Nosocomial infection, including ventilator-associated pneumonia (VAP) affects more than 1 million people each year. The first step in VAP is colonization of the endotracheal tube; prevention of which has failed using traditional approaches such as antibiotic prophylaxis. This work looks at the development of anti-infective materials capable of resisting bacterial adherence. The strategy centres around the use of biocides (QACs) which target the negatively charged bacterial cell wall, disrupting cell structure and causing death. Chapter 2 examines the incorporation of 3 QACs into PVC via the solvent cast method. The materials resisted colonization but possessed poor mechanical properties. Chapter 3 examines an alternative method of incorporation, hot melt extrusion. The QACs and PVC were stable despite the application of heat but when combined, the QACs catalyzed the degradation of PVC and resulted in materials unsuitable for use in a medical device. Chapter 4 reconsiders the solvent cast method, but with ion pairs formed from quaternary ammonium cations and docusate anion. This produced ionic liquids with improved solubility in PVC, which improved the mechanical properties of the materials. However, the antimicrobial activity of the materials was not equivalent to that of the precursor QACs. Chapter 5 examines an alternate approach to the modification of PVC, by the production of an ultrahydrophobic surface. This did not prevent adherence but the materials showed no bacterial viability in adhered biofilm after 24 hours incubation. This was attributed to transition metals used to roughen the surfaces. Chapter 6 reports a second attempt at the exchange of anion paired with the quaternary ammonium cation, for sulfonate based anions. This produced films which showed improved mechanical properties and reduced bacterial adherence. This reduces the need for additional plasticisers, and these materials are suggested as suitable candidates for anti-infective ET tube biomaterials.

PVC accounts for more than 25% of the plastics used in medical devices, with medical tubing, such as that used in catheters and endotraechal the major applications. PVC is often plasticized using phthalate esters, but this group of plasticizers is environmentally contentious and there is evidence to suggest they are dangerous to human health. Furthermore, medical device-related infections and biofilm formation have been major challenges associated with PVC medical devices. Therefore, a dual functional novel additive having both plasticizing and antimicrobial properties could be a solution to address these problems. Two ionic liquids(ILs, organic liquid salts in room temperature), l-ethylpyridiniurn docusate(IL 1) and tributyJ(2-hydroxyethyl)phosphonium docusate(IL2), were designed and synthesized in the hope they would act as both plasticizer and antimicrobial agent for PVc. The plasticization of these composites was assessed based on a reduction in the glass transition temperature(T g), determined from dynamic mechanical thermal analysis(DMTA), changes in torque data during processing, and static mechanical tensile tests. The antimicrobial efficacy of the ILs and their precursors were evaluated with time-kill assay. The antimicrobial activity of PVC-IL composites were assessed by disc diffusion tests, biofilm formation tests, and examination of biofilm growth on PVC samples using scanning electron microscopy(SEM). The leaching of ILs from PVC was also examined from leaching tests, via a combination of gravimetric measurements, UV - Vis spectrophotometry, FTIR-ATR and DMTA. The results indicated that both ILs exhibited a plasticizing effect on both sets of PVC formulations manifest by reduction in Tg, storage modulus, and torque during processing, but enhanced flexibility measured by increased elongation at break from static tensile tests was only observed for the rigid PVC-IL2 samples. Both ILs, both rigid PVC-IL samples and non-rigid PVC-ILl samples were antimicrobially active against most Gram-positive bacteria, and displayed excellent antibiofilm forming properties. Overall, IL2 was a better plasticizer for PVC than IL 1, and IL 1 was a better antimicrobial agent than IL2. The enhanced antimicrobial effectiveness of IL 1 was related to the greater release of IL 1 from the PVC matrix, observed during leaching tests, and increased surface hydrophilicity, evident from contact angle measurements. FTIR-ATR studies on PVC-IL samples during leaching tests revealed a potential interaction between the docusate anion with the surrounding immersant(PBS). The effect of PVC molecular weight on the release behaviour of ILs was also evident from leaching tests carried out on non-rigid PVC-IL samples containing PVC resins with different molecular weight. The addition of these ILs to PVC also reduced the thermal stability of both rigid and non-rigid PVC. Comparing both ILs with conventional PVC plasticizer, di- octylphthalate(DOP) in both PVC formulations, it was found that although DOP has a slightly higher plasticizing efficiency, the ILs have the advantage of dual functionality, as both plasticizers and antimicrobial agents.

