Large-scale Topographical Screen for Investigation of Physical Neural-Guidance Cues

Abstract

A combinatorial approach was used to present primary neurons with a large library of topographical features in the form of micropatterned substrate for high-throughput screening of physical neural-guidance cues that can effectively promote different aspects of neuronal development, including axon and dendritic outgrowth. Notably, the neuronal-guidance capability of specific features was automatically identified using a customized image processing software, thus significantly increasing the screening throughput with minimal subjective bias. Our results indicate that the anisotropic topographies promote axonal and in some cases dendritic extension relative to the isotropic topographies, while dendritic branching showed preference to plain substrates over the microscale features. The results from this work can be readily applied towards engineering novel biomaterials with precise surface topography that can serve as guidance conduits for neuro-regenerative applications. This novel topographical screening strategy combined with the automated processing capability can also be used for high-throughput screening of chemical or genetic regulatory factors in primary neurons.

Nerve guidance conduit with a hybrid structure of a PLGA microfibrous bundle wrapped in a micro/nanostructured membrane

“…However, cells cultured on planar substrates presented dendritic branching over the microscale features. 35 Our previous study demonstrated that the micro/ nanohybrid structures with 30/30 μm microgroove pattern (nanostructures in grooves) exhibited good nerve cell guidance and had less branching than the pure micropatterns. 36 Our experimental results on cell guiding ability of the proposed micro/nanostructured PLGA membrane in this study are consistent with previous studies.…”

Biomaterials for Enhancing Neuronal Repair

“…Such a substrate must be flexible with an elastic modulus matching the native spinal column for an environment that closely resembles the endogenous condition. The scaffold can be enriched with microchannels, which attract the regenerating neurites given their affinity for edges and enclosed spaces (Millet et al, 2007;Froeter et al, 2014;Li et al, 2015). To enhance regrowth and influence its directionality, electronics that support electrical stimuli can be embedded in the scaffold.…”

Controlling the morphology and outgrowth of nerve and neuroglial cells: The effect of surface topography

“…Mahoney et al studied the effect of grooved topography to study the effect on neuritogenesis with groove widths large enough for the PC12 cells to sit inside [75]. Using shown to promote axonal growth with a strong guidance response ( Figure 3C), which was not the case for the cell outgrowth on the discontinuous topographical features (see Section 2.2) [90]. More specifically, the guided axons were following the transition edge between ridges and grooves.…”