TY - JOUR
T1 - 3D Lung-on-Chip Model Based on Biomimetically Microcurved Culture Membranes
AU - Baptista, Danielle
AU - Moreira Teixeira, Liliana
AU - Barata, David
AU - Tahmasebi Birgani, Zeinab
AU - King, Jasia
AU - van Riet, Sander
AU - Pasman, Thijs
AU - Poot, André A.
AU - Stamatialis, Dimitrios
AU - Rottier, Robbert J.
AU - Hiemstra, Pieter S.
AU - Carlier, Aurélie
AU - van Blitterswijk, Clemens
AU - Habibović, Pamela
AU - Giselbrecht, Stefan
AU - Truckenmüller, Roman
N1 - Funding Information:
The following financial support is acknowledged: D. Baptista, S.v.R., T.P., A.A.P., D.S., R.J.R., P.S.H., and R.T., the Lung Foundation Netherlands (project “Microengineered 3D analogues of alveolar tissue for lung regeneration”; no. 6.1.14.010); D. Baptista, L.M.T., and C.v.B., the European Union/Horizon 2020 European Research Council Advanced Grant (project “ORCHESTRATE – Building complex life through self-organization: from organ to organism”; ID 694801); Z.T.B., P.H., S.G., and R.T., the European Union/Interreg Flanders-The Netherlands (project “Biomat on microfluidic chip”, no. 0433); J.K., A.C., S.G., and R.T., RegMed XB (REGenerative MEDicine crossing Borders) powered by Top Sector Life Sciences & Health (Health ∼ Holland); R.J.R. and R.T., The Netherlands Organisation for Health Research and Development (ZonMw)/COVID-19 MKMD Programme (project “Employing a physiological microfluidic lung bioreactor to improve understanding of SARS-CoV2 biology and testing of therapeutics”; no. 114025011); A.C., C.v.B., P.H., S.G., and R.T., the Dutch province of Limburg (program “Limburg INvesteert in haar Kenniseconomie/LINK”; nos. SAS-2014-00837 and SAS-2018-02477); A.C., C.v.B., P.H., S.G., and R.T., The Netherlands Organization for Scientific Research (NWO)/Gravitation program (project “Materials-driven regeneration: Regenerating tissue and organ function with intelligent, life-like materials”; no. 024.003.013).
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/6/13
Y1 - 2022/6/13
N2 - A comparatively straightforward approach to accomplish more physiological realism in organ-on-a-chip (OoC) models is through substrate geometry. There is increasing evidence that the strongly, microscale curved surfaces that epithelial or endothelial cells experience when lining small body lumens, such as the alveoli or blood vessels, impact their behavior. However, the most commonly used cell culture substrates for modeling of these human tissue barriers in OoCs, ion track-etched porous membranes, provide only flat surfaces. Here, we propose a more realistic culture environment for alveolar cells based on biomimetically microcurved track-etched membranes. They recreate the mainly spherical geometry of the cells' native microenvironment. In this feasibility study, the membranes were given the shape of hexagonally arrayed hemispherical microwells by an innovative combination of three-dimensional (3D) microfilm (thermo)forming and ion track technology. Integrated in microfluidic chips, they separated a top from a bottom cell culture chamber. The microcurved membranes were seeded by infusion with primary human alveolar epithelial cells. Despite the pronounced topology, the cells fully lined the alveoli-like microwell structures on the membranes' top side. The confluent curved epithelial cell monolayers could be cultured successfully at the air-liquid interface for 14 days. Similarly, the top and bottom sides of the microcurved membranes were seeded with cells from the Calu-3 lung epithelial cell line and human lung microvascular endothelial cells, respectively. Thereby, the latter lined the interalveolar septum-like interspace between the microwells in a network-type fashion, as in the natural counterpart. The coculture was maintained for 11 days. The presented 3D lung-on-a-chip model might set the stage for other (micro)anatomically inspired membrane-based OoCs in the future.
AB - A comparatively straightforward approach to accomplish more physiological realism in organ-on-a-chip (OoC) models is through substrate geometry. There is increasing evidence that the strongly, microscale curved surfaces that epithelial or endothelial cells experience when lining small body lumens, such as the alveoli or blood vessels, impact their behavior. However, the most commonly used cell culture substrates for modeling of these human tissue barriers in OoCs, ion track-etched porous membranes, provide only flat surfaces. Here, we propose a more realistic culture environment for alveolar cells based on biomimetically microcurved track-etched membranes. They recreate the mainly spherical geometry of the cells' native microenvironment. In this feasibility study, the membranes were given the shape of hexagonally arrayed hemispherical microwells by an innovative combination of three-dimensional (3D) microfilm (thermo)forming and ion track technology. Integrated in microfluidic chips, they separated a top from a bottom cell culture chamber. The microcurved membranes were seeded by infusion with primary human alveolar epithelial cells. Despite the pronounced topology, the cells fully lined the alveoli-like microwell structures on the membranes' top side. The confluent curved epithelial cell monolayers could be cultured successfully at the air-liquid interface for 14 days. Similarly, the top and bottom sides of the microcurved membranes were seeded with cells from the Calu-3 lung epithelial cell line and human lung microvascular endothelial cells, respectively. Thereby, the latter lined the interalveolar septum-like interspace between the microwells in a network-type fashion, as in the natural counterpart. The coculture was maintained for 11 days. The presented 3D lung-on-a-chip model might set the stage for other (micro)anatomically inspired membrane-based OoCs in the future.
KW - Alveolar epithelial cells
KW - Biomimetics
KW - Curvature
KW - Ion track-etched membranes
KW - Microthermoforming
KW - Organ on a chip (OoC)
UR - http://www.scopus.com/inward/record.url?scp=85130035597&partnerID=8YFLogxK
U2 - 10.1021/acsbiomaterials.1c01463
DO - 10.1021/acsbiomaterials.1c01463
M3 - Article
C2 - 35502997
AN - SCOPUS:85130035597
SN - 2373-9878
VL - 8
SP - 2684
EP - 2699
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
IS - 6
ER -