Nanogroove-enhanced hydrogel scaffolds for 3D neuronal cell culture: An easy access brain-on-chip model

Alex Bastiaens, Sijia Xie, Regina Luttge*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)
37 Downloads (Pure)


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.

Original languageEnglish
Article number638
Issue number10
Publication statusPublished - 1 Oct 2019


  • 3D cell culture
  • Image-based screening
  • Nanogrooves
  • Neuronal cell networks
  • Neuronal cells
  • Neuronal guidance
  • SH-SY5Y cells
  • UT-Gold-D


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