Persistent post-covid symptoms in healthcare workers.

BACKGROUND: Recent reports suggest a higher incidence of COVID-19 infections among healthcare workers (HCW). However, information about the long-term complications affecting this population is lacking. AIMS: Investigation of long-term impact of COVID-19 in HCW. METHODS: Seropositivity for SARS-CoV-2 antibodies was evaluated for the majority of HCW in an English teaching hospital 2 months following the peak of COVID-19 first wave. A questionnaire investigating the long-term complications was sent through global e-mail to HCW 4 months following the peak of the wave enquiring about the persistent health issues still affecting them at that point. RESULTS: Out of 3759 subjects tested for SARS-CoV-2 antibodies, 932 were positive (24%). Forty-five per cent of 138 HCW responding to the questionnaire reported persistent symptoms with 32% struggling to cope 3-4 months following the peak of the wave. Moderate-to-severe fatigue stood out as the most disabling symptom (39%) but mild-to-moderate shortness of breath, anxiety and sleep disturbance were almost universal in the subjects still struggling with symptoms. Only 16% consulted their general practitioner (GP) about their symptoms with only 2% taking sick leave after recovering from the acute illness. CONCLUSIONS: Our data suggest that about a third of HCW who responded to the survey were still struggling to cope with the symptoms of what is now known as long covid several months after the acute COVID-19 infections. The overwhelming majority of this group seem to be reluctant to neither seek medical advice nor take sick leave.

The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and hemostasis.

Essentials Heat shock protein 47 (HSP47), a collagen specific chaperone is present on the platelet surface. Collagen mediated platelet function was reduced following blockade or deletion of HSP47. GPVI receptor regulated signalling was reduced in HSP47 deficient platelets. Platelet HSP47 tethers to exposed collagen thus modulating thrombosis and hemostasis. SUMMARY: Objective Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering hemostasis and thrombosis, in this study we sought to characterize the role of HSP47 in these cells. Methods and Results The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI-collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions, was also decreased following the inhibition or deletion of HSP47, in the presence or absence of eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand factor was unaltered following HSP47 inhibition. Laser-induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47-deficient mice or following inhibition of HSP47. Conclusions Our study demonstrates the presence of HSP47 on the platelet surface, where it interacts with collagen, stabilizes platelet adhesion and increases collagen-mediated signalling and therefore thrombus formation and hemostasis.

PPARγ agonists negatively regulate αIIbß3 integrin outside-in signaling and platelet function through up-regulation of protein kinase A activity.

Essentials peroxisome proliferator-activated receptor γ (PPARγ) agonists inhibit platelet function. PPARγ agonists negatively regulate outside-in signaling via integrin αIIbß3. PPARγ agonists disrupt the interaction of Gα13 with integrin ß3. This is attributed to an upregulation of protein kinase A activity. SUMMARY: Background Agonists for the peroxisome proliferator-activated receptor (PPARγ) have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. Objectives Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbß3 mediated signaling. Both GPVI and GPCR signaling pathways lead to αIIbß3 activation, and signaling through αIIbß3 plays a critical role in platelet function and normal hemostasis. Methods The effects of PPARγ agonists on the regulation of αIIbß3 outside-in signaling was determined by monitoring the ability of platelets to adhere and spread on fibrinogen and undergo clot retraction. Effects on signaling components downstream of αIIbß3 activation were also determined following adhesion to fibrinogen by Western blotting. Results Treatment of platelets with PPARγ agonists inhibited platelet adhesion and spreading on fibrinogen and diminished clot retraction. A reduction in phosphorylation of several components of αIIbß3 signaling, including the integrin ß3 subunit, Syk, PLCγ2, focal adhesion kinase (FAK) and Akt, was also observed as a result of reduced interaction of the integrin ß3 subunit with Gα13. Studies of VASP phosphorylation revealed that this was because of an increase in PKA activity following treatment with PPARγ receptor agonists. Conclusions This study provides further evidence for antiplatelet actions of PPARγ agonists, identifies a negative regulatory role for PPARγ agonists in the control of integrin αIIbß3 outside-in signaling, and provides a molecular basis by which the PPARγ agonists negatively regulate platelet activation and thrombus formation.

