A Link Between the Tribology and Corrosive Degradation of Metal-on-Metal THRs

The degradation of Metal-on-Metal (MoM) Total Hip Replacements (THRs) is a complex mix of tribological, corrosive phenomena and their synergistic processes. Previous links between the corrosion of these devices and their sliding conditions over a cycle have been observed in simulator studies instrumented with a three-electrode electrochemical cell. This study further quantifies that link; demonstrating clear repeating periodicity in the anodic current transients of a 28 mm diameter MoM bearing under a standard ISO-14242 walking profile. A simplified 2D model and an expression of the Hamrock-Dowson equation was utilised to estimate the Theoretical Minimum Film Thickness (hmin) over a cycle, which was shown to match closely to the measured anodic current in both shape and magnitude

The use of polymeric meshes for Pelvic Organ Prolapse: current concepts, challenges and future perspectives

Pelvic organ prolapse (POP) is one of the most common chronic disorders in women, impacting the quality of life of millions of them worldwide. More than 100 surgical procedures have been developed over the decades to treat POP. However, the failure of conservative strategies and the number of patients with recurrence risk have increased the need for further adjuvant treatments. Since their introduction, surgical synthetic meshes have dramatically transformed POP repair showing superior anatomic outcomes in comparison to traditional approaches. Although significant progress has been attained, among the meshes in clinical use, there is no single mesh appropriate for every surgery. Furthermore, due to the risk of complications including acute and chronic infection, mesh shrinkage, and erosion of the tissue, the benefits of the use of meshes have recently been questioned. The aim of this work is to review the evolution of POP surgery, analyzing the current challenges, and detailing the key factors pertinent to the design of new mesh systems. Starting with a description of the pelvic floor anatomy, the article then presents the traditional treatments used in pelvic organ disorders. Next, the development of synthetic meshes is described with an insight into how their function is dependent on both mesh design variables (i.e., material, structure, and functional treatment) and surgical applications. These are then linked to common mesh‐related complications, and an indication of current research aiming to address these issues

A porohyperelastic lubrication model for articular cartilage in the natural synovial joint

This work focuses on the proposed mechanisms for the lubrication of synovial joints and applies them to an idealised bearing geometry considering a porohyperelastic material (cartilage) rotating against a stationary rigid impermeable surface. The model captures the behaviour of all lubrication regimes including fluid film formation and boundary contact as the load capacity is increased, representing a major advancement in modelling cartilage mechanics. Transient responses in the fluid phase are shown to be faster than those in the solid phase with the former decaying over time as fluid is exuded from the material. The complex behaviour of fluid migrating to and from the lubricating film is captured which leads to a better understanding of the hydration and friction mechanisms observed

The Effect of Protein Structure and Concentration on Tribocorrosion and Film Formation on CoCrMo Alloys

The formation of tribochemical reaction layers, better known as tribofilms, on cobalt-chromium-molybdenum (CoCrMo) alloys commonly used in orthopaedic applications has been hypothesized to reduce degradation owing to wear and corrosion. However, the mechanisms and pathways influencing tribofilm formation remain largely unknown. This study aims to develop a clearer understanding of the role of protein structures and its concentration on tribocorrosion and surface tribofilms formed on CoCrMo alloys during boundary regime sliding. A reciprocating tribometer with a three-electrode electrochemical cell was employed to simulate and monitor the tribocorrosion of CoCrMo in situ. As-received Foetal Bovine Serum (as-FBS) and pre-heated FBS at 70 °C for 1 h (de-FBS) were diluted with saline (0.9% NaCl) at different concentrations (25% and 75% v/v) and utilized as electrolytes during the tribocorrosion tests. The result shows that the denatured protein structure in electrolyte tends to reduce the volume losses due to wear and corrosion on the CoCrMo samples with an appreciation of the protein tribofilms. On the other hand, an increased protein concentration increased the total volume loss due to corrosive processes. A novel finding revealed in this study is that the tribocorrosion mechanism of the CoCrMo surface is dependent on the protein structure, concentration and sliding duration due to the change in surface condition

Importance of surgical assembly technique on the engagement of 12/14 modular tapers

