Microfluidic organ-on-a-chip models for the gut–liver axis: from structural mimicry to functional insights

Wanlin Hu, Yushen Wang, Junlei Han, Wenhong Zhang, Jun Chen, Xinyu Li and Li Wang

Biomater. Sci., 2025, 13, 1624
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An in vivo mimetic liver-lobule-chip (LLoC) for stem cell maturation, and zonation of hepatocyte-like cells on chip

Philip Dalsbecker, Siiri Suominen, Muhammad Asim Faridi, Reza Mahdavi, Julia Johansson, Charlotte Hamngren Blomqvist, Mattias Goksör, Katriina Aalto-Setälä, Leena E. Viiri and Caroline B. Adiels

Lab Chip, 2025, 25, 4328
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Application of a gut–liver-on-a-chip device and mechanistic modelling to the quantitative in vitro pharmacokinetic study of mycophenolate mofetil

Nicoló Milani, Neil Parrott, Daniela Ortiz Franyuti, Patricio Godoy, Aleksandra Galetin, Michael Gertz and Stephen Fowler

Lab Chip, 2022, 22, 2853
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Complex in vitro models positioned for impact to drug testing in pharma: a review

Serah Kang, Eugene C Chen, Helen Cifuentes, Julia Y Co, Gabrielle Cole, Jessica Graham, Rebecca Hsia, Tomomi Kiyota, Jessica A Klein, Katharina T Kroll, Lenitza M Nieves Lopez, Leah M Norona, Heshan Peiris, Ratnakar Potla, Monica Romero-Lopez, Julien G Roth, Min Tseng, Aaron M Fullerton and Kimberly A Homan

Biofabrication, 2024, 16, 042006
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Enhancing the Maturity and Diclofenac Metabolism Ability of Mesenchymal Stem Cell‐Derived Human Hepatocytes In Vitro Using Microfluidics Technology

Joana Saraiva Rodrigues, Sofia Relvas, Pedro Monteiro Condelipes, Bárbara Silva, Raquel Bozzo, Paula Guedes de Pinho, Virginia Chu, Fernando Remião, João Pedro Conde and Joana Paiva Miranda

Biotechnology Journal, 2025, 20
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Visual electrophoresis titration model for portable enzyme inhibition assays by moving reaction boundary chip

Qiang Zhang, Ran Zhong, Weiwen Liu, Liuyin Fan, Yuxing Wang and Chengxi Cao

Talanta, 2026, 297, 128725
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Liver-on-a-chip: Considerations, advances, and beyond

Zhenxu Yang, Xiaochen Liu, Elise M. Cribbin, Alice M. Kim, Jiao Jiao Li and Ken-Tye Yong

Biomicrofluidics, 2022, 16
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Microfluidic Devices: A Tool for Nanoparticle Synthesis and Performance Evaluation

Sara Gimondi, Helena Ferreira, Rui L. Reis and Nuno M. Neves

ACS Nano, 2023, 17, 14205
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Reproducibility and Robustness of a Liver Microphysiological System PhysioMimix LC12 under Varying Culture Conditions and Cell Type Combinations

Alicia Y. Lim, Yuki Kato, Courtney Sakolish, Alan Valdiviezo, Gang Han, Piyush Bajaj, Jason Stanko, Stephen S. Ferguson, Remi Villenave, Philip Hewitt, Rhiannon N. Hardwick and Ivan Rusyn

Bioengineering, 2023, 10, 1195
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Construction of in vitro liver-on-a-chip models and application progress

Jie Liu, Yimei Du, Xinxin Xiao, Daopeng Tan, Yuqi He and Lin Qin

BioMed Eng OnLine, 2024, 23
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Setup of human liver-chips integrating 3D models, microwells and a standardized microfluidic platform as proof-of-concept study to support drug evaluation

Benoit Cox, Patrick Barton, Reiner Class, Hannah Coxhead, Claude Delatour, Eric Gillent, Jamie Henshall, Emre M. Isin, Lloyd King and Jean-Pierre Valentin

Biomaterials and Biosystems, 2022, 7, 100054
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A Novel Milli-fluidic Liver Tissue Chip with Continuous Recirculation for Predictive Pharmacokinetics Applications

