Trabecular bone organoids:a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration

Abstract

Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.

Publication DOI: https://doi.org/10.1038/s41526-021-00146-8
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: © 2021, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Funding: The authors would like to thank the National Centre for the Replacement Refinement and Reduction of Animals in Research (NC3Rs) for funding this research through the award of a research grant to A.I (NC/S001859/1), who is the Principal Investigator of this work. The authors would also like to thank the manufacturers of the medical grade ceramic bone (Botiss Biomaterials GmbH via Straumann UK) for providing the clinical particles used in this study.
Uncontrolled Keywords: Biological techniques,biomineralization,chemical engineering,osteoporosis,tissues,Medicine (miscellaneous),Materials Science (miscellaneous),Biochemistry, Genetics and Molecular Biology (miscellaneous),Agricultural and Biological Sciences (miscellaneous),Physics and Astronomy (miscellaneous),Space and Planetary Science
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.nat ... 526-021-00146-8 (Publisher URL)
PURE Output Type: Article
Published Date: 2021-05-21
Accepted Date: 2021-04-25
Authors: Iordachescu, Alexandra
Hughes, Erik A.B.
Joseph, Stephan
Hill, Eric J. (ORCID Profile 0000-0002-9419-1500)
Grover, Liam M.
Metcalfe, Anthony D.

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