title: A vertical-flow bioreactor array compacts hepatocytes for enhanced polarity and functions.
abstract: Although hepatocytes in vivo experience intra-abdominal pressure (IAP), pressure is typically not incorporated in hepatocyte culture systems. The cuboidal cell shape and extent of intercellular contact between cultured hepatocytes are critical parameters that influence the differentiated hepatic phenotype. Using a microfluidic device, the application of pressure to artificially compact cells and forge cell-cell interactions was previously demonstrated to be effective in accelerating hepatic repolarization. In seeking to implement this approach to higher throughput culture platforms for potential drug screening applications, we specifically designed a vertical-flow compaction bioreactor array (VCBA) that compacts hepatocytes within the range of IAP and portal pressure in vivo in a multi-well setup. As a result of vertical perfusion-generated forces, hepatocytes not only exhibited accelerated repolarization, an in vivo-like cuboidal morphology, but also better maintained hepatic functions in long-term culture as compared to the same cells cultured under static conditions. As a novel engineering tool to modulate cell compaction and intercellular interactions, this platform is a promising approach to confer tight control over hepatocyte repolarization for in vitro culture.
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore. hanry_yu@nuhs.edu.sg and Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, 638075 Singapore and Institute of Biotechnology and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, 638075 Singapore and School of Mechanical Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei St., Nanjing, Jiangsu, China 210094.
authors.forename: Huanming
authors.initials: H
authors.lastname: Xia
authors.affiliation: Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, 638075 Singapore.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, Singapore 117597, Singapore.
authors.forename: Eliza Li Shan
authors.initials: EL
authors.lastname: Fong
authors.affiliation: Institute of Biotechnology and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore and Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #10-01 CREATE Tower, Singapore 138602, Singapore and Fourth Military Medical University, 408-4 Changying West Road, Xincheng District, Xi'an City, Shanxi Province, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, Singapore 117597, Singapore and Institute of Biotechnology and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
authors.forename: Wen Hao
authors.initials: WH
authors.lastname: Tong
authors.affiliation: Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, 638075 Singapore.
authors.forename: Yen Peng Daphne
authors.initials: YP
authors.lastname: Seah
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, Singapore 117597, Singapore.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore. hanry_yu@nuhs.edu.sg.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore. hanry_yu@nuhs.edu.sg and Department of Physiology, Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, Singapore 117597, Singapore and Institute of Biotechnology and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore and Gastroenterology Department, Nanfang Hospital, Southern Medical University, TongHe, Guangzhou 510515, China.
authors.forename: Hanry
authors.identifier: 0000-0002-0339-3685
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D019149:Bioreactors; D016764:Cell Polarity; D022781:Hepatocytes / Q000166:cytology*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D046888:Tissue Array Analysis / Q000295:instrumentation*