Automated platform for the micro-perfusion of bioengineered tissues

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Boder-Pasche, Stéphanie
Heub, Sarah
Garzuel, Manon
Fonta, Charlotte
Atakan, H. Baris
Goldowsky, Jonas
Ischer, Réal
Ledroit, Diane
Valentin, Thomas
Schneeberger, Kerstin
Oxygen and nutrient delivery are vital in tissue engineering. Perfusion systems aimed at mimicking in-vivo conditions are essential to recreating a physiological micro-environment for in vitro tissue maturation. Unidirectional and continuous medium flow through the engineered tissue is required to provide oxygen and encourage the growth of a vascularized network. Proposing a disruptive alternative to donor organs for liver regenerative medicine, the EU project ORGANTRANS is developing a liver tissue printing platform from cell source to functional tissue, relying on organoid technology as building block for liver tissue transplantation [1]. In this context, a fluidic platform was developed to perfuse printed liver bioconstructs, while supporting standardization. The system is compatible with multi-well plates and relies on a microfluidic “Smart Lid” for perfusion, leading to automated and parallelized medium circulation, enabling long-term tissue growth vascularization and maturation. The perfusion platform consists of six disposable sterile inserts, into which the bioconstruct is printed, and that fit into a standard 6-well plate; a sterile lid with integrated microfluidic features that is sealed onto the inserts and creates a closed perfusion chamber; a multi-channel peristaltic pump with fluidic tubing and connectors; as well as electronic supply and control. Biocompatible and sterilizable materials are used for all parts that are in contact with the tissue and cell culture media for biocompatibility. The perfusion platform enables continuous and unidirectional flow through the six wells in parallel, with tunable flow rates ranging from 10 to 500 µL/min without any leakage. Perfusion of 2D cell culture was demonstrated for two weeks in an incubator, showing cell proliferation and no impact on cell viability. Continuous perfusion through six 1x1x0.5 cm3 freshly printed spheroid-laden liver bioconstructs containing channels lined with endothelium will be presented. The perfusion platform is used to test and tune the maturation process of liver tissue bioconstructs for several weeks, promoting vascularization while ensuring a sterile and closed environment. The platform can be adapted to other tissues and geometries, thereby enabling standardization of tissue engineering processes for regenerative medicine and drug testing applications. [1] ORGANTRANS project, EU Horizon 2020 research and innovation programme (grant agreement No 874586),
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