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Review

Organ-On-A-Chip: An Emerging Research Platform

, , , & ORCID Icon
Article: 2278236 | Received 21 Apr 2023, Accepted 27 Oct 2023, Published online: 15 Nov 2023

References

  • Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol. 2014;32(8):760–19. doi:10.1038/nbt.2989.
  • Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature. 2014;507(7491):181–89. doi:10.1038/nature13118.
  • Low LA, Mummery C, Berridge BR, Austin CP, Tagle DA. Organs-on-chips: into the next decade. Nat Rev Drug Discov. 2021;20(5):345–61. doi:10.1038/s41573-020-0079-3.
  • Marx U, Akabane T, Andersson TB, Baker E, Beilmann M, Beken S, Brendler-Schwaab S, Cirit M, David R, Dehne EM, et al. Biology-inspired microphysiological systems to advance medicines for patient benefit and animal welfare. ALTEX. 2020;37:365–94. doi:10.14573/altex.2001241.
  • Kim S, Takayama S. Organ-on-a-chip and the kidney. Kidney Res Clin Pract. 2015;34(3):165–69. doi:10.1016/j.krcp.2015.08.001.
  • Kang S, Park SE, Huh DD. Organ-on-a-chip technology for nanoparticle research. Nano Converg. 2021;8(1). doi:10.1186/s40580-021-00270-x.
  • Maoz BM, Herland A, Fitzgerald EA, Grevesse T, Vidoudez C, Pacheco AR, Sheehy SP, Park TE, Dauth S, Mannix R, et al. A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells. Nat Biotechnol. 2018;36(9):865–74. doi:10.1038/nbt.4226.
  • Valverde G, Faria M, Sendino Garví E, Janssen MJ, Masereeuw R, Mihăilă SM. Organs-on-chip technology: a tool to tackle genetic kidney diseases. Pediatr Nephrol. 2022;37(12):2985–96. doi:10.1007/s00467-022-05508-2.
  • Zhao Q, Cole T, Zhang Y, Tang SY. Mechanical strain-enabled reconstitution of dynamic environment in organ-on-a-chip platforms: a review. Micromach (Basel) [Internet]. 2021 [[cited 2023 Oct 19]];12(7):765. doi:10.3390/mi12070765.
  • Zhou J, Niklason LE. Microfluidic artificial “vessels” for dynamic mechanical stimulation of mesenchymal stem cells. Integrative Biol [Internet]. 2012 [Accessed 2023 Oct 19];4(12):1487–97. doi:10.1039/c2ib00171c.
  • Delon LC, Guo Z, Oszmiana A, Chien CC, Gibson R, Prestidge C, Thierry B. A systematic investigation of the effect of the fluid shear stress on caco-2 cells towards the optimization of epithelial organ-on-chip models. Biomater [Internet]. 2019 [Accessed 2023 Oct 19];225:119521–119521. https://europepmc.org/article/MED/31600674.
  • Arik YB, Buijsman W, Loessberg-Zahl J, Cuartas-Vélez C, Veenstra C, Logtenberg S, Grobbink AM, Bergveld P, Gagliardi G, Den Hollander AI, et al. Microfluidic organ-on-a-chip model of the outer blood–retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure. Lab Chip. 2021;21(2):272–83. doi:10.1039/D0LC00639D.
  • Schultze M, Fieß M, Karpowicz N, Gagnon J, Korbman M, Hofstetter M, Neppl S, Cavalieri AL, Komninos Y, Mercouris T, et al. Delay in photoemission. Sci. 2010;328(5986):1658–62. doi:10.1126/science.1189401.
  • Xia Y, Whitesides GM. Soft lithography. Annu Rev Mater Sci. 1998;28(1):153–84. doi:10.1146/annurev.matsci.28.1.153.
  • van Meer BJ, de Vries H, Firth KSA, van Weerd J, Tertoolen LGJ, Karperien HBJ, Jonkheijm P, Denning C, IJzerman AP, Mummery CL. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem Biophys Res Commun. 2017;482(2):323–28. doi:10.1016/j.bbrc.2016.11.062.
