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University of North Texas

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Adv. Healthc. Mater., Aug 24 2023 | https://doi.org/10.1002/adhm.202302502 A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis.

Soo-Yeon Kang ^1§, Masaki Kimura ^2,3§, Sunil Shrestha ¹, Phillip Lewis ^3,4, Sangjoon Lee¹, Yuqi Cai ^2,3, Pranav Joshi ⁵, Prabha Acharya ¹, Jiafeng Liu ¹, Yong Yang ¹, J Guillermo Sanchez ^3,4, Sriramya Ayyagari ⁶, Eben Alsberg ^6,7, James M Wells ^3,4*, Takanori Takebe^2,3*, Moo-Yeal Lee ^1,5*

¹Department of Biomedical Engineering, University of North Texas, Denton, TX, 76205, USA.

²Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

³Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

⁴Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

⁵Bioprinting Laboratories Inc., USA.

⁶Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.

⁷Departments of Orthopedics, Pharmacology, and Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.

^§SYK and MK are equally contributed first authors

^*JMW, TT, and MYL are corresponding authors.

CORRESPONDING AUTHORS: James M. Wells, Takanori Takebe, Moo-Yeal Lee

Abstract

Human organoids have potential to revolutionize in vitro disease modeling by providing multicellular architecture and function that are similar to those in vivo. This innovative and evolving technology, however, still suffers from assay throughput and reproducibility to enable high-throughput screening (HTS) of compounds due to cumbersome organoid differentiation processes and difficulty in scale-up and quality control. Using organoids for HTS is further challenged by lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Here, we overcome these challenges by engineering "microarray three-dimensional (3D) bioprinting" technology and associated 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 liver and intestine 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. This article is protected by copyright. All rights reserved.

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형식Research article
게재일2023년 08월 (BRIC 등록일 2023-09-11)
연구진국외 연구진
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