am8b10233_si_001.pdf (8.09 MB)
Aligning Synthetic Hippocampal Neural Circuits via Self-Rolled-Up Silicon Nitride Microtube Arrays
journal contribution
posted on 2018-09-25, 00:00 authored by Olivia
V. Cangellaris, Elise A. Corbin, Paul Froeter, Julian A. Michaels, Xiuling Li, Martha U. GilletteDirecting
neurons to form predetermined circuits with the intention
of treating neurological disorders and neurodegenerative diseases
is a fundamental goal and current challenge in neuroengineering. Until
recently, only neuronal aggregates were studied and characterized
in culture, which can limit information gathered to populations of
cells. In this study, we use a substrate constructed of arrays of
strain-induced self-rolled-up membrane 3D architectures. This results
in changes in the neuronal architecture and altered growth dynamics
of neurites. Hippocampal neurons from postnatal rats were cultured
at low confluency (∼250 cells mm–2) on an
array of transparent rolled-up microtubes (μ-tubes; 4–5
μm diameter) of varying topographical arrangements. Neurite
growth on the μ-tubes was characterized and compared to controls
in order to establish a baseline for alignment imposed by the topography.
Compared to control substrates, neurites are significantly more aligned
toward the 0° reference on the μ-tube array. Pitch (20–60
and 100 μm) and μ-tube length (30–80 μm)
of array elements were also varied to investigate their impact on
neurite alignment. We found that alignment was improved by the gradient
pitch arrangement and with longer μ-tubes. Application of this
technology will enhance the ability to construct intentional neural
circuits through array design and manipulation of individual neurons
and can be adapted to address challenges in neural repair, reinnervation,
and neuroregeneration.