  • Toepke MW, Beebe DJ. PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip. 2006;6(12):1484–86. doi:10.1039/b612140c.
  • Jang KJ, Mehr AP, Hamilton GA, McPartlin LA, Chung S, Suh KY, Ingber DE. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integrative Biol (United Kingdom). 2013;5(9):1119–29. doi:10.1039/c3ib40049b.
  • Sontheimer-Phelps A, Hassell BA, Ingber DE. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer. 2019;19(2):65–81. doi:10.1038/s41568-018-0104-6.
  • Tran TTT, Delgado A, Jeong S. Organ-on-a-chip: The future of therapeutic aptamer research? Biochip J. 2021;15(2):109–22. doi:10.1007/s13206-021-00016-1.
  • Bein A, Shin W, Jalili-Firoozinezhad S, Park MH, Sontheimer-Phelps A, Tovaglieri A, Chalkiadaki A, Kim HJ, Ingber DE. Microfluidic organ-on-a-chip models of human intestine. Cellul Molecul Gastroenterol Hepatol CMGH. 2018;5(4):659–68. doi:10.1016/j.jcmgh.2017.12.010.
  • Viravaidya K, Sin A, Shuler ML. Development of a microscale cell culture analog to probe naphthalene toxicity. Biotechnol Prog. 2004;20(1):316–23. doi:10.1021/bp0341996.
  • Jodat YA, Kang MG, Kiaee K, Kim GJ, Martinez AFH, Rosenkranz A, Bae H, Shin SR. Human-derived organ-on-a-chip for personalized drug development. Curr Pharm Des. 2019;24(45):5471–86. doi:10.2174/1381612825666190308150055.
  • Marin TM, de Carvalho Indolfo N, Rocco SA, Basei FL, de Carvalho M, de Almeida Gonçalves K, Pagani E. Acetaminophen absorption and metabolism in an intestine/liver microphysiological system. Chem Biol Interact. 2019;299:59–76. doi:10.1016/j.cbi.2018.11.010.
  • Cipriano M, Schlünder K, Probst C, Linke K, Weiss M, Fischer MJ, Mesch L, Achberger K, Liebau S, Mesquida M, et al. Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs. Commun Biol. 2022;5(1). doi:10.1038/s42003-021-02977-3.
  • Azizipour N, Avazpour R, Rosenzweig DH, Sawan M, Ajji A. Evolution of biochip technology: a review from lab-on-a-chip to organ-on-a-chip. Micro (Basel). 2020;11(6):1–15. doi:10.3390/mi11060599.
  • Zhang B, Radisic M. Organ-on-A-chip devices advance to market. Lab Chip. 2017;17(14):2395–420. doi:10.1039/C6LC01554A.
  • Sosa-Hernández JE, Villalba-Rodríguez AM, Romero-Castillo KD, Aguilar-Aguila-Isaías MA, García-Reyes IE, Hernández-Antonio A, Ahmed I, Sharma A, Parra-Saldívar R, Iqbal HMN. Organs-on-a-chip module: a review from the development and applications perspective. Micromach(Basel). 2018;9(10):536. doi:10.3390/mi9100536.
  • Kim HJ, Huh D, Hamilton G, Ingber DE. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip. 2012;12(12):2165–74. doi:10.1039/c2lc40074j.
  • Zamprogno P, Wüthrich S, Achenbach S, Stucki JD, Hobi N, Schneider-Daum N, Lehr C-M, Huwer H, Geiser T, Schmid RA, et al. Second-generation lung-on-a-chip array with a stretchable biological membrane. doi:10.1101/608919.
  • Ross AE, Belanger MC, Woodroof JF, Pompano RR. Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo. Analyst (Lond). 2017;142(4):649–59. doi:10.1039/C6AN02042A.
  • Rajan SAP, Aleman J, Wan MM, Pourhabibi Zarandi N, Nzou G, Murphy S, Bishop CE, Sadri-Ardekani H, Shupe T, Atala A, et al. Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform. Acta Biomater. 2020;106:124–35. doi:10.1016/j.actbio.2020.02.015.
