Total joint replacement is the most successful method of treating end-stage arthritis. It significantly improves the quality of life and the functional capability of patients suffering from arthritis. Currently an estimated 40,000 total joint arthroplasties are performed each year in the United Kingdom, and over 42% of these are performed in patients younger than 65 years. Poly(methylmethacrylate) bone cement is used to fill the space between the bone and the prosthesis in joint replacements and thus forms a mechanical bond between the two surfaces. The cement layer transfers the load from the prosthesis to the bone and increases the load bearing capacity of the implant-cement-bone system. Surgeons require bone cement to be radiopaque on radiographs in order to monitor the position of the implant after a joint replacement surgery. Therefore heavy metal salts such as barium sulphate and zirconium dioxide are added to bone cement to impart such radiopacity. The addition of these radiopacifiers, however, degrades the mechanical properties of the bone cement due to the lack of chemical bonding between the radiopacifier and the polymer matrix. Barium sulphate is known to adversely affect the mechanical strength and fracture toughness of bone cement. Various studies have also shown that barium sulphate and zirconium dioxide may contribute to the pathological bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation. In this study an organo-bismuth compound, triphenyl bismuth (TPB) has been investigated as a potential radiopaque alternative to barium sulphate in bone cements. The inclusion of TPB has been shown to improve the mechanical properties of bone cement including fracture toughness. Furthermore, it has also been shown to cause less bone resorption, which is usually associated with aseptic loosening in joint replacement.

There are many surgical implanted devices in current use and all are prone to biomaterial-related infections (BRI) associated with staphylococcal biofilm formation. BRI are usually associated with S. epidermidis or S. Aureus and are characterized by treatment failure and chronicity resulting in reoperation, removal of the implant, and loss of function or death. Staphylococcal small colony variants (SCVs) may be generated by exposure to sublethal concentrations of antibiotics or nutrient limitation which may occur in biofilms. Although the characteristics of S. aureus SCVs have been well studied, little information on SCVs of S. epidermidis and their potential role in BRI is currently available. This study was designed to investigate the biochemical and phenotypic characteristics of S. epidermidis SCVs to further identify characteristics which may contribute to their ability to cause these increasingly important infections. Exposure to two to four times the gentamicin MIC led to the emergence of stable S. epidermidis SCVs, and the ability to produce SCVs was strain dependent. These variants were isogenic by PFGE and less immunogenic by western blotting, and SDS-PAGE analysis of whole cell preparations and cell wall fractions showed altered protein profiles when compared to wild type strains. S epidermidis SCVs were resistant to aminoglycosides such as amikacin and/or netilmicin and they were thiamine and/or menadione auxotrophs. Chemiluminescence assays showed a decreased ATP content reflecting the deficiency in electron transport systems which results in a growth rate – all characteristics similar to those of S. aureus SCVs. Analysis of virulence factor production indicated that S. epidermidis SCVs showed increased lipolytic and proteolytic activity when compared to those of S. aureus. Some S. epidermidis SCVs showed phase variation in exopolysaccharide production which enabled them to be more adherent to uncoated plastic -a property that may also be important for the later stages of development of biofilms. Invasion assays demonstrated that some S. epidermidis and S. aureus SCVs were internalised by HUVECs by a receptor-mediated mechanism which differed from that of the wild type strains. Interaction of staphylococci with HUVECs induced cytokine production but SCVs stimulated production of IL1, IL-6 and IL-8 at lower concentrations than their related wild type parents in the first 6 hours of co-incubation. SCVs were also less damaging to the HUVEC cell line after 24 hours when compared to wild type strains. This study supports the suggestion that a switch to the S. epidermidis SCV phenotype could be a mechanism exploited by the wild type strains to facilitate their survival inside the host. The chronicity and increased antibiotic resistance associated with BRI could in part, be explained by the characteristics of SCVs identified in this study. In particular the ability to survive intracellularly combined with reduced immunogenicity and resulting decreased cytokine production, may contribute to persistence of infection. Although SCVs are resistant to some antibiotics, surviving intracellularly may further protect staphylococci from other drugs which are unable to enter mammalian cells. Resistance may be further enhanced for some strains in biofilms where enhanced polysaccharide production may also limit antibiotic access.

