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Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies
Open accessAbstract
Investigation of the pharmacokinetics (PK) of a compound is of significant importance during the early stages of drug development, and therefore several in vitro systems are routinely employed for this purpose. However, the need for more physiologically realistic in vitro models has recently fueled the emerging field of tissue-engineered 3D cultures, also referred to as organs-on-chips, or microphysiological systems (MPSs). We have developed a novel fluidic platform that interconnects multiple MPSs, allowing PK studies in multi-organ in vitro systems along with the collection of high-content quantitative data. This platform was employed here to integrate a gut and a liver MPS together in continuous communication, and investigate simultaneously different PK processes taking place after oral drug administration in humans (e.g., intestinal permeability, hepatic metabolism). Measurement of tissue-specific phenotypic metrics indicated that gut and liver MPSs can be fluidically coupled with circulating common medium without compromising their functionality. The PK of diclofenac and hydrocortisone was investigated under different experimental perturbations, and results illustrate the robustness of this integrated system for quantitative PK studies. Mechanistic model-based analysis of the obtained data allowed the derivation of the intrinsic parameters (e.g., permeability, metabolic clearance) associated with the PK processes taking place in each MPS. Although these processes were not substantially affected by the gut-liver interaction, our results indicate that inter-MPS communication can have a modulating effect (hepatic metabolism upregulation). We envision that our integrative approach, which combines multi-cellular tissue models, multi-MPS platforms, and quantitative mechanistic modeling, will have broad applicability in pre-clinical drug development.
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“Furthermore, microfluidic systems can link different organs-on-a-chip to potentially simulate the complexity of multiorgan drug metabolism and pharmacokinetics9,47,50,68–71.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [69]
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Citations
Cites
Inference from iterative simulation using multiple sequences
Gelman, A., & Rubin, D. B. (1992) · Statistical Science · doi:10.1214/ss/1177011136 · Cited by 16,627
CODA: convergence diagnosis and output analysis for MCMC
Plummer, M., Best, N., Cowles, K., & Vines, K. (2006) · Open Research Online (The Open University) · Cited by 3,317
Bhatia, S. N., & Ingber, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2989 · Cited by 3,305
Physiological Parameter Values for Physiologically Based Pharmacokinetic Models
Brown, R. P., Delp, M. D., Lindstedt, S. L., Rhomberg, L. R., & Beliles, R. P. (1997) · Toxicology and Industrial Health · doi:10.1177/074823379701300401 · Cited by 1,408
Markov Chain Monte Carlo in Practice.
Kass, R. E., Gilks, W. R., Richardson, S. T., & Spiegelhalter, D. J. (1997) · Journal of the American Statistical Association · doi:10.2307/2965438 · Cited by 1,380
PDMS absorption of small molecules and consequences in microfluidic applications
Toepke, M. W., & Beebe, D. J. (2006) · Lab on a Chip · doi:10.1039/b612140c · Cited by 1,193
Organs-on-chips at the frontiers of drug discovery
Esch, E. W., Bahinski, A., & Huh, D. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4539 · Cited by 1,185
Maschmeyer, I., Lorenz, A. K., Schimek, K., Hasenberg, T., Ramme, A. P., Hübner, J., Lindner, M., Drewell, C., Bauer, S., Thomas, A., et al. (2015) · Lab on a Chip · doi:10.1039/c5lc00392j · Cited by 861
Surface area of the digestive tract – revisited
Helander, H. F., & Fändriks, L. (2014) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2014.898326 · Cited by 860
VanDussen, K. L., Marinshaw, J. M., Shaikh, N., Miyoshi, H., Moon, C., Tarr, P. I., Ciorba, M. A., & Stappenbeck, T. S. (2015) · Gut · doi:10.1136/gutjnl-2013-306651 · Cited by 525
Cited by
Sorted by citations
Items 101–200 of 222
Technologies for Measuring Pharmacokinetic Profiles
Heller, A. A., Lockwood, S. Y., Janes, T., & Spence, D. M. (2018) · Annual Review of Analytical Chemistry · doi:10.1146/annurev-anchem-061417-125611 · Cited by 27
Emerging Models of Drug Metabolism, Transporters, and Toxicity
Sawant‐Basak, A., & Obach, R. S. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.084293 · Cited by 24
Necrotizing Enterocolitis: Overview on In Vitro Models
Fazio, L. D., Beghetti, I., Bertuccio, S. N., Marsico, C., Martini, S., Masetti, R., Pession, A., Corvaglia, L., & Aceti, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136761 · Cited by 26
“These microdevices can be used to test and to create in vitro models of human disease, to closely monitor cell-level and tissue-level events [75], simulate and reverse pathological situations, and study the effect of etiological factors on tissue [76].”
