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Osseointegration of Novel Silver-Doped Hydroxyapatite Coated

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Osseointegration of Novel Silver-Doped Hydroxyapatite Coated Osseointegration of novel silver-doped hydroxyapatite coated and acid-etched titanium implants in an ovine model Dasun Abeygoonawardana A thesis in fulfilment of the requirements for the degree of Master of Science Prince of Wales Clinical School Faculty of Medicine March 2017 COPYRIGHT STATEMENT 'I hereby grant the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstract International (this is applicable to doctoral theses only). I have either used no substantial portions of copyright material in my thesis or I have obtained permission to use copyright material; where permission has not been granted I have applied/will apply for a partial restriction of the digital copy of my thesis or dissertation.' Signed . Date AUTHENTICITY STATEMENT 'I certify that the Library deposit digital copy is a direct equivalent of the final officially approved version of my thesis. No emendation of content has occurred and if there are any minor variations in formatting, they are the result of the conversion to digital format.' Signed ..... ............................................................... Date ORIGINALITY STATEMENT 'I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged.' Signed Date Abstract Despite advances in technology and surgical procedures, periprosthetic infection of orthopaedic implants remains a common and costly cause of implant failure and revision. Novel materials and coatings have been developed in an effort to improve implant resistance to the onset of infection, including those utilising the antimicrobial properties of silver ions. The aims of this study were to evaluate the osseointegration of a novel silver-doped hydroxyapatite coating and a second acid-etching process, applied to a titanium implant substrate implanted using a well-established ovine model. The subsequent results from the silver-doped coating could be compared to conventional hydroxyapatite coatings, to evaluate the effect of silver ions upon potential bone ongrowth. In this study, the silver HA coated implants demonstrated significantly higher shear stresses of mechanical pushout when compared to the acid etched implants after 4 weeks and 12 weeks in situ. Similarly, the bone-implant contact percentage was significantly higher for the silver HA coated implants indicating greater osseointegration at both timepoints. When compared to conventional HA coated implants in an identical ovine model, there was no significant difference observed in mechanical pushout or bone- implant contact of the silver HA coated implants. These results indicate that the novel silver-doped HA coating does not adversely affect the osseointegration of titanium implants. Therefore, this represents a viable solution for an antimicrobial implant coating which continues to facilitate effective osseointegration following implantation. ii Table of Contents List of Figures .......................................................................................................... v List of Tables ......................................................................................................... vii Acknowledgements .............................................................................................. viii Chapter 1. Introduction .......................................................................................... 9 1.1 Infection and revision of orthopaedic implants ............................................................ 9 1.2 Economic impact of prosthetic infection .......................................................................... 10 1.3 Mechanisms of prosthetic infection ................................................................................. 11 1.4 Antimicrobial properties of silver ions .............................................................................. 14 1.5 Use of silver in current implant technology ...................................................................... 15 Chapter 2. Method ................................................................................................. 18 2.1 Study Design Summary ..................................................................................................... 18 2.2 Implant Manufacture ........................................................................................................ 19 2.3 Animal Preparation ........................................................................................................... 21 2.4 Cortical Site Implantation ................................................................................................. 21 2.5 Cancellous Site Implantation ............................................................................................ 23 2.6 Post-operative Recovery ................................................................................................... 24 2.7 Harvest and Sample Preparation ...................................................................................... 25 2.8 Mechanical Testing ........................................................................................................... 28 2.9 SEM Sample Preparation .................................................................................................. 30 2.10 SEM Imaging.................................................................................................................... 32 2.11 Histomorphometry ......................................................................................................... 33 2.12 Histology ......................................................................................................................... 34 Chapter 3. Results .................................................................................................. 35 3.1 SEM Coating Characterisation .......................................................................................... 35 3.2 Surgery and Harvest .......................................................................................................... 37 3.3 Radiography ...................................................................................................................... 38 3.4 Mechanical Testing ........................................................................................................... 43 3.5 SEM Imaging...................................................................................................................... 48 3.6 Histomorphometry ........................................................................................................... 48 3.7 Histology Findings ............................................................................................................. 51 iii Chapter 4. Discussion ........................................................................................... 55 4.2 Comparison of results with other ovine model studies .................................................... 57 4.3 Effect of surface topology upon bone ongrowth .............................................................. 61 4.4 Current developments of silver in implants...................................................................... 68 4.4.1 Functionalised HA Coatings ....................................................................................... 68 4.4.2 Silver-doped Strontium coatings................................................................................ 72 4.4.3. Agluna® material ....................................................................................................... 76 4.4.4 PorAg® coating ........................................................................................................... 80 4.5 Silver concentrations of current implants and coatings ................................................... 81 4.6 Ag HA compared to conventional HA ............................................................................... 83 4.7 Study Limitations and Future Studies ............................................................................... 87 Chapter 5. Conclusions ......................................................................................... 90 References ............................................................................................................... 92 Appendix A Histomorphometric Results .......................................................... 97 Results from W2602...............................................................................................................
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