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TY - THES AU - Günther, Daniel TI - Synthetic molecular and colloidal building blocks for biofabrication of complex tissues PB - RWTH Aachen University VL - Dissertation CY - Aachen M1 - RWTH-2025-08482 SP - 1 Online-Ressource : Illustrationen PY - 2025 N1 - Veröffentlicht auf dem Publikationsserver der RWTH Aachen University N1 - Dissertation, RWTH Aachen University, 2025 AB - 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. LB - PUB:(DE-HGF)11 DO - DOI:10.18154/RWTH-2025-08482 UR - https://publications.rwth-aachen.de/record/1019643 ER -