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@PHDTHESIS{Jung:1046903,
      author       = {Jung, Marie},
      title        = {3{D} neural implants for in vivo applications},
      volume       = {300},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {FZJ-2025-03984},
      isbn         = {978-3-95806-852-0},
      series       = {Schriften des Forschungszentrums Jülich Reihe
                      Schlüsseltechnologien / Key Technologies},
      pages        = {xvi, 215},
      year         = {2025},
      note         = {Dissertation, RWTH Aachen University, 2025},
      abstract     = {3D microelectrode arrays (MEAs) have become increasingly
                      prominent in the field of brainmachine interfaces (BMI),
                      particularly in the context of studying electrophysiological
                      activity. The interaction between these arrays and neural
                      tissue is influenced not only by the electrochemical
                      characteristics of the electrodes, but also by the
                      mechanical and spatial characteristics of the recording
                      platform. While 2D MEA are constrained in their capacity to
                      capture the complexity of neural cell networks, conventional
                      3D platforms continue to necessitate enhancement with regard
                      to resolution and tissue integration. Thus, the objective of
                      this project was to increase the number of penetrating
                      shanks on a 3D MEA thereby increasing the number of
                      electrodes. Flexible polymers were selected as the primary
                      material in order to minimize insertion damage and foreign
                      body reactions (FBR). Two approaches to create a 3D
                      structure out of a 2D design were followed: The electrodes
                      were either printed on a flexible substrate (PiRi) or cut
                      out to obtain kirigami structures (KiRi). The first approach
                      utilizes a highly customizable 3D printing process in
                      combination with template-assisted electrodeposition to
                      fabricate up to 400 μm high 3D microelectrodes on a
                      flexible substrate. The latter approach employs a
                      matched-die forming process, enabling the fabrication of up
                      to 512 electrodes distributed across 128 shanks within a
                      single, flexible device, with shank heights reaching up to 1
                      mm. In order to test the implants in in vivo applications,
                      it is necessary to take into consideration the
                      characteristics of the design and the surgical methods to be
                      employed. Thus, the objective of the research was to
                      demonstrate the implantation feasibility, biocompatibility,
                      long-term stability, and safety of the fabricated implants
                      by performing a number of electrical and mechanical
                      characterizations of the probes. The advantages inherent in
                      both approaches are evident in the extent and flexibility of
                      customization. This extends to the electrode count and
                      configuration, allowing for the employment of the approaches
                      in a number of different neural applications, such as the
                      retina or the cortex. Healthy and degenerated retinas of
                      rats were used to validate 3D-printed and kirigami
                      electrodes demonstrating how electrophysiological activity
                      differs throughout the 3D space of the retina. In Royal
                      College of Surgeons (RCS) rats, characteristic pathological
                      activity in the form of oscillations was identified and
                      investigated. Following intraretinal insertions, cell
                      stainings were conducted to evaluate the insertion impact,
                      which was found to be low for both implants. Furthermore, in
                      preparation for acute in vivo retinal applications, surgical
                      approaches for 3D retinal implants were conducted in a
                      cadaveric setting, including open-sky surgery as well as
                      pars-plana implantation. Moreover, the KiRis and PiRis were
                      optimized for use in cortical applications. In human brain
                      slices, epileptic seizures were induced by treating them
                      with modified artificial cerebrospinal fluid (aCSF) (high
                      potassium and low magnesium). 3D recordings revealed
                      seizure-like activity in distinct local networks at
                      different time points. Furthermore, kirigami intraneural
                      implants (KiRi)s and 3D printed intraneural implants (PiRi)s
                      were implanted in the cortex of living mice in acute and
                      short-term chronic settings, allowing the capture of spiking
                      activity in the somatosensory cortex upon whisker
                      stimulation and foot-pinches, and of typical local field
                      potentials (LFP)s in the visual cortex upon visual stimuli,
                      respectively. In summary, the present study examines the
                      development, characterization and validation of two novel
                      approaches to the fabrication of 3D flexible penetrating
                      neural implants, PiRi and KiRi. As proven with the in vitro
                      and in vivo studies, these tools offer enhanced capabilities
                      for analyzing neural disorders and disease models where high
                      spatial resolution is required.},
      cin          = {IBI-3},
      cid          = {I:(DE-Juel1)IBI-3-20200312},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
      urn          = {urn:nbn:de:0001-2602091253199.560156941591},
      doi          = {10.34734/FZJ-2025-03984},
      url          = {https://juser.fz-juelich.de/record/1046903},
}