  • Guo Z, Yang CT, Maritz MF, Wu H, Wilson P, Warkiani ME, Chien CC, Kempson I, Aref AR, Thierry B. Validation of a vasculogenesis microfluidic model for radiobiological studies of the human microvasculature. Adv Materials Technol. 2019 [Accessed 2023 Aug 22];4(4):1800726. doi:10.1002/admt.201800726.
  • Nguyen D-H, Lee E, Alimperti S, Norgard RJ, Wong A, June-Koo Lee J, Eyckmans J, Stanger BZ, Chen CS. A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling. Sci Adv. 2019;5(8). http://advances.sciencemag.org/.
  • Varone A, Nguyen JK, Leng L, Barrile R, Sliz J, Lucchesi C, Wen N, Gravanis A, Hamilton GA, Karalis K, et al. A novel organ-chip system emulates three-dimensional architecture of the human epithelia and the mechanical forces acting on it. Biomater. 2021;275:275. doi:10.1016/j.biomaterials.2021.120957.
  • Ramirez A, Amosu M, Lee P, Maisel K. Microfluidic systems to study tissue barriers to immunotherapy. Drug Deliv Transl Res. 2021;11(6):2414–29. doi:10.1007/s13346-021-01016-2.
  • Pocock K, Delon L, Bala V, Rao S, Priest C, Prestidge CA, Thierry B. Intestine-on-a-chip microfluidic model for efficient in vitro screening of oral chemotherapeutic uptake. ACS Biomater Sci Eng. 2017;3(6):951–59. doi:10.1021/acsbiomaterials.7b00023.
  • Guo Y, Luo R, Wang Y, Deng P, Song T, Zhang M, Wang P, Zhang X, Cui K, Tao T, et al. SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip. Sci Bull (Beijing). 2021;66(8):783–93. doi:10.1016/j.scib.2020.11.015.
  • Villenave R, Wales SQ, Hamkins-Indik T, Papafragkou E, Weaver JC, Ferrante TC, Bahinski A, Elkins CA, Kulka M, Ingber DE, et al. Human gut-on-a-chip supports polarized infection of coxsackie B1 virus in vitro. PloS One. 2017;12(2):12. doi:10.1371/journal.pone.0169412.
  • Gjorevski N, Avignon B, Gérard R, Cabon L, Roth AB, Bscheider M, Moisan A. Neutrophilic infiltration in organ-on-a-chip model of tissue inflammation. Lab Chip. 2020;20(18):3365–74. doi:10.1039/D0LC00417K.
  • Beaurivage C, Naumovska E, Chang YX, Elstak ED, Nicolas A, Wouters H, van Moolenbroek G, Lanz HL, Trietsch SJ, Joore J, et al. Development of a gut-on-a-chip model for high throughput disease modeling and drug discovery. Int J Mol Sci. 2019;20(22):20. doi:10.3390/ijms20225661.
  • Bein A, Shin W, Jalili-Firoozinezhad S, Park MH, Sontheimer-Phelps A, Tovaglieri A, Chalkiadaki A, Kim HJ, Ingber DE. Microfluidic organ-on-a-chip models of human intestine. Cellul Molecul Gastroenterol Hepatol CMGH. 2018;5(4):659–68. doi:10.1016/j.jcmgh.2017.12.010.
  • Beckwitt CH, Clark AM, Wheeler S, Lansing Taylor D, Stolz DB, Griffith L, Wells A. Liver ‘organ on a chip’. Exp Cell Res. 2017;363(1):15–25. doi:10.1016/j.yexcr.2017.12.023.
  • Ebrahimkhani MR, Neiman JAS, Raredon MSB, Hughes DJ, Griffith LG. Bioreactor technologies to support liver function in vitro. Adv Drug Deliv Rev. 2014;69-70:132–57. doi:10.1016/j.addr.2014.02.011.
  • Wang Y, Wang H, Deng P, Chen W, Guo Y, Tao T, Qin J. In situ differentiation and generation of functional liver organoids from human iPscs in a 3D perfusable chip system. Lab Chip. 2018;18(23):3606–16. doi:10.1039/C8LC00869H.