BackgroundDonkers, J. M., van der Vaart, J. I., & van de Steeg, E. (2023) · Biomimetics · doi:10.3390/biomimetics8020226 · Cited by 25
“and hydrocortisone kinetics [149], a small intestine-liver-lung combination that evaluated the anti-cancer effects of two orally and one systemically administered drug [150] and a four-organ system consisting of intestine, liver, cancer and connective tissue models that demonstrated intestinal absorption, hepatic meta…”
BackgroundArtificial Intelligence for Organoids Multidimensional Assessment
Mo, Y., Wang, J., Yang, H., Bai, L., Xu, K., & Su, J. (2025) · SmartMat · doi:10.1002/smm2.70016 · Cited by 25
Hu, W., Wang, Y., Han, J., Zhang, W., Chen, J., Li, X., & Wang, L. (2025) · Biomaterials Science · doi:10.1039/d4bm01273a · Cited by 27
Chunduri, V., & Maddi, S. (2022) · ADMET & DMPK · doi:10.5599/admet.1513 · Cited by 30
“Other than organoids, drug screening studies showed that liver-on-chip or liver-MPS demonstrated significant potential for drug PKs and toxicity research [155,156,157].”
BackgroundWu, J., Zhang, B., Liu, X., Peng, L., Liu, J., Hu, Y., Ji, X., Lv, H., & Wang, S. (2023) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2023.02.013 · Cited by 24
Docci, L., Parrott, N. J., Krähenbühl, S., & Fowler, S. M. (2019) · SLAS DISCOVERY · doi:10.1177/2472555219831407 · Cited by 24
Kurth, F., Györvary, E., Heub, S., Ledroit, D., Paoletti, S., Renggli, K., Revol, V., Verhulsel, M., Weder, G., & Loizeau, F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817202-5.00003-6 · Cited by 26
Deguchi, S., Yamashita, T., Igai, K., Harada, K., Ueyama-Toba, Y., Hirata, K., Takayama, K., & Mizuguchi, H. (2019) · Drug Metabolism and Disposition · doi:10.1124/dmd.119.086322 · Cited by 23
“One such cell model has already been reported: a microphysiological system using PHHs as hepatocytes and Caco-2 cells as intestinal enterocytes (Tsamandouras et al., 2017).”
