Biofabrication of organ-specific functional micro- and macrovasculature

The biofabrication of 3D biomimetic tissue analogs, which accurately mimic the properties of native tissue, have an enormous potential in biomedical applications (drug discovery, cancer research, regenerative medicine,…). A basic prerequisite for the survival, maturation and function of 3D engineered tissues is the establishment of blood vessels. The most critical challenge in complex tissue engineering is the integration of an organ-specific hierarchical vascular network. This project will integrate biomimetic approaches with bioprinting by combining self-organizing multicellular spheroids with cell-instructive-biomaterials for guiding organ-specific endothelial cell differentiation and generating vascularized tissues. Spheroids are composed of endothelial and/or mural cells (pericytes, smooth muscle cells) allowing the engineering of micro- and macrovasculature embedded in a tissue-specific environment. To enhance the maturation state of the tissue, electroactive hydrogels will be applied. By incorporating the vascularized tissue in a bioreactor, we will strive to an organ-on-a-chip system with a higher physiologically relevance than current models. With this model, the response to microenvironmental stimuli (mechanical and biological factors comprising flow, tissue/extracellular matrix stiffness, mural cell interactions) of endothelial cell differentiation towards an organ specific behavior will be elucidated.