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Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices

The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to imple...

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Autores principales: Goldstein, Yoel, Spitz, Sarah, Turjeman, Keren, Selinger, Florian, Barenholz, Yechezkel, Ertl, Peter, Benny, Ofra, Bavli, Danny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227399/
https://www.ncbi.nlm.nih.gov/pubmed/34071476
http://dx.doi.org/10.3390/mi12060627
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author Goldstein, Yoel
Spitz, Sarah
Turjeman, Keren
Selinger, Florian
Barenholz, Yechezkel
Ertl, Peter
Benny, Ofra
Bavli, Danny
author_facet Goldstein, Yoel
Spitz, Sarah
Turjeman, Keren
Selinger, Florian
Barenholz, Yechezkel
Ertl, Peter
Benny, Ofra
Bavli, Danny
author_sort Goldstein, Yoel
collection PubMed
description The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units. The device was designed for culturing different tissues in separate compartments by integrating individual pairs of inlets and outlets, thus enabling tissue-specific perfusion rates that facilitate the generation of individual tissue-adapted perfusion profiles. The device allowed tissue crosstalk using microchannel configuration and permeable membranes used as barriers between individual cell culture compartments. Computational fluid dynamics (CFD) simulation confirmed the capability to generate significant differences in shear stress between the two individual culture compartments, each with a selective shear force. In addition, we provide preliminary findings that indicate the feasibility for biological compatibility for cell culture and long-term incubation in 3D-printed wells. Finally, we offer a cost-effective, accessible protocol enabling the design and fabrication of advanced multi-organ-on-a-chip devices.
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spelling pubmed-82273992021-06-26 Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices Goldstein, Yoel Spitz, Sarah Turjeman, Keren Selinger, Florian Barenholz, Yechezkel Ertl, Peter Benny, Ofra Bavli, Danny Micromachines (Basel) Article The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units. The device was designed for culturing different tissues in separate compartments by integrating individual pairs of inlets and outlets, thus enabling tissue-specific perfusion rates that facilitate the generation of individual tissue-adapted perfusion profiles. The device allowed tissue crosstalk using microchannel configuration and permeable membranes used as barriers between individual cell culture compartments. Computational fluid dynamics (CFD) simulation confirmed the capability to generate significant differences in shear stress between the two individual culture compartments, each with a selective shear force. In addition, we provide preliminary findings that indicate the feasibility for biological compatibility for cell culture and long-term incubation in 3D-printed wells. Finally, we offer a cost-effective, accessible protocol enabling the design and fabrication of advanced multi-organ-on-a-chip devices. MDPI 2021-05-28 /pmc/articles/PMC8227399/ /pubmed/34071476 http://dx.doi.org/10.3390/mi12060627 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Goldstein, Yoel
Spitz, Sarah
Turjeman, Keren
Selinger, Florian
Barenholz, Yechezkel
Ertl, Peter
Benny, Ofra
Bavli, Danny
Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices
title Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices
title_full Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices
title_fullStr Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices
title_full_unstemmed Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices
title_short Breaking the Third Wall: Implementing 3D-Printing Techniques to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices
title_sort breaking the third wall: implementing 3d-printing techniques to expand the complexity and abilities of multi-organ-on-a-chip devices
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227399/
https://www.ncbi.nlm.nih.gov/pubmed/34071476
http://dx.doi.org/10.3390/mi12060627
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