In this thesis, I examined all four fields of tissue engineering while exploring different techniques to optimize vascular growth in 3D hydrogels, especially with the help of GFs, and creating more complex systems to enable better, more advanced tissue models. After discussing the motivation of my work in Chapter 1, which concerns vascularization, synergy of different tissues, and hydrogels as neuronal tissue models, Chapter 2 provides an overview of the current state of the art in these fields. This includes GFs for vascularization and neurons, the synergistic effects between vascular cell types and neuronal tissues, and advances in spinal cord tissue models. In Chapter 3, I describe how vascularization in synthetic 3D hydrogels can be influenced by various factors such as material stiffness, cell ratios and concentrations, GFs, supporting cells, and anisotropic factors. I observed that adding Ang1 and PDGF-BB on day 4, followed by Ang2 on day 6, resulted in increased vascularization across all conditions. By combining these factors, I established vascularization in the hydrogel, which I further adapted towards an innervated model in Chapter 4 by incorporating a DRG into the system. Here, I created a synergistic effect that supported the growth of vascular structures and demonstrated how specific GFs can negatively impact neurite outgrowth. I found that this effect could surprisingly be reversed by introducing anisotropy. To develop a more complex and human-like system, I examined motor and sensory neurons instead of DRGs in Chapter 5 and designed an accessible system to observe the behaviors of these cell types within a 3D hydrogel. Additionally, I added my optimal GF cocktail to a cardiac organoid and monitored vascular formation. The final section, Chapter 6, explores two different drug delivery systems: the CMPs system, which shows promise for delivering larger biomolecules, such as the enzyme cellulase to degrade nanocellulose, and hollow microgel capsules that successfully encapsulated and released VEGF, as an example of smaller GFs.In conclusion, this thesis provides a comprehensive overview of how biomaterials, anisotropy, and GFs can affect cell behavior, from inducing positive to negative effects, and how they can help to receive more advanced in vitro systems.
Céline Bastard (Wed,) studied this question.