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Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture

M.A.M. Vis, Feihu Zhao Orcid Logo, E.S.R. Bodelier, C.M. Bood, J. Bulsink, M. van Doeselaar, H. Eslami Amirabadi, K. Ito, S. Hofmann

Bone, Volume: 173, Start page: 116812

Swansea University Author: Feihu Zhao Orcid Logo

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DOI (Published version): 10.1016/j.bone.2023.116812

Abstract

Healthy bone is maintained by the process of bone remodeling. An unbalance in this process can lead to pathologies such as osteoporosis which are often studied with animal models. However, data from animals have limited power in predicting the results that will be obtained in human clinical trials....

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Published in: Bone
ISSN: 8756-3282
Published: Elsevier BV 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa63546
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In search for alternatives to animal models, human in vitro models are emerging as they address the principle of reduction, refinement, and replacement of animal experiments (3Rs). At the moment, no complete in vitro model for bone-remodeling exists. Microfluidic chips offer great possibilities, particularly because of the dynamic culture options, which are crucial for in vitro bone formation. In this study, a scaffold free, fully human, 3D microfluidic coculture model of bone remodeling is presented. A bone-on-a-chip coculture system was developed in which human mesenchymal stromal cells differentiated into the osteoblastic lineage and self-assembled into scaffold free bone-like tissues with the shape and dimensions of human trabeculae. Human monocytes were able to attach to these tissues and to fuse into multinucleated osteoclast-like cells, establishing the coculture. Computational modeling was used to determine the fluid flow induced shear stress and strain in the formed tissue. Furthermore, a set-up was developed allowing for long-term (35 days) on-chip cell culture with benefits including continuous fluid-flow, low bubble formation risk, easy culture medium exchange inside the incubator and live cell imaging options. 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Eslami</firstname><surname>Amirabadi</surname><order>7</order></author><author><firstname>K.</firstname><surname>Ito</surname><order>8</order></author><author><firstname>S.</firstname><surname>Hofmann</surname><order>9</order></author></authors><documents><document><filename>63546__27627__d7e298533ffb4625919e763f347c54bd.pdf</filename><originalFilename>63546.pdf</originalFilename><uploaded>2023-05-30T09:33:14.5605412</uploaded><type>Output</type><contentLength>6253344</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling v2 63546 2023-05-30 Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture 1c6e79b6edd08c88a8d17a241cd78630 0000-0003-0515-6808 Feihu Zhao Feihu Zhao true false 2023-05-30 MEDE Healthy bone is maintained by the process of bone remodeling. An unbalance in this process can lead to pathologies such as osteoporosis which are often studied with animal models. However, data from animals have limited power in predicting the results that will be obtained in human clinical trials. In search for alternatives to animal models, human in vitro models are emerging as they address the principle of reduction, refinement, and replacement of animal experiments (3Rs). At the moment, no complete in vitro model for bone-remodeling exists. Microfluidic chips offer great possibilities, particularly because of the dynamic culture options, which are crucial for in vitro bone formation. In this study, a scaffold free, fully human, 3D microfluidic coculture model of bone remodeling is presented. A bone-on-a-chip coculture system was developed in which human mesenchymal stromal cells differentiated into the osteoblastic lineage and self-assembled into scaffold free bone-like tissues with the shape and dimensions of human trabeculae. Human monocytes were able to attach to these tissues and to fuse into multinucleated osteoclast-like cells, establishing the coculture. Computational modeling was used to determine the fluid flow induced shear stress and strain in the formed tissue. Furthermore, a set-up was developed allowing for long-term (35 days) on-chip cell culture with benefits including continuous fluid-flow, low bubble formation risk, easy culture medium exchange inside the incubator and live cell imaging options. This on-chip coculture is a crucial advance towards developing in vitro bone remodeling models to facilitate drug testing. Journal Article Bone 173 116812 Elsevier BV 8756-3282 1 8 2023 2023-08-01 10.1016/j.bone.2023.116812 http://dx.doi.org/10.1016/j.bone.2023.116812 COLLEGE NANME Biomedical Engineering COLLEGE CODE MEDE Swansea University This work is part of the research program TTW with project number TTW 016.Vidi.188.021, which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO). 2023-06-13T14:19:59.2207267 2023-05-30T09:30:48.5820368 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering M.A.M. Vis 1 Feihu Zhao 0000-0003-0515-6808 2 E.S.R. Bodelier 3 C.M. Bood 4 J. Bulsink 5 M. van Doeselaar 6 H. Eslami Amirabadi 7 K. Ito 8 S. Hofmann 9 63546__27627__d7e298533ffb4625919e763f347c54bd.pdf 63546.pdf 2023-05-30T09:33:14.5605412 Output 6253344 application/pdf Version of Record true © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) true eng http://creativecommons.org/licenses/by/4.0/
title Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
spellingShingle Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
Feihu Zhao
title_short Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
title_full Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
title_fullStr Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
title_full_unstemmed Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
title_sort Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
author_id_str_mv 1c6e79b6edd08c88a8d17a241cd78630
author_id_fullname_str_mv 1c6e79b6edd08c88a8d17a241cd78630_***_Feihu Zhao
author Feihu Zhao
author2 M.A.M. Vis
Feihu Zhao
E.S.R. Bodelier
C.M. Bood
J. Bulsink
M. van Doeselaar
H. Eslami Amirabadi
K. Ito
S. Hofmann
format Journal article
container_title Bone
container_volume 173
container_start_page 116812
publishDate 2023
institution Swansea University
issn 8756-3282
doi_str_mv 10.1016/j.bone.2023.116812
publisher Elsevier BV
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical Engineering
url http://dx.doi.org/10.1016/j.bone.2023.116812
document_store_str 1
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description Healthy bone is maintained by the process of bone remodeling. An unbalance in this process can lead to pathologies such as osteoporosis which are often studied with animal models. However, data from animals have limited power in predicting the results that will be obtained in human clinical trials. In search for alternatives to animal models, human in vitro models are emerging as they address the principle of reduction, refinement, and replacement of animal experiments (3Rs). At the moment, no complete in vitro model for bone-remodeling exists. Microfluidic chips offer great possibilities, particularly because of the dynamic culture options, which are crucial for in vitro bone formation. In this study, a scaffold free, fully human, 3D microfluidic coculture model of bone remodeling is presented. A bone-on-a-chip coculture system was developed in which human mesenchymal stromal cells differentiated into the osteoblastic lineage and self-assembled into scaffold free bone-like tissues with the shape and dimensions of human trabeculae. Human monocytes were able to attach to these tissues and to fuse into multinucleated osteoclast-like cells, establishing the coculture. Computational modeling was used to determine the fluid flow induced shear stress and strain in the formed tissue. Furthermore, a set-up was developed allowing for long-term (35 days) on-chip cell culture with benefits including continuous fluid-flow, low bubble formation risk, easy culture medium exchange inside the incubator and live cell imaging options. This on-chip coculture is a crucial advance towards developing in vitro bone remodeling models to facilitate drug testing.
published_date 2023-08-01T14:19:57Z
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