  • Chen WL, Edington C, Suter E, Yu J, Velazquez JJ, Velazquez JG, Shockley M, Large EM, Venkataramanan R, Hughes DJ, et al. Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk. Biotech & Bioengg. 2017;114(11):2648–59. doi:10.1002/bit.26370.
  • Wu G, Wu J, Li Z, Shi S, Wu D, Wang X, Xu H, Liu H, Huang Y, Wang R, et al. Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy. Biodes Manuf. 2022;5(3):437–50. doi:10.1007/s42242-022-00188-1.
  • Kostrzewski T, Cornforth T, Snow SA, Ouro-Gnao L, Rowe C, Large EM, Hughes DJ. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease. World J Gastroenterol. 2017;23(2):204–15. doi:10.3748/wjg.v23.i2.204.
  • Gori M, Simonelli MC, Giannitelli SM, Businaro L, Trombetta M, Rainer A, Gracia-Sancho J. Investigating nonalcoholic fatty liver disease in a liver-on-a-chip microfluidic device. PloS One. 2016;11(7):11. doi:10.1371/journal.pone.0159729.
  • Siwczak F, Cseresnyes Z, Hassan MIA, Aina KO, Carlstedt S, Sigmund A, Groger M, Surewaard BGJ, Werz O, Figge MT, et al. Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based infection model. Biomater. 2022;287:287. doi:10.1016/j.biomaterials.2022.121632.
  • Dhwaj A, Roy N, Jaiswar A, Prabhakar A, Verma D. 3D-printed impedance micropump for continuous perfusion of the sample and nutrient medium integrated with a liver-on-chip prototype. ACS Omega. 2022;7(45):40900–10. doi:10.1021/acsomega.2c03818.
  • Banaeiyan AA, Theobald J, Paukštyte J, Wölfl S, Adiels CB, Goksör M. Design and fabrication of a scalable liver-lobule-on-a-chip microphysiological platform. Biofabricat. 2017;9(1):015014. doi:10.1088/1758-5090/9/1/015014.
  • Vriend J, Nieskens TTG, Vormann MK, van den Berge BT, van den Heuvel A, Russel FGM, Suter-Dick L, Lanz HL, Vulto P, Masereeuw R, et al. Screening of drug-transporter interactions in a 3D microfluidic renal proximal tubule on a chip. AAPS J. 2018;20(5):20. doi:10.1208/s12248-018-0247-0.
  • Schutgens F, Rookmaaker MB, Margaritis T, Rios A, Ammerlaan C, Jansen J, Gijzen L, Vormann M, Vonk A, Viveen M, et al. Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol. 2019;37(3):303–13. doi:10.1038/s41587-019-0048-8.
  • Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T, Bonventre JV, et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods. 2019;16(3):255–62. doi:10.1038/s41592-019-0325-y.
  • Jang KJ, Mehr AP, Hamilton GA, McPartlin LA, Chung S, Suh KY, Ingber DE. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol (Camb) [Internet]. 2013 [Accessed 2023 Aug 24];5(9):1119–29. doi:10.1039/c3ib40049b.
  • Musah S, Dimitrakakis N, Camacho DM, Church GM, Ingber DE. Directed differentiation of human induced pluripotent stem cells into mature kidney podocytes and establishment of a glomerulus chip. Nat Protoc. 2018;13(7):1662–85. doi:10.1038/s41596-018-0007-8.
  • Gold K, Gaharwar AK, Jain A. Emerging trends in multiscale modeling of vascular pathophysiology: organ-on-a-chip and 3D printing. Biomater. 2019;196:2–17. doi:10.1016/j.biomaterials.2018.07.029.
  • Mittal R, Woo FW, Castro CS, Cohen MA, Karanxha J, Mittal J, Chhibber T, Jhaveri VM. Organ-on-chip models: implications in drug discovery and clinical applications. J Cell Physiol. 2019;234(6):8352–80. doi:10.1002/jcp.27729.
  • Oleaga C, Bernabini C, Smith AST, Srinivasan B, Jackson M, McLamb W, Platt V, Bridges R, Cai Y, Santhanam N, et al. Multi-organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep. 2016;6(1):6. doi:10.1038/srep20030.
