The primary scientific objective of the project is the discovery of physical principles behind multicellular organization that takes place during morphogenesis and self-healing. Understanding how external mechanical loads are intertwined with the cell-mediated forces to jointly control the formation and maintenance of tissue shape informs tissue engineering strategies and creation of artificial biological machines. The distinguishing features of our technological approach are the fine control, extreme dexterity, high-throughput, and multi-dimensionality. We have developed microrobotic technologies integrated with state-of-the-art microscopes that allow application of spatiotemporally resolved dynamic stimuli and real-time imaging. From the scientific perspective, our work serves as a test-bed for some of the most intriguing questions in development biology, mechanobiology, and regenerative medicine. What are the governing equations that relate the magnitude, timing and direction of force generation to the tissue mechanical properties, such as fibre alignment, viscosity and stiffness? How far, over what time, and in what geometry locally generated forces are transmitted? How cells maintain tissue boundaries, when they decide to move and expand the tissue and how the equilibrium achieved after an injury or change in boundary conditions are other important questions we are trying to address. Our aim was to quantitatively describe how matrix architecture and mechanics influence transmission of forces, and elucidate principles of physical organization instantiated by remodeling of a fibrillar substrate. Answering this question would allow us to solve the inverse problem: setting the initial conditions and applying controlled dynamic mechanical signals so that, at the equilibrium state, the engineered tissue would attain the desired morphology. Regulation of mechanical signals and cues has implications in many aspects of physiology and pathology including cancer, immunology, cardiology, and orthopaedics. Our technology is important to study cells and tissues associated with all these systems and develop new therapies to address malfunctioning in mechanotransduction pathways. In addition to the contributions to healthcare, our project has important educational value. A synergistic collaboration among different disciplines including mechanics, microtechnology, materials science, robotics and biomedical engineering is essential to ensure the success of this project. The principal investigator created two new unique masters courses at the host institution, one on microrobotic technologies and another on mechanobiology. The lecture notes and exercises are freely accessible by researchers at other institutes and public.