Projection-microstereolithography (PMSL) is an additive manufacturing technique based on the digitally supported and spatially controlled solidification of photopolymers and increasingly investigated as an enabling technique for novel applications in regenerative medicine. To better match the complex requirements defined by these emerging applications in terms of the biocompatibility of the fabricated components and their accuracy at micro scale, the process capabilities of this fabrication method need to be further extended. In this Ph.D. thesis, a methodology is proposed that comprises a set of novel experimental procedures and models to capture and predict the effects of essential but potentially toxic process additives such as photoinitiators and dyes on the output parameters of the process. Furthermore, a metrological concept is presented to assess the dimensional capabilities of this fabrication method by monitoring and predicting the level of accuracy in cylindrical micro-features that are highly relevant to biomedical applications.

This thesis describes the design, implementation and evaluation of a tri-axial in-shoe force measurement system using single element PZT piezoelectric transducers and charge multiplexing system. The system is expected to be applied in the area of clinical gait analysis, where it will provide an effective tool in the diagnosis of foot problems and the evaluation of the efficacy of treatment.A review of methodologies and technologies for the plantar force measurement and their advantages and limitations have been provided. Based upon this review the method of developing a minimal tri-axial force transducer with single piezoelectric element has been proposed.

Electron microscopy and atomic force microscopy can provide structural information on the surface of a membrane and spectroscopic techniques tell us about the structure and dynamics i integral membrane proteins. However none of these techniques relate to what is happenmg in the 5 to 6 nm thick layer under the surface of the membrane. Only reflection methods can provide information about the distribution of materials on the axis perpendicular to the membrane surface (the z-axis). Neutron scattering can discriminate between hydrogen and its isotope deuterium, making neutron reflection a powerfiil tool for dissecting how lipid, protein and solvent relate to one another along the z-axis and providing a method in which certain components can be highhghted or made invisible by choosing the correct solvent contrast. This data helped in the design of new antibody-binding biosensors that have a greater efficiency for antibody binding and greater stability for transportation.

The electro spinning and properties of fibrous webs containing drugs, biomolecules and other potentially therapeutic compounds was studied. Two different technologies were investigated. The first dealt with incorporation and release of compounds including drugs using insoluble electrospun fibres comprised of cellulose acetate. A systematic parameter study was completed for producing electro spun cellulose acetate fibres that were substantially free of bead defects and the effect of different solvent systems and process parameters during electrospinning cellulose acetate were evaluated in respect of mean fibre diameter. A ternary solvent system consisting of AcetonelDimethylacetamide (DMAc) /Methanol (2:1:2) enabled a variety of molecules including L-Tryptophan. Ibuprofen, Nicotine and creatinine to be introduced in to cellulose acetate electrospinning solutions and converted in to fibres. The molecular diffusion kinetics in water of the as-spun electrospun fibres was studied. Using the same electrospinning production platform and solvent system, the research was then extended to investigate the feasibility of a second technology. The molecular imprinting of Cellulose Acetate electrospun fibres was investigated using the metabolite, creatinine as the template molecule. The study was extended to explore the feasibility of molecular-imprinting polysulphone electrospun fibres using the same template molecule. To facilitate this, a new solvent system was developed for electrospinning polysulphone that enabled low temperature solvation of the polymer. Both of technology platforms (molecular loading and molecular-imprinting of electrospun fibres) were relevant to the design of improved therapeutic products for applications in healthcare.

Mouse calvarial organ cultures have been widely utilized for investigating the biologic behaviour of intramembranous bones. This technique can be used to analyze bone both at the tissue and at the cellular level. It also has the ability to isolate local effects from systemic factors. The aim of this study was to establish a mouse calvarial critical size defect (CSD) model for evaluation of biomaterials in vitro.

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