BackgroundYu, Y., Sun, B., Ye, X., Wang, Y., Zhao, M., Song, J., Geng, X., Marx, U., Li, B., & Zhou, X. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2024.115016 · Cited by 22
Wang, J., Zhang, H., Qu, Y., Yang, Y., Xu, S., Ji, Z., Wang, Y., Zhang, X., & Luo, Y. (2025) · Microsystems & Nanoengineering · doi:10.1038/s41378-025-00933-3 · Cited by 26
Reactive oxygen species limit intestinal mucosa-bacteria homeostasis in vitro
Luchan, J., Choi, C., & Carrier, R. L. (2021) · Scientific Reports · doi:10.1038/s41598-021-02080-x · Cited by 24
Advancements in Microfluidic Systems for the Study of Female Reproductive Biology
Bodke, V. V., & Burdette, J. E. (2021) · Endocrinology · doi:10.1210/endocr/bqab078 · Cited by 22
Roy, S., Parveen, M., Bala, A., & Sur, D. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.4c00661 · Cited by 22
Microtechnology-based in vitro models: Mimicking liver function and pathophysiology
Lee, S. Y., Kim, D., Sung, J. H., & Sung, J. H. (2021) · APL Bioengineering · doi:10.1063/5.0061896 · Cited by 23
Zhang, S., Xu, G., Wu, J., Liu, X., Fan, Y. Z., Chen, J., Wallace, G. G., & Gu, Q. (2023) · Small Methods · doi:10.1002/smtd.202300685 · Cited by 26
How organ-on-a-chip is advancing cancer research and oncology - a cancer hallmarks’ perspective
Avula, L. R., & Grodzinski, P. A. (2024) · Frontiers in Lab on a Chip Technologies · doi:10.3389/frlct.2024.1487377 · Cited by 23
Engineering Patient-on-a-Chip Models for Personalized Cancer Medicine
Caballero, D., Reis, R. L., & Kundu, S. C. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-36588-2_4 · Cited by 21
Hwang, S.-H., Lee, S., Park, J. Y., Jeon, J. S., Cho, Y., & Kim, S. (2021) · Micromachines · doi:10.3390/mi12020215 · Cited by 23
Mina, S. G., Alaybeyoglu, B., Murphy, W. L., Thomson, J. A., Stokes, C. L., & Cirit, M. (2019) · Frontiers in Big Data · doi:10.3389/fdata.2019.00023 · Cited by 21
“Likewise, drug absorption and metabolism processes have been studied in an integrated gut-liver platform that enables observation of organ-organ crosstalk (Chen et al., 2017; Tsamandouras et al., 2017).”
BackgroundSelf-citationTrapečar, M. (2021) · FEBS Letters · doi:10.1002/1873-3468.14260 · Cited by 21
Wang, M., Sasaki, Y., Sakagami, R., Minamikawa, T., Tsuda, M., Ueno, R., Deguchi, S., Negoro, R., So, K., Higuchi, Y., et al. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c00605 · Cited by 20
Integrated Microphysiological Systems: Transferable Organ Models and Recirculating Flow
Renggli, K., Rousset, N., Lohasz, C., Nguyen, O. T. P., & Hierlemann, A. R. (2019) · Advanced Biosystems · doi:10.1002/adbi.201900018 · Cited by 20
Stevens, L. J., Donkers, J. M., Dubbeld, J., Vaes, W. H. J., Knibbe, C. A. J., Alwayn, I. P. J., & van de Steeg, E. (2020) · Drug Metabolism Reviews · doi:10.1080/03602532.2020.1772280 · Cited by 19
“Tsamandouras et al. (2017) developed a coupled gut-liver-chip model to study PK of multiple organs and the interconnection between the organs.”
BackgroundMilani, N., Parrott, N. J., Galetin, A., Fowler, S. M., & Gertz, M. (2024) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.13110 · Cited by 18
“24,26 Figure 3a illustrates the impact of the surface area on the in vitro PK profiles of a metabolically stable compound with low permeability (e.g., etoposide, P app of 0.4 nm/s, 31 additional information is available in the Supplementary Information).”
BackgroundInfluentialPerspective on the Application of Microphysiological Systems to Drug Transporter Studies
Caetano-Pinto, P., & Stahl, S. H. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.082750 · Cited by 20
Kaiser, K. N., Snyder, J. R., Koppes, R. A., & Koppes, A. N. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202409718 · Cited by 17
Apáti, Á., Varga, N., Berecz, T., Erdei, Z., Homolya, L., & Sarkadi, B. (2018) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2019.1558207 · Cited by 17
“Such multiple systems (body-on-a-chip) contain 2 [141] to 13 [142] organs, interlinked in a controlled microfluidic arrangement.”
