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Microfluidic gut-on-a-chip with three-dimensional villi structure

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Abstract

Current in vitro gut models lack physiological relevance, and various approaches have been taken to improve current cell culture models. For example, mimicking the three-dimensional (3D) tissue structure or fluidic environment has been shown to improve the physiological function of gut cells. Here, we incorporated a collagen scaffold that mimics the human intestinal villi into a microfluidic device, thus providing cells with both 3D tissue structure and fluidic shear. We hypothesized that the combined effect of 3D structure and fluidic shear may provide cells with adequate stimulus to induce further differentiation and improve physiological relevance. The physiological function of our ‘3D gut chip’ was assessed by measuring the absorptive permeability of the gut epithelium and activity of representative enzymes, as well as morphological evaluation. Our results suggest that the combination of fluidic stimulus and 3D structure induces further improvement in gut functions. Our work provides insight into the effect of different tissue environment on gut cells.

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References

  • J.W. Allen, S.N. Bhatia, Biotechnol. Bioeng. 82(3), 253–262 (2003)

    Article  Google Scholar 

  • P. Artursson, K. Palm, K. Luthman, Adv. Drug Deliv. Rev. 46(1–3), 27–43 (2001)

    Article  Google Scholar 

  • A. Beduneau, C. Tempesta, S. Fimbel, Y. Pellequer, V. Jannin, F. Demarne, A. Lamprecht, Eur. J. Pharm. Biopharm. 87(2), 290–298 (2014)

    Article  Google Scholar 

  • I. Behrens, P. Stenberg, P. Artursson, T. Kissel, Pharm. Res. 18(8), 1138–1145 (2001)

    Article  Google Scholar 

  • E. Berthier, E.W. Young, D. Beebe, Lab Chip 12(7), 1224–1237 (2012)

    Article  Google Scholar 

  • V. Bieghs, C. Trautwein, Hepatobiliary Surg Nutr. 3(6), 377–385 (2014)

    Google Scholar 

  • M.B. Chen, S. Srigunapalan, A.R. Wheeler, C.A. Simmons, Lab Chip 13(13), 2591–2598 (2013)

    Article  Google Scholar 

  • M. Chi, B. Yi, S. Oh, D.J. Park, J.H. Sung, S. Park, Biomed. Microdevices 17(3), 9966 (2015)

    Article  Google Scholar 

  • A. Choe, S.K. Ha, I. Choi, N. Choi, J.H. Sung, Biomed. Microdevices 19(1), 4 (2017)

    Article  Google Scholar 

  • C.M. Costello, J. Hongpeng, S. Shaffiey, J. Yu, N.K. Jain, D. Hackam, J.C. March, Biotechnol. Bioeng. 111(6), 1222–1232 (2014a)

    Article  Google Scholar 

  • C.M. Costello, R.M. Sorna, Y.L. Goh, I. Cengic, N.K. Jain, J.C. March, Mol. Pharm. 11(7), 2030–2039 (2014b)

    Article  Google Scholar 

  • L.G. van der Flier, H. Clevers, Annu. Rev. Physiol. 71, 241–260 (2009)

    Article  Google Scholar 

  • A. Galetin, J.B. Houston, J. Pharmacol. Exp. Ther. 318(3), 1220–1229 (2006)

    Article  Google Scholar 

  • D. Haller, P. Serrant, G. Peruisseau, C. Bode, W.P. Hammes, E. Schiffrin, S. Blum, Microbiol. Immunol. 46, 195–205 (2002)

    Article  Google Scholar 

  • X. He, D.O. Mishchuk, J. Shah, B.C. Weimer, C.M. Slupsky, Sci Rep. 33, 3416 (2013)

    Article  Google Scholar 

  • M.W. van der Helm, M. Odijk, J.P. Frimat, A.D. van der Meer, J.C. Eijkel, A. van den Berg, L.I. Segerink, Biosens. Bioelectron. 85, 924–929 (2016)

    Article  Google Scholar 

  • K. Hu, H. Shi, J. Zhu, D. Deng, G. Zhou, W. Zhang, Y. Cao, W. Liu, Biomed. Microdevices 12(4), 627–635 (2010)

    Article  Google Scholar 

  • D. Huh, B.D. Matthews, A. Mammoto, M. Montoya-Zavala, H.Y. Hsin, D.E. Ingber, Science 328 (2010)

