High-Scale 3D-Bioprinting Platform for the Automated Production of Vascularized Organs-on-a-Chip

3D bioprinting possesses the potential to revolutionize contemporary methodologies for fabricating tissue models employed in pharmaceutical research and experimental investigations. This is enhanced by combining bioprinting with advanced organs-on-a-chip (OOCs), which includes a complex arrangement of multiple cell types representing organ-specific cells, connective tissue, and vasculature. However, both OOCs and bioprinting so far demand a high degree of manual intervention, thereby impeding efficiency and inhibiting scalability to meet technological requirements. Through the combination of drop-on-demand bioprinting with robotic handling of microfluidic chips, a print procedure is achieved that is proficient in managing three distinct tissue models on a chip within only a minute, as well as capable of consecutively processing numerous OOCs without manual intervention. This process rests upon the development of a post-printing sealable microfluidic chip, that is compatible with different types of 3D-bioprinters and easily connected to a perfusion system. The capabilities of the automized bioprint process are showcased through the creation of a multicellular and vascularized liver carcinoma model on the chip. The process achieves full vascularization and stable microvascular network formation over 14 days of culture time, with pronounced spheroidal cell growth and albumin secretion of HepG2 serving as a representative cell model. This work shows how the fabrication process of vascularized Organs-on-a-Chip can be automated using drop-on-demand 3D-bioprinting in combination with robotics. This includes a microfluidic chip design that is accessible to different types of 3D-bioprinters. A multi-material bioprinting process is presented for an exemplary liver carcinoma model with HepG2 cells as cell islets supported by a surrounding self-assembled microvascular network. image