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An in-vitro model for the development of mature bone containing an osteocyte network

Iordachescu, Alexandra (2018)
Ph.D. thesis, University of Birmingham.

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Abstract

Bone tissue continuously adapts to changes in mechanical load. This process can also result in a maladaptive ectopic bone response to mechanical insult, known as heterotopic ossification. The pathological differences at the molecular and structural levels are poorly understood. In vivo models exist but can often be too complex to allow isolation of factors which may stimulate disease progression.
This thesis presents the development of a biologically self-structuring bone culture system using a fibrin gel which self-organises between two calcium phosphate anchors when seeded with cells. These bioinspired wound analogues are seeded with primary femoral periosteal cells - key players in bone repair and a range of pathologies- and develop longitudinally over time, allowing to study the temporal evolution of bone mineral and microstructure in excess of a year.
Raman spectroscopy and XRD revealed that the mineral was hydroxyapatite and associated with collagen, which was organized like the in vivo tissue. The initial stem cell population differentiated to the terminal osteocytic phase, was linked by longitudinal canalicular networks (demonstrated using nanoCT) and remained viable over the year of culture. This work also demonstrated that pharmacological compounds can prevent the progress of ossification, displaying promise for applications in drug screening.

Type of Work:Ph.D. thesis.
Supervisor(s):Grover, Liam and Hulley, Philippa Anne
School/Faculty:Colleges (2008 onwards) > College of Engineering & Physical Sciences
Department:School of Chemical Engineering
Additional Information:

Publications resulting from research:

Iordachescu A, Amin HD, Rankin SM, Williams RL, Yapp C, Bannerman A, Pacureanu A, Addison O, Bullock AN, Hulley PA and Grover LM. An in-vitro model for the development of mature bone containing an osteocyte network. Advanced Biosystems (2017).

http://doi.org/10.1002/adbi.201700156

Iordachescu A, Hulley PA and Grover LM (2017). A novel method for the collection of nanoscopic vesicles from an organotypic culture model. Royal Society of Chemistry Advances (2018).

http://doi.org/10.1039/C7RA12511A

Subjects:QP Physiology
TP Chemical technology
Institution:University of Birmingham
ID Code:8064
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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