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Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture
,
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
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© 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/)
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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....
| Published in: | Bone |
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| ISSN: | 8756-3282 |
| Published: |
Elsevier BV
2023
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa63546 |
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| 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. 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. |
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| College: |
Faculty of Science and Engineering |
| Funders: |
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). |
| Start Page: |
116812 |