Platelet signaling: a complex interplay between inhibitory and activatory networks.

The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology, and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation, or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators.

Protein kinase Cε and protein kinase Cθ double-deficient mice have a bleeding diathesis.

BACKGROUND: In comparison to the classical isoforms of protein kinase C (PKC), the novel isoforms are thought to play minor or inhibitory roles in the regulation of platelet activation and thrombosis. OBJECTIVES: To measure the levels of PKCθ and PKCε and to investigate the phenotype of mice deficient in both novel PKC isoforms. METHODS: Tail bleeding and platelet activation assays were monitored in mice and platelets from mice deficient in both PKCθ and PKCε. RESULTS: PKCε plays a minor role in supporting aggregation and secretion following stimulation of the collagen receptor GPVI in mouse platelets but has no apparent role in spreading on fibrinogen. PKCθ, in contrast, plays a minor role in supporting adhesion and filopodial generation on fibrinogen but has no apparent role in aggregation and secretion induced by GPVI despite being expressed at over 10 times the level of PKCε. Platelets deficient in both novel isoforms have a similar pattern of aggregation downstream of GPVI and spreading on fibrinogen as the single null mutants. Strikingly, a marked reduction in aggregation on collagen under arteriolar shear conditions is observed in blood from the double but not single-deficient mice along with a significant increase in tail bleeding. CONCLUSIONS: These results reveal a greater than additive role for PKCθ and PKCε in supporting platelet activation under shear conditions and demonstrate that, in combination, the two novel PKCs support platelet activation.

Wear and surface analysis of 38 mm ceramic-on-metal total hip replacements under standard and severe wear testing conditions.

The purpose of this study was to compare the wear of zirconia-toughened alumina (ZTA) and alumina femoral heads tested against as-cast CoCrMo alloy acetabular cups under both standard and severe wear conditions. A new severe test, which included medio-lateral displacement of the head and rim impact upon relocation, was developed. This resulted in an area of metal transfer and an area of increased wear on the superior-anterior segment of the head that were thought to be due to dislocation and rim impact respectively. While the wear of all ceramic heads was immeasurable using the gravimetric method, the wear rates for the metallic cups from each test were readily calculated. An average steady state wear rate of 0.023 +/- 0.005 mm3/10(6) cycles was found for the cups articulating against ZTA under standard wear conditions. A similar result had previously been obtained for the wear of cups articulated against alumina heads of the same size (within the same laboratory). Under severe wear conditions an increase in the metallic cup steady state wear rate was found with the ZTA and alumina tests giving 0.623 +/- 0.252 and 1.35 +/- 0.154 mm3/10(6) cycles respectively. Wear of the ceramic heads was detected using atomic force microscopy which showed, under severe wear conditions, a decrease in polishing marks and occasional grain removal. The surfaces of the ZTA heads tested under standard conditions were virtually unchanged from the unworn samples. Friction tests showed low friction factors for all components, pre and post wear.

Compliant layer bearings in artificial joints. Part 2: simulator and fatigue testing to assess the durability of the interface between an elastomeric layer and a rigid substrate.

