Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs

References

• Tsaioun K, Blaauboer BJ, Hartung T. Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods. ALTEX. 2016;33(4):343–358.
   PubMedGoogle Scholar
• Sung JH, Wang YI, Narasimhan Sriram N, et al. Recent advances in Body-on-a-Chip systems. Anal Chem. 2019 Jan 2;91(1):330–351.
   PubMed Web of Science ®Google Scholar
• Dehne EM, Hasenberg T, Marx U. The ascendance of microphysiological systems to solve the drug testing dilemma. Future Sci OA. 2017 Jun;3(2):FSO185.
   PubMed Web of Science ®Google Scholar
• Lee SH, Sung JH. Organ-on-a-Chip Technology for Reproducing Multiorgan Physiology. Adv Healthc Mater. 2018 Jan;7:2.
   Web of Science ®Google Scholar
• Lee SH, Choi N, Sung JH. Pharmacokinetic and pharmacodynamic insights from microfluidic intestine-on-a-chip models. Expert Opin Drug Metab Toxicol. 2019 Dec;15(12):1005–1019.
   PubMed Web of Science ®Google Scholar
• Okumura R, Takeda K. Roles of intestinal epithelial cells in the maintenance of gut homeostasis. Exp Mol Med. 2017 May 26;49(5):e338.
   PubMedGoogle Scholar
• Bujard A, Sol M, Carrupt PA, et al. Predicting both passive intestinal absorption and the dissociation constant toward albumin using the PAMPA technique. Eur J Pharm Sci. 2014 Oct;15(63):36–44.
   Google Scholar
• Nauli AM, Nauli SM. Intestinal transport as a potential determinant of drug bioavailability. Curr Clin Pharmacol. 2013. 8. Aug(3):247–255.
   Google Scholar
• Johnson BM, Charman WN, Porter CJ. The impact of P-glycoprotein efflux on enterocyte residence time and enterocyte-based metabolism of verapamil. J Pharm Pharmacol. 2001 Dec;53(12):1611–1619.
   PubMed Web of Science ®Google Scholar
• Artursson P, Palm K, Luthman K. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv Drug Deliv Rev. 2001 Mar 1;46(1–3):27–43.
   PubMed Web of Science ®Google Scholar
• Sun H, Chow EC, Liu S, et al. The Caco-2 cell monolayer: usefulness and limitations. Expert Opin Drug Metab Toxicol. 2008 4;Apr(4):395–411.
   Google Scholar
• Bein A, Shin W, Jalili-Firoozinezhad S, et al. Microfluidic Organ-on-a-Chip Models of Human Intestine. Cell Mol Gastroenterol Hepatol. 2018;5(4):659–668.
   PubMed Web of Science ®Google Scholar
• Chi M, Yi B, Oh S, et al. A microfluidic cell culture device (muFCCD) to culture epithelial cells with physiological and morphological properties that mimic those of the human intestine. Biomed Microdevices. 2015;17(3):9966.
   PubMed Web of Science ®Google Scholar
• Kimura H, Yamamoto T, Sakai H, et al. An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models. Lab Chip. 2008 May;8(5):741–746.
   PubMed Web of Science ®Google Scholar
• Imura Y, Asano Y, Sato K, et al. A microfluidic system to evaluate intestinal absorption. Anal Sci. 2009 Dec;25(12):1403–1407.
   PubMed Web of Science ®Google Scholar
• Gao D, Liu H, Lin JM, et al. Characterization of drug permeability in Caco-2 monolayers by mass spectrometry on a membrane-based microfluidic device. Lab Chip. 2013 Mar 7;13(5):978–985.
   PubMed Web of Science ®Google Scholar
• Langerak N, Ahmed HMM, Li Y, et al. A Theoretical and Experimental Study to Optimize Cell Differentiation in a Novel Intestinal Chip. Front Bioeng Biotechnol. 2020;8:763.
   PubMed Web of Science ®Google Scholar
• Kulthong K, Duivenvoorde L, Sun H, et al. Microfluidic chip for culturing intestinal epithelial cell layers: characterization and comparison of drug transport between dynamic and static models. Toxicol In Vitro. 2020;65:104815.
   PubMed Web of Science ®Google Scholar
• Shim KY, Lee D, Han J, et al. Microfluidic gut-on-a-chip with three-dimensional villi structure. Biomed Microdevices. 2017 Jun;19(2):37.
   PubMed Web of Science ®Google Scholar
• Trietsch SJ, Naumovska E, Kurek D, et al. Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes. Nat Commun. 2017 Aug 15;8(1):262.
   PubMedGoogle Scholar
• Guo Y, Li Z, Su W, et al. A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine. Artif Organs. 2018 Dec;42(12):1196–1205.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Huh D, Hamilton G, et al. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip. 2012 Jun 21;12(12):2165–2174.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Ingber DE. Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr Biol (Camb). 2013 Sep;5(9):1130–1140.
