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%0 Thesis
%A Vedaraman, Sitara
%T 3D artificial extracellular matrices for directed in vitro cell growth
%I RWTH Aachen University
%V Dissertation
%C Aachen
%M RWTH-2023-06997
%P 1 Online-Ressource : Illustrationen, Diagramme
%D 2023
%Z Veröffentlicht auf dem Publikationsserver der RWTH Aachen University
%Z Dissertation, RWTH Aachen University, 2023
%X This doctoral thesis reports multiple strategies to develop 3D aECM for directed in vitro cell growth, considering the influence of different biomaterial parameters, such as chemical, physical, and architectural cues. Beginning with research motivation and highlighting the relevant literature, the thesis probes into aECM development of hierarchical scaffolds, its limitations, and the approaches to specifically address these limitations. Chapter 2 mainly highlights the state-of-the-art in detail starting with the ECM development, engineering integrin-binding domains, and fabrication techniques for surface topographies closing with synthetically derived 3D scaffolds. Chapter 3 describes the role of architectural cues in orienting nerve cells on 2D platforms developed using a high-throughput TPL system and the ability of nerves to follow discreet anisometric microelements is systematically investigated for the first time. Further, the role of supporting cells in creating aECM platforms is realized. In Chapter 4, the need for transition from 2D to 3D scaffolds is highlighted, which is essential for mimicking relevant tissue models in vivo. Here, synthetic PEG hydrogels tethered with novel integrin-specific bicyclic RGD peptides are investigated, reporting superior nerve growth compared to linear or monocyclic RGD peptides. ANISOGELS made with magnetically orientable fibers provided oriented nerve growth. Chapter 5 illustrates the importance of the viscoelastic and strain-stiffening microenvironment in aECM design and the role of interpenetrating networks of PIC and PEG showing superior mechanical properties compared to the individual gels for cell growth. Finally, chapter 6 discusses in detail the techniques to spatially photo-pattern biomolecules relevant for cell adhesion. Here, two different photo-patterning systems are explored that do not alter the biomechanical properties. The caged RGD system and the caged Q/K systems both show possibilities for directed and spatial control of cells. The variety of photo protective groups available in different wavelengths paves the way from in vitro photopatterning towards in vivo photopatterning to create biochemical gradients in injectable aECM scaffold. To summarize, the hydrogel reported in this thesis is a versatile system that can be employed as a promising injectable scaffold with integrin selective adhesion cues, imparting viscoelastic properties in combination with PIC-PEG IPNs, and finally enabling oriented cell growth using ANISOGELS or through bio-patterning.
%F PUB:(DE-HGF)11
%9 Dissertation / PhD Thesis
%R 10.18154/RWTH-2023-06997
%U https://publications.rwth-aachen.de/record/961720