  • J.D. Huizinga, W.J. Lammers, Am. J. Physiol. Gastrointest. Liver Physiol. 296(1), G1–G8 (2009)

    Article  Google Scholar 

  • E.L. Jackson, H. Lu, Integr Biol (Camb) 8(6), 672–683 (2016)

    Article  Google Scholar 

  • H.J. Kim, D.E. Ingber, Integr Biol (Camb) 5(9), 1130–1140 (2013)

    Article  Google Scholar 

  • H.J. Kim, D. Huh, G. Hamilton, D.E. Ingber, Lab Chip 12(12), 2156–2164 (2012)

    Article  Google Scholar 

  • S.H. Kim, J.W. Lee, I. Choi, Y.C. Kim, J.B. Lee, J.H. Sung, J. Nanosci. Nanotechnol. 13(11), 7220–7228 (2013)

    Article  Google Scholar 

  • S.H. Kim, M. Chi, B. Yi, S.H. Kim, S. Oh, Y. Kim, S. Park, J.H. Sung, Integr Biol (Camb) 6(6), 1222–1232 (2014)

    Google Scholar 

  • J. Kublbeck, J.J. Hakkarainen, A. Petsalo, K.S. Vellonen, A. Tolonen, P. Reponen, M.M. Forsberg, P. Honkakoski, J. Pharm. Sci. 105(2), 941–949 (2016)

    Article  Google Scholar 

  • J. Kuttenberger, E. Polska, B.M. Schaefer, Clin Oral Investig. 17(6), 1547–1555 (2013)

    Article  Google Scholar 

  • M. Leonard, E. Creed, D. Brayden, A.W. Baird, Pharm. Res. 17(10), 1181–1188 (2000)

    Article  Google Scholar 

  • F. Leonard, E.M. Collnot, C.M. Lehr, Mol. Pharm. 7(6), 2103–2119 (2010)

    Article  Google Scholar 

  • T. Li, J.Y. Chiang, Pharmacol. Rev. 66(4), 948–983 (2014)

    Article  Google Scholar 

  • J.H. Lin, M. Chiba, T.A. Baillie, Pharmacol. Rev. 51(2), 135–158 (1999)

    Google Scholar 

  • H.F. Lodish, Molecular cell biology (W.H. Freeman, New York, 2000)

    Google Scholar 

  • T.T. Nieskens, M.J. Wilmer, Eur. J. Pharmacol. 790, 46–56 (2016)

    Article  Google Scholar 

  • G. Noel, N.W. Baetz, J.F. Staab, M. Donowitz, O. Kovbasnjuk, M.F. Pasetti, N.C. Zachos, Sci Rep. 7, 45270 (2017)

    Article  Google Scholar 

  • K.S. Pang, Drug Metab. Dispos. 31(12), 1507–1519 (2003)

    Article  Google Scholar 

  • C. Piana, I. Gull, S. Gerbes, R. Gerdes, C. Mills, J. Samitier, M. Wirth, F. Gabor, Differentiation 75, 308–317 (2007)

    Article  Google Scholar 

  • J.M. Prot, C. Aninat, L. Griscom, F. Razan, C. Brochot, C.G. Guillouzo, C. Legallais, A. Corlu, E. Leclerc, Biotechnol. Bioeng. 108(7), 1704–1715 (2011)

    Article  Google Scholar 

  • J. Pusch, M. Votteler, S. Gohler, J. Engl, M. Hampel, H. Walles, K. Schenke-Layland, Biomaterials 32(30), 7469–7478 (2011)

    Article  Google Scholar 

  • E.M. Quigley, Gastroenterol Hepatol (NY) 9(9), 560–569 (2013)

    Google Scholar 

  • Q. Ramadan, L. Jing, Biomed. Microdevices 18(1), 11 (2016)

    Article  Google Scholar 

  • J. N. Rao, J. Y. Wang (2010). Regulation of Gastrointestinal Mucosal Growth. San Rafael (CA)

  • M. Rousset, Biochimie 68, 1035–1040 (1986)

    Article  Google Scholar 

  • M.T. Salmela, S.L. Pender, M.L. Karjalainen-Lindsberg, P. Puolakkainen, T.T. Macdonald, U. Saarialho-Kere, Scand. J. Gastroenterol. 39(11), 1095–1104 (2004)

