Numerical investigation of dynamic microorgan devices as drug screening platforms. Part II: Microscale modeling approach and validation

Biotechnology and Bioengineering
Filippos Tourlomousis, Robert C Chang

Abstract

The authors have previously reported a rigorous macroscale modeling approach for an in vitro 3D dynamic microorgan device (DMD). This paper represents the second of a two-part model-based investigation where the effect of microscale (single liver cell-level) shear-mediated mechanotransduction on drug biotransformation is deconstructed. Herein, each cell is explicitly incorporated into the geometric model as single compartmentalized metabolic structures. Each cell's metabolic activity is coupled with the microscale hydrodynamic Wall Shear Stress (WSS) simulated around the cell boundary through a semi-empirical polynomial function as an additional reaction term in the mass transfer equations. Guided by the macroscale model-based hydrodynamics, only 9 cells in 3 representative DMD domains are explicitly modeled. Dynamic and reaction similarity rules based on non-dimensionalization are invoked to correlate the numerical and empirical models, accounting for the substrate time scales. The proposed modeling approach addresses the key challenge of computational cost towards modeling complex large-scale DMD-type system with prohibitively high cell densities. Transient simulations are implemented to extract the drug metabolite profile wi...Continue Reading

References

Jun 17, 1998·Biotechnology Progress·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
Mar 12, 2002·Tissue Engineering·Torsten BlunkLisa E Freed
Jun 14, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nicoline TreijtelJan C H van Eijkeren
Sep 14, 2006·Tissue Engineering·Milica RadisicGordana Vunjak-Novakovic
Feb 12, 2008·Trends in Biotechnology·Dietmar W Hutmacher, Harmeet Singh
Apr 9, 2008·Nature Biotechnology·Todd M SquiresScott R Manalis
Aug 13, 2008·Tissue Engineering. Part a·Jason A Burdick, Gordana Vunjak-Novakovic
Oct 10, 2008·Journal of Cell Science·Christopher S Chen
May 8, 2009·Biotechnology and Bioengineering·Mamatha DevarapalliSundararajan V Madihally
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
Apr 22, 2011·Nature Reviews. Molecular Cell Biology·Christopher C DuFortValerie M Weaver
Jul 19, 2011·Developmental Cell·Jeroen EyckmansChristopher S Chen
Nov 9, 2011·Annals of Biomedical Engineering·Christopher MoraesShuichi Takayama
Nov 19, 2011·Drug Discovery Today·Amir M GhaemmaghamiAli Khademhosseini
Apr 24, 2012·Journal of Pharmacological and Toxicological Methods·Anna GrosbergKevin Kit Parker
May 5, 2012·Lab on a Chip·Dongeun HuhDonald E Ingber
Jul 17, 2012·Journal of Cell Science·Brendon M Baker, Christopher S Chen
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Megan L McCainKevin Kit Parker
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
Apr 11, 2014·Annals of Biomedical Engineering·Jagdeep T PodichettySundararajan V Madihally
Apr 17, 2014·Experimental Biology and Medicine·Elisa Cimetta, Gordana Vunjak-Novakovic
May 14, 2014·Experimental Biology and Medicine·Amanda M ClarkAlan Wells
Jun 11, 2014·Experimental Biology and Medicine·Cindy S ChengGeorge A Truskey
Aug 6, 2014·Nature Biotechnology·Sangeeta N Bhatia, Donald E Ingber
Aug 15, 2014·Biotechnology and Bioengineering·Jagdeep T PodichettySundararajan V Madihally

❮ Previous
Next ❯

Citations

Oct 2, 2019·Frontiers in Bioengineering and Biotechnology·Fatemeh SharifiKeikhosrow Firoozbakhsh
Oct 17, 2017·Annual Review of Pharmacology and Toxicology·Lorna EwartPeter Newham

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.