Cardiovascular disease is the primary cause of death worldwide. Although researchers have been committed to finding cures and treatments for heart disease, to date the number of identified drugs for successful treatment has been extremely limited, despite increased expenditure in recent years. The major bottleneck is the lack of proper human heart models that enable the study of human heart disease and consequent development of new cardiovascular drugs. Although current models can give relevant fundamental insights and options for cardiotoxicity testing, they are unable to offer meaningful prediction of heart function based on clinical parameters. For example, the main function of the heart is the pumping of blood, but current models are unable to do this.
We will develop and produce a human mini-heart that will allow for in vitro measurement of pumping function (pressure and volume output), which will enable for the first time the development of human-based cardiac disease models that are crucial for the urgently needed therapeutic drug discovery and development. This result will impact greatly the cardiovascular research field by enabling researchers to model the main function of the heart in vitro and measure the same pressure and flow outputs that are assessed in the clinic. This will accelerate development of new cardiac drugs, while decreasing risk of drug failure in human clinical trials, and potentially reduce use of experimental animals. Equally important, we anticipate that such cardiac tissues can also be used as autonomous soft-robots (e.g. biorobots) to test cardiac toxicity in an environmental setting. The proposed development of engineered living matter for delivering next-generation cardiac tissues thus holds significantly economic and societal impact.
To this end, our consortium aim to create two different and independent human 3D tissue constructs with cardiac cells (e.g. a mini-heart and a bio-robot) using novel molding and 3D print technologies, which will be used for the following objectives:
Objective 1- Make a “mini-heart” able to pump fluid autonomously, enabling the measurement output pressure and flow from the functioning construct. The mini-heart will be composed by multiple layers of cells that are made by various cardiac cells types. The mini-heart will have vascularization promoted by endothelial-cardiomyocyte interaction and by the fluidic motion generated by the pumping action.
Objective 2- Make a bio-robot that is able to swim autonomously and be used as a detector for environmental toxins. The biorobot will generate thrust by contraction of the tissue and the minimum viable pressure to generate movement will be measured. The body of the biorobot will be composed mostly be ventricular-like and/or atrium-like cardiomyocytes, while having a “head” composed by pace-maker cells. The pacemaker cells will determine which part of the tissue will contract first and therefore determine the direction of the electrical impulse propagation, and consequently determine the direction of the tissue propulsion. This biorobot will be used as an environmental toxin detector by assessing changes in its swimming capacity as cardiomyocytes are quite sensitive to external factors and therefore stop contracting.