Artificial joints have been much improved since their introduction but they still have a limited lifetime. In an attempt to increase their life by improving the lubrication acting within these prostheses, compliant layered polyurethane (PU) joints have been devised. These joints mimic the natural synovial joint more closely by promoting fluid film lubrication. In this study, tests were performed on compliant layer joints to determine their ability to function under a range of conditions. Both static and dynamic compression tests were undertaken on compliant artificial hip joints of two different radial clearances. Friction tests were also performed before and after static loading. In addition to this, knee wear tests were conducted to determine the suitability of a compliant layer in these applications. In the knee tests, variations in experimental testing conditions were investigated using both active and passive rotation and severe malalignment of the tibial inserts. The static compression tests together with the friction studies suggest that a small radial clearance is likely to result in 'grabbing' contact between the head and cup. The larger radial clearance (0.33 microm) did not exhibit these problems. The importance of the design of the compliant layer joints was highlighted with delamination occurring on the lateral bearings during the knee wear studies. The bearings with a layer 2 mm thick performed better than the bearings with a layer 3 mm thick. Tests conducted on flat PU bearings resulted in no delamination; therefore, it was concluded that the layer separation was caused by design issues rather than by material issues. It was found that, with careful material choice, consideration of design, and effective manufacturing techniques, the compliant layer joint functioned well and demonstrated durability of the union between the hard and soft layers. These results give encouragement for the suitability of these joints for clinical use.

Pitch-based carbon-fibre-reinforced poly (ether-ether-ketone) OPTIMA assessed as a bearing material in a mobile bearing unicondylar knee joint.

The introduction of unicondylar knee prostheses has allowed the preservation of the non-diseased compartment of the knee while replacing the diseased or damaged compartment. In an attempt to reduce the likelihood of aseptic loosening, new material combinations have been investigated within the laboratory. Tribological tests (friction, lubrication, and wear) were performed on metal-on-carbon-fibre-reinforced (CFR) poly (ether-ether-ketone) (PEEK) (pitch-based) mobile unicondylar knee prostheses up to 5 x 10(6) cycles. Both a loaded soak control and an unloaded soak control (both medial and lateral components) were used to compensate for weight change due to lubricant absorption. For this material combination the loaded soak control gave slightly lower wear for both the medial and the lateral components than did the unloaded soak control. The medial components gave higher steady state wear than the lateral components (1.70 mm3 per 10(6) cycles compared with 1.02 mm3 per 10(6) cycles with the loaded soak control). The results show that the CFR PEEK unicondylar knee joints performed well in these wear tests. They gave lower volumetric wear rates than conventional metal-on-ultra-high-molecular-weight polyethylene prostheses have given in the past when tested under similar conditions. The friction tests showed that, at physiological viscosities, these joints operated in the boundary-mixed-lubrication regime. The low wear produced by these joints seems to be a function of the material combination and not of the lubrication regime.

Tribological and surface analysis of 38 mm alumina-as-cast Co-Cr-Mo total hip arthroplasties.

There is currently much discussion over the use of ceramic femoral components against metal acetabular cups, for use in total hip arthroplasty. The current study investigates six hot isostatically pressed alumina femoral heads of 38 mm diameter articulating against six as-cast Co-Cr-Mo metallic acetabular cups. Standard walking-cycle simulator wear testing was carried out to 5 x 10(6) cycles using the Durham Mark II hip wear simulator, and wear was determined gravimetrically. In addition, surface topography, using a non-contacting profilometer, an atomic force microscope, and an optical microscope, was monitored throughout the wear test. The wear of the ceramic heads was found to be undetectable using the current gravimetric method; however, a change in the surface topography was seen, as grain removal on the pole was observed through atomic force microscopy analysis. A biphasic wear pattern was found for the metallic cups, with low wear rates of 1.04 +/- 0.293 mm3/10(6) cycles (mean, +/- 95 per cent confidence interval) and 0.0209 +/- 0.004 mm3/10(6) cycles (mean, +/- 95 per cent confidence interval) for running-in and steady state wear phases respectively. Frictional measurement revealed that the joints were tending towards full fluid-film lubrication in parts of the walking cycle. The results show that the combination of hot isostatically pressed alumina and as-cast Co-Cr-Mo is a promising alternative for total hip arthroplasties.

Wear studies on the likely performance of CFR-PEEK/CoCrMo for use as artificial joint bearing materials.