   PubMed Web of Science ®Google Scholar
• Shin W, Hinojosa CD, Ingber DE, et al. Human Intestinal Morphogenesis Controlled by Transepithelial Morphogen Gradient and Flow-Dependent Physical Cues in a Microengineered Gut-on-a-Chip. iScience. 2019 May;31(15):391–406.
   Google Scholar
• Baptista D, Teixeira L, Van Blitterswijk C, et al. Overlooked? Underestimated? Effects of Substrate Curvature on Cell Behavior. Trends Biotechnol. 2019 Aug;37(8):838–854.
   PubMed Web of Science ®Google Scholar
• Koppes AN, Kamath M, Pfluger CA, et al. Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C. Biofabrication. 2016 Aug 22;8(3):035011.
   PubMed Web of Science ®Google Scholar
• Wang Y, Ahmad AA, Sims CE, et al. In vitro generation of colonic epithelium from primary cells guided by microstructures. Lab Chip. 2014 May 7;14(9):1622–1631.
   PubMed Web of Science ®Google Scholar
• Kim SH, Chi M, Yi B, et al. Three-dimensional intestinal villi epithelium enhances protection of human intestinal cells from bacterial infection by inducing mucin expression. Integr Biol (Camb). 2014 Dec;6(12):1122–1131.
   PubMed Web of Science ®Google Scholar
• Esch MB, Sung JH, Yang J, et al. On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic ‘body-on-a-chip’ devices. Biomed Microdevices. 2012 Oct;14(5):895–906.
   PubMed Web of Science ®Google Scholar
• Sung JH, Yu J, Luo D, et al. Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. Lab Chip. 2011 Feb 7;11(3):389–392.
   PubMed Web of Science ®Google Scholar
• Yu J, Peng S, Luo D, et al. In vitro 3D human small intestinal villous model for drug permeability determination. Biotechnol Bioeng. 2012 Sep;109(9):2173–2178.
   PubMed Web of Science ®Google Scholar
• Wang Y, Gunasekara DB, Reed MI, et al. A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium. Biomaterials. 2017;128:44–55.
   PubMed Web of Science ®Google Scholar
• Wang Y, Kim R, Gunasekara DB, et al. Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer. Cell Mol Gastroenterol Hepatol. 2018;5(2):113–130.
   PubMed Web of Science ®Google Scholar
• Kasendra M, Tovaglieri A, Sontheimer-Phelps A, et al. Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids. Sci Rep. 2018 Feb 13;8(1):2871.
   PubMedGoogle Scholar
• Workman MJ, Gleeson JP, Troisi EJ, et al. Enhanced Utilization of Induced Pluripotent Stem Cell-Derived Human Intestinal Organoids Using Microengineered Chips. Cell Mol Gastroenterol Hepatol. 2018;5(4):669–677 e2.
   PubMed Web of Science ®Google Scholar
• Morgan XC, Tickle TL, Sokol H, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012 Apr 16;13(9):R79.
   PubMed Web of Science ®Google Scholar
• Shah P, Fritz JV, Glaab E, et al. A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nat Commun. 2016 May;11(7):11535.
   Google Scholar
• Kim HJ, Li H, Collins JJ, et al. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):E7–15.
   PubMed Web of Science ®Google Scholar
• Sunuwar L, Yin J, Kasendra M, et al. Mechanical Stimuli Affect Escherichia coli Heat-Stable Enterotoxin-Cyclic GMP Signaling in a Human Enteroid Intestine-Chip Model. Infect Immun. Vol. 88. Feb 20; 2020. p. 3.
   Google Scholar
• Shin W, Kim HJ. Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip. Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10539–E10547.
   PubMed Web of Science ®Google Scholar
• Sawant-Basak A, Obach RS. Emerging Models of Drug Metabolism, Transporters, and Toxicity. Drug Metab Dispos. 2018 Nov;46(11):1556–1561.
   PubMed Web of Science ®Google Scholar
• Jungermann K. Functional heterogeneity of periportal and perivenous hepatocytes. Enzyme. 1986;35(3):161–180.
   PubMedGoogle Scholar
• Allen JW, Khetani SR, Bhatia SN. In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol Sci. 2005 Mar;84(1):110–119.
   PubMed Web of Science ®Google Scholar
• Khetani SR, Bhatia SN. Microscale culture of human liver cells for drug development. Nat Biotechnol. 2008 Jan;26(1):120–126.
   PubMed Web of Science ®Google Scholar
• Tetsuka K, Ohbuchi M, Tabata K. Recent Progress in Hepatocyte Culture Models and Their Application to the Assessment of Drug Metabolism, Transport, and Toxicity in Drug Discovery: the Value of Tissue Engineering for the Successful Development of a Microphysiological System. J Pharm Sci. 2017 Sep;106(9):2302–2311.
   PubMed Web of Science ®Google Scholar
• Bale SS, Borenstein JT. Microfluidic Cell Culture Platforms to Capture Hepatic Physiology and Complex Cellular Interactions. Drug Metab Dispos. 2018 Nov;46(11):1638–1646.
