Silicones are used to manufacture finger and wrist joints. However these joints have fractured prematurely in vivo. There is a lack of literature on the mechanical properties of silicones. The aim of this thesis was to investigate the viscoelastic and related properties of elastomers such as silicones and polyurethanes (suggested as a possible substitute for silicones in the implants) and to relate the properties to how an implant may perform in vivo. The viscoelastic properties of medical-grade silicones and Elast-Eon\(^{TM}\)3 were found to depend on frequency in compression. Above a certain frequency, the silicones appeared to undergo a transition from the rubbery to the glassy state. There is a danger that this could lead to the creation of fracture surfaces. The viscoelastic properties of the silicones were not significantly affected by the temperature; pre-treatment of specimens had no appreciable effect on the results. When the viscoelastic properties were measured in tension, there was a significant difference between the properties measured in tension and compression. Accelerated aging significantly increased the moduli of Elast-Eon\(^{TM}\)3, which is of some concern. The cross-link densities of the silicones were measured using a solvent swelling technique and the Flory-Rehner equation. The results showed that this method is useful as an approximate model.

Background: Osteoarthritis affects approximately 40% of older adults but molecular mediation of OA pain in the dorsal horn is unexplored clinically. This study explored amino acids and cytokines related to pain signalling and sensitisation to determine whether significant differences existed in their concentration in comparison with pain-free controls after adjustment for age, gender and psychological distress. Method: After ethical approval people having primary hip or knee arthroplasty (OA group) or urological surgery (pain-free controls) were recruited. Pain at rest, (PAR), pain on movement (POM) (0-10 numerical rating scale), and HADS data was collected before aspiration of 2ml sample of CSF. HPLC and multiplex bead array assay was conducted and data explored using ANCOVA and logistic regression. Results: Data from 21 control (75% male) and 59 OA (46% male) participants revealed that HADS, serine, leucine, valine, and TNFα were significantly higher and IL-12 was significantly lower in the OA group. IFNγ was significantly lower in the PAR group. Discussion: This study suggests central sensitisation is involved in OA. Psychological distress is an integral part of the OA experience. Amino acid and cytokine involvement in pain transmission is complex; further work exploring human CSF in painful conditions with clinical follow up is recommended.

The demand for reconstructive orthopaedic implants continues expanding at a reasonable pace as the incidence of fracture injuries and infectious diseases rises. There has been an increase in the clinical need for more effective synthetic bone graft materials due to the drawbacks of autogenous grafts. Since the 1980’s calcium phosphate cements (CPC’s) have attracted a great deal of interest due to their chemical similarities to natural bone; chemical, physical and mechanical characteristics have been investigated and manipulated to maximise osteoconductivity and osteointegration of these CPC’s since the start of their commercialisation. Here in this thesis, a series of investigation are complied to demonstrate novel and inventive approaches to expand the application of CPC’s: (1) limiting the liquid phase in the setting reaction of a brushite cement to produce monetite (dehydrated brushite) based cement, with increased solubility to overcome the problems faced by long term stability of hydroxyapatite (HA) cements; (2) manipulating the cement formulation to produce a cement that can set on a change in temperature, upon implantation, increasing handling time during surgeries; (3) incorporating therapeutic molecules to eliminate secondary surgeries following infectious diseases; (4) to enhance osteointegration of CPC’s by synchronising the degradation to natural bone formation. Results exhibit compressive strength appropriate for the application of cranioplasty; long term ageing studies demonstrates that the novel cement formulations do not hydrolyse to HA, eliminating the risk of catastrophic brittle failure that is commonly associated with CPC’s.

Bone screws are used to fix various implants to the human spine. Screw fixation can be difficult in osteoporotic bone because of its reduced strength. This research aimed to investigate screw fixation techniques in the spine. A questionnaire study, representing British and Irish spine surgeons, confirmed the potential for a simple screw positioning device and identified the need for an improved screw for osteoporotic bone. Determination of the compressive mechanical properties of 0.32 g.cm\(^{-3}\), 0.16 g.cm\(^{-3}\) and 0.09 g.cm\(^{-3}\) polyurethane foam enabled them to be used as models for normal, osteoporotic and very low density osteoporotic, human cancellous bone, respectively. The screw pullout force from these bone models decreased with polyurethane foam density, implying that the quality of bone principally influences the strength of screw fixation. The angle of screw insertion and thread design was also found to affect screw pullout force, but not a small amount of screw toggling prior to axial pullout. No benefits in pullout strength were found when placing screws at 40° in a normal bone model or when using closely placed multiple screws in an osteoporotic bone model.

Maintenance of anaesthesia using the intravenous agent propofol has increased following development of pharmacokinetic models. An analyser capable of determining propofol concentrations at the point of care may lead to an improved accuracy of drug delivery. Validation work on a novel analyser measuring propofol concentration in near real time demonstrate a high level of precision for samples in the clinical range. Further work in the clinical setting was carried out using the novel propofol analyser to further research its potential use in a diverse patient cohort. Studies were performed in intensive care correlating blood propofol concentrations with depth of sedation, demonstrating a correlation with organ failure. The Marsh model of Target Controlled Anaesthesia was poorer at predicting propofol concentration in patients with significant organ dysfunction than in those without organ failure (correlation coefficient 0.36 vs. 0.73 respectively). Studies in the operating room were performed in which measured propofol concentrations were compared with those predicted using the Marsh model. Results demonstrated significant inaccuracies of the model (bias 32%, precision -8.7 to 72.6%). A method of Marsh model bias correction using a single blood propofol measurement was tested. Results demonstrated insufficient predictability to allow a single point calibration.