It is well known that a reduction in the volume of wear produced by articulating surfaces in artificial joints is likely to result in a lower incidence of failure due to wear particle induced osteolysis. Therefore, new materials have been introduced in an effort to produce bearing surfaces with lower, more biologically acceptable wear. Polyetheretherketone (PEEK-OPTIMA) has been successfully used in a number of implant applications due to its combination of mechanical strength and biocompatibility. Pin-on-plate wear tests were performed on various combinations of PEEK-OPTIMA and carbon fibre reinforced PEEK-OPTIMA (CFR-PEEK) against various CoCrMo alloys to assess the potential of this material combination for use in orthopaedic implants. The PEEK/low carbon CoCrMo produced the highest wear. CFR-PEEK against high carbon or low carbon CoCrMo provided low wear factors. Pin-on-plate tests performed on ultra-high molecular weight polyethylene (UHMWPE) against CoCrMo (using comparable test conditions) have shown similar or higher wear than that found for CFR-PEEK/CoCrMo. This study gives confidence in the likelihood of this material combination performing well in orthopaedic applications.

Compliant layer bearings in artificial joints. Part 1: the effects of different manufacturing techniques on the interface strength between an elastomeric layer and a rigid substrate.

The premise that elastomeric materials could be used as one or more of the articulating components in both hip and knee prostheses was postulated first by Unsworth and co-workers. It was thought that such materials might have the capacity to mimic natural joint behaviour more closely than the more rigid bearing surfaces commonly in use. A more natural joint function in artificial joints should promote better tribology, with full fluid-film lubrication being the goal. Early tests showed that this objective could potentially be achieved with a judicious choice of materials and carefully controlled manufacturing techniques. This paper (Part 1 of a two-part series) describes and explains the techniques used to verify the material selection as well as to determine the most appropriate manufacturing procedure to obtain a strong and robust interface between the support and bearing material of the prosthesis. Two polycarbonate urethane (PU) materials with different hardness values (Corethane 80A and Corethane 75D) gave sufficient interfacial strength when moulded under optimum conditions. Corethane 80A was used as the soft bearing material while Corethane 75D provided the rigid backing component. Peel tests revealed strong interface bonds, varying with processing conditions between 350 and 862 N. Fourier transform infrared spectroscopy and micro-thermal analysis showed that a fusion bond over 30 microm thick formed at the interface. The results of the range of tests and analyses, which have been used in this study, have provided sufficient evidence to validate the process used to manufacture these components.

The wear of high-carbon metal-on-metal bearings after different heat treatments.

To study the tribological performance of metal-on-metal hip joint resurfacings, the wear performance of three pairs of Co-Cr-Mo alloy samples (pins and plates) were tested in a multidirectional pin-on-plate wear machine. An 'as-cast', a single-heat-treated, and a double-heat-treated set of specimens were tested to 3 x 10(6) cycles. The two heat treatments resulted in partial and full solution of the carbides into the matrix. An increasing trend in wear rate was found from 'as-cast' to the double-heat-treated specimens. The as-cast specimens showed the lowest wear rate (1.69 x 10(-6) mm3/N m), the reduced carbide samples had the next lowest wear rate (2.1 x 10(-6) mm3/N m), while the specimens without carbides wore the most (2.41 x 10(-6) mm3/N m).

Tribological assessment of a flexible carbon-fibre-reinforced poly(ether-ether-ketone) acetabular cup articulating against an alumina femoral head.

New material combinations have been introduced as the bearing surfaces of hip prostheses in an attempt to prolong their life by overcoming the problems of failure due to wear-particle-induced osteolysis. This will hopefully reduce the need for revision surgery. The study detailed here used a hip simulator to assess the volumetric wear rates of large-diameter carbon-fibre-reinforced pitch-based poly(ether-ether-ketone) (CFR-PEEK) acetabular cups articulating against alumina femoral heads. The joints were tested for 25 x 10(6) cycles. Friction tests were also performed on these joints to determine the lubrication regime under which they operate. The average volumetric wear rate of the CFR-PEEK acetabular component of 54 mm diameter was 1.16 mm(3)/10(6) cycles, compared with 38.6 mm(3)/10(6) cycles for an ultra-high-molecular-weight polyethylene acetabular component of 28 mm diameter worn against a ceramic head. This extremely low wear rate was sustained over 25 x 10(6) cycles (the equivalent of up to approximately 25 years in vivo). The frictional studies showed that the joints worked under the mixed-boundary lubrication regime. The low wear produced by these joints showed that this novel joint couple offers low wear rates and therefore may be an alternative material choice for the reduction of osteolysis.

