Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa

Mounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrat...

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Authors: Vila, Anna, Torras, Núria, Castaño, Albert G., Garcia-Diaz, Maria, Comelles Pujadas, Jordi, Pérez Berezo, Teresa, Corregidor, Carmen, Castaño Linares, Óscar, Engel, Elisabeth, Fernandez-Majada, Vanesa, Martinez, Elena
Format: article
Status:Versión aceptada para publicación
Publication Date:2019
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/155998
Online Access:https://hdl.handle.net/2445/155998
Access Level:Open access
Keyword:Microfluídica
Mucosa gastrointestinal
Enginyeria de teixits
Microfluidics
Gastrointestinal mucosa
Tissue engineering
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spelling Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosaVila, AnnaTorras, NúriaCastaño, Albert G.Garcia-Diaz, MariaComelles Pujadas, JordiPérez Berezo, TeresaCorregidor, CarmenCastaño Linares, ÓscarEngel, ElisabethFernandez-Majada, VanesaMartinez, ElenaMicrofluídicaMucosa gastrointestinalEnginyeria de teixitsMicrofluidicsGastrointestinal mucosaTissue engineeringMounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrates. These two-dimensional (2D) models lack the cellular and mechanical components of the non-epithelial compartment of the intestinal barrier, the stroma, which are key contributors to the barrier permeability in vivo. Thus, advanced in vitro models approaching the in vivo tissue composition are fundamental to improve precision in drug absorption predictions, to provide a better understanding of the intestinal biology, and to faithfully represent related diseases. Here, we generate photo-crosslinked gelatine methacrylate (GelMA) - poly(ethylene glycol) diacrylate (PEGDA) hydrogel co-networks that provide the required mechanical and biochemical features to mimic both the epithelial and stromal compartments of the intestinal mucosa, i.e., they are soft, cell adhesive and cell-loading friendly, and suitable for long-term culturing. We show that fibroblasts can be embedded in the GelMA-PEGDA hydrogels while epithelial cells can grow on top to form a mature epithelial monolayer that exhibits barrier properties which closely mimic those of the intestinal barrier in vivo, as shown by the physiologically relevant transepithelial electrical resistance (TEER) and permeability values. The presence of fibroblasts in the artificial stroma compartment accelerates the formation of the epithelial monolayer and boosts the recovery of the epithelial integrity upon temporary barrier disruption, demonstrating that our system is capable of successfully reproducing the interaction between different cellular compartments. As such, our hydrogel co-networks offer a technologically simple yet sophisticated approach to produce functional three-dimensional (3D) in vitro models of epithelial barriers with epithelial and stromal cells arranged in a spatially relevant manner and near-physiological functionality.Institute of Physics Pub.2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/155998Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1088/1758-5090/ab5f50Biofabrication, 2019, vol. 12, num. 2https://doi.org/10.1088/1758-5090/ab5f50info:eu-repo/grantAgreement/EC/H2020/647863(c) Institute of Physics Pub., 2019info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1559982026-05-27T06:46:51Z
dc.title.none.fl_str_mv Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
title Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
spellingShingle Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
Vila, Anna
Microfluídica
Mucosa gastrointestinal
Enginyeria de teixits
Microfluidics
Gastrointestinal mucosa
Tissue engineering
title_short Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
title_full Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
title_fullStr Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
title_full_unstemmed Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
title_sort Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa
dc.creator.none.fl_str_mv Vila, Anna
Torras, Núria
Castaño, Albert G.
Garcia-Diaz, Maria
Comelles Pujadas, Jordi
Pérez Berezo, Teresa
Corregidor, Carmen
Castaño Linares, Óscar
Engel, Elisabeth
Fernandez-Majada, Vanesa
Martinez, Elena
author Vila, Anna
author_facet Vila, Anna
Torras, Núria
Castaño, Albert G.
Garcia-Diaz, Maria
Comelles Pujadas, Jordi
Pérez Berezo, Teresa
Corregidor, Carmen
Castaño Linares, Óscar
Engel, Elisabeth
Fernandez-Majada, Vanesa
Martinez, Elena
author_role author
author2 Torras, Núria
Castaño, Albert G.
Garcia-Diaz, Maria
Comelles Pujadas, Jordi
Pérez Berezo, Teresa
Corregidor, Carmen
Castaño Linares, Óscar
Engel, Elisabeth
Fernandez-Majada, Vanesa
Martinez, Elena
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Microfluídica
Mucosa gastrointestinal
Enginyeria de teixits
Microfluidics
Gastrointestinal mucosa
Tissue engineering
topic Microfluídica
Mucosa gastrointestinal
Enginyeria de teixits
Microfluidics
Gastrointestinal mucosa
Tissue engineering
description Mounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrates. These two-dimensional (2D) models lack the cellular and mechanical components of the non-epithelial compartment of the intestinal barrier, the stroma, which are key contributors to the barrier permeability in vivo. Thus, advanced in vitro models approaching the in vivo tissue composition are fundamental to improve precision in drug absorption predictions, to provide a better understanding of the intestinal biology, and to faithfully represent related diseases. Here, we generate photo-crosslinked gelatine methacrylate (GelMA) - poly(ethylene glycol) diacrylate (PEGDA) hydrogel co-networks that provide the required mechanical and biochemical features to mimic both the epithelial and stromal compartments of the intestinal mucosa, i.e., they are soft, cell adhesive and cell-loading friendly, and suitable for long-term culturing. We show that fibroblasts can be embedded in the GelMA-PEGDA hydrogels while epithelial cells can grow on top to form a mature epithelial monolayer that exhibits barrier properties which closely mimic those of the intestinal barrier in vivo, as shown by the physiologically relevant transepithelial electrical resistance (TEER) and permeability values. The presence of fibroblasts in the artificial stroma compartment accelerates the formation of the epithelial monolayer and boosts the recovery of the epithelial integrity upon temporary barrier disruption, demonstrating that our system is capable of successfully reproducing the interaction between different cellular compartments. As such, our hydrogel co-networks offer a technologically simple yet sophisticated approach to produce functional three-dimensional (3D) in vitro models of epithelial barriers with epithelial and stromal cells arranged in a spatially relevant manner and near-physiological functionality.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/155998
url https://hdl.handle.net/2445/155998
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1088/1758-5090/ab5f50
Biofabrication, 2019, vol. 12, num. 2
https://doi.org/10.1088/1758-5090/ab5f50
info:eu-repo/grantAgreement/EC/H2020/647863
dc.rights.none.fl_str_mv (c) Institute of Physics Pub., 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Institute of Physics Pub., 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Institute of Physics Pub.
publisher.none.fl_str_mv Institute of Physics Pub.
dc.source.none.fl_str_mv Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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