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Open AccessArticle

Nanogroove-Enhanced Hydrogel Scaffolds for 3D Neuronal Cell Culture: An Easy Access Brain-on-Chip Model

by Alex Bastiaens 1,†, Sijia Xie 2,†,‡ and Regina Luttge 1,*
1
Neuro-Nanoscale Engineering Group, Department of Mechanical Engineering and Institute of Complex Molecular Systems (ICMS), Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
2
MESA+ Institute for Nanotechnology, University of Twente, 7500AE Enschede, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
Current affiliation: Laboratory for Micro- and Nanotechnology, Paul Scherrer Institute (PSI), 5232 Villigen PSI, Switzerland.
Micromachines 2019, 10(10), 638; https://doi.org/10.3390/mi10100638
Received: 30 August 2019 / Revised: 17 September 2019 / Accepted: 20 September 2019 / Published: 23 September 2019
(This article belongs to the Special Issue Organs-on-chips)
In order to better understand the brain and brain diseases, in vitro human brain models need to include not only a chemically and physically relevant microenvironment, but also structural network complexity. This complexity reflects the hierarchical architecture in brain tissue. Here, a method has been developed that adds complexity to a 3D cell culture by means of nanogrooved substrates. SH-SY5Y cells were grown on these nanogrooved substrates and covered with Matrigel, a hydrogel. To quantitatively analyze network behavior in 2D neuronal cell cultures, we previously developed an automated image-based screening method. We first investigated if this method was applicable to 3D primary rat brain cortical (CTX) cell cultures. Since the method was successfully applied to these pilot data, a proof of principle in a reductionist human brain cell model was attempted, using the SH-SY5Y cell line. The results showed that these cells also create an aligned network in the 3D microenvironment by maintaining a certain degree of guidance by the nanogrooved topography in the z-direction. These results indicate that nanogrooves enhance the structural complexity of 3D neuronal cell cultures for both CTX and human SH-SY5Y cultures, providing a basis for further development of an easy access brain-on-chip model. View Full-Text
Keywords: 3D cell culture; neuronal cells; SH-SY5Y cells; image-based screening; nanogrooves; neuronal cell networks; neuronal guidance 3D cell culture; neuronal cells; SH-SY5Y cells; image-based screening; nanogrooves; neuronal cell networks; neuronal guidance
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Bastiaens, A.; Xie, S.; Luttge, R. Nanogroove-Enhanced Hydrogel Scaffolds for 3D Neuronal Cell Culture: An Easy Access Brain-on-Chip Model. Micromachines 2019, 10, 638.

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