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@PHDTHESIS{Belu:837121,
author = {Belu, Andreea Anamaria},
title = {{N}eurons on 3{D} {P}olymer {N}anostructures},
volume = {161},
school = {RWTH Aachen},
type = {Dr.},
address = {Jülich},
publisher = {Forschungszentrum Jülich GmbH Zenralbibliothek, Verlag},
reportid = {FZJ-2017-06110},
isbn = {978-3-95806-296-2},
series = {Schriften des Forschungszentrums Jülich. Reihe
Schlüsseltechnologien / Key Technologies},
pages = {VII, 135 S.},
year = {2018},
note = {RWTH Aachen, Diss., 2017},
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.},
cin = {ICS-8},
cid = {I:(DE-Juel1)ICS-8-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
urn = {urn:nbn:de:0001-2018032800},
url = {https://juser.fz-juelich.de/record/837121},
}