Title
A Theoretical and Experimental Study to Optimize Cell Differentiation in a Novel Intestinal Chip
Author
Langerak, N.
Ahmed, H.M.M.
Li, Y.
Middel, I.R.
eslami Amirabadi, H.
Malda, J.
Masereeuw, R.
van Roij, R.
Publication year
2020
Abstract
Microphysiological systems have potential as test systems in studying the intestinal barrier, in which shear stress is critical for the differentiation of Caco-2 cells into enterocytes. The most commonly used in vitro gut model for intestinal barrier studies is based on trans-well cultures. Albeit useful, these culture systems lack physiological shear stress which is believed to be critical for the differentiation of Caco-2 cells into enterocytes and to form tight monolayers. Conversely, organ-on-chip models have presented themselves as a promising alternative since it provides cells with the required shear stress. To this end, a novel biocompatible 3D-printed microfluidic device was developed. In this device, Caco-2 cells were seeded under physiologically-relevant unidirectional shear stress and compared to cells cultured under gravity-driven flow. Using numerical studies, the flow rate that corresponds to the required shear stress was calculated. Experimental tests were conducted to verify the effect of this on cell differentiation. The experiments clearly showed an enhancement of cell differentiation potential in a unidirectional physiologically-relevant pump-driven flow system (PDFS) as opposed to the simpler bidirectional gravity-driven flow system (GDFS). Additionally, computational modeling of an adapted design confirmed its ability to supply all cells with a more homogeneous shear stress, potentially further enhancing their differentiation. The shear stress in the adapted design can be well-approximated with analytic methods, thus allowing for efficient predictions for all parameter values in the system. The developed novel microfluidic device led to the formation of a tighter monolayer and enhanced functional properties of the differentiated Caco-2 cells, which presents a promising tool for preclinical in vitro testing of drugs in an animal-free platform. © Copyright © 2020 Langerak, Ahmed, Li, Middel, Eslami Amirabadi, Malda, Masereeuw and van Roij.
Subject
3D printing
Gut-on-chip
Numerical computation
3D printers
Biocompatibility
Fluidic devices
Microfluidics
Monolayers
Physiology
Shear flow
Cell differentiation
Computational model
Efficient predictions
Experimental test
Functional properties
Gravity driven flow
Intestinal barriers
Micro-fluidic devices
Shear stress
To reference this document use:
http://resolver.tudelft.nl/uuid:19cf4435-0242-4086-9991-ab34bd6f430f
DOI
https://doi.org/10.3389/fbioe.2020.00763
TNO identifier
878808
ISSN
2296-4185
Source
Frontiers in Bioengineering and Biotechnology, 8 (8)
Document type
article