BackgroundLatest impact of engineered human liver platforms on drug development
Monckton, C. P., Brown, G. E., & Khetani, S. R. (2021) · APL Bioengineering · doi:10.1063/5.0051765 · Cited by 17
Sawant‐Basak, A., Rodrigues, A. D., Lech, M. P., Doyonnas, R., Kasaian, M. T., Prasad, B., & Tsamandouras, N. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.082784 · Cited by 16
Self-citationRamadan, Q., Gourikutty, S. B. N., & Zhang, Q. (2020) · Micromachines · doi:10.3390/mi11060565 · Cited by 17
Opportunities for Microphysiological Systems in Toxicity Testing of New Drug Modalities
Maulana, T. I., Wevers, N. R., Kristoforus, T., Chandler, M. R., Lanz, H. L., Joore, J., Vulto, P., Villenave, R., Kustermann, S., Loskill, P., et al. (2024) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-061724-080621 · Cited by 18
Samantasinghar, A., Sunildutt, N., Ahmed, F., Memon, F. H., Kang, C.-U., & Choi, K. H. (2025) · ACS Omega · doi:10.1021/acsomega.4c11227 · Cited by 15
Zwi‐Dantsis, L., Jayarajan, V., Church, G. M., Kamm, R. D., de Magalhães, J. P., & Moeendarbary, E. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202500217 · Cited by 16
Computational pharmacokinetic modeling of organ-on-chip devices and microphysiological systems
Przekwas, A. J., & Somayaji, M. R. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817202-5.00011-5 · Cited by 15
Zamora, C. Y., Ward, E. M., Kester, J. C., Chen, W. L. K., Velazquez, J. G., Griffith, L. G., & Imperiali, B. (2019) · Glycobiology · doi:10.1093/glycob/cwz105 · Cited by 17
Self-citationA primary human Gut/Liver microphysiological system to estimate human oral bioavailability
Abbas, Y., van Wyk, M., Sze, H., Christophi, J., Spreen, A., Bliton, R. J., Boazak, E. M., & Kostrzewski, T. M. (2025) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2025.100130 · Cited by 17
“16,17 We demonstrate that our primary gut model contains cells capable of transient proliferation and differentiation into multiple lineages and a distinct layer of mucus, both characteristics of the human intestinal lining.”
Ohri, S., Parekh, P., Nichols, L., Rajan, S. A. P., & Cirit, M. (2024) · Drug Metabolism and Disposition · doi:10.1124/dmd.124.001497 · Cited by 14
“…platform would enable investigation of DDIs caused by induction at both hepatic and intestinal MPSs and evaluation of multiple PK parameters related to oral drug administration, such as clearance values in gut and liver MPS, gut MPS drug permeability, and bioavailability (Tsamandouras et al, 2017).”
Self-citationA body-on-a-chip (BOC) system for studying gut-liver interaction
Sung, J. H. (2020) · Methods in cell biology · doi:10.1016/bs.mcb.2020.01.003 · Cited by 14
A similarity scaling approach for organ-on-chip devices
Feng, J. J., & Hedtrich, S. (2022) · Lab on a Chip · doi:10.1039/d2lc00641c · Cited by 13
Myszczyszyn, A., Muench, A., Lehmann, V., Sinnige, T., van Steenbeek, F. G., Bouwmeester, M., Samsom, R.-A., Keuper-Navis, M., van der Made, T. K., Kogan, D., et al. (2025) · Biofabrication · doi:10.1088/1758-5090/adc3ce · Cited by 14
“…cultured organoid-based small intestine-like Transwell system [40] to study the first-pass effect and bioavailability of midazolam and coumarin upon oral administration (apical/luminal-like compartment) (figure 6(A)), similar to previous dual-organ system studies using different compounds [59–62].”
