期刊
BIOMATERIALS
卷 85, 期 -, 页码 111-127出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.01.065
关键词
Bilayered; Collagen; Hyaluronate; Epithelium; Co-culture; Respiratory
资金
- Programme for Research in Third Level Institutions Cycle
- European Regional Development Fund, part of the European Union Structural Funds Programme
- European Molecular Biology Organisation (EMBO) [ASTF 567-2014]
- Science Foundation Ireland (SET) [SFI/12/RC/2278]
- European Research Council under the EU [239685]
- European Research Council (ERC) [239685] Funding Source: European Research Council (ERC)
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 12-15 kPa. Crosslinked scaffolds had a compressive modulus of 1.9 kPa and mean pore diameters of 70 mu m and 80 mu m, 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. (C) 2016 Elsevier Ltd. All rights reserved.
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