Shiny Amala Priya Rajan, Jason Sherfey, Shivam Ohri, Lauren Nichols, J. Tyler Smith, Paarth Parekh, Eugene P. Kadar, Frances Clark, Billy T. George, Lauren Gregory, David Tess, James R. Gosset, Jennifer Liras, Emily Geishecker, R. Scott Obach and Murat Cirit

AAPS J, 2023, 25
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A primary human Gut/Liver microphysiological system to estimate human oral bioavailability

Yassen Abbas, Morné van Wyk, Hailey Sze, James Christophi, Ashley A. Spreen, Robert Jarrett Bliton, Elizabeth M. Boazak and Tomasz Kostrzewski

Drug Metabolism and Disposition, 2025, 53, 100130
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A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport

Adam Myszczyszyn, Anna Muench, Vivian Lehmann, Theo Sinnige, Frank G van Steenbeek, Manon Bouwmeester, Roos-Anne Samsom, Marit Keuper-Navis, Thomas K van der Made, Daniel Kogan, Sarah Braem, Luc J W van der Laan, Hossein Eslami Amirabadi, Evita van de Steeg, Rosalinde Masereeuw and Bart Spee

Biofabrication, 2025, 17, 025035
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Compelling standardized and high-throughput micro-/millifluidic plates for biomedical research: from laboratory to market

Longjun Gu, Peidi Liu, Wen Zhao, Yuhang Fan, Yuwen Wang and Pu Chen

MedMat, 2025, 2, 101
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In silico modeling and simulation of organ‐on‐a‐chip systems to support data analysis and a priori experimental design

Nicoló Milani, Neil Parrott, Aleksandra Galetin, Stephen Fowler and Michael Gertz

CPT Pharmacom & Syst Pharma, 2024, 13, 524
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Organ‐on‐Chip: The Future of Nutrition Research in a One Health World

Manuela Cassotta, Maria Elexpuru‐Zabaleta, Sandra Sumalla Cano, Yasmany Armas Diaz, Francesca Giampieri, Zou Xiaobo, Di Zhang, Giuseppe Grosso and Maurizio Battino

Food Frontiers, 2025, 6, 1205
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The Combination of a Human Biomimetic Liver Microphysiology System with BIOLOGXsym, a Quantitative Systems Toxicology (QST) Modeling Platform for Macromolecules, Provides Mechanistic Understanding of Tocilizumab- and GGF2-Induced Liver Injury

James J. Beaudoin, Lara Clemens, Mark T. Miedel, Albert Gough, Fatima Zaidi, Priya Ramamoorthy, Kari E. Wong, Rangaprasad Sarangarajan, Christina Battista, Lisl K. M. Shoda, Scott Q. Siler, D. Lansing Taylor, Brett A. Howell, Lawrence A. Vernetti and Kyunghee Yang

IJMS, 2023, 24, 9692
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Liver-on-chips for drug discovery and development

Viraj Mehta, Guruswamy Karnam and Vamsi Madgula

Materials Today Bio, 2024, 27, 101143
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In vitro cellular model systems provide a promising alternative to animal experiments for studying the intestine-organ axis

Alessandra Vitale, Cristiana De Musis, Marida Bimonte, Josep Rubert and Vincenzo Fogliano

Critical Reviews in Biotechnology, 2025, 45, 1189
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Challenges and Opportunities for In Vitro–In Vivo Extrapolation of Aldehyde Oxidase-Mediated Clearance: Toward a Roadmap for Quantitative Translation

Nihan Izat, Jayaprakasam Bolleddula, Armina Abbasi, Lionel Cheruzel, Robert S. Jones, Darren Moss, Fatima Ortega-Muro, Yannick Parmentier, Vincent C. Peterkin, Dan-Dan Tian, Karthik Venkatakrishnan, Michael A. Zientek, Jill Barber, J. Brian Houston, Aleksandra Galetin and Daniel Scotcher

Drug Metabolism and Disposition, 2023, 51, 1591
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Leveraging 3D cell culture and AI technologies for next-generation drug discovery

