Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures

Advanced in vitro models are crucial for studying human airway biology. Our objective was the development and optimization of 3D in vitro models representing diverse airway regions, including deep lung alveolar region. This initiative was aimed at assessing the influence of selective scaffold materi...

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Main Authors: Rasika S Murkar, Cornelia Wiese-Rischke, Tobias Weigel, Sascha Kopp, Heike Walles
Format: Article
Language:English
Published: SAGE Publishing 2025-01-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/20417314241299076
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author Rasika S Murkar
Cornelia Wiese-Rischke
Tobias Weigel
Sascha Kopp
Heike Walles
author_facet Rasika S Murkar
Cornelia Wiese-Rischke
Tobias Weigel
Sascha Kopp
Heike Walles
author_sort Rasika S Murkar
collection DOAJ
description Advanced in vitro models are crucial for studying human airway biology. Our objective was the development and optimization of 3D in vitro models representing diverse airway regions, including deep lung alveolar region. This initiative was aimed at assessing the influence of selective scaffold materials on distinct airway co-culture models. While PET membranes (30 µm thickness) were unsuitable for alveolar models due to their stiffness and relatively high Young’s modulus, a combination of collagenous scaffolds seeded with Calu-3 cells and fibroblasts, showed increased mucus production going from week 1 to week 4 of air lift culture. Meanwhile standard electrospun polymer membrane (50–60 µm thick), which possesses a considerably low modulus of elasticity, offered higher flexibility and supported co-cultures of primary alveolar epithelial (huAEC) and endothelial cells (hEC) in concert with lung biopsy-derived fibroblasts which enhanced maturation of the tissue model. As published, designing human alveolar in vitro models require thin scaffold to mimic the required ultra-thin ECM, in addition to assuring right balanced AT1/AT2 ratio for biomimetic representation. We concluded that co-cultivation of primary/stem cells or cell lines has a higher influence on the function of the airway tissue models than the applied scaffolds.
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publisher SAGE Publishing
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series Journal of Tissue Engineering
spelling doaj-art-7ad48c769fab4dfb9a72ef80ac0cd0b22025-01-30T15:03:27ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-01-011610.1177/20417314241299076Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-culturesRasika S Murkar0Cornelia Wiese-Rischke1Tobias Weigel2Sascha Kopp3Heike Walles4Core Facility Tissue Engineering, Institute of Chemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyUniversity Clinic for Cardiac and Thoracic Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyFraunhofer Translational Center for Regenerative Medicine, Fraunhofer ISC, Wuerzburg, GermanyCore Facility Tissue Engineering, Institute of Chemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyCore Facility Tissue Engineering, Institute of Chemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyAdvanced in vitro models are crucial for studying human airway biology. Our objective was the development and optimization of 3D in vitro models representing diverse airway regions, including deep lung alveolar region. This initiative was aimed at assessing the influence of selective scaffold materials on distinct airway co-culture models. While PET membranes (30 µm thickness) were unsuitable for alveolar models due to their stiffness and relatively high Young’s modulus, a combination of collagenous scaffolds seeded with Calu-3 cells and fibroblasts, showed increased mucus production going from week 1 to week 4 of air lift culture. Meanwhile standard electrospun polymer membrane (50–60 µm thick), which possesses a considerably low modulus of elasticity, offered higher flexibility and supported co-cultures of primary alveolar epithelial (huAEC) and endothelial cells (hEC) in concert with lung biopsy-derived fibroblasts which enhanced maturation of the tissue model. As published, designing human alveolar in vitro models require thin scaffold to mimic the required ultra-thin ECM, in addition to assuring right balanced AT1/AT2 ratio for biomimetic representation. We concluded that co-cultivation of primary/stem cells or cell lines has a higher influence on the function of the airway tissue models than the applied scaffolds.https://doi.org/10.1177/20417314241299076
spellingShingle Rasika S Murkar
Cornelia Wiese-Rischke
Tobias Weigel
Sascha Kopp
Heike Walles
Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures
Journal of Tissue Engineering
title Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures
title_full Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures
title_fullStr Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures
title_full_unstemmed Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures
title_short Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures
title_sort developing human upper lower and deep lung airway models combining different scaffolds and developing complex co cultures
url https://doi.org/10.1177/20417314241299076
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AT tobiasweigel developinghumanupperloweranddeeplungairwaymodelscombiningdifferentscaffoldsanddevelopingcomplexcocultures
AT saschakopp developinghumanupperloweranddeeplungairwaymodelscombiningdifferentscaffoldsanddevelopingcomplexcocultures
AT heikewalles developinghumanupperloweranddeeplungairwaymodelscombiningdifferentscaffoldsanddevelopingcomplexcocultures