No description available.

No description available.

No description available.

Introduction: Osteoarthritis (OA) is one of the leading causes of disability, and the knee is the most commonly affected joint in the body. The last resort for treatment of knee OA is Total Knee Replacement (TKR) surgery. Despite numerous advances in prosthetic design, patients do not reach normal function after surgery. Current surgical decisions are made on 2D radiographs and patient interviews. Aims: The aim of this study was to compare knee kinematics pre and post TKR surgery using computer animated images of patient specific models under every day conditions. Methods: 7 subjects were recruited for the study. Subjects underwent 3D gait analysis during 4 every day activities, and medical imaging of the knee joint pre and one month post surgery. A 3D model was created from each of the scans, and the kinematic gait analysis data was used to animate the images. Results: Improvements were seen in range of motion in all 4 activities 1 year post surgery. The preoperative 3D images provide detailed information on the anatomy of the osteoarthritic knee. The postoperative images demonstrate potential future problems associated with the implant. Although not accurate enough to be of clinical use, the animated data can provide a valuable insight into what conditions cause damage to both the osteoarthritic and prosthetic knee joint. As the animated data does not require specialist training to view, the images can be utilised across the fields of health professionals and manufacturing in the assessment and treatment of patients pre and post knee replacement surgery. Future improvements in the collection and processing of data may yield clinically useful data. Conclusion: Although not yet of clinical use, the potential application of 3D animations of the knee joint pre and post surgery is widespread.

No description available.

No description available.

Background: Extracorporeal membrane oxygenation (ECMO) is a treatment used to temporarily replace the function of the heart and/or lungs over an extended period of time to allow for organ recovery. The first successful use of an extracorporeal life support system over an extended period of time was achieved in 1972. Since then ECMO has been responsible for saving the lives of many thousands of patients, particularly in the neonatal population. Despite this technical success, ECMO is associated with high morbidity and mortality rates due to the invasive nature of the treatment and the technical complexity of the system. Complications associated with ECMO can be considered in two categories; patient related and technical complications or failures. These complications include but are not limited to haemolysis, thrombosis and inflammatory response. After extensive review of the medical literature and consideration of ECMO system design requirements it was determined that a miniaturized and integrated system represents a natural evolution of life support technology, addressing the failings of current system designs. Such a system should allow for reduced blood contact surface area, reduce priming volume, increased accessibility of the patient to other treatments and should allow for rapid deployment of the system, which has been shown to be essential in improving patient outcomes. Materials and Methods: The work strategy adopted throughout employed the following steps: concept development, computational design and simulation, physical testing and ultimately animal testing under clinically mimetic conditions. Computational simulation was used as a tool for design optimization and to provide quantitative and qualitative feedback on the performance of the physical prototypes. This allowed the number of design iterations to be reduced minimizing the time and cost associated with an iterative design based strategy. Physical testing was conducted under clinically mimetconditions wherever possible to ensure that the performance of each component and the complete integrated design was satisfactory prior to animal testing. Results: This project has produced a miniaturized blood pump, oxygenator and heat exchange system and corresponding computer models. Physical testing of each component indicated that the designs were capable of achieving acceptable hydrodynamic and haemodynamic performance. These results were verified with the computational models, which showed a close correlation. Testing of the integrated strategy showed that the complete device was capable of meeting the performance requirements of a live animal experiment, producing acceptable levels of oxygen transfer, heat addition and overcoming significant pressure head over an extended period of time. The results of the large animal testing indicated that the miniaturized and integrated design was capable of reliably producing acceptable gas exchange, temperature maintenance and blood flow rate allowing for the successful support of a live animal over an extended period of time. The following are the main achievements of this work; 1) T he use of computational models to reduce the iterative load associated complex device development was confirmed as viable. 2) We were able to utilize an integrated rapid prototyping approach to develop working prototypes of individual components for laboratory testing. 3) There was a clear correlation between the results predicted by computational methods and those obtained in the laboratory. 4) We were able to employ computational design approach to optimizing integration thereby reducing the number of rapid prototypes required for testing. 5) It is possible to produce a fully integrated low foot print, priming volume and blood-material contact surface area EMCO system with adequate performance characteristics suitable for clinical use. 6) The integrated ECMO system was proven computationally and in the lab was compatible with deployment under near clinical conditions.

