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Molecular mechanism of multiscale aligned mineralisation on uni-directional hydroxyapatite liquid crystals

Chen, Jishizhan; (2023) Molecular mechanism of multiscale aligned mineralisation on uni-directional hydroxyapatite liquid crystals. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Liquid crystalline (LC) arrangement such as bone is a chosen structure in biological evolution1. It can self-assemble into hierarchical long-range-ordered structures with complex biofunctions in organisms. Artificial bone has become a popular resolution for bone defects or fractures. However, there is not sufficient evidence showing how the ordered structure of native bone is generated. Inspired by the natural liquid crystalline organisation of bone, we investigate the role of the LC structure in guiding the proliferation, differentiation, and secretion of cells and its underlying molecular mechanism. A uni-directional (UD) LC phase of hydroxyapatite nanorods (HAp NRs) was developed. Taking advantage of such a self-assembled ordered nanostructure, we investigate the mechanism that controls the growth direction of long-range aligned extracellular matrix (ECM) and calcium deposit formation during the osteogenic differentiation of human bone marrow-derived stem cells (hBMSCs) for the first time. RNA sequencing revealed that the genes COL1A1 and COL4A6 are key regulators, which results in ECM alignment and PI3K-Akt signalling pathway activation. This study shows evidence depicting the mechanism of LC-induced anisotropic calcium deposition at the molecular level, shedding more important insight on bone regeneration. It may also inspire biomimetic artificial bone design and fabrication and studies on more types of biological LC for medical applications in the future.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Molecular mechanism of multiscale aligned mineralisation on uni-directional hydroxyapatite liquid crystals
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10176663
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