Date of Award

2010

Document Type

Doctoral Thesis

Degree Name

Doctor of Philosophy

Department

Biomedical, Manufacturing & Facilities Engineering

First Advisor

Dr. Daniel Boyd

Second Advisor

Dr. Helen O'Shea

Third Advisor

Dr. Keith Bryan

Abstract

Silicate glasses function effectively as bone grafts by stimulating bone regeneration through gene activation. However these materials offer little therapeutic potential for the regeneration of healthy bone in those suffering from metabolic bone diseases such as osteoporosis. Examining the composition-structure-property relationships arising from the incorporation of therapeutic ions such as strontium (Sr) and zinc (Zn) into such glasses in order to allow for healthy bone regeneration and antibacterial efficacy, as well as sodium (Na) to allow for controlled ion release was the objective of this work. Eight calcium-strontium-sodium-zinc-silicate glass compositions were produced, based on incremental additions of Sr and Na. Glasses were characterised using x-ray diffraction (XRD), differential scanning calorimetry (DSC), network connectivity calculations, and magic angle spinning nuclear magnetic resonance spectroscopy (MAS-NMR). Glasses were subsequently sterilised (30kGy y-irradiation) and re-characterised. Comparison of characterisation data pre-and post-irradiation confirmed that sterilisation by this method did not structurally effect the examined glass compositions. Based on the characterisation data, Sr2+and Zn2+ release was quantified over 1, 7 and 30 days, under normal and extreme physiological conditions for six glass compositions, BTllO-BTl 15. The Zn2+ release results at pH 7.4 ranged from 3ppm-19ppm and indicated that under normal physiological conditions, all examined Zn-containing glass compositions may have potential as therapeutic bone grafts, but under extremely acidic physiological conditions, the high Zn2+ levels (124ppm-750ppm) may produce cytotoxic effects. Sr- containing glasses demonstrated Sr2+ release in the range 7.5ppm-3500ppm at pH 7.4 and 88ppm-1280ppm at pH 3, and indicated that all examined glass compositions may have therapeutic potential under both physiological conditions. Based on this therapeutic ion release data, extracts of the three most promising glass compositions, BT110-BT112, incubated over 1, 7 and 30 days were examined using cell culture testing (L929 fibroblasts and MTT assay) and compared to the state-of-the-art glass bone graft Novabone. In general, the results from the viability assay indicated that the experimental groups showed either no difference or significantly increased cell viabilities when compared to the commercial control Novabone, demonstrating the equivalent or even enhanced in vitro compatibility of these glass compositions in relation to a current stateof the art material. The antibacterial activity of zinc-containing BTIIO, BTlll and Novabone was then assessed using five bacterial strains commonly associated with orthopaedic implant infections - Methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis. Pseudomonas aeruginosa and Enterococcus faecalis. The results indicated that both experimental compositions demonstrated antibacterial properties, with the best effects noted against S. epidermidis and P.aeruginosa, and that overall both BTl 10 and BTl 11 demonstrated better antibacterial efficacy than Novabone. The results of this research have established the excellent potential of the examined glass compositions to function as therapeutic, antibacterial bone grafts.

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info:eu-repo/semantics/openAccess

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