   PubMed Web of Science ®Google Scholar
• Chan TS, Yu H, Moore A, et al. Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. Drug Metab Dispos. 2013 Dec;41(12):2024–2032.
   PubMed Web of Science ®Google Scholar
• Bonn B, Svanberg P, Janefeldt A, et al. Determination of Human Hepatocyte Intrinsic Clearance for Slowly Metabolized Compounds: comparison of a Primary Hepatocyte/Stromal Cell Co-culture with Plated Primary Hepatocytes and HepaRG. Drug Metab Dispos. 2016 Apr;44(4):527–533.
   PubMed Web of Science ®Google Scholar
• Hultman I, Vedin C, Abrahamsson A, et al. Use of HmuREL Human Coculture System for Prediction of Intrinsic Clearance and Metabolite Formation for Slowly Metabolized Compounds. Mol Pharm. 2016 Aug 1;13(8):2796–2807.
   PubMedGoogle Scholar
• Choi YY, Kim J, Lee SH, et al. Lab on a chip-based hepatic sinusoidal system simulator for optimal primary hepatocyte culture. Biomed Microdevices. 2016 Aug;18(4):58.
   PubMed Web of Science ®Google Scholar
• Novik E, Maguire TJ, Chao P, et al. A microfluidic hepatic coculture platform for cell-based drug metabolism studies. Biochem Pharmacol. 2010 Apr 1;79(7):1036–1044.
   PubMed Web of Science ®Google Scholar
• Grime K, Paine SW. Species differences in biliary clearance and possible relevance of hepatic uptake and efflux transporters involvement. Drug Metab Dispos. 2013 Feb;41(2):372–378.
   PubMed Web of Science ®Google Scholar
• Lee PJ, Hung PJ, Lee LP. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng. 2007 Aug 1;97(5):1340–1346.
   PubMed Web of Science ®Google Scholar
• Toh YC, Lim TC, Tai D, et al. A microfluidic 3D hepatocyte chip for drug toxicity testing. Lab Chip. 2009 Jul 21;9(14):2026–2035.
   PubMed Web of Science ®Google Scholar
• Toh YC, Zhang C, Zhang J, et al. A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip. 2007 Mar;7(3):302–309.
   PubMed Web of Science ®Google Scholar
• Mi S, Yi X, Du Z, et al. Construction of a liver sinusoid based on the laminar flow on chip and self-assembly of endothelial cells. Biofabrication. 2018 Feb 20;10(2):025010.
   PubMed Web of Science ®Google Scholar
• Ma C, Zhao L, Zhou EM, et al. On-Chip Construction of Liver Lobule-like Microtissue and Its Application for Adverse Drug Reaction Assay. Anal Chem. 2016 Feb 2;88(3):1719–1727.
   PubMed Web of Science ®Google Scholar
• Banaeiyan AA, Theobald J, Paukstyte J, et al. Design and fabrication of a scalable liver-lobule-on-a-chip microphysiological platform. Biofabrication. 2017 Feb 3;9(1):015014.
   PubMed Web of Science ®Google Scholar
• Marrone G, Shah VH, Gracia-Sancho J. Sinusoidal communication in liver fibrosis and regeneration. J Hepatol. 2016 Sep;65(3):608–617.
   PubMed Web of Science ®Google Scholar
• Beckwitt CH, Clark AM, Wheeler S, et al. Liver ‘organ on a chip’. Exp Cell Res. 2018 Feb 1;363(1):15–25.
   PubMed Web of Science ®Google Scholar
• Domansky K, Inman W, Serdy J, et al. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip. 2010 Jan 7;10(1):51–58.
   PubMed Web of Science ®Google Scholar
• Ebrahimkhani MR, Neiman JA, Raredon MS, et al. Bioreactor technologies to support liver function in vitro. Adv Drug Deliv Rev. 2014;69-70:132–157.
   PubMed Web of Science ®Google Scholar
• Du Y, Li N, Yang H, et al. Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip. Lab Chip. 2017 Feb 28;17(5):782–794.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wang H, Deng P, et al. Modeling Human Nonalcoholic Fatty Liver Disease (NAFLD) with an Organoids-on-a-Chip System. ACS Biomater Sci Eng. 2020 Oct 12;6(10):5734–5743.
   PubMed Web of Science ®Google Scholar
• Yin F, Zhang X, Wang L, et al. In: HiPSC-derived multi-organoids-on-chip system for safety assessment of antidepressant drugs. Lab Chip. Dec, 2020. 15.
   Google Scholar
• Sudo M, Nishihara M, Takahashi J, et al. Long-Term Stability of Cryopreserved Human Hepatocytes: evaluation of Phase I and II Drug-Metabolizing Enzyme Activities and CYP3A4/5 Induction for More than a Decade. Drug Metab Dispos. 2017 Jul;45(7):734–736.