Raj Dave, Kshipra Pandey, Ritu Patel, Nidhi Gour and Dhiraj Bhatia

Cell Biomaterials, 2025, 1, 100050
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Microfluidic Liver-on-a-Chip for Preclinical Drug Discovery

Jingyu Fu, Hailong Qiu and Cherie S. Tan

Pharmaceutics, 2023, 15, 1300
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Recent advances in environmental toxicology: Exploring gene editing, organ-on-a-chip, chimeric animals, and in silico models

Yanyi Zhao, Nuoya Yin, Renjun Yang and Francesco Faiola

Food and Chemical Toxicology, 2024, 193, 115022
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Current Research Trends in the Application of In Vitro Three-Dimensional Models of Liver Cells

Chawon Yun, Sou Hyun Kim and Young-Suk Jung

Pharmaceutics, 2022, 15, 54
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Computational prediction of the metabolites of agrochemicals formed in rats

Vincent-Alexander Scholz, Conrad Stork, Markus Frericks and Johannes Kirchmair

Science of The Total Environment, 2023, 895, 165039
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Evaluating Drug–Drug Interaction Risk Associated with Peptide Analogs Using advanced In Vitro Systems

Rune Aa. Nørgaard, Deepak K. Bhatt, Erkka Järvinen, Tore B. Stage, Charlotte Gabel-Jensen, Aleksandra Galetin and Carolina Säll

Drug Metabolism and Disposition, 2024, 52, 1170
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Human induced pluripotent stem cell–derived liver-on-a-chip for studying drug metabolism: the challenge of the cytochrome P450 family

Isabel Tamargo-Rubio, Anna Bella Simpson, Joanne A. Hoogerland and Jingyuan Fu

Front. Pharmacol., 2023, 14
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Bioengineered human gut-on-a-chip for advancing non-clinical pharmaco-toxicology

Yong Cheol Shin, Nam Than, Soo Jin Park and Hyun Jung Kim

Expert Opinion on Drug Metabolism & Toxicology, 2024, 20, 593
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The application of organ-on-chip models for the prediction of human pharmacokinetic profiles during drug development

Marit Keuper-Navis, Markus Walles, Birk Poller, Adam Myszczyszyn, Thomas K. van der Made, Joanne Donkers, Hossein Eslami Amirabadi, Martijn J. Wilmer, Saskia Aan, Bart Spee, Rosalinde Masereeuw and Evita van de Steeg

Pharmacological Research, 2023, 195, 106853
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The Current Status and Use of Microphysiological Systems by the Pharmaceutical Industry: The International Consortium for Innovation and Quality Microphysiological Systems Affiliate Survey and Commentary

Thomas K. Baker, Terry R. Van Vleet, Prathap Kumar Mahalingaiah, Taraka Sai Pavan Grandhi, Raymond Evers, Jason Ekert, James R. Gosset, Silvi A. Chacko and Anna K. Kopec

Drug Metabolism and Disposition, 2024, 52, 198
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Can We Predict Clinical Pharmacokinetics of Highly Lipophilic Compounds by Integration of Machine Learning or In Vitro Data into Physiologically Based Models? A Feasibility Study Based on 12 Development Compounds

Neil Parrott, Nenad Manevski and Andrés Olivares-Morales

Mol. Pharmaceutics, 2022, 19, 3858
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Considerations from an International Regulatory and Pharmaceutical Industry (IQ MPS Affiliate) Workshop on the Standardization of Complex In Vitro Models in Drug Development

Lindsay Tomlinson, Diane Ramsden, Sofia Batista Leite, Sonja Beken, Jessica A. Bonzo, Paul Brown, Pelin L. Candarlioglu, Tom S. Chan, Eugene Chen, Colin K. Choi, Rhiannon David, Nathalie Delrue, Patrick J. Devine, Kevin Ford, Martha Iveth Garcia, James R. Gosset, Philip Hewitt, Kimberly Homan, Onyi Irrechukwu, Anna K. Kopec, Jennifer L. Liras, Sandhya Mandlekar, Arek Raczynski, Nakissa Sadrieh, Melanie Z. Sakatis, Jeffrey Siegel, Kyung Sung, Ilona Sunyovszki, Terry R. Van Vleet, Jason E. Ekert and Rhiannon N. Hardwick

