To test our idea that we can re-align heart tissue non-invasively and remotely (which is crucial for future medical use), we started by creating living lab models of the heart at both the cell level and the tissue level. We also used computer models to predict how re-aligning the tissue would affect the heart's function. At the same time, we developed a system to study how we can use ultrasound to guide the organisation of cells and tissues.
At the cell level, we conducted experiments on heart cells (i.e. cardiac fibroblasts and/or cardiomyocytes) on different materials to mimic the conditions of a heart after a heart attack. We used advanced techniques, like live imaging and traction force microscopy, to study how these cells behave, collaborate, communicate, and function mechanically following a heart attack. Next, we developed new methods and protocols to use low-intensity ultrasound to move and manipulate the cells without harming them. Using these protocols, we could (re)arrange and pattern cells to designated locations as a first step in re-aligning heart tissue after a heart attack.
At the tissue level, we built three-dimensional miniature models of living heart tissue that can be adjusted regarding cell types, tissue structure, and tissue size. By locally damaging the tissues and adding inflammation agents, we simulated heart attacks in these models to study tissue response and healing. These models will be instrumental in investigating the effects of ultrasound-induced restoration of tissue organisation.
Advanced computer simulations were performed to predict how changes in heart tissue structure and organisation will affect heart function after a heart attack. From these simulations, it was concluded that improving tissue alignment during healing slightly enhances heart function in the early stages following the attack. The following steps will concentrate on the effect of long-term remodelling on heart function.