    Article  Google Scholar 

  • J.H. Sung, J. Yu, D. Luo, M.L. Shuler, J.C. March, Lab Chip 11(3), 389–392 (2011)

    Article  Google Scholar 

  • J.H. Sung, M.B. Esch, J.M. Prot, C.J. Long, A. Smith, J.J. Hickman, M.L. Shuler, Lab Chip 13(7), 1201–1212 (2013)

    Article  Google Scholar 

  • N. Tobey, W. Heizer, R. Yeh, T.I. Huang, C. Hoffner, Gastroenterology 88(4), 913–926 (1985)

    Article  Google Scholar 

  • Y.S. Torisawa, C.S. Spina, T. Mammoto, A. Mammoto, J.C. Weaver, T. Tat, J.J. Collins, D.E. Ingber, Nat. Methods 11(6), 663–669 (2014)

    Article  Google Scholar 

  • G.J. Tortora, S.R. Grabowski, Principles of anatomy and physiology (HarperCollins College, New York, 1993)

    Google Scholar 

  • M.D. Troutman, D.R. Thakker, Pharm. Res. 20(8), 1200–1209 (2003)

    Article  Google Scholar 

  • V.J. Wacher, J.A. Silverman, Y. Zhang, L.Z. Benet, J. Pharm. Sci. 87(11), 1322–1330 (1998)

    Article  Google Scholar 

  • L. Wang, S.K. Murthy, G.A. Barabino, R.L. Carrier, Biomaterials 31(29), 7586–7598 (2010)

    Article  Google Scholar 

  • Y. Wang, A.A. Ahmad, C.E. Sims, S.T. Magness, N.L. Allbritton, Lab Chip 14(9), 1622–1631 (2014)

    Article  Google Scholar 

  • B.R. Ware, S.R. Khetani, Trends Biotechnol. 8(30), 19343–19352 (2016)

    Google Scholar 

  • J. Yu, S. Peng, D. Luo, J.C. March, Biotechnol. Bioeng. 109(9), 2173–2178 (2012)

    Article  Google Scholar 

  • R. Yumoto, T. Murakami, Y. Nakamoto, R. Hasegawa, J. Nagai, M. Takano, J. Pharmacol. Exp. Ther. 289(1), 149–155 (1999)

    Google Scholar 

  • R. Yumoto, T. Murakami, M. Sanemasa, R. Nasu, J. Nagai, M. Takano, Drug Metab. Dispos. 29(2), 145–151 (2001)

    Google Scholar 

  • Q.Y. Zhang, D. Dunbar, A. Ostrowska, S. Zeisloft, J. Yang, L.S. Kaminsky, Drug Metab. Dispos. 27(7), 804–809 (1999)

    Google Scholar 

  • Y. Zheng, J. Chen, M. Craven, N.W. Choi, S. Totorica, A. Diaz-Santana, P. Kermani, B. Hempstead, C. Fischbach-Teschl, J.A. Lopez, A.D. Stroock, Proc. Natl. Acad. Sci. U. S. A. 109(24), 9342–9347 (2012)

    Article  Google Scholar 

  • J. Zhou, L.E. Niklason, Integr Biol (Camb) 4(12), 1487–1497 (2012)

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical Engineering, Hongik University, Seoul, South Korea

    Kyu-Young Shim, Dongwook Lee & Jong Hwan Sung

  2. School of Mechanical Engineering, Sungkyunkwan University, Suwon, South Korea

    Jeonghun Han & Sungsu Park

  3. Queensland Micro- and Nanotechnology Centre, Griffith University, South East Queensland, QLD, Australia

    Nam-Trung Nguyen

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  1. Kyu-Young Shim
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  2. Dongwook Lee
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  3. Jeonghun Han
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  4. Nam-Trung Nguyen
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  5. Sungsu Park
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  6. Jong Hwan Sung
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Corresponding authors

Correspondence to Sungsu Park or Jong Hwan Sung.

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Shim, KY., Lee, D., Han, J. et al. Microfluidic gut-on-a-chip with three-dimensional villi structure. Biomed Microdevices 19, 37 (2017). https://doi.org/10.1007/s10544-017-0179-y

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