Issue 2, 2022

Intestinal explant barrier chip: long-term intestinal absorption screening in a novel microphysiological system using tissue explants

Abstract

The majority of intestinal in vitro screening models use cell lines that do not reflect the complexity of the human intestinal tract and hence often fail to accurately predict intestinal drug absorption. Tissue explants have intact intestinal architecture and cell type diversity, but show short viability in static conditions. Here, we present a medium throughput microphysiological system, Intestinal Explant Barrier Chip (IEBC), that creates a dynamic microfluidic microenvironment and prolongs tissue viability. Using a snap fit mechanism, we successfully incorporated human and porcine colon tissue explants and studied tissue functionality, integrity and viability for 24 hours. With a proper distinction of transcellular over paracellular transport (ratio >2), tissue functionality was good at early and late timepoints. Low leakage of FITC–dextran and preserved intracellular lactate dehydrogenase levels indicate maintained tissue integrity and viability, respectively. From a selection of low to high permeability drugs, 6 out of 7 properly ranked according to their fraction absorbed. In conclusion, the IEBC is a novel screening platform benefitting from the complexity of tissue explants and the flow in microfluidic chips.

Graphical abstract: Intestinal explant barrier chip: long-term intestinal absorption screening in a novel microphysiological system using tissue explants

Supplementary files

Article information

Article type
Paper
Submitted
27 Jul 2021
Accepted
18 Nov 2021
First published
29 Nov 2021
This article is Open Access
Creative Commons BY-NC license

Lab Chip, 2022,22, 326-342

Intestinal explant barrier chip: long-term intestinal absorption screening in a novel microphysiological system using tissue explants

H. Eslami Amirabadi, J. M. Donkers, E. Wierenga, B. Ingenhut, L. Pieters, L. Stevens, T. Donkers, J. Westerhout, R. Masereeuw, I. Bobeldijk-Pastorova, I. Nooijen and E. van de Steeg, Lab Chip, 2022, 22, 326 DOI: 10.1039/D1LC00669J

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