Li, Y., Cui, H., & Cui, H. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202503391 · Cited by 15
Maschmeyer, I., & Kakava, S. (2020) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2020_135 · Cited by 13
Integrative microphysiological tissue systems of cancer metastasis to the liver
Clark, A. M., Allbritton, N. L., & Wells, A. H. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.06.010 · Cited by 11
Microphysiological Systems: A Pathologist’s Perspective
Sura, R., Vleet, T. V., & Berridge, B. R. (2020) · Veterinary Pathology · doi:10.1177/0300985820908794 · Cited by 12
“Another example of combined gut- and liver-model MPS has been described(82) and was used to model the pharmacokinetics of diclofenac and hydrocortisone.(81) The temporal and phenotypic resolution offered by MPS provides significant opportunity to address discrete mechanistic questions at the cellular and/or tissue lev…”
MethodMicrofluidic systems in cancer research
Caballero, D., Luque‐González, M. A., Reis, R. L., & Kundu, S. C. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818128-7.00015-0 · Cited by 11
Gan, J., Bolon, B. N., Vleet, T. V., & Wood, C. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821044-4.00005-4 · Cited by 11
Silvestri, A., Vicente, F., Vicent, M. J., Stechmann, B., & Fecke, W. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.02.024 · Cited by 12
Deguchi, S., Shintani, T., Harada, K., Okamoto, T., Takemura, A., Hirata, K., Ito, K., Takayama, K., & Mizuguchi, H. (2021) · Hepatology Communications · doi:10.1002/hep4.1729 · Cited by 10
Kim, H. Y., Moon, J.-O., & Kim, S. W. (2024) · Animal nutrition · doi:10.1016/j.aninu.2024.01.006 · Cited by 11
Microfluidic gut-axis-on-a-chip models for pharmacokinetic-based disease models
Kim, R., & Sung, J. H. (2024) · Biomicrofluidics · doi:10.1063/5.0206271 · Cited by 12
An in vitro intestinal model captures immunomodulatory properties of the microbiota in inflammation
Lock, J. Y., Caboni, M., Strandwitz, P., Morrissette, M., DiBona, K. C., Joughin, B. A., Lewis, K., & Carrier, R. L. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2039002 · Cited by 9
“Recently, dendritic cells representing immune cells in the gut have been added to the Caco-2/HT29MTX cell culture system to obtain a more representative intestinal model.(19,20) Within the intestine, dendritic cells are recruited to injury sites and can extend dendrites into the lumen to capture resident bacteria,(21)…”
Kester, J. C., Brubaker, D. K., Velazquez, J. G., Wright, C. W., Lauffenburger, D. A., & Griffith, L. G. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01404-19 · Cited by 9
“To test the commensal-independent effects of antibiotics on human tissue, we used a transwell-based in vitro epithelial barrier without bacteria to model a germfree human gut (33, 34).”
MethodSelf-citationA microphysiological systems approach to design gastrointestinal system
Mathur, V., Gadre, M. A., Amrutha, H. K., & Vasanthan, K. S. (2025) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2025.2532567 · Cited by 8
Evolution of human pharmacokinetics prediction methods: from allometry to artificial intelligence
Choi, N., Shin, B. S., & Shin, S. (2026) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-026-00805-6 · Cited by 9
“Recent advances have linked quantitative outputs from OoC systems with PBPK modeling and ML–based computational methods, establishing an integrated framework that enhances IVIVE and improves the prediction of human pharmacokinetics (Tsamandouras et al. 2017 ).”
Aminian-Dehkordi, J., Valiei, A., & Mofrad, M. R. K. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.987104 · Cited by 6
State of the Art in Integrated Biosensors for Organ-on-a-Chip Applications
Dey, T., Mitra, P., Chakraborty, B., Sanyal, A., Acharjee, A., Ghosh, A., & Mandal, D. (2024) · Smart nanomaterials technology · doi:10.1007/978-981-99-6597-7_10 · Cited by 7
Design and engineering of multiorgan systems
Renggli, K., & Frey, O. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817202-5.00012-7 · Cited by 7
Jeong, C. G., Negro, G. D., Getsios, S., & Ekert, J. E. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813671-3.00005-0 · Cited by 8
Technical aspects of megaureter repair.