  • Vatine GD, Barrile R, Workman MJ, Sances S, Barriga BK, Rahnama M, Barthakur S, Kasendra M, Lucchesi C, Kerns J, et al. Human iPSC-derived blood-brain barrier chips enable disease modeling and personalized medicine applications. Cell Stem Cell. 2019;24(6):995–1005.e6. doi:10.1016/j.stem.2019.05.011.
  • Adriani G, Ma D, Pavesi A, Kamm RD, Goh ELK. A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood–brain barrier. Lab Chip. 2017;17(3):448–59. doi:10.1039/C6LC00638H.
  • Sun W, Luo Z, Lee J, Kim HJ, Lee KJ, Tebon P, Feng Y, Dokmeci MR, Sengupta S, Khademhosseini A. Organ-on-a-chip for cancer and immune organs modeling. Adv Health Mater. 2019;8(15). doi:10.1002/adhm.201900754.
  • Irimia D, Wang X. Inflammation-on-a-chip: probing the immune system ex vivo. Trends Biotechnol. 2018;36(9):923–37. doi:10.1016/j.tibtech.2018.03.011.
  • Younis S, Deeba F, Fatima Saeed R, Mothana RA, Ullah R, Faheem M, Javed Q, Blumenberg M. Regulation of cell cycle and differentiation markers by pathogenic, non-pathogenic and opportunistic skin bacteria. Saudi J Biol Sci. 2022;29(3):1717–29. doi:10.1016/j.sjbs.2021.10.058.
  • Kim K, Jeong S, Sung GY. Effect of periodical tensile stimulation on the human skin equivalents by magnetic stretching skin-on-a-chip (MSSC). Biochip J. 2022;16(4):501–14. doi:10.1007/s13206-022-00092-x.
  • Sun S, Jin L, Zheng Y, Zhu J. Modeling human HSV infection via a vascularized immune-competent skin-on-chip platform. Nat Commun. 2022;13(1). doi:10.1038/s41467-022-33114-1.
  • Yu Z, Hao R, Du J, Wu X, Chen X, Zhang Y, Li W, Gu Z, Yang H. A human cornea-on-a-chip for the study of epithelial wound healing by extracellular vesicles. iScience. 2022;25(5):104200. doi:10.1016/j.isci.2022.104200.
  • Lee SH, Jun BH. Advances in dynamic microphysiological organ-on-a-chip: design principle and its biomedical application. J Indus Engg Chem. 2019;71:65–77. doi:10.1016/j.jiec.2018.11.041.
  • Pires De Mello CP, Carmona-Moran C, McAleer CW, Perez J, Coln EA, Long CJ, Oleaga C, Riu A, Note R, Teissier S, et al. Microphysiological heart–liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery. Lab Chip. 2020;20(4):749–59. doi:10.1039/C9LC00861F.
  • Ghanem A, Shuler ML. Combining cell culture analogue reactor designs and PBPK models to probe mechanisms of naphthalene toxicity. Biotechnol Prog. 2000;16(3):334–45. doi:10.1021/bp9901522.
  • Ghanem A, Shuler ML. Characterization of a perfusion reactor utilizing mammalian cells on microcarrier beads. Biotechnol Prog. 2000;16(3):471–79. doi:10.1021/bp000047o.
  • Sin A, Chin KC, Jamil MF, Kostov Y, Rao G, Shuler ML. The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors. Biotechnol Prog. 2004;20(1):338–45. doi:10.1021/bp034077d.
  • Sung JH. Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs. Expert Opin Drug Metab Toxicol. 2021;17(8):969–86. doi:10.1080/17425255.2021.1908996.
  • Lee SH, Sung JH. Organ-on-a-chip technology for reproducing multiorgan physiology. Adv Health Mater. 2018;7(2). doi:10.1002/adhm.201700419.
  • West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Sci. 1997;276(5309):122–26. doi:10.1126/science.276.5309.122.
