nanofiber scaffolds to generate a structure with both qualities. Primary cortical neurons from E18 Sprague–Dawley rats cultured on aligned PLLA nanofibers generated 3D clusters of cells that extended highly aligned, fasciculated neurite bundles within 10 days. These clusters were viable for 28 days and responsive to AMPA and GABA. Relative to the 2D culture, the 3D cultures exhibited a more developed profile; mass spectrometry demonstrated an upregulation of proteins involved in cortical lamination, polarization, and axon fasciculation and a downregulation of immature neuronal markers. The use of artificial neural network inference suggests that the increased formation of synapses may drive the increase in development that is observed for the 3D cell clusters. This research suggests that aligned PLLA nanofibers may be highly useful for generating advanced 3D cell cultures for high-throughput systems.

Item Type: Journal article
Publication Title: ACS Biomaterials Science and Engineering
Creators: Weir, N., Stevens, B., Wagner, S., Miles, A., Ball, G., Howard, C., Chemmarappally, J., McGinnity, M., Hargreaves, A.J. and Tinsley, C.
Publisher: American Chemical Society
Date: 14 February 2022
Volume: 8
Number: 2
ISSN: 2373-9878
Identifiers:
NumberType
10.1021/acsbiomaterials.1c01102DOI
1518541Other
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 15 Feb 2022 19:36
Last Modified: 27 Jan 2023 03:00
URI: https://irep.ntu.ac.uk/id/eprint/45686

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