Advanced Biology, 2024, 8
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Advances in Microfluidic Systems and Numerical Modeling in Biomedical Applications: A Review

Mariana Ferreira, Violeta Carvalho, João Ribeiro, Rui A. Lima, Senhorinha Teixeira and Diana Pinho

Micromachines, 2024, 15, 873
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Simulation of sildenafil metabolism using an electrochemical oxidation system

Unyong Kim, Sumin Seo, Jiyu Kim, Chohee Jeong, Woojin Jeong, Han Young Eom, Joon Hyuk Suh, Junghyun Kim, Hyun-Deok Cho and Sang Beom Han

Journal of Chromatography B, 2025, 1263, 124695
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The Current State of Biotransformation Science – Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends

John P. Savaryn, Kevin Coe, Matthew A. Cerny, Kevin Colizza, Patricia Moliner, Lloyd King, Bin Ma, Jim Atherton, Adam Auclair, Mark T. Cancilla, Marsha Eno, Ulrik Jurva, Qin Yue, Sean Xiaochun Zhu, Elyse Freiberger, Guo Zhong, Ben Barlock, Jonny Nachtigall, Laurent Laboureur, Sandeepraj Pusalkar, Runcong Guo, Michael Niehues, Simon Hauri, Ester Tor Carreras, Christine Maurer, Chandra Prakash and Gary J. Jenkins

Pharm Res, 2024, 41, 2079
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Computational and experimental advances in liver-on-a-chip technology for cancer research: a systematic review

Violeta Carvalho, Mariana Ferreira, Raquel O. Rodrigues, Senhorinha F. C. F. Teixeira and Rui A. Lima

Biophys Rev, 2025, 17, 151
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Advances and Challenges in 3D Modelling of Organ-on-a-Chip Devices with a Focus on the Glomerular Basement Membrane (GBM) and Tubular Systems: A Critical Review

Jumanah Bahig, Ahmed Shoker, Huu Doan, Katalin Szaszi and Amira Abdelrasoul

BioChip J, 2025, 19, 22
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Evaluation of Metabolism of a Defined Pesticide Mixture through Multiple In Vitro Liver Models

Alan Valdiviezo, Yuki Kato, Erin S. Baker, Weihsueh A. Chiu and Ivan Rusyn

Toxics, 2022, 10, 566
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Synthetic human gonadal tissues for toxicology

Toshiya Nishimura and Takanori Takebe

Reproductive Toxicology, 2024, 126, 108598
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Liver-on-a-chip devices: the pros and cons of complexity

Philip Dalsbecker, Caroline Beck Adiels and Mattias Goksör

American Journal of Physiology-Gastrointestinal and Liver Physiology, 2022, 323, G188
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Validation of HepG2/C3A Cell Cultures in Cyclic Olefin Copolymer Based Microfluidic Bioreactors

Leire Etxeberria, Taha Messelmani, Jon Haitz Badiola, Andreu Llobera, Luis Fernandez, José Luis Vilas-Vilela, Eric Leclerc, Cécile Legallais, Rachid Jellali and Ane Miren Zaldua

Polymers, 2022, 14, 4478
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DigiLoCS: A leap forward in predictive organ-on-chip simulations

Manoja Rajalakshmi Aravindakshan, Chittaranjan Mandal, Alex Pothen, Stephan Schaller, Christian Maass and Alberto Rainer

PLoS ONE, 2025, 20, e0314083
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Digital twin-enhanced three-organ microphysiological system for studying drug pharmacokinetics in pregnant women

Katja Graf, José Martin Murrieta-Coxca, Tobias Vogt, Sophie Besser, Daria Geilen, Tim Kaden, Anne-Katrin Bothe, Diana Maria Morales-Prieto, Behnam Amiri, Stephan Schaller, Ligaya Kaufmann, Martin Raasch, Ramy M. Ammar and Christian Maass

Front. Pharmacol., 2025, 16
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