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Elucidating the biological role of silicon and designing a delivery system to enhance early bone mineralisation

Birdi, Gurpreet (2014)
Ph.D. thesis, University of Birmingham.

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Abstract

Silicon has been shown to be an important trace element in bone formation and metabolism, and a decrease in silicon in the mammalian diet leads to abnormal bone formation. Consequently, silicon has been incorporated into many biomaterials to enhance bone generation around implants. Despite this, the mechanism of action has still not been elucidated and a therapeutic dosage has not been determined.
In this thesis, the optimum concentration of orthosilicic acid (OSA) to enable cell survival and early mineralisation has been identified. It was noted that a dosage of 5µg/ml of OSA enhanced bone nodule formation. The presence of OSA increased the expression of early osteogenic markers such as osteopontin, osteocalcin and type 1 collagen. In addition, increasing OSA concentration resulted in the development of a collagen fibril network of increasing complexity, up to supraphysiological OSA concentrations when the fibril network became fragmented. It was hypothesised that this may assist with mineral deposition.
A sustained delivery system was also developed using a combination of PLGA and calcium silicate. A sustained dose of orthosilicic acid ideal for cell survival was released from the PLGA micro-particles containing calcium silicate. As well as providing a source of OSA, the presence of the alkaline degradation products of calcium silicate aided in the neutralisation of the acidic degradation products of PLGA, which might enhance cell viability in the local environment. In addition to influencing cell behaviour, the OSA was shown to have a strong interaction with alginate, modifying its properties and preventing degradation. This finding is of importance as the molecules comprising alginate bear a structural resemblance to the glycosaminoglycans that are found in the majority of tissues.

Type of Work:Ph.D. thesis.
Supervisor(s):Grover, Liam
School/Faculty:Colleges (2008 onwards) > College of Engineering & Physical Sciences
Department:School of Chemical Engineering
Subjects:TP Chemical technology
Institution:University of Birmingham
ID Code:5018
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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