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@PHDTHESIS{Milos:892864,
      author       = {Milos, Frano},
      title        = {{T}hree-{D}imensional {P}olymeric {T}opographies for
                      {N}eural {I}nterfaces},
      volume       = {72},
      school       = {RWTH Aachen},
      type         = {Dissertation},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {FZJ-2021-02403},
      isbn         = {978-3-95806-586-4},
      series       = {Schriften des Forschungszentrums Jülich. Reihe Information
                      / Information},
      pages        = {154 S.},
      year         = {2021},
      note         = {RWTH Aachen, Diss., 2021},
      abstract     = {Optimal integration of artificial interfaces with neural
                      tissue is critical to develop novel neural regeneration
                      scaffolds and neuroprosthetic implants. The topography of
                      the implantable device can promote nerve repair as it
                      affects neuronal growth via contact guidance. Furthermore,
                      topography may be utilized to establish a stable and close
                      contact with neural tissue required to improve the
                      electrical neuron-device coupling. The goal of this thesis
                      is to investigate the effects of nano- and microtopographies
                      on the development and adhesion of embryonic cortical
                      neurons. Three different polymer surfaces with topographical
                      structures of varying dimensions were used – namely,
                      i)anisotropic poly(N-isopropylacrylamide) (PNIPAAm)
                      nanogels, ii) isotropic OrmoComp nanopillars, and iii)
                      isotropic poly(3-hexylthiophene-2,5-diyl) (P3HT)
                      micropillars. Anisotropic PNIPAAm nanogel arrays induced
                      perpendicular alignment of major neurites and accelerated
                      axon development, resulting in an $~80\%$ increase in axon
                      length compared to either unstructured nanogel substrates or
                      glass substrates. Despite being relatively soft compared to
                      glass substrates, unstructured nanogels did not induce
                      substantial changes in neuronal morphology, indicating that
                      neurons “perceive” unstructured nanogels as equivalent
                      to glass. Isotropic OrmoComp nanopillars aligned neurites
                      along topographically dictated angles (0°, 90°) with
                      higher pillars (400 nm) confining neurites to a greater
                      extent compared to lower pillars (100 nm). Furthermore,
                      higher nanopillars promoted growth cone elongation and axon
                      development resulting in $~40\%$ longer axons compared to
                      flat substrates. A larger surface area of the nanopillars
                      was correlated with higher density of point contact
                      adhesions in the growth cone and a reduction in actin
                      retrograde flow rates, indicating a stronger coupling
                      between the growth cone and the substrate which enables
                      accelerated and persistent neurite outgrowth. Furthermore,
                      F-actin accumulations and paxillin-rich adhesions were
                      observed in the neuronal soma at nanopillars, indicating
                      that neurons form a close contact with the nanoscale
                      topography. Isotropic P3HT micropillars represent a
                      relatively soft interface that enables neurons to achieve a
                      close and conformal contact mediated by membrane
                      rearrangements. Optical stimulation of embryonic neurons
                      growing on photosensitive P3HT substrates induced a
                      significant increase in neurite outgrowth compared to
                      control substrates without deleterious effects on neuronal
                      viability. The effects of photostimulation were further
                      enhanced by the microtopography, indicating that P3HT acts
                      as an active interface with possible applications in
                      $\textit{in vitro}$ neural regeneration scaffolds.
                      Furthermore, MEAs functionalized with P3HT micropillars
                      yielded a significant increase in the signal-to-noise ratio
                      (SNR) compared to flat MEAs, indicating that micropillars
                      improve the cell-electrode coupling. Optical stimulation of
                      spontaneous network activity on P3HT-functionalized MEAs
                      induced neuronal firing and increased the firing rate.
                      Although the process was not fully reproducible, optical
                      excitation of P3HT interfaces provides a promising strategy
                      for modulating network activity in a non-invasive manner.},
      cin          = {IBI-3},
      cid          = {I:(DE-Juel1)IBI-3-20200312},
      pnm          = {524 - Molecular and Cellular Information Processing
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-524},
      typ          = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
      urn          = {urn:nbn:de:0001-2021122104},
      url          = {https://juser.fz-juelich.de/record/892864},
}