In these barrier model applications, the track-etched membranes are typically integrated into cell culture inserts/Boyden chambers in multiwell plates, microfluidic chips/OoC devices, or a combination of both. The probably most commonly employed cell culture substrates for in vitro modeling of human tissue barriers, such as the air−blood barrier in the lungs, are ion track-etched porous membranes (26,27) from polycarbonate (PC) or polyethylene terephthalate (PET). (23−25) Epithelial and endothelial cells lining small acinar or tubular body lumens of internal human barrier tissues, such as in the lung alveoli, kidney tubules, or small-diameter blood vessels, experience such strongly, milli- to micrometer-scale curved surfaces. More and more studies evidence that surface curvature with curvature radii in a cell size-near range impacts cell behavior. (21,22) Another microenvironmental factor that is technically comparatively straightforward to implement is, as already indicated, substrate geometry, including substrate topography/topology.
![mouse recorder pro 2 chip mouse recorder pro 2 chip](https://skytechgaming.com/wp-content/themes/skytech_2020/images/keyboard-mouse.png)
This model was followed by others with even more realistic extension/dilation of the culture substrate. (20) The lung on a chip includes cyclic mechanical stretching of its elastic culture membrane through lateral vacuum actuator channels. A prototypic example for this approach again in the lung field and potentially the most popular OoC is the human alveolar−capillary interface mimic of Huh et al. (19) The second approach can be implemented without significantly compromising the robustness of OoCs. An example for such a system in the field of lung research is a biomimetic model of the airways using airway epithelial cells, lung fibroblasts, and microvascular endothelial cells. (18) The first approach means in the first instance complex multicellular (coculture) systems.
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(13−17) The desired and essential physiological realism in OoCs can be accomplished basically by two approaches: (i) correspondingly high biological complexity or (ii) artificially engineered physiologically relevant microenvironments mimicking geometrical, mechanical, or biochemical key aspects of the tissue or organ of interest. (10−12) This includes OoC models of (tissues of) the lung. The presented 3D lung-on-a-chip model might set the stage for other (micro)anatomically inspired membrane-based OoCs in the future.Īn exciting and promising development in the field of in vitro models are organ-on-a-chip (OoC) models.
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The coculture was maintained for 11 days. Thereby, the latter lined the interalveolar septum-like interspace between the microwells in a network-type fashion, as in the natural counterpart. 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. The confluent curved epithelial cell monolayers could be cultured successfully at the air−liquid interface for 14 days. Despite the pronounced topology, the cells fully lined the alveoli-like microwell structures on the membranes’ top side.
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The microcurved membranes were seeded by infusion with primary human alveolar epithelial cells. Integrated in microfluidic chips, they separated a top from a bottom cell culture chamber. 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. They recreate the mainly spherical geometry of the cells’ native microenvironment. Here, we propose a more realistic culture environment for alveolar cells based on biomimetically microcurved track-etched membranes. 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. 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. 1 gmail com txt 2022.A comparatively straightforward approach to accomplish more physiological realism in organ-on-a-chip (OoC) models is through substrate geometry.