Vascular disease leading to stenotic or occluded arteries and subsequent ischemia is often treated using bypass grafts. Although autologous material, the preferred source for constructing a bypass graft, often provides a graft with satisfactory patency rates, it is not always available and suitable for use. In these cases synthetic material is often utilised but these rarely produce the patency of autologous material. The causes of their failure are compliance mismatch and thrombus formation. For this reason, polyurethane was studied as a suitable graft material due to its compliant nature and excellent thromboresistance. Investigations into the effect of the material stiffness and potential to allow adsorption of blood-borne proteins were conducted, showing that an optimum combination of the two existed for the migration of vascular tissue onto the graft. As this migration can lead to restenosis and reocclusion of a graft, the ability to control the migration rate could limit the failure of the graft through these processes. The electrospinning technique was utilised to develop a polyurethane processing method for producing fibrous materials which better replicate the geometry of the native vessel than do other materials commonly used. The effect of this fibrous structure was to maintain the differentiated state of the vascular cells resident upon it. This contractile state is consistent with that in which cells are found in a healthy vessel and is the opposite state to that of the synthetic phenotype in which cells are found when on planar surfaces in vitro and in diseased vessels. It therefore follows that the control of the phenotypic state can prevent the dedifferentiation of the cells into the synthetic state, whereupon they form a thickening of the vessel wall which, again, ultimately results in restenosis. Mechanical deformation of these electrospun materials was conducted in a dynamic system, replicating the motion in the vascular system in vivo. The effect of this dynamic system was to further develop the degree to which the cells demonstrated a contractile phenotype. This highlights that the electrospun polyurethane graft material represents a promising alternative to those commonly used, perhaps due to it somewhat recapitulating the topographical and mechanical nature of the native vessel.

A complete understanding of endothelial calcium (Ca²⁺) signalling has been hampered by the inability to directly image the endothelium in arteries exposed to physiological conditions. To date, most studies have been performed in cultured cell models, or in preparations where arteries have been sliced open and flattened out to expose the endothelium to microscopic investigation. Such techniques have provided much useful information, but cannot fully replicate in vivo responses because of the unphysiological arrangements. The focus of the work presented in this thesis is the investigation of endothelial Ca²⁺ signalling in a physiologically relevant model. This thesis describes a novel microscopic imaging system that enables direct visualisation of the endothelium from within the lumen of intact and pressurised arteries. The system incorporates a custom-built, side-viewing imaging probe (consisting of a gradient-index relay lens and an aluminium-coated micro-optical prism), and permits direct visualisation of an area of the endothelium encompassing ~200 cells with subcellular resolution. The system allows arteries to be pressurised within a normal physiological range, and cytosolic Ca²⁺ concentration ([Ca²⁺]i) to be measured in endothelial cells labelled with fluorescent chemical Ca²⁺ indicators. Using this system, the endothelial Ca²⁺ response to haemodynamic stimuli (chemical and mechanical) and its alterations in ageing were investigated. The data indicate that coordinated Ca²⁺ signalling contributes to the physiological endothelial response, and that sustained mechanical stimulation dramatically alters endothelial Ca²⁺ signals. Moreover, endothelial Ca²⁺ signalling is significantly altered in ageing. Histological analysis and computational modelling provide evidence that changes in cell geometry may regulate endothelial Ca²⁺ signalling, and highlight the importance of studying the endothelium in a physiologically relevant model. Furthermore, gradientindex imaging provides parallel access to hundreds of endothelial cells in intact arteries, permitting examination of macroscopic endothelial regulatory functions that are inaccessible by traditional microscopic approaches.

Infection control is a key aspect of wound management strategies. An infected wound results in chemical imbalances in the wound and may lead to prolonged healing times and wound surface degradation. Wound dressings changes may result in damage to healing tissues and an increased risk of infection. This thesis presents details of a measurement system based on sensors that can be placed at the wound-dressing interface and potentially monitor the bacteria in real time. Two systems were developed, one to grow bacteria in suspension and the second to encourage biofilms to grow on the electrode surfaces. Both systems allow the electrical impedance to be measured and were used to evaluate the impedance characteristics of bacterial growth with two sensor materials, silver-silver chloride and carbon. The bacteria Staphylococcus aureus and Staphylococcus epidermidis were selected as species commonly isolated from wounds. The growth of bacteria was confirmed by plate counting methods from the suspensions and by microscopy staining techniques of the biofilms. The impedance data was analysed for discernible differences in the impedance profiles to distinguish the absence and/or presence of bacteria. Equivalent circuit modelling was performed to provide further information on the physical processes occurring within the systems. The main findings were that the impedance profiles of silver-silver chloride sensors in bacterial suspensions could detect the presence of high cell densities. However, the electrodes tended to inhibit the growth of bacteria and also prevented biofilms forming on the electrode surfaces. The Staphylococcus aureus strains adhered to the carbon sensors and in at least one strain the impedance profiles had discernible differences. All the strains with carbon sensors produced noticeable differences in the equivalent circuit model analysis. These results show that there is potential to create a real-time infection monitor for wounds.