Flow-induced mechano-modulation of intestinal permeability on chip

The comprehension of the working principles behind the intestinal transepithelial transport is critical in nutrient and drug development research. Within this framework, microfluidic microphysiological platforms are on the verge of overshadowing traditional in vitro systems due to their accuracy in...

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Main Authors: Raffaele Mennella, Sara Sibilio, Francesco Urciuolo, Giorgia Imparato, Paolo A. Netti
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425005216
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author Raffaele Mennella
Sara Sibilio
Francesco Urciuolo
Giorgia Imparato
Paolo A. Netti
author_facet Raffaele Mennella
Sara Sibilio
Francesco Urciuolo
Giorgia Imparato
Paolo A. Netti
author_sort Raffaele Mennella
collection DOAJ
description The comprehension of the working principles behind the intestinal transepithelial transport is critical in nutrient and drug development research. Within this framework, microfluidic microphysiological platforms are on the verge of overshadowing traditional in vitro systems due to their accuracy in replicating key physiological features of the native tissue. Nevertheless, the effects of fluid mechanical stimuli on the selective permeation characteristics of the gut barrier are still unexplored. This is an indispensable feature for designing more biorelevant organ-on-chip models. Here, an intestine-on-chip platform is conceived to mechanically stimulate cells with three different fluid shear stresses and investigate the relative flow-induced changes of molecule transport alongside the resulting epithelial architecture and barrier functionality. Our results reveal that epithelia grown at lower shears exhibit a ∼1.5 higher and faster paracellular permeability while showing a ∼3 times lower and delayed transcellular uptake compared to layers exposed to higher shear stress. This is corroborated by impedance spectroscopy measurements that display altered tight junctional and bilayer resistance, as well as an increased capacitance of the epithelium in response to variations in mechanical stress within the culture. Taken together, these findings advocate that fluid shear stress can serve as mechano-modulator not only for intestinal transport but also for other epithelial cell lines under physiological circumstances.
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issn 2590-0064
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publishDate 2025-08-01
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spelling doaj-art-2b4c28fea46c4a8a9e0424deead219062025-08-20T03:46:45ZengElsevierMaterials Today Bio2590-00642025-08-013310195110.1016/j.mtbio.2025.101951Flow-induced mechano-modulation of intestinal permeability on chipRaffaele Mennella0Sara Sibilio1Francesco Urciuolo2Giorgia Imparato3Paolo A. Netti4Centre for Advanced Biomaterials for Health Care (IIT@CRIB), Istituto Italiano di Tecnologia, Naples, 80125, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Naples Federico II, Naples, 80125, ItalyCentre for Advanced Biomaterials for Health Care (IIT@CRIB), Istituto Italiano di Tecnologia, Naples, 80125, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Naples Federico II, Naples, 80125, ItalyCentre for Advanced Biomaterials for Health Care (IIT@CRIB), Istituto Italiano di Tecnologia, Naples, 80125, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Naples Federico II, Naples, 80125, Italy; Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, 80125, ItalyCentre for Advanced Biomaterials for Health Care (IIT@CRIB), Istituto Italiano di Tecnologia, Naples, 80125, Italy; Corresponding author.Centre for Advanced Biomaterials for Health Care (IIT@CRIB), Istituto Italiano di Tecnologia, Naples, 80125, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Naples Federico II, Naples, 80125, Italy; Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, 80125, ItalyThe comprehension of the working principles behind the intestinal transepithelial transport is critical in nutrient and drug development research. Within this framework, microfluidic microphysiological platforms are on the verge of overshadowing traditional in vitro systems due to their accuracy in replicating key physiological features of the native tissue. Nevertheless, the effects of fluid mechanical stimuli on the selective permeation characteristics of the gut barrier are still unexplored. This is an indispensable feature for designing more biorelevant organ-on-chip models. Here, an intestine-on-chip platform is conceived to mechanically stimulate cells with three different fluid shear stresses and investigate the relative flow-induced changes of molecule transport alongside the resulting epithelial architecture and barrier functionality. Our results reveal that epithelia grown at lower shears exhibit a ∼1.5 higher and faster paracellular permeability while showing a ∼3 times lower and delayed transcellular uptake compared to layers exposed to higher shear stress. This is corroborated by impedance spectroscopy measurements that display altered tight junctional and bilayer resistance, as well as an increased capacitance of the epithelium in response to variations in mechanical stress within the culture. Taken together, these findings advocate that fluid shear stress can serve as mechano-modulator not only for intestinal transport but also for other epithelial cell lines under physiological circumstances.http://www.sciencedirect.com/science/article/pii/S2590006425005216Gut-on-chipPermeabilityShear stressTEERMicrofluidics
spellingShingle Raffaele Mennella
Sara Sibilio
Francesco Urciuolo
Giorgia Imparato
Paolo A. Netti
Flow-induced mechano-modulation of intestinal permeability on chip
Materials Today Bio
Gut-on-chip
Permeability
Shear stress
TEER
Microfluidics
title Flow-induced mechano-modulation of intestinal permeability on chip
title_full Flow-induced mechano-modulation of intestinal permeability on chip
title_fullStr Flow-induced mechano-modulation of intestinal permeability on chip
title_full_unstemmed Flow-induced mechano-modulation of intestinal permeability on chip
title_short Flow-induced mechano-modulation of intestinal permeability on chip
title_sort flow induced mechano modulation of intestinal permeability on chip
topic Gut-on-chip
Permeability
Shear stress
TEER
Microfluidics
url http://www.sciencedirect.com/science/article/pii/S2590006425005216
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AT francescourciuolo flowinducedmechanomodulationofintestinalpermeabilityonchip
AT giorgiaimparato flowinducedmechanomodulationofintestinalpermeabilityonchip
AT paoloanetti flowinducedmechanomodulationofintestinalpermeabilityonchip