4D Imaging for Mechanobiology (AKUL/17/032)

Mechanical forces are critical in shaping a variety of biological processes, and have an important influence on our ability to maintain normal physiological function; the disregulation of these processes leads to degeneration and disease. The ability to recreate and visualize these phenomena in the laboratory is important to understand the basic mechanisms involved, and to guide our strategies for engineering tissues for regenerative medicine applications and for creating relevant disease models. This presents a double challenge: to apply active mechanical stimulation on lab-grown constructs, and to visualize its effects on the resulting optically dense three-dimensional tissue. In this proposal, we have brought together various research groups at KU Leuven with a common interest in mechanobiology, the study of mechanical forces in biology, to request instruments which combine mechanical stimulation of lab-grown 3D tissue with state-of-the-art two-photon microscopy for deep tissue imaging. This novel combination will allow us to track multicellular organization and maturation over periods of days to weeks resulting from active stimulation of a variety of stem-cell derived tissues and organoids, including liver, skeletal and cardiac muscles, cartilage, bone, and blood vessels. This platform, unique in Flanders, is also critical to our efforts to develop valorizable technologies, including novel biomaterials, imaging probes and computational methods for biomedical applications.