   PubMed Web of Science ®Google Scholar
• Dietrich CG, Gotze O, Geier A. Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance. World J Gastroenterol. 2016 Jan 7;22(1):72–88.
   PubMed Web of Science ®Google Scholar
• Chen WLK, Edington C, Suter E, et al. Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk. Biotechnol Bioeng. 2017 Nov;114(11):2648–2659.
   PubMed Web of Science ®Google Scholar
• Jeon JW, Choi N, Lee SH, et al. Three-tissue microphysiological system for studying inflammatory responses in gut-liver Axis. Biomed Microdevices. 2020 Sep 11;22(4):65.
   PubMed Web of Science ®Google Scholar
• Gori M, Simonelli MC, Giannitelli SM, et al. Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device. PLoS One. 2016;11(7):e0159729.
   PubMed Web of Science ®Google Scholar
• Lee SY, Sung JH. Gut-liver on a chip toward an in vitro model of hepatic steatosis. Biotechnol Bioeng. 2018 Nov;115(11):2817–2827.
   PubMed Web of Science ®Google Scholar
• Ortega-Prieto AM, Skelton JK, Wai SN, et al. 3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection. Nat Commun. 2018 Feb 14;9(1):682.
   PubMedGoogle Scholar
• Bello-Reuss ER, L. Homeostatic and excretory functions of the kidney the kidney and body fluids in health and disease. 1983.
   Google Scholar
• Fowler S, Chen WLK, Duignan DB, et al. Microphysiological systems for ADME-related applications: current status and recommendations for system development and characterization. Lab Chip. 2020 Feb 7;20(3):446–467.
   PubMed Web of Science ®Google Scholar
• Anders MW. Metabolism of drugs by the kidney. Kidney Int. 1980 Nov;18(5):636–647.
   PubMed Web of Science ®Google Scholar
• Mathialagan S, Piotrowski MA, Tess DA, et al. Quantitative Prediction of Human Renal Clearance and Drug-Drug Interactions of Organic Anion Transporter Substrates Using In Vitro Transport Data: a Relative Activity Factor Approach. Drug Metab Dispos. 2017 Apr;45(4):409–417.
   PubMed Web of Science ®Google Scholar
• Essig M, Terzi F, Burtin M, et al. Mechanical strains induced by tubular flow affect the phenotype of proximal tubular cells. Am J Physiol Renal Physiol. 2001 Oct;281(4):F751–62.
   PubMed Web of Science ®Google Scholar
• Jang KJ, Mehr AP, Hamilton GA, et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol (Camb). 2013 Sep;5(9):1119–1129.
   PubMed Web of Science ®Google Scholar
• Mihajlovic M, Fedecostante M, Oost MJ, et al. Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions. Int J Mol Sci. 2017 Nov 26;18:12.
   Web of Science ®Google Scholar
• Nieskens TTG, Persson M, Kelly EJ, et al. A Multicompartment Human Kidney Proximal Tubule-on-a-Chip Replicates Cell Polarization-Dependent Cisplatin Toxicity. Drug Metab Dispos. 2020 Dec;48(12):1303–1311.
   PubMed Web of Science ®Google Scholar
• Vriend J, Nieskens TTG, Vormann MK, et al. Screening of Drug-Transporter Interactions in a 3D Microfluidic Renal Proximal Tubule on a Chip. Aaps J. 2018 Jul 26;20(5):87.
   PubMed Web of Science ®Google Scholar
• Schutgens F, Rookmaaker MB, Margaritis T, et al. Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol. 2019 Mar;37(3):303–313.
   PubMed Web of Science ®Google Scholar
• Homan KA, Gupta N, Kroll KT, et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods. 2019 Mar;16(3):255–262.
   PubMed Web of Science ®Google Scholar
• Homan KA, Kolesky DB, Skylar-Scott MA, et al. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips. Sci Rep. 2016 Oct 11;6:34845.
   PubMed Web of Science ®Google Scholar
• Weinberg E, Kaazempur-Mofrad M, Borenstein J. Concept and computational design for a bioartificial nephron-on-a-chip. Int J Artif Organs. 2008 Jun;31(6):508–514.
   PubMed Web of Science ®Google Scholar
• Miller NA, Reddy MB, Heikkinen AT, et al. Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: an Updated Model Building Strategy Illustrated with Challenging Industry Case Studies. Clin Pharmacokinet. 2019 Jun;58(6):727–746.
   PubMed Web of Science ®Google Scholar
• Sung JH, Srinivasan B, Esch MB, et al. Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure. Exp Biol Med (Maywood). 2014 Sep;239(9):1225–1239.
   PubMed Web of Science ®Google Scholar
• Shuler ML, Ghanem A, Quick D, et al. A self-regulating cell culture analog device to mimic animal and human toxicological responses. Biotechnol Bioeng. 1996 Oct 5;52(1):45–60.
   PubMed Web of Science ®Google Scholar
• Sweeney LM, Shuler ML, Babish JG, et al. A cell culture analogue of rodent physiology: application to naphthalene toxicology. Toxicol In Vitro. 1995 Jun;9(3):307–316.
