Screenen en engineeren van extracellulaire matrix omgevingen voor de controle van bloedvatvorming

Tissues and organs must form new blood vessels in order to develop, grow and repair after injury. Unfortunately, cancerous tumours adopt similar mechanisms of vessel formation. As a result, understanding and controlling blood vessel growth from existing blood vessels (termed angiogenesis) is of critical importance in medicine. The extracellular matrix (ECM) is composed of many different molecules, including proteins, glycoproteins, proteoglycans and polysaccharides. Many different ECM components have been described to have a pro- or anti-angiogenic effect. Apart from composition, the ECM influences angiogenesis through its mechanical properties. Given the complexity of natural ECM environments, it is important to develop in vitro tools that can recapitulate this complexity in an efficient way, and therefore pave the way towards novel treatments that are either pro-or anti-angiogenic (depending on the application) and that are tailored to the ECM’s complexity, including disease-specificity. In this PhD project we will develop experimental tools that allow us (1) to explore the effect of the 3D extracellular microenvironment on angiogenesis using artificial extracellular matrix microarrays, (2) to investigate angiogenic sprouting in response to combinations of extracellular matrices and directional presentation of soluble factors using a microfluidic gradient-generating device. Both chemical and physical (mechanical) cues will be explored.