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@PHDTHESIS{Gnther:1019643,
      author       = {Günther, Daniel},
      othercontributors = {De Laporte, Laura and Jockenhövel, Stefan},
      title        = {{S}ynthetic molecular and colloidal building blocks for
                      biofabrication of complex tissues},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Aachen},
      publisher    = {RWTH Aachen University},
      reportid     = {RWTH-2025-08482},
      pages        = {1 Online-Ressource : Illustrationen},
      year         = {2025},
      note         = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
                      University; Dissertation, RWTH Aachen University, 2025},
      abstract     = {In this thesis, I explore different strategies to create
                      complex tissues by optimizing materials that are compatible
                      with biofabrication techniques to support cell growth, while
                      investigating the formation of vascular structures,
                      essential for ensuring the long-term viability of the
                      engineered constructs. After discussing the motivation of my
                      work to create complex tissues and their potential use in
                      clinical transplantation as well as in vitro model systems,
                      Chapter 2 gives an overview of the current state of the art
                      in that field. This includes methods to control the porosity
                      of artificial matrices, strategies to create vascular
                      structures on different scales, and different bioprinting
                      techniques used for the fabrication of complex tissues. In
                      Chapter 3, I describe the optimization of a PEG-based bioink
                      to support the growth of prevascularized spheroids, which
                      are sensitive to the stiffness of the surrounding matrix and
                      preferably grow in soft hydrogels. By combining hydrolytic
                      and enzymatic degradation mechanisms, I compensate for the
                      initial high stiffness required to ensure the shape fidelity
                      of bioprinted constructs, while enabling extensive cellular
                      network formation. This approach bridges the gap between the
                      mechanical demands of bioprinting and the biological needs
                      of 3D cell culture, enabling rapid material softening to
                      create space for cell growth. In Chapter 4, I demonstrate
                      that these spheroids can reorganize into uniluminal
                      structures resembling the inherent structure of simplified
                      blood vessel. This depends on the cell ratio, the spheroid
                      size and hydrogel stiffness. Additionally, such spheroids
                      can fuse with neighboring spheroids to create tubular
                      structures with a continuous lumen. For better control over
                      hydrogel degradation, which is particularly challenging to
                      regulate in vivo after transplantation, the establishment of
                      an on-demand hydrogel degradation mechanism is presented in
                      Chapter 5. The integration of thrombin-cleavable
                      crosslinkers into PEG hydrogels allows for controlled
                      degradation via thrombin that is supplemented to the media
                      or integrated into the polymer network as part of a
                      biocatalytic system that can be activated with ultrasound.
                      While media-supplemented thrombin has proven effective to
                      promote cell growth in vitro, the ultrasound-triggered
                      degradation is particularly promising for in vivo
                      application. Finally, Chapter 6 describes the formation of
                      cell/microgel assemblies without the need for material
                      degradation. While this process is fully driven by cellular
                      self-organization, it can be influenced by external guiding
                      cues.},
      cin          = {154610 / 150000},
      ddc          = {540},
      cid          = {$I:(DE-82)154610_20140620$ / $I:(DE-82)150000_20140620$},
      pnm          = {ORGANTRANS - Controlled Organoids transplantation as
                      enabler for regenerative medicine translation (874586) /
                      Heartbeat - 3D-assembly of interactive microgels to grow in
                      vitro vascularized, structured, and beating human cardiac
                      tissues in high-throughput (101043656)},
      pid          = {G:(EU-Grant)874586 / G:(EU-Grant)101043656},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2025-08482},
      url          = {https://publications.rwth-aachen.de/record/1019643},
}