Intestinal explant barrier chip: long-term intestinal absorption screening in a novel microphysiological system using tissue explants. Issue 2 (8th December 2021)

• Record Type: Journal Article
• Authors: Eslami Amirabadi, Hossein; Donkers, Joanne M.; Wierenga, Esmée; Ingenhut, Bastiaan; Pieters, Lisanne; Stevens, Lianne; Donkers, Tim; Westerhout, Joost; Masereeuw, Rosalinde; Bobeldijk-Pastorova, Ivana; Nooijen, Irene; van de Steeg, Evita
• Is Part Of: Lab on a chip. Volume 22:Issue 2(2022)
• Page Start: 326
• Page End: 342
• Publication Date: 2021-12-08
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/d1lc00669j
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : The Intestinal Explant Barrier Chip (IEBC) mechanically fixes human and porcine intestinal tissue explants between an apical and basolateral microchannel and is the first microphysiological system to study intestinal drug absorption ex vivo . 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.