Fretting-corrosion at the modular taper junction in total hip replacements (THR), leading to implant failure, has been identified as a clinical concern and has received increased interest in recent years. There are many parameters thought to affect the performance of the taper junction, with the assembly process being one of the few consistently identified to have a direct impact. Despite this, the assembly process used by surgeons during THR surgery differs from a suggested ‘ideal’ process. For example, taper junctions of cutting tools should be pushed together rather than impacted, while ensuring as much concentricity as possible between the male and female taper and loading axis. This study devised six simple assembly methodologies to investigate how surgical variations affect the success of the compressive fit achieved at the taper interface compared to a controlled assembly method, designed to represent a more ‘ideal’ scenario. Key findings from this study suggest that a more successful and repeatable engagement can be achieved by quasi-statically loading the male and female taper concentrically with the loading axis. This was shown by a greater disassembly to assembly force ratio of 0.626 ± 0.07 when assembled using the more ‘ideal’ process, compared to 0.480 ± 0.05 when using a method closer to that used by a surgeon intraoperatively. Findings from this study can be used to help inform new surgical instrumentation and an improved surgical assembly method

Adverse loading effects on tribocorrosive degradation of 28 mm metal-on-metal hip replacement bearings

Following the high clinical failure rates of metal-on-metal total hip replacements much work has been undertaken to investigate their poor performance. So called adverse loading scenarios such as acetabular inclination and microseparation have been attributed to indicators for failure of the implants. The ISO hip simulation standards (ISO 14242:1) still rely on gravimetric and ex situ analysis, considering only the total wear during articulation. Live in situ sensing can provide valuable insight into the degradation mechanisms of metallic interfaces under such scenarios. Clinical 28 mm diameter metal-on-metal components were articulated in a full-ISO hip simulator. The bearings were subjected to increasing angles of acetabular inclination and retroversion over short-term periods of articulation. Corrosive degradation was monitored during sliding by means of an in situ three-electrode cell. Changing acetabular inclination from 30° to 50° resulted in greater cathodic shifts in OCP upon the initiation of sliding; from −50 mV to as much as −150 mV. Under anodic polarisation (0 mV vs. Ag/AgCl) the resultant currents at the initiation of sliding also increased significantly with inclination; from approximately 4–10 µA to over 120 µA. Increased retroversion of 20° also resulted in increased anodic currents of 55–60 µA. Changing the nature of articulation demonstrated increased corrosive material loss compared to a standard ISO 14242 profile. The sole use of gravimetric assessment to determine a wear rate for hip replacement bearings under simulation can therefore neglect important degradation mechanisms, such as tribocorrosive loss in devices with metal sliding interfaces

Fabrication of cartilage-inspired hydrogel/entangled polymer–elastomer structures possessing poro-elastic properties

The ability to replicate the load-bearing properties of articular cartilage is attractive for many engineering applications, particularly bearings where low friction, low wear, and high durability are required. Hydrogels are widely used materials spanning many diverse applications owing to their lubricity and unique mechanical/chemical properties. The poor mechanical characteristics of conventional hydrogels, especially their compressive behavior, limit their application in load-bearing applications despite their favorable properties such as poro/viscoelasticity and lubricity. This paper demonstrates a cartilage-inspired approach to produce a structure that benefits from water-swelling resistant and ultrafast recovery behavior of elastomers as well as the stress-relaxation and energy dissipation properties of hydrogels. A method is presented in this work to fabricate interconnected macro-porous elastomers based on sintering poly(methyl methacrylate) beads. The porous elastomer imparted structural support and resilience to its composite with an infused-grafted hydrogel. At 30% strain and depending upon the strain rate, the composite exhibited a load-bearing behavior that was 14–19 times greater than that of pristine hydrogel and approximately 3 times greater than that of the porous elastomer. The equilibrium elastic modulus of the composite was 452 kPa at a strain range of 10%–30%, which was close to the values reported for the modulus of cartilage tested with similar experimental parameters defined in this study. The dissipated energy for the composite at strain rates of 1 and 10–3 s–1 was enhanced by 25-, 25-, 5-, and 15-fold as compared to that for the pristine hydrogel and the porous elastomer, respectively. The cyclic loading tests at two strain rates showed that the composite immediately recovers its load-bearing properties with the maximum load recovery staying above 95% of its initial values throughout the testing. The permeability of the structures was measured experimentally, and the results showed a decrease of permeability by 3 orders of magnitude following hydrogel grafting

