Numerical investigation of dynamic microorgan devices as drug screening platforms. Part I: Macroscale modeling approach & validation

Biotechnology and Bioengineering
Filippos Tourlomousis, Robert Chang

Abstract

The dynamic nature of in vitro drug metabolism models demands reliable numerical tools to determine key design parameter values towards high-fidelity cell-based platforms of in vivo drug metabolism. This paper represents the first of a two-part model-based investigation of a 3D dynamic microorgan device (DMD). The prescribed tissue model in this paper is precisely embedded within a DMD by 3D bioprinting hydrogel encapsulated liver cells into a patterned array of microchannels. A perfusing drug substrate is biotransformed by liver cells encapsulated within porous hydrogel walls. Therefore, the free and porous flow regime equations are first solved in tandem to derive the laminar velocity profile and wall shear stresses in the entire shear-mediated flow regime. These equations are then coupled with a convection-diffusion equation and Michaelis-Menten reaction terms, resulting in an effective convection-diffusion-cell kinetics model. A key consideration addressed herein is mechanotransduction where shear stresses on the encapsulated cells alter subcellular liver enzyme reaction rates. Cells are incorporated into the geometric model implicitly (macroscale) as enzyme reaction structures uniformly distributed throughout the DMD lengt...Continue Reading

References

May 30, 1997·Science·C S ChenD E Ingber
Nov 6, 1998·ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs·P KanN Ohshima
Jul 12, 2001·Annual Review of Biomedical Engineering·G M WhitesidesD E Ingber
Jan 19, 2002·Annals of the New York Academy of Sciences·Y G ParkY Ikada
Apr 19, 2005·Biotechnology and Bioengineering·Jaesung ParkArno W Tilles
Jun 14, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nicoline TreijtelJan C H van Eijkeren
Jul 20, 2005·Biomaterials·E LeclercC Legallaisa
Jul 13, 2007·Biotechnology and Bioengineering·Jaesung ParkArno W Tilles
Sep 13, 2007·Biomedical Microdevices·Eric LeclercLaurent Griscom
Feb 12, 2008·Trends in Biotechnology·Dietmar W Hutmacher, Harmeet Singh
Jun 12, 2008·Tissue Engineering. Part C, Methods·Robert ChangWei Sun
Jul 8, 2008·Biomedical Microdevices·Amedeo CarraroCraig Neville
Jun 26, 2010·Science·Dongeun HuhDonald E Ingber
Feb 22, 2011·Tissue Engineering. Part C, Methods·Silvia TruscelloHans Van Oosterwyck
Apr 2, 2011·Nature·Monya Baker
Apr 16, 2011·Biotechnology and Bioengineering·Federico VozziArti Ahluwalia
Jul 19, 2011·Developmental Cell·Jeroen EyckmansChristopher S Chen
Oct 29, 2011·Trends in Cell Biology·Dongeun HuhDonald E Ingber
Nov 2, 2011·Annals of Biomedical Engineering·Vasiliy N Goral, Po Ki Yuen
Nov 9, 2011·Annals of Biomedical Engineering·Christopher MoraesShuichi Takayama
Nov 19, 2011·Drug Discovery Today·Amir M GhaemmaghamiAli Khademhosseini
May 5, 2012·Lab on a Chip·Dongeun HuhDonald E Ingber
Jul 10, 2012·IEEE Transactions on Bio-medical Engineering·X YanX B Chen
Jan 3, 2013·Biotechnology and Bioengineering·Guo-Dong Sean TanHwa Liang Leo
Jul 9, 2013·Enzyme and Microbial Technology·Jungwoo LeeJong Hwan Sung
Jul 16, 2013·Current Opinion in Pharmacology·Seila SelimovićAli Khademhosseini
Sep 4, 2013·BioMed Research International·Nasim Salehi-NikBehrouz Zandieh-Doulabi
Dec 7, 2013·Biotechnology and Bioengineering·Myat Noe HsuHwa Liang Leo
Mar 29, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Linda G GriffithDonna B Stolz
Apr 17, 2014·Experimental Biology and Medicine·Elisa Cimetta, Gordana Vunjak-Novakovic
May 14, 2014·Experimental Biology and Medicine·Amanda M ClarkAlan Wells
Aug 6, 2014·Nature Biotechnology·Sangeeta N Bhatia, Donald E Ingber
Aug 15, 2014·Biotechnology and Bioengineering·Jagdeep T PodichettySundararajan V Madihally
Jan 1, 2014·Hepatology International·Britta BurkhardtAndreas K Nüssler

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Citations

Apr 18, 2016·Drug Discovery Today·Ibrahim T OzbolatVeli Ozbolat
Jun 6, 2020·Biotechnology and Bioengineering·Mohammad R NikmaneshiLance L Munn
Oct 2, 2019·Frontiers in Bioengineering and Biotechnology·Fatemeh SharifiKeikhosrow Firoozbakhsh
May 16, 2020·Frontiers in Bioengineering and Biotechnology·Barbara SchmiegMatthias Franzreb

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