The lasting integrity of the bond between bone cement and bone defines the long-term stability of cemented acetabular replacements. Although several studies have been carried out on bone-cement interface at continuum level, micromechanics of the interface has been studied only recently for tensile and shear loading cases. Furthermore, the mechanical and microstructural behaviour of this interface is complex due to the variation in morphology and properties that can arise from a range of factors. In this work in vitro studies of the bone-cement interfacial behaviour under selected loading conditions were carried out using a range of experimental techniques. Damage development in cemented acetabular reconstructs was studied under a combined physiological loading block representative of routine activities in a saline environment. A custom-made environmental chamber was developed to allow testing of acetabular reconstructs in a wet condition for the first time and damage was monitored and detected by scanning at selected loading intervals using micro-focus computed tomography (μCT). Preliminary results showed that, as in dry cases, debonding at the bone-cement interface defined the failure of the cement fixation. However, the combination of mechanical loading and saline environment seems to affect the damage initiation site, drastically reducing the survival lives of the reconstructs. Interfacial behaviour of the bone-cement interface was studied under tensile, shear and mixed-mode loading conditions. Bone-cement coupons were first mechanically tested and then μCT imaged. The influence of the loading angle, the extent of the cement penetration and the failure mechanisms with regard to the loading mode on the interfacial behaviour were examined. Both mechanical testing and post failure morphologies seem to suggest an effect of the loading angle on the failure mechanism of the interface. The micromechanical performance of bone-cement interface under compression was also examined. The samples were tested in step-wise compression using a custom-made micromechanical loading stage within the μCT chamber, and the damage evolution with load was monitored. Results showed that load transfer in bone-cement interface occurred mainly in the bone-cement contact region, resulting in progressively developed deformation due to trabeculae bending and buckling. Compressive and fatigue behaviour of bovine cancellous bone and selected open-cell metallic foams were studied also, and their suitability as bone analogous materials for cemented biomechanical testing was investigated. Whilst the morphological parameters of the foams and the bone appear to be closer, the mechanical properties vary significantly between the foams and the bone. However, despite the apparent differences in their respective properties, the general deformation behaviour is similar across the bone and the foams. Multi-step fatigue tests were carried out to study the deformation behaviour under increasing compressive cyclic stresses. Optical and scanning electron microscopy (SEM) were used to characterise the microstructure of foams and bone prior to and post mechanical testing. The results showed that residual strain accumulation is the predominant driving force leading to failure of foams and bones. Although foams and bone fail by the same mechanism of cyclic creep, the deformation behaviour at the transient region of each step was different for both materials. Preliminary results of foam-cement interface performance under mixed-mode loading conditions are also presented.

Η χρήση της προηγμένης τεχνολογίας για την παροχή υγειονομικής περίθαλψης από απόσταση έχει τη δυνατότητα να είναι μία από τις πιο καθοριστικές ιατρικές επαναστάσεις του 21ου αιώνα. Είναι κοινώς αποδεκτό ότι η σύγχρονη ασύρματη τεχνολογία θα διαδραματίσει σημαντικό ρόλο στην εξέλιξη της προηγμένης τηλεϊατρικής. Η ανάπτυξη των εμφυτεύσιμων ιατρικών συσκευών (IMDs) είναι μία από τις πιο σημαντικές πτυχές για την εγκαθίδρυση ενός τέτοιου προηγμένου συστήματος υγειονομικής περίθαλψης. Σημαντικό στοιχείο των εμφυτεύσιμων συσκευών είναι κεραίες που ενσωματώνονται σε τέτοια συστήματα και επιτρέπουν την ανταλλαγή δεδομένων μεταξύ των εμφυτεύσιμων συσκευών με το εξωτερικό περιβάλλον. Η εν λόγω εργασία έγινε σε συνεργασία με την ερευνητική ομάδα της MediWise Ltd. Η λύση που προτείνεται στην παρούσα εργασία είναι μια βελτιστοποιημένη εμφυτεύσιμη κεραία για ασύρματη δοσιμετρία ακτινοβολίας για χρήση σε ακτινοθεραπεία εξωτερικής δέσμης, που έχει ως στόχο να αναπτυχθεί περαιτέρω στο μέλλον, προκειμένου να παραχθεί ένα εμπορικά βιώσιμο προϊόν. Η διατριβή παρουσιάζει το σχεδιασμό των δύο τύπων των εμφυτεύσιμων δομών κεραίας που είναι πιο κατάλληλα για την ελαχιστοποίηση των διαστάσεων, και επικεντρώνεται στην ανάπτυξη ενός εμφυτεύσιμου σχεδιασμού της κεραίας που είναι μικρότερο από 5 x 5 χιλιοστά σε μέγεθος το οποίο λειτουργεί στα 402 - 405 MHz MICS μπάντα και στην βελτιστοποίηση της επιλεγμένης εμφυτεύσιμης κεραία για εύρος ζώνης, απώλεια επιστροφής, ακτινοβολία, κλπ. και αποσκοπεί στην περαιτέρω σμίκρυνση της κεραίας σε μέγεθος 1 x 1 χιλιοστά. / The use of advanced technology to deliver healthcare from a distance has the potential to be one of the defining medical revolutions of the 21st century. It is commonly recognized that modern wireless technology will play an important role in making advanced telemedicine possible. The development of implantable medical devices (IMDs) is one of the most important aspects towards establishing such an advanced healthcare system. Essential element of implantable devices are antennas embedded in such systems, which enable the exchange of data between implantable devices and external environment. The underlying project was ran in collaboration with MediWise Ltd. The solution proposed in this dissertation is an optimised implantable antenna, for wireless radiation dosimetry for usage within external-beam radiotherapy, which aims to be further developed in the future in order to produce a commercially viable product. The dissertation presents the design of two types of implantable antenna structures that are suitable for miniaturisation, and focuses on the development of an implantable antenna design that is smaller than 5 x 5 mm in size which operates at 402 - 405 MHz MICS band and on the optimization of the chosen implantable antenna for bandwidth, return loss, radiation, etc. and aim to miniaturise further the antenna at 1 x 1 mm in size.