Femoral stem failure is a significant problem with health-related, social and economic costs. It has a poorly understood aetiology which has both biological and mechanical components. Subsidence is a poor indicator of outcome in these devices.

There are an estimated 1 million metal-on-metal implants in use worldwide and at least 65,000 of these are in the UK. In 2007 over half of the metal-on-metal hip resurfacings performed in women were in women of childbearing age. These metal implants produce nanoparticle size wear debris. The effects of these nanoparticles are unknown in vivo, but in vitro they can damage a cell's DNA. Nanoparticles are able to induce damage in cells indirectly across a cellular barrier. This effect was shown in vitro across a model barrier of three to five cells' thickness and was dependent upon a signalling mechanism within the barrier and not the direct passage of nanoparticles across the barrier. The placental barrier in vivo is predominantly bi-layered in the first trimester and becomes predominantly monolayered as the pregnancy progresses. To test whether this signalling mechanism could potentially damage a fetus, cobaltchrome nanoparticles were placed above predominantly bi-layered or predominantly mono-layered BeWo barriers and the DNA damage in fibroblasts underneath the barrier was assessed using the alkaline comet assay. To assess whether the DNA damage seen after an indirect nanoparticle exposure could potentially affect a developing foetus, human embryonic stem cells were also indirectly exposed to nanoparticles across predominantly mono-layered and predominantly bi-layered barriers, and their differentiation into the different germ cell layers assessed using A2B5 and CXCR4 as markers for primitive neuroendoderm and mesendoderm respectively. This work confirms nanoparticles induce DNA damage in cells across predominantly bi-layered but not predominalty mono-layered barriers. This DNA damage is dependent upon gap junctions or hemichannels. The generation of free radicals pharmacologically or by hypoxic culture conditions also induces a DNA damaging signal across a predominantly bi-layered but not a predominantly monolayered barrier. Human embryonic stem cell expression of A2B5 was altered following indirect nanoparticle exposure or change of oxygen tension in the predominantly bi-layered barrier but not the predominantly mono-layered barrier. The AS corneal cell also seems to signal in a gap junction or hemichannel dependent manner when it is predominantly bi-layered but not when it is predominantly monolayered. This suggests that this principle may be applicable to other cellular barriers. The human foetus is most susceptible to teratogenic stimuli in the first trimester. Many teratogenic stimuli are thought to involve free radical generation across the placenta in the first trimester. The first trimester is also the time during which the placenta is predominantly bi-layered and so it is speculated that placental barrier signalling in the first trimester may be implicated in teratogenisis. However further epidemiological studies are required to confirm whether orthopaedic implant wear debris is a potential teratogen in a women with metal-on-metal implants.

A recent technique developed in hip arthroplasty is hip resurfacing (HR) which is a much smaller and less invasive implant system as compared to the commonly used total hip replacement (THR) and therefore more attractive. In the current design, both implant parts used in HR are made of CoCrMo alloy which provide sufficient mechanical strength to the implant under load-bearing situations. Metal on metal implants have however been reported to cause metal ion release and wear debris in these coupling bearings. Ceramics would offer a much better solution in terms of wear resistance, but are too brittle for use in HR where excellent mechanical and tribological properties are a prerequisite. This project aimed at the development of ceramic/metal graded interpenetrating phase composites (GIPCs) for possible application in HR implants in order to reduce metal wear debris and ion release while providing the necessary mechanical properties. Graded porosity ceramics with continuously aligned open pores were successfully fabricated using a double-side cooling freeze casting setup and subsequently infiltrated with metal to produce ceramic/metal GIPCs. The effects of slurry solid content, temperature, cooling rate and the introduction of electrophoretic deposition (EPD) on the microstructure of freeze cast ceramic preforms were investigated. The addition of EPD before freeze casting altered the microstructure substantially with decreasing lamellar spacing and reduced porosity gradient. Processing conditions of ceramic preforms that were suitable for the fabrication of GIPCs were identified. Vacuum and centrifugal casting techniques were investigated and compared for the metal infiltration. The centrifugal casting turned out to be a more efficient method. The fabricated GIPCs possessed high compression strength, good wear resistance and could potentially be used as a candidate for the HR implants. Finally, the fabrication of a prototype in acetabular shape was demonstrated with a hemisphere shaped mould using the freeze casting and metal infiltration techniques.

