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Pillar/Perfusion Plates for Miniature Human Tissue Culture and Predictive Compound ScreeningKang, Sooyeon 05 1900 (has links)
Human organoids have potential to revolutionize in vitro disease modeling by providing multicellular architecture and functional that are similar to those in vivo. Nonetheless, organoid-based, high-throughput screening (HTS) of compounds is challenged by lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Therefore, we first fabricated a pillar plate, which was coupled with a complementary deep well plate and a perfusion well plate for static and dynamic culture via injection molding. We established various cell loading methods in hydrogels on the pillar plate. In addition, we investigated the effect of flow on the necrotic core of spheroids in the pillar/perfusion plate. Finally, we developed microarray three-dimensional (3D) bioprinting technology using the pillar and perfusion plates for human organoid culture and analysis. High-precision, high-throughput stem cell printing and encapsulation techniques were demonstrated on a pillar plate, which was coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels were differentiated into organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384-well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts.
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