Compliant-layer tibial bearing inserts: friction testing of different materials and designs for a new generation of prostheses that mimic the natural joint.

Total joint replacements (TJRs) have a limited lifetime, but the introduction of devices that exhibit good lubricating properties with low friction and low wear could well extend this. A novel tibial bearing design, using polyurethane (PU) as a compliant layer, to mimic the natural joint, has been developed. To determine accurately the mode of lubrication under which these joints operate, a synthetic lubricant was used in all these tests. Friction tests were carried out to assess the effects of material modulus and surface roughness, together with bearing design parameters such as bearing thickness and conformity, on lubrication. Corethane 80A was the preferred material and was chosen as the compliant layer for subsequent testing. A low surface roughness resulted in lower asperity contact as the asperities were depressed by the pressurized entraining fluid and full-fluid-film lubrication was approached. The three different tibial bearing conformities (low, medium, and high) did not appear to influence the mode of lubrication and all these bearings performed with extremely low friction. Similarly, the bearing thickness effects on lubrication at the levels tested (2 mm, 3 mm, and 4 mm) were minimal, although the effects of layer thickness on interface shear stress could be expected to be significant. This study describes a series of friction tests that have been used to select the most appropriate material and to optimize the design parameters to establish optimum conditions for these compliant layer joints.

Design and development of a novel automatic valve system for long-term catheterized urinary incontinence patients.

It has been estimated that over 3 million patients in the UK suffer from urinary incontinence, the result of which is often long-term catheterization. However, many catheters block prematurely through encrustation and their continuous drainage limits bladder rehabilitation. Although evidence shows that a catheter valve may overcome such weaknesses, only manual valves are currently available and many patients are not able to benefit from these owing to a lack of manual dexterity. A novel electronically controlled automatic valve system, the Shan-Lai (SL) valve system, has been designed and prototyped. The prototype is compact, reliable, and cost effective, and it has low power consumption. The mass of the overall packaged valve system is 34.2 g and it measures 4.5 cm x 4.5 cm x 1.2 cm. With an orifice of 3 mm diameter, the SL valve has achieved high flowrates with relatively low energy consumption. A flowrate-energy relationship (FER) has been introduced to assess the performance of a catheter valve, and the SL valve system prototype has achieved an FER of 0.66 m/s(-1) mJ(-1) while a commercially available electronic valve has an FER of 0.28 m/s(-1) mJ(-1). The valve demonstrated outstanding mechanical reliability after a series of performance tests and also indicated remarkable encrustation resistance in the vicinity of the valve during an in-vitro test.

The wear properties of CFR-PEEK-OPTIMA articulating against ceramic assessed on a multidirectional pin-on-plate machine.

In an attempt to prolong the lives of rubbing implantable devices, several 'new' materials have been examined to determine their suitability as joint couplings. Tests were performed on a multidirectional pin-on-plate machine to determine the wear of both pitch and PAN (polyacrylonitrile)-based carbon fibre reinforced-polyetheretherketone (CFR-PEEK-OPTIMA) pins articulating against both BioLox Delta and BioLox Forte plates (ceramic materials). Both reciprocation and rotational motion were applied to the samples. The tests were conducted using 24.5 per cent bovine serum as the lubricant (protein concentration 15 g/l). Although all four material combinations gave similar low wear with no statistically significant difference (p > 0.25), the lowest average total wear of these pin-on-plate tests was provided by CFR-PEEK-OPTIMA pitch pins versus BioLox Forte plates. This was much lower than the wear produced by conventional joint materials (metal-on-polyethylene) and metal-on-metal combinations when tested on the pin-on-plate machine. This therefore indicates optimism that these PEEK-OPTIMA-based material combinations may perform well in joint applications.