   PubMed Web of Science ®Google Scholar
• Ghanem A, Shuler ML. Combining cell culture analogue reactor designs and PBPK models to probe mechanisms of naphthalene toxicity. Biotechnol Prog. 2000 May-Jun;16(3):334–345.
   PubMed Web of Science ®Google Scholar
• Ghanem A, Shuler ML. Characterization of a perfusion reactor utilizing mammalian cells on microcarrier beads. Biotechnol Prog. 2000 May-Jun;16(3):471–479.
   PubMed Web of Science ®Google Scholar
• Sin A, Chin KC, Jamil MF, et al. The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors. Biotechnol Prog. 2004 Jan-Feb;20(1):338–345.
   PubMed Web of Science ®Google Scholar
• Viravaidya K, Sin A, Shuler ML. Development of a microscale cell culture analog to probe naphthalene toxicity. Biotechnol Prog. 2004 Jan-Feb;20(1):316–323.
   PubMed Web of Science ®Google Scholar
• Tatosian DA, Shuler ML. A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers. Biotechnol Bioeng. 2009 May 1;103(1):187–198.
   PubMed Web of Science ®Google Scholar
• Sung JH, Shuler ML. A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip. 2009 May 21;9(10):1385–1394.
   PubMed Web of Science ®Google Scholar
• Sung JH, Kam C, Shuler ML. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip. 2010 Feb 21;10(4):446–455.
   PubMed Web of Science ®Google Scholar
• Huh D, Matthews BD, Mammoto A, et al. Reconstituting organ-level lung functions on a chip. Science. 2010 Jun 25;328(5986):1662–1668.
   PubMed Web of Science ®Google Scholar
• Ma C, Peng Y, Li H, et al. Organ-on-a-Chip: a New Paradigm for Drug Development. Trends Pharmacol Sci. 2020 Dec 16.
   Web of Science ®Google Scholar
• Ewart L, Dehne EM, Fabre K, et al. Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery. Ann Rev Pharmacol. 2018;58:65–82.
   Google Scholar
• Miller PG, Shuler ML. Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol Bioeng. 2016 Oct;113(10):2213–2227.
   PubMed Web of Science ®Google Scholar
• Edington CD, Chen WLK, Geishecker E, et al. Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies. Sci Rep. 2018 Mar 14;8(1):4530.
   PubMedGoogle Scholar
• Cho HJ, Kim JE, Kim DD, et al. In vitro-in vivo extrapolation (IVIVE) for predicting human intestinal absorption and first-pass elimination of drugs: principles and applications. Drug Dev Ind Pharm. 2014 Aug;40(8):989–998.
   PubMed Web of Science ®Google Scholar
• Bricks T, Hamon J, Fleury MJ, et al. Investigation of omeprazole and phenacetin first-pass metabolism in humans using a microscale bioreactor and pharmacokinetic models. Biopharm Drug Dispos. 2015 Jul;36(5):275–293.
   PubMed Web of Science ®Google Scholar
• Bricks T, Paullier P, Legendre A, et al. Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. Toxicol In Vitro. 2014 Aug;28(5):885–895.
   PubMed Web of Science ®Google Scholar
• Prot JM, Maciel L, Bricks T, et al. First pass intestinal and liver metabolism of paracetamol in a microfluidic platform coupled with a mathematical modeling as a means of evaluating ADME processes in humans. Biotechnol Bioeng. 2014 Oct;111(10):2027–2040.
   PubMed Web of Science ®Google Scholar
• McAuliffe GJ, Chang JY, Glahn RP, et al. Development of a gastrointestinal tract microscale cell culture analog to predict drug transport. Mol Cell Biomech. 2008 Jun;5(2):119–132.
   PubMedGoogle Scholar
• Mahler GJ, Esch MB, Glahn RP, et al. Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity. Biotechnol Bioeng. 2009 Sep 1;104(1):193–205.
   PubMed Web of Science ®Google Scholar
• Esch MB, Mahler GJ, Stokol T, et al. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip. 2014 Aug 21;14(16):3081–3092.
   PubMed Web of Science ®Google Scholar
• Lee DW, Ha SK, Choi I, et al. 3D gut-liver chip with a PK model for prediction of first-pass metabolism. Biomed Microdevices. 2017 Nov 7;19(4):100.
   PubMed Web of Science ®Google Scholar
• Choe A, Ha SK, Choi I, et al. Microfluidic Gut-liver chip for reproducing the first pass metabolism. Biomed Microdevices. 2017 Mar;19(1):4.
   PubMed Web of Science ®Google Scholar
• Lee H, Kim DS, Ha SK, et al. A pumpless multi-organ-on-a-chip (MOC) combined with a pharmacokinetic-pharmacodynamic (PK-PD) model. Biotechnol Bioeng. 2017 Feb;114(2):432–443.