Hendren, W. H. (1977) · PubMed · Cited by 7
-Omics approaches to study and model cell-cell interactions in engineered tissues
Stark, C., Jenison, S. E., & Ngo, M. T. (2025) · Frontiers in Chemical Engineering · doi:10.3389/fceng.2025.1629455 · Cited by 7
“When coupled with -omics, these patient-speci fi c platforms can be used to model and study individualized drug responses (Soldatow et al., 2013; Tsamandouras et al., 2017; Vlachogiannis et al., 2018).”
A comprehensive overview of advanced dynamic in vitro intestinal and hepatic cell culture models
Leal, F., Zeiringer, S., Jeitler, R., Costa, P. F., & Roblegg, E. (2023) · Tissue Barriers · doi:10.1080/21688370.2022.2163820 · Cited by 7
“190 Some studies manufactured devices with materials that show minimal absorption of hydrophobic compounds to ensure that the drug loss is negligible, and the exposure can be controlled; 135,166,191 nonetheless, the number of studies using these materials is still scarce and needs further research.”
BackgroundYang, J., Hirai, Y., Iida, K., Ito, S., Trumm, M., Terada, S., Sakai, R., Tsuchiya, T., Tabata, O., & Kamei, K.-I. (2020) · doi:10.1101/2020.06.10.141606 · Cited by 110
Liver-on-a-Chip (LoC) Models: Case Studies of Academic Platforms and Commercial Products
Benzait, Z., Tomsuk, Ö., Ebrahimi, A., Ghorbanpoor, H., Özel, C., Didarian, R., Cevizlidere, B. D., Kaya, M., Gür, T., Gasimzade, N., et al. (2026) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c01122 · Cited by 6
Sherfey, J. S., Rajan, S. A. P., Nichols, L. M., Parekh, P., Smith, J. T., Gregory, L., Clark, F., Kadar, E. P., Ohri, S., George, B. T., et al. (2026) · Lab on a Chip · doi:10.1039/d6lc00008h · Cited by 5
Self-citationIngelman‐Sundberg, M., & Lauschke, V. M. (2024) · Drug Metabolism and Disposition · doi:10.1124/dmd.123.001302 · Cited by 6
Saridis, M. R., Salmina, A. B., Korsakova, S. A., & Yurchenko, S. O. (2025) · Biotechnology Journal · doi:10.1002/biot.70065 · Cited by 6
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Marin, T. M., Indolfo, N. D. C., Rocco, S. A., Carvalho, M. D. O., Dias, M. M., Bento, G. I. V., Bortot, L. O., Schuck, D. C., Lorencini, M., & Pagani, E. (2020) · Journal of Visualized Experiments · doi:10.3791/60184 · Cited by 5
Lungu, I. I., & Grumezescu, A. M. (2019) · Biomedical Engineering International · doi:10.33263/biomed11.002008 · Cited by 6
Sepsis modelling: current approaches and organ-on-chip perspectives
Silva, M. J., Fehrenbach, G. W., Pogue, R. E., Murray, P., Rezoagli, E., Laffey, J. G., & Murphy, E. J. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106120 · Cited by 6
Microphysiological Systems: Transforming Biomedical and Clinical Research
Sahoo, O. S., Tyagi, A., Sharma, A. K., Gill, G. S., Dhar, R., & Karmakar, S. (2026) · Biotechnology and Bioengineering · doi:10.1002/bit.70229 · Cited by 4
“…volume ratio is orders of magnitude higher than in vivo, leading to excessive dilution of secreted proteins (albumin, coagulation factors, bile acids), under-estimation of hepatocellular drug metabolism, and failure to accumulate reactive metabolites to toxic thresholds (Tsamandouras et al. 2017).”
