Have you ever thought whether blood vessels are all the same throughout our body? (Answer: they are not!) Can we then engineer organ-specific blood vessels? And what organ-specific properties affect vessel formation? If these questions pique your curiosity, you could be the person we are looking for.
InformationBlood vessels have a critical role in our health to enable transport of blood throughout the body. There are different types of blood vessels—e.g., arteries, veins, microvessels—each with their unique characteristics and functions. Moreover, different body parts demand specific blood transport requirements, resulting in organ- and tissue-specific vasculature, such as their size, vascular wall composition, blood flow rate, mechanical properties and stresses, hemodynamics, and permeability. Efforts to engineer or regenerate vessels, as well as to vascularize tissues and organ(oid)s, should therefore take these variations into account.
A vital feature shared by all these diverse blood vessels is the presence of endothelial cells (ECs), the specialized cells that line the vessel lumens and are in continuous contact with blood. Similar to blood vessels, it is increasingly recognized that ECs are also heterogeneous; their phenotype and behavior are highly organ specific. However, little is yet known about where, why, and how ECs acquire this specificity, and how permanent or adaptable it is. Recent
in vitro experiments have shown that ECs from different tissue origins have distinct capacities to sense and respond to mechanical signals (e.g., stiffness, shear stress), to initiate angiogenesis, and to form luminal vessels. These findings offer clues that can be used to better understand and to exploit organ-specific vascularization.
This PhD project primarily aims to elucidate the mechanobiological influences that drive endothelial organ-specification and phenotype, and to use this knowledge to engineer organ-specific ECs. The obtained insights will be used to explore experimental approaches to control vascularization of engineered tissues and organoids. You will work with human induced pluripotent stem cells, differentiate them towards organ-specific endothelial cells, and develop
in vitro approaches and assays to study how this differentiation process can be modulated. These experiments will be complemented with computational simulations of mechanobiology-mediated angiogenesis, to further dissect the contributions of cell signaling and environmental mechanical properties.
The research will be conducted in the
Department of Biomedical Engineering at the
Eindhoven University of Technology (TU/e) under the supervision of
Dr. Nicholas A. Kurniawan and
Dr. Tommaso Ristori. Dr. Kurniawan’s research strives to make an impact on healthcare through an improved understanding of cell–matrix physical interactions and (multi)cellular sensing, whereas
Dr. Tommaso Ristori’s research focuses on blood vessel formation aimed at inducing physiological vascularization of diseased and engineered tissues. Their teams are respectively embedded within the
Soft Tissue Engineering and Mechanobiology (STEM) group headed by
Prof. Carlijn V.C. Bouten and the
Modelling in Mechanobiology (MMB) group led by
Dr. Sandra Loerakker. As a member of these groups, you will have access to the Cell and Tissue Engineering laboratory, a state-of-the-art research infrastructure operating at the international forefront of the engineering of living tissues.