   PubMed Web of Science ®Google Scholar
• Imura Y, Sato K, Yoshimura E. Micro total bioassay system for ingested substances: assessment of intestinal absorption, hepatic metabolism, and bioactivity. Anal Chem. 2010 Dec 15;82(24):9983–9988.
   PubMed Web of Science ®Google Scholar
• Imura Y, Yoshimura E, Sato K. Micro total bioassay system for oral drugs: evaluation of gastrointestinal degradation, intestinal absorption, hepatic metabolism, and bioactivity. Anal Sci. 2012;28(3):197–199.
   PubMed Web of Science ®Google Scholar
• Kimura H, Ikeda T, Nakayama H, et al. An on-chip small intestine-liver model for pharmacokinetic studies. J Lab Autom. 2015 Jun;20(3):265–273.
   PubMedGoogle Scholar
• Maschmeyer I, Hasenberg T, Jaenicke A, et al. Chip-based human liver-intestine and liver-skin co-cultures–A first step toward systemic repeated dose substance testing in vitro. Eur J Pharm Biopharm. 2015;95(Pt:A):77–87.
   Web of Science ®Google Scholar
• Maschmeyer I, Lorenz AK, Schimek K, et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip. 2015 Jun 21;15(12):2688–2699.
   PubMed Web of Science ®Google Scholar
• Wagner I, Materne EM, Brincker S, et al. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab Chip. 2013 Sep 21;13(18):3538–3547.
   PubMed Web of Science ®Google Scholar
• Materne EM, Ramme AP, Terrasso AP, et al. A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing. J Biotechnol. 2015 Jul 10;205:36–46.
   PubMed Web of Science ®Google Scholar
• Kuhnl J, Tao TP, Brandmair K, et al. Characterization of application scenario-dependent pharmacokinetics and pharmacodynamic properties of permethrin and hyperforin in a dynamic skin and liver multi-organ-chip model. Toxicology. 2020;18:152637.
   Google Scholar
• Lin N, Zhou X, Geng X, et al. Repeated dose multi-drug testing using a microfluidic chip-based coculture of human liver and kidney proximal tubules equivalents. Sci Rep. 2020 Jun 1;10(1):8879.
   PubMed Web of Science ®Google Scholar
• Schimek K, Frentzel S, Luettich K, et al. Human multi-organ chip co-culture of bronchial lung culture and liver spheroids for substance exposure studies. Sci Rep. 2020 May 12;10(1):7865.
   PubMed Web of Science ®Google Scholar
• An F, Qu Y, Luo Y, et al. A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process. Sci Rep. 2016 Apr;28(6):25022.
   Google Scholar
• Vernetti L, Gough A, Baetz N, et al. Functional Coupling of Human Microphysiology Systems: intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle. Sci Rep. 2017 Feb;8(7):42296.
   Google Scholar
• Skardal A, Murphy SV, Devarasetty M, et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep. 2017 Aug 18;7(1):8837.
   PubMedGoogle Scholar
• Rajan SAP, Aleman J, Wan M, et al. Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform. Acta Biomater. 2020 Apr;1(106):124–135.
   Google Scholar
• Oleaga C, Bernabini C, Smith AS, et al. Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep. 2016 Feb;3(6):20030.
   Google Scholar
• Oleaga C, Riu A, Rothemund S, et al. Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system. Biomaterials. 2018;182:176–190.
   PubMed Web of Science ®Google Scholar
• Cp PDM, Carmona-Moran C, Cw M, et al. Microphysiological heart-liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery. Lab Chip. 2020 Feb 21;20(4):749–759.
   PubMed Web of Science ®Google Scholar
• Satoh T, Sugiura S, Shin K, et al. A multi-throughput multi-organ-on-a-chip system on a plate formatted pneumatic pressure-driven medium circulation platform. Lab Chip. 2017 Dec 19;18(1):115–125.
   PubMed Web of Science ®Google Scholar
• Chramiec A, Teles D, Yeager K, et al. Integrated human organ-on-a-chip model for predictive studies of anti-tumor drug efficacy and cardiac safety. Lab Chip. 2020 Nov 24;20(23):4357–4372.
   PubMed Web of Science ®Google Scholar
• Lee J, Mehrotra S, Zare-Eelanjegh E, et al. A Heart-Breast Cancer-on-a-Chip Platform for Disease Modeling and Monitoring of Cardiotoxicity Induced by Cancer Chemotherapy. Small. 2020;23:e2004258.
   Google Scholar
• Sasserath T, Rumsey JW, McAleer CW, et al. Differential Monocyte Actuation in a Three-Organ Functional Innate Immune System-on-a-Chip. Adv Sci (Weinh). 2020 7;Jul(13):2000323.
   Google Scholar
• Essaouiba A, Okitsu T, Kinoshita R, et al. Development of a pancreas-liver organ-on-chip coculture model for organ-to-organ interaction studies. Biochem Eng J. 2020;164:107783.