Myocardial protective strategies during cardiac surgery continue to improve yet they remain imperfect. Patients with left ventricular hypertrophy (LVH) are considered to be at greater risk of myocardial injury post cardiac surgery. Perhexiline is an anti-anginal agent known to modulate myocardial metabolism towards a more efficient glucose metabolic pathway. This metabolic modulation may improve myocardial protection. In this thesis I present a multi-centre double-blind randomised placebo controlled trial evaluating the role of perhexiline as an adjunct to standard myocardial protection in patients with LVH secondary to aortic stenosis undergoing an aortic valve replacement. Perhexiline does not augment myocardial protection. Magnetic Resonance Spectroscopy based energetic studies, echocardiographic and functional assessments in a homogenous patient cohort show no added benefit with perhexiline therapy in LVH. Therefore perhexiline should be limited to those patients refractory to maximum medical therapy. Metabolomic assessment of LVH has shown no change in the metabolomic profile within the myocardium. However any changes that do exist may be subtle. In LVH there is an increased activity of some innate cardioprotective mechanistic pathways in patients that do not sustain a low cardiac output episode post cardiac surgery. Further examination of these cardioprotective regulators is warranted.

Total Disc Replacement aims to maintain the natural movement of the spine by replacing the intervertebral disc with an articulating or flexible implant. One reason Total Disc Replacements fail is aseptic loosening of the implant, caused by osteolysis, an inflammatory response to the wear debris produced by the articulating surfaces of the implant. Therefore, it is important to understand the wear performance of different designs and materials. The overall aim of this thesis was to investigate the use of ceramics in Total Disc Replacements and evaluate their tribological performance. This was achieved through the manufacture of alumina cervical implants, which were then used for in vitro wear and friction tests. Despite high wear rates, caused by chipping and a high surface roughness on the articulating surfaces, there were some issues with measuring the wear using the gravimetric method. Therefore, the rest of the thesis was focused on developing and validating new methods for measuring volumetric wear using non-contacting optical microscopy. The results showed that the new optical method had several advantages over the traditional gravimetric method, including better measurement precision and the ability to visualise the location of the wear damage.

There are various problems with the treatments for bladder cancer. The studies in this thesis aimed to decrease these problems or conduct research that would aid future work and development in the area. The mechanical properties of normal and malignant bladder tissue were quantified using dynamic mechanical analysis (DMA). A uniaxial testing machine applied sinusoidally varying strains to specimens and the response stresses were measured; from this the elastic and viscous components of the soft tissues were calculated. \(Porcine\) bladder tissue was used as a model for normal bladder and exhibited a higher modulus than tumourous bladder tissue. Potentially these viscoelastic properties have many utilities, which include but are not limited to: diagnosis of bladder tumours, computational modelling of the bladder, comparison to current replacement materials, manufacture of more appropriate bladder replacement materials and manufacture of synthetic tumours for surgical trainers. One problem with the procedure for removing non-muscle invasive bladder cancer (NMIBC) is tumour re-implantation. An add-on instrument was designed, manufactured and tested to attempt to stop the travel of tumourous cells which could then re-implant. A prototype of the device was manufactured using the shape memory metal nickel titanium in conjunction with latex. The device would open into a cone shape once inside the bladder to physically prevent the movement of tumour cells away from the tumour site. The prototype was successfully tested in replica surgical conditions with blue dyes. With development, it is hoped that this design can assist in reducing the high recurrence rate of NMIBC.

The metacarpophalangeal joint is vital for hand function. It is frequently affected by rheumatoid arthritis or osteoarthritis and in some cases the diseased joint is replaced with an implant. The past and current metacarpophalangeal joint replacements can be divided into three main categories: hinge implants, flexible implants and surface replacement implants. There is some frustration among hand surgeons as these implants fail in vivo in comparison with the replacement of larger joints such as the hip or knee. The aim of this study was a new design concept for the replacement of the diseased metacarpophalangeal joint. The biomechanics of the diseased rather than the normal metacarpophalangeal joint have been considered during the design requirements procedure. Retrospective analysis of the past and present designs has been considered. Following selection of the concept of the new metacarpophalangeal joint replacement design well established methods like lubrication analysis and contact stress analysis studies, laboratory wear tests and finite element analysis studies have been used for the evaluation of the final design. In this study a new metacarpophalangeal joint replacement has been proposed. The new implant is intended to provide a functional range of motion, sustain the forces that a diseased joint experiences and provide pain relief for the patient. The new proposed metacarpophalangeal joint replacement design tries to combine the benefits of a one piece flexible implant with those of a surface replacement implant design that utilizes the soft layered concept which has been proposed for larger synovial joints

The work in this thesis presents the development of two novel orthopaedic devices as potential improvements for the surgery of the spine. The preliminary design of a novel device to replace the intervertebral disc of the lumbar spine was investigated. The design was driven by the synergistic application of brainstorming, TRIZ and morphological chart methods. One concept solution was chosen and its preliminary design verification was performed with finite element analysis and additive manufacturing. Furthermore, the mechanical behaviour of various polyurethanes as potential materials for the implant core were analysed with mechanical testing. The main research of this thesis focuses on the development of an orthopaedic device to treat severe spinal deformities in children. A novel implant was designed following the application of additive manufacturing, tolerance analysis, finite element analysis and risk analysis. Five working prototypes were successfully manufactured and were tested to evaluate their mechanical behaviour under simulated spinal compressive loading. Improved fatigue strength was obtained in comparison with a current device on the market. Therefore, with further development, the novel implant has the potential for clinical use.