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Title: Novel approaches to the development of PMMA bone cement
Author: Ayre, Wayne Nishio
ISNI:       0000 0004 2742 724X
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2013
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With an ageing population on the increase, there is a growing need for more effective treatments to enhance the quality of life of patients. Biomaterials employed in such treatments are therefore required to last longer and function more effectively. A biomaterial of particular interest is polymethyl methacrylate (PMMA) bone cement, which is widely employed in joint replacement surgery. Although this replacement procedure reduces pain and restores joint function, it is associated with a failure rate of approximately 10% after 15 years usually as a consequence of cement functional deterioration. Failure usually requires a complicated revision surgery, which is a burden on both the patient and health care services. This study has therefore applied novel interdisciplinary approaches to the design of PMMA bone cements in an effort to reduce failure in cemented joint replacements. Failure of PMMA bone cements has been previously linked to agglomerations of the radiopacifier employed, which create stress concentrations and initiate cracks. A model cement was therefore developed, with compositional, mechanical, fatigue and rheological properties similar to commercial cements, which enabled two novel radiopacifiers to be tested (anatase TiO2 and yttria-stabilised ZrO2). Regardless of the material employed, agglomerations of the radiopacifiers were found to be a significant problem. Silane treating the radiopacifiers enhanced their dispersion, improving the mechanical and fatigue properties of the cement. Furthermore, anatase TiO2 and silane-treated anatase TiO2 were found to induce hydroxylapatite mineralisation in vitro and enhance the adhesion of MC3T3-E1 osteoblast precursor cells on the surface of the cement. The silane treatment however, was found to decrease the rate of osteoblast proliferation. Ageing effects and moisture uptake in PMMA bone cements were also examined as cement is known to fail predominantly after long periods of use. Ageing cements in isotonic fluid resulted in a maximum moisture uptake of approximately 2%w/w, which was found to induce structural changes over time and caused degradation in the mechanical properties of the cement, potentially contributing to cement failure. A major obstacle with joint replacements is the likelihood of post-operative infections. In an attempt to prevent this, many commercial cements incorporate large amounts of powdered antibiotic to achieve a local therapeutic release. The powdered antibiotic was found to be poorly dispersed and resulted in an uncontrolled initial release from surface agglomerations within the first 6 hours, with potentially sub-inhibitory resistance-inducing levels thereafter. Furthermore, only a small percentage (2-9%) of the antibiotic was released, the commercial cements demonstrated poor bacterial inhibition and incorporating powdered antibiotics was detrimental to the mechanical and fatigue performance of the cement. To overcome these limitations a novel delivery system was developed based on drug-entrapped liposome vesicles. A block co-polymer coating was applied to phospholipid liposomes (100nm diameter) to achieve a uniform dispersion in a commercial bone cement (Palacos R). When antibiotic-loaded liposomes (gentamicin sulphate) were dispersed in the cement, greater levels of antibiotic were released in a more prolonged manner, with enhanced antimicrobial, mechanical, fracture toughness and fatigue properties. Techniques from a variety of disciplines were employed in this study and this inter-disciplinary approach has allowed many features of PMMA bone cement to be investigated. The experiments have offered an insight into cement failure while novel techniques and formulations have been developed, which have the potential to reduce failure and infection in cemented implants and may have wider application in a variety of biomaterials.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General) ; TA Engineering (General). Civil engineering (General)