In vitro models of soft tissue damage by implant-associated frictional shear stresses

Silicone elastomer medical implants are ubiquitous in medicine, particularly for breast augmentation. However, when these devices are placed within the body, disruption of the natural biological interfaces occurs, which significantly changes the native energy-dissipation mechanisms of living systems. These new interfaces can introduce non-physiological contact pressures and tribological conditions that provoke inflammation and soft tissue damage. Despite their significance, the biotribological properties of implant-tissue and implant-extracellular matrix (ECM) interfaces remain poorly understood. Here, we developed an in vitro model of soft tissue damage using a custom-built in situ biotribometer mounted onto a confocal microscope. Sections of commercially-available silicone breast implants with distinct and clinically relevant surface roughness (Ra=0.2±0.03μm, 2.7±0.6μm, and 32±7.0μm) were mounted to spherically-capped hydrogel probes and slid against collagen-coated hydrogel surfaces as well as healthy breast epithelial (MCF10A) cell monolayers to model implant-ECM and implant-tissue interfaces. In contrast to the “smooth” silicone implants (Ra100  Pa), which led to greater collagen removal and cell rupture/delamination. Our studies may provide insights into post-implantation tribological interactions between silicone breast implants and soft tissues

Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.

By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC50s) in the sub-micromolar and low micromolar range

Does domiciliary welfare rights advice improve health-related quality of life in independent-living, socio-economically disadvantaged people aged ≥60 years? Randomised controlled trial, economic and process evaluations in the North East of England.

BACKGROUND: There are major socio-economic gradients in health that could be influenced by increasing personal resources. Welfare rights advice can enhance resources but has not been rigorously evaluated for health-related impacts. METHODS: Randomised, wait-list controlled trial with individual allocation, stratified by general practice, of welfare rights advice and assistance with benefit entitlements, delivered in participants' homes by trained advisors. Control was usual care. Participants were volunteers sampled from among all those aged ≥60 years registered with general practices in socio-economically deprived areas of north east England. Outcomes at 24 months were: CASP-19 score (primary), a measure of health-related quality of life; changes in income, social and physical function, and cost-effectiveness (secondary). Intention to treat analysis compared outcomes using multiple regression, with adjustment for stratification and key covariates. Qualitative interviews with purposive samples from both trial arms were thematically analysed. FINDINGS: Of 3912 individuals approached, 755 consented and were randomised (381 Intervention, 374 Control). Results refer to outcomes at 24 months, with data available on 562 (74.4%) participants. Intervention was received as intended by 335 (88%), with 84 (22%) awarded additional benefit entitlements; 46 did not receive any welfare rights advice, and none of these were awarded additional benefits. Mean CASP-19 scores were 42.9 (Intervention) and 42.4 (Control) (adjusted mean difference 0.3 [95%CI -0.8, 1.5]). There were no significant differences in secondary outcomes except Intervention participants reported receiving more care at home at 24m (53.7 (Intervention) vs 42.0 (Control) hours/week (adjusted mean difference 26.3 [95%CIs 0.8, 56.1]). Exploratory analyses did not support an intervention effect and economic evaluation suggested the intervention was unlikely to be cost-effective. Qualitative data from 50 interviews suggested there were improvements in quality of life among those receiving additional benefits. CONCLUSIONS: We found no effects on health outcomes; fewer participants than anticipated received additional benefit entitlements, and participants were more affluent than expected. Our findings do not support delivery of domiciliary welfare rights advice to achieve the health outcomes assessed in this population. However, better intervention targeting may reveal worthwhile health impacts.All authors received a grant of £798,884 from the UK National Institute of Health Research, Public Health Research Programme (No. 09/3009/ 02). www.nihr.ac.uk. All authors received a grant of £28,000 from the North East Strategic Health Authority in 2012 to cover the costs of delivering the intervention, associated training and other nonresearch costs of this study. North East SHA no longer exists. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript