Book/Dissertation / PhD Thesis

FZJ-2017-06110

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurons on 3D Polymer Nanostructures

Belu, A. A. (Corresponding author)FZJ*

2018
Forschungszentrum Jülich GmbH Zenralbibliothek, Verlag Jülich
ISBN: 978-3-95806-296-2

Please use a persistent id in citations: http://hdl.handle.net/2128/17696  urn:nbn:de:0001-2018032800

Abstract: The interface between living cells and artificial surfaces is highly relevant for biomedical applications such as implants and organized cell growth for tissue reconstruction as well as for basic science purposes. The topography of implantable biomaterials is critical for optimizing the electrical coupling between cells and device surface. One way to modulate cellular responses is to vary surface topographies. Instructive biomaterials with different surface topographies can regulate cellular behavior from initial attachment and further dictate the response of surrounding tissue. A considerable attention was directed towards 3D micro- and nanostructured polymers. In this study, the influence of isotropic andanisotropic 3D polymer surfaces on the adhesion and maturation of primary neurons ispresented. This work mainly consists of three parts: the 3D micro- and nanostructured polymer fabrication and characterization, followed by the evaluation of the influence of surface topographies on neuronal behaviour responses. Additionally, a novel resin embedding procedure was developed for morphological visualization of neuron interface with 3D surfaces at the nanoscale. Particular attention was given to the cell membrane wrapping around the nanostructures studied by scanning electron microscopy and focused ion beam sectioning. First, a reliable method for the fabrication of 3D structures was established with the possibility of using large range of sizes and heights (on 1 cm$^{2}$ surface area) based on nanoimprint lithography: i) Isotropic surfaces with 100 nm and 400 nm high posts with diameter and distance ranging from 250 nm to 2 μm and ii) Gradient patterns of 250 nm diameter posts and linear slopes of 0.15·10$^{-3}$, 0.75·10$^{-3}$, 1.95·10$^{-3}$, and 3.95·10$^{-3}$/mm. These polymer substrates exhibited high cell viability and neuronal maturation. Employing the systematic design variations of the surface topographies, the engulfment-like process of the 3D nanostructures by the cell membrane has been quantified. An optimal 3D structured area (100 nm high posts with 250 nm diameter and 1 μm pitch) has been found to increase the cell membrane adhesion in comparison to the planar surface. In addition, the 3D pillars enhanced axon growth and alignment to the topography, an effect that diminished with decreasing pillars height. However, for the lower pillar height the alignment could be induced by gradient patterns with 1 μm and 4 μm distance between the pillars. Finally, 3D asymmetric surfaces characterized by dense inclined PPX polymer nanopillars, have been used to induce axon elongation and initial directionality of axon formation. This thesis contributes to the understanding of neuron adhesion, neuritogenesis, and neurite elongation in response to micro- and nanometer range pattern dimensions. Implementing axonal guidance and elongation by use of topography (3D nano-modified surfaces) can be a versatile tool for neuronal applications, such as nerve regeneration.

Note: RWTH Aachen, Diss., 2017

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Contributing Institute(s):

1. Bioelektronik (ICS-8)

Research Program(s):

1. 552 - Engineering Cell Function (POF3-552) (POF3-552)

Appears in the scientific report 2017

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