Chen, W. L. K., Suter, E., Miyazaki, H., Velazquez, J. G., Lauffenburger, D. A., Griffith, L. G., & Carrier, R. L. (2021) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.0c00762 · Cited by 4
Self-citationOrgan Chips and Visualization of Biological Systems
Tian, T., Liu, J., & Zhu, H. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9902-3_8 · Cited by 4
From organ-on-a-chip towards body-on-a-chip
Sung, J. H. (2022) · Biocell · doi:10.32604/biocell.2022.019055 · Cited by 4
Microfluidic Systems and Organ (Human) on a Chip
Bahnemann, J., Enders, A., & Winkler, S. (2021) · Learning materials in biosciences · doi:10.1007/978-3-030-66749-8_8 · Cited by 5
Bioengineered intestinal models: structural precision drives functional and microbial fidelity
Gao, Z., Du, H., Yu, S., Li, Q., Li, Y., Yin, J., Yang, H., Wang, Y., Zhou, H., & Shen, L. (2025) · Bio-Design and Manufacturing · doi:10.1631/bdm.2500353 · Cited by 3
On-Chip modeling of drug-gut interactions in Oral drug delivery
Abdollahi, S., Vajhadin, F., Rafiei, A., Tamrin, S. H., Daniel, S. D., Banoei, M. M., Zarin, B., Sen, A., Kim, K., & Sanati‐Nezhad, A. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115864 · Cited by 3
Kida, R., Rajendran, A. R. J., Tsugane, M., Duclos‐Vallée, J., Mahé, M. M., Bensalem, S., Suzuki, H., & Pioufle, B. L. (2024) · Talanta Open · doi:10.1016/j.talo.2024.100289 · Cited by 3
“For instance, Tsa-mandouras et al. [19] and Yang et al. [20] separately established MPS models for simulating non-alcoholic fatty liver disease (NAFLD) on a microchip integrated with pneumatic pumps for drug testing.”
Multiorgan-on-a-chip: Design and Applications
Khan, H., Khan, S. A., & Parvez, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13782-2.00009-7 · Cited by 3
A bladder blueprint to build better models for understanding homeostasis and disease
Deltourbe, L. G., Durand, M., Costas, A., & Ingersoll, M. A. (2025) · Nature Reviews Urology · doi:10.1038/s41585-025-01013-x · Cited by 4
Varnekar, S., Sohal, M., Tikale, N., Ruchitha Reddy, S., Bose, A., Pawar, S., & Kurkute, P. (2025) · Springer eBooks · doi:10.1007/978-981-96-4154-3_14 · Cited by 3
Microphysiological system as a promising technology for drug assay
Ishida, S., & Kanamori, T. (2019) · Folia Pharmacologica Japonica · doi:10.1254/fpj.154.345 · Cited by 3
Mirzababaei, S., Nigjeh, M. N., Abdollahi, M. R., & Shamloo, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823536-2.00011-0 · Cited by 3
Marin, T. M., & Pagani, E. (2018) · Vigilância Sanitária em Debate · doi:10.22239/2317-269x.01053 · Cited by 3
Taute, F., Homs-Corbera, A., & Gaudriault, P. (2021) · Open Research Europe · doi:10.12688/openreseurope.13335.1 · Cited by 2
Integrating mass spectrometry with microphysiological systems for improved neurochemical studies
Tillmaand, E. G., & Sweedler, J. V. (2018) · Microphysiological Systems · doi:10.21037/mps.2018.05.01 · Cited by 3
“In addition to creating physiologically relevant environments through the introduction of chemicals, gradients, and 3D structures or geometries within a system, microphysiological devices also improve the ability to spatially and temporally define physical sampling steps within an experiment (23-28).”
BackgroundIn vitro models of the gut-liver axis: what we’ve learned and what remains to be built
Sung, J. H., & Kim, R. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1858289 · Cited by 2
Schnepper, M. T., Roles, J., & Hickman, J. J. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c00350 · Cited by 3
Microphysiological systems for modeling gut-organ interaction
Sung, J. H. (2024) · Biocell · doi:10.32604/biocell.2024.050365 · Cited by 2
“Some researchers suggested theoretical methodologies to approach this issue [33], with some pioneering, proof-of-concept works using model drugs [34 – 36].”