   Web of Science ®Google Scholar
• Ramme AP, Koenig L, Hasenberg T, et al. Autologous induced pluripotent stem cell-derived four-organ-chip. Future Sci OA. 2019 Sep 10;5(8):FSO413.
   PubMed Web of Science ®Google Scholar
• Ong LJY, Ching T, Chong LH, et al. Self-aligning Tetris-Like (TILE) modular microfluidic platform for mimicking multi-organ interactions. Lab Chip. 2019 Jun 25;19(13):2178–2191.
   PubMed Web of Science ®Google Scholar
• Theobald J, Ma AEM, Kusterer N, et al. In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform. Sci Rep. 2019 Mar 15;9(1):4616.
   PubMedGoogle Scholar
• Hubner J, Raschke M, Rutschle I, et al. Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model. Sci Rep. 2018 Oct 9;8(1):15010.
   PubMedGoogle Scholar
• Bauer S, Wennberg Huldt C, Kanebratt KP, et al. Functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model. Sci Rep. 2017 Nov 6;7(1):14620.
   PubMedGoogle Scholar
• Skardal A, Devarasetty M, Forsythe S, et al. A reductionist metastasis-on-a-chip platform for in vitro tumor progression modeling and drug screening. Biotechnol Bioeng. 2016 Sep;113(9):2020–2032.
   PubMed Web of Science ®Google Scholar
• Xu Z, Li E, Guo Z, et al. Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis. ACS Appl Mater Interfaces. 2016 Oct 5;8(39):25840–25847.
   PubMed Web of Science ®Google Scholar
• Frey O, Misun PM, Fluri DA, et al. Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun. 2014 Jun;30(5):4250.
   Google Scholar
• Sung JH, Wang Y, Shuler ML. Strategies for using mathematical modeling approaches to design and interpret multi-organ microphysiological systems (MPS). APL Bioeng. 2019 Jun;3(2):021501.
   PubMed Web of Science ®Google Scholar
• Abaci HE, Shuler ML. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling. Integr Biol (Camb). 2015 Apr;7(4):383–391.
   PubMed Web of Science ®Google Scholar
• Nestorov I. Whole body pharmacokinetic models. Clin Pharmacokinet. 2003;42(10):883–908.
   PubMed Web of Science ®Google Scholar
• Meibohm B, Derendorf H. Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling. Int J Clin Pharmacol Ther. 1997 Oct;35(10):401–413.
   PubMed Web of Science ®Google Scholar
• Sung JH, Esch MB, Shuler ML. Integration of in silico and in vitro platforms for pharmacokinetic-pharmacodynamic modeling. Expert Opin Drug Metab Toxicol. 2010 Sep;6(9):1063–1081.
   PubMed Web of Science ®Google Scholar
• Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res. 1993 Jul;10(7):1093–1095.
   PubMed Web of Science ®Google Scholar
• Helander HF, Fandriks L. Surface area of the digestive tract - revisited. Scand J Gastroenterol. 2014 Jun;49(6):681–689.
   PubMed Web of Science ®Google Scholar
• West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science. 1997 Apr 4;276(5309):122–126.
   PubMed Web of Science ®Google Scholar
• Vinci B, Murphy E, Iori E, et al. An in vitro model of glucose and lipid metabolism in a multicompartmental bioreactor. Biotechnol J. 2012 Jan;7(1):117–126.
   PubMed Web of Science ®Google Scholar
• Guzzardi MA, Domenici C, Ahluwalia A. Metabolic control through hepatocyte and adipose tissue cross-talk in a multicompartmental modular bioreactor. Tissue Eng Part A. 2011 Jun;17(11–12):1635–1642.
   PubMed Web of Science ®Google Scholar
• Vozzi F, Heinrich JM, Bader A, et al. Connected culture of murine hepatocytes and HUVEC in a multicompartmental bioreactor. Tissue Eng Part A. 2009 Jun;15(6):1291–1299.
   PubMed Web of Science ®Google Scholar
• Sbrana T, Ahluwalia A. Engineering Quasi-Vivo in vitro organ models. Adv Exp Med Biol. 2012;745:138–153.
   PubMed Web of Science ®Google Scholar
• Ucciferri N, Sbrana T, Ahluwalia A. Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism. Front Bioeng Biotechnol. 2014;2:74.
   PubMedGoogle Scholar
• Moraes C, Labuz JM, Leung BM, et al. On being the right size: scaling effects in designing a human-on-a-chip. Integr Biol (Camb). 2013 Sep;5(9):1149–1161.
   PubMed Web of Science ®Google Scholar
• West GB, Woodruff WH, Brown JH. Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals. Proc Natl Acad Sci U S A. 2002 Feb 19;99(Suppl 1):2473–2478.
   PubMedGoogle Scholar
• Labuz JM, Moraes C, Mertz DR, et al. Building an experimental model of the human body with non-physiological parameters. Technology (Singap World Sci). 2017 Mar;5(1):42–59.