Total hip replacement is an effective treatment for arthritis of the hip. Its use has expanded to include younger patients with higher functional demands resulting in poor implant survival when conventional arthroplasty designs are employed. This has resulted in the development of alternative bearing materials and designs including resurfacing arthroplasties. The effects of particulate and ionic debris generated by these bearings have recently come to light. Metal alloys including cobalt chromium are often employed as bearings in young patients and are associated with genotoxic and teratogenic effects. The potential for this debris to cause damage to the foetus of a mother with a metal implant is a cause for concern. This risk is difficult to assess using epidemiological methods. The aim of this study was to investigate factors associated with an increase in metal levels in the blood and urine of patients undergoing resurfacing arthroplasty. We aimed to investigate the potential for debris generated by metal hip replacements to cause chromosomal aberrations in the foetus. To do this, we employed an in vitro cellular barrier to investigate the transport of material across the human placenta, and human fibroblasts and embryonic stem cells to record the effect. Nanoparticles of cobalt chrome but not ceramic or ionic cobalt and chromium, induced chromosomal aberrations, the majority of which were tetraploidy. When indirectly exposed to human embryonic stem cells, nanoparticles of cobalt chrome resulted in DNA damage only when exposed to differentiated cells. Metallic debris indirectly induces chromosomal aberrations in human cells, depending on the nature of the material and its surface characteristics. The foetus is most susceptible to damage at the time of differentiation. These results raise further concerns about the use of metallic bearings in women of child bearing age.

The number of hip replacement operations performed is currently increasing due to the ageing population and the need for revision surgery after around 15 years. Improving the materials used for hip replacements would decrease the need for revision surgery and have an important economic effect as well as increasing quality of life for patients. To ensure the success and longevity of a bone implant, osteoblast cells must adhere and differentiate on the implant material to form a tight junction with the surface.

The biological response to ultra-high molecular weight polyethylene (UHMWPE) wear particles has been shown to play a key role in the development of osteolysis, which leads to aseptic loosening of total hip replacements (THR). Recently, nanometre-sized UHMWPE particles have been identified in vivo and in vitro from hip and knee replacements. It has been shown that nanometre-sized Ceridust, which are model polymer particles. can stimulate human macrophages to produce significant levels of osteolytic cytokines. Therefore, the aims of this study were to investigate the cellular response to and cellular uptake mechanisms of clinically-relevant nanometre-sized UHMWPE wear particles. A large volume of aseptic clinically-relevant nanometre-sized UHMWPE wear particles with a mode size of 30•40 nm was isolated from RPMI 1640 medium lubricants from pin-on- plate wear testing. Nanometre-sized UHMWPE wear particles with a mode size of 30-40 nm and nanometre-sized Ceridust with a mode size of 20•30 nm had no significant effect on osteolytic cytokine re lease, including TNF•α, IL•Iβ, IL•6 and lL-8, from human peripheral blood mononuclear cells (PBMNC's) isolated from all donors (3 donors) tested at a concentration of 100 J..lm3 particles per cell after 12 hours and 24 hours. The micrometre-size UHMWPE wear particles with a mode size of 0.1 - 1.0 μm and 40 nm polystyrene particles (FluoSpheres) with a mode size of 50•60 nm caused significantly elevated osteolytic cytokine release from all of the donors tested at a concentration of 100 μm3 particles per cell after 12 hours and 24 hours. The results indicated that there is a lower size limit « 50 nm) for cellular activation. Clathrin-mediated endocytosis and caveolae-mediated endocytosis were both involved in the internalisation of nanometre-sized UHMWPE wear particles with a size mode of 30•40 nm and micrometre-sized UHMWPE wear particles with a size mode of 0.1•1.0 μm within PBMNC's. Clathrin-mediated endocytosis but not the caveolae-mediated pathway was involved in the internalisation of the 40 nm FluoSpheres within PBMNC's. The results showed clear evidence that there was a relationship between the mechanism of particle uptake and the cellular response to particles with different compositions.

Ultra high molecular weight polyethylene (UHMWPE) wear particles have been implicated as one of the major causes of late aseptic loosening. Particles of a critical and volume promote an inflammatory response from macrophages, primarily. which leads to cytokine release and the resorption of bone at the bone-implant interface.

No description available.

Introduction: Impaction allografting has proved a successful means of restoring deficient bone stock during revision athroplasty of the hip.  Mechanical and clinical studies were performed to investigate the role of IG-Pore, a synthetic hydroxyapatite Graft expander, in impaction grafting. Methods: 32 synthetic femoral models underwent impaction grafting using allograft mixed with varying proportions of IG-Pore (0%, 50%, 70% and 90% IG-Pore).  The cyclical displacements induced by repetitive loading on an Instron were measured, and overall migration of the prosthesis was determined using radiostereometric analysis (RSA).  A randomised controlled clinical trial comparing impaction grafting using pure allograft and a 1:1 mixture of allograft and IG-Pore is also described.  Migration of the revised femoral and acetabular components was determined using RSA, and clinical outcomes were monitored.  A preliminary analysis of the first 14 patients in this study with follow-up of up to six months is presented. Results: The mechanical data indicate that IG-Pore confers a greater resistance to subsidence (p=0.034) and cyclical movement (p=0.005).  In particular, subsidence at the prosthesis-cement interface is lower than with pure allograft (p=0.019).  The clinical study shows similar patterns of migration, although it is too early for definite conclusions.  Movement of individual graft particles is greater with IG-Pore, however, and graft handling may be more difficult. Discussion: Synthetic hydroxyapatite graft expanders may indeed be beneficial in impaction grafting, and the clinical study which is described herein should, in due course, definitely characterise their role.

No description available.