3D bioprinting of heart tissue for transplantation - Effects of materials and endothelial factors on stem cell maturation to functional myocardial tissue

Heart disease is the cause of most deaths worldwide. Although some patients can be treated by heart transplantation, thousands of patients suffer due to a lack of donor organs.

Therefore, it is important in the field of regenerative medicine to develop new therapies in order to meet the emergency. In this project, artificial heart tissue will be produced by 3D bioprinting. In a proof of principle study a prototype murine heart tissue will be produced in 3D in order to test its functionality, cell communication and tissue differentiation in vivo and ex vivo. In a second step, the structure will be prepared to be scaled to a size of a human heart.

Different cardiovascular cell types, differentiated from mouse embryonic stem cells (mESCs) will be printed in individually adapted hydrogels with different printing processes and spatial resolutions to produce an artificial heart that comes as close as possible to a murine heart in terms of shape, topography and functionality. Vascularization will be achieved by printing of sacrificial hydrogel structures to form a pre-formed vascular network, which will be subsequently colonized with endothelial cells. During and after the printing process, the artificial blood vessels will be perfused with a newly developed microperfusion system in order to supply the printed organ with oxygen and nutrients ex vivo. The printed organs will be further subjected to structural and functional testing in vitro and in vivo after transplantation in mice. Here, the role of endothelial-derived signals through direct cellular contacts or angiocrine signals on cardiomyocyte proliferation, survival and maturation will be investigated. Within this project, we will closely collaborate with the Tal Dvir’s group that has achieved a major breakthrough in the field of 3D bioprinting.

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