Engineering Volumetric Tissue Analogs via Assembly of Endothelial Cell-Covered Spheroidal Microtissues

Tissue engineering holds a significant promise for the development of bioartificial organs applicable to transplantation. However, the size of engineered tissues remains limited, primarily due to the challenge of establishing microvascular networks within tissue constructs. In this study, engineered tissues are fabricated and embedded with functional microvascular networks by assembling endothelial cell-covered spheroidal microtissues. Utilizing a preset extrusion bioprinting and microfluidic emulsification approach, spheroidal microtissues covered with endothelial cells are successfully fabricated, demonstrating high structural integrity compared with non-structured spheroidal microtissues. Upon assembling endothelial cell-covered microtissues, vascularized tissue structures are generated. Additionally, perfusion of the culture medium through the tissue structure created by microtissue assembly preserves the intermicrotissue spaces, which can be considered vascular channels, facilitating the development of highly vascularized tissues. By controlling the medium perfusion rate, volumetric functional tissues are produced that can be cultured for 7 days in vitro. This innovative technique for fabricating highly vascularized volumetric tissues holds potential as a foundational technology for producing artificial organs.