Development of a villi-like micropatterned porous membrane for intestinal magnesium and calcium uptake studies

Gommers, Lisanne M. M.; Skrzypek, Katarzyna; Bolhuis-Versteeg, Lydia A.M.; Pinckaers, Nicole; Vrijhof, Rob; Wijst, Jenny van der; Baaij, Jeroen H. F. de; Stamatialis, Dimitrios; Hoenderop, Joost G. J.

doi:10.1016/j.actbio.2019.08.041

Cited by 11 publications

(7 citation statements)

References 46 publications

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“… 65 This hypothesis may be in accordance with the literature supporting a negative linear correlation between TEER and the epithelial height in well-differentiated cultures. 45,66,67 Additionally, on day 14 from the cell seeding, when perfused samples showed a better development, the static ones started organizing in cell agglomerations, likely villi prodromes. At this time, we observed small villi-like and multilayer formations in the static samples, in accordance with reports of Caco-2 layer full development around 21 days of culture.…”

Section: Discussionmentioning

confidence: 99%

Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device

Donnaloja,

Izzo,

Campanile

et al. 2023

APL Bioengineering

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We developed an innovative millifluidic organ-on-a-chip device, named MINERVA 2.0, that is optically accessible and suitable to serial connection. In the present work, we evaluated MINERVA 2.0 as millifluidic gut epithelium-on-a-chip by using computational modeling and biological assessment. We also tested MINERVA 2.0 in a serially connected configuration prodromal to address the complexity of multiorgan interaction. Once cultured under perfusion in our device, human gut immortalized Caco-2 epithelial cells were able to survive at least up to 7 days and form a three-dimensional layer with detectable tight junctions (occludin and zonulin-1 positive). Functional layer development was supported by measurable trans-epithelial resistance and FITC-dextran permeability regulation, together with mucin-2 expression. The dynamic culturing led to a specific transcriptomic profile, assessed by RNASeq, with a total of 524 dysregulated transcripts (191 upregulated and 333 downregulated) between static and dynamic condition. Overall, the collected results suggest that our gut-on-a-chip millifluidic model displays key gut epithelium features and, thanks to its modular design, may be the basis to build a customizable multiorgan-on-a-chip platform.

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Section: Discussionmentioning

confidence: 99%

Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device

Donnaloja,

Izzo,

Campanile

et al. 2023

APL Bioengineering

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“…Apart from our approach, there are some other processes for fabricating microstructured 3D porous culture membranes, such as by phase separation micromolding (PSμM), also including microscale curved features, such as by casting and curing of PDMS resin on top of curved and at the same time, on a smaller scale, pillared micromolds, the latter creating the columnar pores . For the fabrication of thin-walled 3D microstructures from porous membranes for cell culture, only a few approaches exist, such as the membrane micro emboss(ing) (MeME) process, which is also a process based on microthermoforming, and a process on the basis of collapsing or draping of porous membranes from partially cross-linked SU-8 over sacrificial silicon microstructures …”

Section: Results and Discussionmentioning

confidence: 99%

3D Lung-on-Chip Model Based on Biomimetically Microcurved Culture Membranes

Baptista

Teixeira

Barata

et al. 2022

ACS Biomater. Sci. Eng.

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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.

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“…3D printing is a serial process with limited throughput, is constrained in design, and can be a costly method for patterning features smaller than 50 μm. − Electrospun mats mimic the fibrous nature of the ECM but exhibit nonuniform cell spreading . Strategies based on techniques like electrochemical etching or laser ablation are complex and not easily accessible, whereas conventional lithographic patterning techniques yield only flat or cuboidal patterns. − Moreover, these techniques are challenging to implement with soft materials that have a stiffness below 10 kPa . Patterning on soft materials is crucial as matrix stiffness is a major effector in cellular functions like proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Hierarchically Curved Gelatin for 3D Biomimetic Cell Culture

Pahapale

Gao

Romer³

et al. 2019

ACS Appl. Bio Mater.

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The stiffness, microcurvature, and meso-curvature of cellular microenvironments can significantly alter cell and tissue function. However, it is challenging to produce in vitro tissue models that feature tunability in shape, stiffness, and curvature simultaneously in a high-throughput and costeffective manner. One of the significant challenges is the fragility of micropatterns in soft and biocompatible hydrogels.Here, we describe an approach that combines reflow photolithography, soft lithography, and strain engineering to create soft anatomically mimetic gelatin cell culture models. The models can be mechanically tuned to have stiffnesses as low as 400 Pa to as high as 50 kPa featuring hierarchical curvature at two length scales: the cellular length scale of 12 to 120 μm, and the mesoscale of 1−4 mm. We characterize the microstructured gels using optical microscopy and rheometry, highlighting tunability in the hierarchical curvature, modulus, and shape. Also, collagenbased gelatin offers high-level biocompatibility and bypasses the need for additional surface modification to enhance cell adhesion. We anticipate that this approach could advance anatomically accurate in vitro 3D cell culture models of relevance to biofabrication, cell biology, and drug screening.

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Development of a villi-like micropatterned porous membrane for intestinal magnesium and calcium uptake studies

Cited by 11 publications

References 46 publications

Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device

Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device

3D Lung-on-Chip Model Based on Biomimetically Microcurved Culture Membranes

Hierarchically Curved Gelatin for 3D Biomimetic Cell Culture

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