O'Leary, Cian and Cavanagh, Brenton and Unger, Ronald E. and Kirkpatrick, C. James and O'Dea, Shirley and O'Brien, Fergal J. and Cryan, Sally-Ann
(2016)
The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold.
Biomaterials, 85.
pp. 111-127.
ISSN 0142-9612
Abstract
Today, chronic respiratory disease is one of the leading causes of mortality globally. Epithelial
dysfunction can play a central role in its pathophysiology. The development of physiologically-representative in vitro model systems using tissue-engineered constructs might improve our understanding of epithelial tissue and disease. This study sought to engineer a bilayered collagen-hyaluronate
(CHyA-B) scaffold for the development of a physiologically-representative 3D in vitro tracheobronchial
epithelial co-culture model. CHyA-B scaffolds were fabricated by integrating a thin film top-layer into a
porous sub-layer with lyophilisation. The film layer firmly connected to the sub-layer with delamination
occurring at stresses of 12e15 kPa. Crosslinked scaffolds had a compressive modulus of 1.9 kPa and mean
pore diameters of 70 mm and 80 mm, depending on the freezing temperature. Histological analysis
showed that the Calu-3 bronchial epithelial cell line attached and grew on CHyA-B with adoption of an
epithelial monolayer on the film layer. Immunofluorescence and qRT-PCR studies demonstrated that the
CHyA-B scaffolds facilitated Calu-3 cell differentiation, with enhanced mucin expression, increased
ciliation and the formation of intercellular tight junctions. Co-culture of Calu-3 cells with Wi38 lung
fibroblasts was achieved on the scaffold to create a submucosal tissue analogue of the upper respiratory
tract, validating CHyA-B as a platform to support co-culture and cellular organisation reminiscent of
in vivo tissue architecture. In summary, this study has demonstrated that CHyA-B is a promising tool for
the development of novel 3D tracheobronchial co-culture in vitro models with the potential to unravel
new pathways in drug discovery and drug delivery.
| Item Type: |
Article
|
| Keywords: |
Bilayered;
Collagen;
Hyaluronate;
Epithelium;
Co-culture;
Respiratory; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
16287 |
| Identification Number: |
https://doi.org/10.1016/j.biomaterials.2016.01.065 |
| Depositing User: |
Dr. Shirley O'Dea
|
| Date Deposited: |
12 Jul 2022 11:37 |
| Journal or Publication Title: |
Biomaterials |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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