Application of Microfluidics in Drug Development
Parhizkar, M., Wang, F., Tsitouridou, A., & Tsaoulidis, D. A. (2024) · AAPS introductions in the pharmaceutical sciences · doi:10.1007/978-3-031-60717-2_12 · Cited by 2
“Organs on a Chip”: Revolutionization in personalized treatment
Sahoo, S., Patel, P., & Goswami, M. (2021) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v11i4.4909 · Cited by 2
Human organ-on-a-chip technology as a catalyst for drug discovery
Posey, R. R., Özkan, A., & Ingber, D. E. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115920 · Cited by 1
Kang, S. J., Bong, S. H., Jo, M. J., Lee, J. M., Yoon, M. S., Park, S., Lee, Y., Shin, Y., Lee, H. J., Park, C., et al. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18091117 · Cited by 1
“By embedding barrier transport within a controlled and time-resolved microfluidic environment, these systems contribute a critical upstream component to multi-organ PK reconstruction [19].”
Historical and Technological Background to ‘Organ on a Chip’
Wilkinson, J. M. (2022) · Springer eBooks · doi:10.1007/978-981-19-1379-2_1 · Cited by 1
Sailaja, A., & Bachchhav, M. B. (2024) · Practice, progress, and proficiency in sustainability · doi:10.4018/979-8-3693-1638-2.ch014 · Cited by 1
Tissue chips as headway model and incitement technology
Modi, P. S., Singh, A., Chaturvedi, A., Agarwal, S., Dutta, R., Nayak, R., & Singh, A. (2024) · Synthetic and Systems Biotechnology · doi:10.1016/j.synbio.2024.08.007 · Cited by 1
“Some of the multi-OoC include systems with gut and liver co-culture [39, 40], liver and kidney co-culture [41,42], liver and heart co-culture [43, 44], and many other [45 – 48].”
BackgroundWorkshop Report: USP Workshop on Exploring the Science of Drug Absorption
Martinez, M. N., Bhoopathy, S., Carlert, S., Cirit, M., Fahmy, R. M., Flanagan, T. R., Forbes, B., Jamei, M., Khan, M. A., Lukáčová, V., et al. (2019) · Dissolution Technologies · doi:10.14227/dt260319p38 · Cited by 1
Self-citationHadjizadeh, A., Alavi, M., Tajvar, S., & Hadjizadeh, A. (2021) · Journal of Integrative Cardiology Open Access · doi:10.31487/j.jicoa.2021.03.07 · Cited by 1
“Although the multi-organ-chip face many challenges, significant improvements that to date has been made by researchers such as two-organs, three-organs, four-organs, and ten organs on the chip, increase the possibility of creating such a model in the future [34, 51, 58-62].”
Background
Metadata
- Authors
- Tsamandouras, N., Chen, W. L. K., Edington, C. D., Stokes, C. L., Griffith, L. G., & Cirit, M.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Cirit, Murat
- Venue
- The AAPS Journal
- Published
- 2017-07-27
- Volume
- 19
- Issue
- 5
- Pages
- 1499-1512
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC6540747
- OpenAlex
- W2741120316
- Cited by
- 222
- References
- 56
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 24 · 2023: 18 · 2022: 21 · 2021: 40 · 2020: 33 · 2019: 20 · 2018: 23 · 2017: 3
- FWCI
- 9.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The AAPS Journal (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (UH3TR000496)
- National Center for Advancing Translational Sciences
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- microphysiological systems, organ-on-a-chip, in vitro pharmacokinetics, intestinal permeability, hepatic metabolism, diclofenac, cortisol, mechanistic modeling, oral administration
- MeSH terms
- Diclofenac, Humans, Hydrocortisone, Intestinal Mucosa, Liver, In Vitro Techniques
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