  • Vinci B, Murphy E, Iori E, Meduri F, Fattori S, Marescotti MC, Castagna M, Avogaro A, Ahluwalia A. An in vitro model of glucose and lipid metabolism in a multicompartmental bioreactor. Biotechnol J. 2012;7(1):117–26. doi:10.1002/biot.201100177.
  • 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;17(11–12):1635–42. doi:10.1089/ten.tea.2010.0541.
  • Sung JH, Srinivasan B, Esch MB, McLamb WT, Bernabini C, Shuler ML, Hickman JJ. Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure. Exp Biol Med (Maywood). 2014;239(9):1225–39. doi:10.1177/1535370214529397.
  • Bricks T, Paullier P, Legendre A, Fleury MJ, Zeller P, Merlier F, Anton PM, Leclerc E. Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. Toxicol In Vitro. 2014;28(5):885–95. doi:10.1016/j.tiv.2014.02.005.
  • Prot JM, Maciel L, Bricks T, Merlier F, Erô Me Cotton J, Paullier P, Ederic F, Bois Y. 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. Biotech & Bioengg. 2014;111(10):2027–40. doi:10.1002/bit.25232.
  • Bricks T, Hamon J, Fleury MJ, Jellali R, Merlier F, Herpe YE, Seyer A, Regimbeau JM, Bois F, Leclerc E. Investigation of omeprazole and phenacetin first-pass metabolism in humans using a microscale bioreactor and pharmacokinetic models. Biopharm Drug Dispos. 2015;36(5):275–93. doi:10.1002/bdd.1940.
  • Mcauliffe GJ, Chang JY, Glahn RP, Shuler ML. Development of a gastrointestinal tract microscale cell culture analog to predict drug transport. Mol Cell Biomech. 2008;5:119–32.
  • Esch MB, Mahler GJ, Stokol T, Shuler ML. 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;14(16):3081–92. doi:10.1039/C4LC00371C.
  • Mahler GJ, Esch MB, Glahn RP, Shuler ML. Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity. Biotechnol Bioeng. 2009;104(1):193–205. doi:10.1002/bit.22366.
  • Sung JH, Shuler ML. A micro cell culture analog (µCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip. 2009;9(10):1385–94. doi:10.1039/b901377f.
  • Kühnl J, Tao TP, Brandmair K, Gerlach S, Rings T, Müller-Vieira U, Przibilla J, Genies C, Jaques-Jamin C, Schepky A, 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. 2021;448:448. doi:10.1016/j.tox.2020.152637.
  • Dehne EM, Hasenberg T, Marx U. The ascendance of microphysiological systems to solve the drug testing dilemma. Future Sci. 2017;3(2):3. doi:10.4155/fsoa-2017-0002.
  • Lee DW, Ha SK, Choi I, Sung JH. 3D gut-liver chip with a PK model for prediction of first-pass metabolism. Biomed Microdevices. 2017;19(4). doi:10.1007/s10544-017-0242-8.
  • Ahn SI, Sei YJ, Park HJ, Kim J, Ryu Y, Choi JJ, Sung HJ, MacDonald TJ, Levey AI, Kim YT. Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms. Nat Commun. 2020;11(1):11. doi:10.1038/s41467-019-13896-7.
  • Koenig L, Ramme AP, Faust D, Mayer M, Flötke T, Gerhartl A, Brachner A, Neuhaus W, Appelt-Menzel A, Metzger M, et al. A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs. Cells. 2022;11(20):11. doi:10.3390/cells11203295.
  • Milani N, Parrott N, Ortiz Franyuti D, Godoy P, Galetin A, Gertz M, Fowler S. Application of a gut–liver-on-a-chip device and mechanistic modelling to the quantitative in vitro pharmacokinetic study of mycophenolate mofetil. Lab Chip. 2022;22(15):2853–68. doi:10.1039/D2LC00276K.
  • Nguyen VVT, Ye S, Gkouzioti V, van Wolferen ME, Yengej FY, Melkert D, Siti S, de Jong B, Besseling PJ, Spee B, et al. A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles. J Of Extracellular Vesicle. 2022;11(11):12280. doi:10.1002/jev2.12280.