In-situ tissue engineering of heart valves (TEHVs) is an emerging strategy to grow living valves inside the heart. In this approach, a scaffold material is implanted at the location of a damaged heart valve where it recruits cells from the environment to gradually transforms into a living valve. This transformation process depends on a tight balance between scaffold properties and the regenerative capacity of the host. In recent years, major scientific progress has been made, resulting in great control over the fabrication process of materials and scaffolds to match the physical properties of TEHVs to those of native valves. However, it is unclear which type of scaffold will have the best regenerative potential and whether the scaffold should be a cell-free material or pre-seeded with cells. This is accompanied by insufficient knowledge of the tissue transformation process. The focus of my research is to improve our understanding of host-material interactions for in-situ TEHVs, more specifically, on the potential of circulating cells and immune cells, their interaction with each other and with scaffold materials. In this regard, I am investigating and comparing several types of scaffolding, including bioprosthetic and synthetic heart valve scaffolds in-vitro and in-vivo models.