   PubMed Web of Science ®Google Scholar
• Wikswo JP, Curtis EL, Eagleton ZE, et al. Scaling and systems biology for integrating multiple organs-on-a-chip. Lab Chip. 2013 Sep 21;13(18):3496–3511.
   PubMed Web of Science ®Google Scholar
• Stokes CL, Cirit M, Lauffenburger DA. Physiome-on-a-Chip: the Challenge of “Scaling” in Design, Operation, and Translation of Microphysiological Systems. CPT Pharmacometrics Syst Pharmacol. 2015 Oct;4(10):559–562.
   PubMedGoogle Scholar
• Ouattara DA, Choi SH, Sakai Y, et al. Kinetic modelling of in vitro cell-based assays to characterize non-specific bindings and ADME processes in a static and a perfused fluidic system. Toxicol Lett. 2011 Sep 10;205(3):310–319.
   PubMed Web of Science ®Google Scholar
• Lee DW, Lee SH, Choi N, et al. Construction of pancreas-muscle-liver microphysiological system (MPS) for reproducing glucose metabolism. Biotechnol Bioeng. 2019 Dec;116(12):3433–3445.
   PubMed Web of Science ®Google Scholar
• Yu J, Na C, Em L, et al. Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): data Interpretation and Multi-MPS Integration. CPT Pharmacometrics Syst Pharmacol. 2015 Oct;4(10):585–594.
   PubMedGoogle Scholar
• Tsamandouras N, Chen WLK, Edington CD, et al. Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies. Aaps J. 2017 Sep;19(5):1499–1512.
   PubMed Web of Science ®Google Scholar
• Maass C, Stokes CL, Griffith LG, et al. Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS). Integr Biol (Camb). 2017 Apr 18;9(4):290–302.
   PubMed Web of Science ®Google Scholar
• Wang X, Cirit M, Wishnok JS, et al. Analysis of an Integrated Human Multiorgan Microphysiological System for Combined Tolcapone Metabolism and Brain Metabolomics. Anal Chem. 2019 Jul 2;91(13):8667–8675.
   PubMed Web of Science ®Google Scholar
• Somayaji MR, Das D, Przekwas A. Computational approaches for modeling and analysis of human-on-chip systems for drug testing and characterization. Drug Discov Today. 2016 Dec;21(12):1859–1862.
   PubMed Web of Science ®Google Scholar
• Herland A, Maoz BM, Das D, et al. Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips. Nat Biomed Eng. 2020 4;Apr(4):421–436.
   Google Scholar
• Novak R, Ingram M, Marquez S, et al. Robotic fluidic coupling and interrogation of multiple vascularized organ chips. Nat Biomed Eng. 2020 4;Apr(4):407–420.
   Google Scholar
• Schurdak M, Vernetti L, Bergenthal L, et al. Applications of the microphysiology systems database for experimental ADME-Tox and disease models. Lab Chip. 2020 Apr 14;20(8):1472–1492.
   PubMed Web of Science ®Google Scholar
• Gough A, Vernetti L, Bergenthal L, et al. The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ Models. Appl In Vitro Toxicol. 2016 Jun 1;2(2):103–117.
   PubMedGoogle Scholar
• Prantil-Baun R, Novak R, Das D, et al. Physiologically Based Pharmacokinetic and Pharmacodynamic Analysis Enabled by Microfluidically Linked Organs-on-Chips. Annu Rev Pharmacol Toxicol. 2018 Jan;6(58):37–64.
   Google Scholar
• Wang YI, Carmona C, Hickman JJ, et al. Multiorgan Microphysiological Systems for Drug Development: strategies, Advances, and Challenges. Adv Healthc Mater. 2018;7:2.
   Web of Science ®Google Scholar
• Mohammed M, Thurgood P, Gilliam C, et al. Studying the Response of Aortic Endothelial Cells under Pulsatile Flow Using a Compact Microfluidic System. Anal Chem. 2019 Sep 17;91(18):12077–12084.
   PubMed Web of Science ®Google Scholar
• Thurgood P, Suarez SA, Chen S, et al. Self-sufficient, low-cost microfluidic pumps utilising reinforced balloons. Lab Chip. 2019 Sep 7;19(17):2885–2896.
   PubMed Web of Science ®Google Scholar
• Zhu JY, Suarez SA, Thurgood P, et al. Reconfigurable, Self-Sufficient Convective Heat Exchanger for Temperature Control of Microfluidic Systems. Anal Chem. 2019 Dec 17;91(24):15784–15790.
   PubMed Web of Science ®Google Scholar
• He X, Wang B, Meng J, et al. How to Prevent Bubbles in Microfluidic Channels. Langmuir. 2021 Feb 16;37(6):2187–2194.
   PubMed Web of Science ®Google Scholar
• Sung JH, Shuler ML. Prevention of air bubble formation in a microfluidic perfusion cell culture system using a microscale bubble trap. Biomed Microdevices. 2009 Aug;11(4):731–738.
   PubMed Web of Science ®Google Scholar