Laboratory studies on the tribology of hard bearing hip prostheses: ceramic on ceramic and metal on metal.

Total hip replacements offer relief to a great many patients every year around the world. With an expected service life of around 25 years on most devices, and with younger and younger patients undergoing this surgery, it is of great importance to understand the mechanisms of their function. Tribological testing of both conventional and hard bearing joint combinations have been conducted in many centres throughout the world, and, after being initially abandoned owing to premature failures, hard bearing combinations have been revisited as viable options for joint replacements. Improved design, manufacturing procedures, and material compositions have led to improved performance over first-generation designs in both metal-on-metal and ceramic-on-ceramic hip prostheses. This paper offers a review of the work conducted in an attempt to highlight the most important factors affecting joint performance and tribology of hard bearing combinations. The tribological performance of these joints is superior to that of conventional metal- or ceramic-on-polymer designs.

Polyurethane unicondylar knee prostheses: simulator wear tests and lubrication studies.

Many materials are used as artificial joint bearing surfaces; these include conventional stainless steel or CoCrMo-on-ultra-high molecular weight polyethylene (UHMWPE), CoCrMo on itself and alumina-on-alumina. However, these joints have a limited lifespan resulting in failure of the prosthesis and the need for revision surgery. A number of materials have been introduced recently in an attempt to overcome these problems. Polycarbonate urethane (PU) is a compliant material that can be used as an artificial joint bearing surface which has been developed to mimic the natural synovial joint more accurately by promoting fluid film lubrication. Tribological tests were performed on CoCrMo-on-PU unicondylar knee prostheses to assess their performance in vitro. The wear produced by these components was considerably lower than that found for conventional joints. They also exhibited low friction and operated close to full-fluid film lubrication with viscosities of lubricant similar to those found in patients with arthritis. These tests gave encouraging results for the tribological performance of this material couple for use as an alternative bearing combination.

The effects of proteins on the friction and lubrication of artificial joints.

The tribological testing of artificial hip and knee joints in the laboratory has been ongoing for several decades. This work has been carried out in an attempt to simulate the loading and motion conditions applied in vivo and, therefore, the potential for the success of the joint. However, several different lubricants have been used in these tests. The work documented in this paper compares results obtained using different lubricants and makes suggestions for future work. Hip joints and knee joints of different material combinations were tested in a friction simulator to determine their friction and lubrication properties. Both carboxymethyl cellulose (CMC) fluids and bovine serum (with CMC fluids added) were used as the lubricants. These were prepared to various viscosities to produce the Stribeck plots. Human synovial fluid, of just one viscosity, was used as the lubricant with some of the joints to give a true comparison with physiological lubricants. The results showed that, in most cases, the lubricant had a significant effect on the friction developed between the joint surfaces. This is thought to be due to the proteins that are present within the bovine serum adsorbing to the bearing surfaces, creating 'solid-like' films which rub together, protecting the surfaces from solid-to-solid contact. This would be beneficial in terms of wear but can either increase or decrease the friction between the contacting surfaces. It is important to simulate the conditions in vivo as closely as possible when testing these joints to try to obtain a better comparison between the joints and to simulate more accurately the way that these joints will operate in the body. In an attempt to simulate synovial fluid, bovine serum seems to be the most popular lubricant used at present. It would be beneficial, however, to develop a new synthetic lubricant that more closely matches synovial fluid. This would allow us to predict more accurately how these joints would operate long-term in vivo.

Compliant layer acetabular cups: friction testing of a range of materials and designs for a new generation of prosthesis that mimics the natural joint.

Total joint replacements (TJRs) have a limited lifetime, but the introduction of components that exhibit good lubricating properties with low friction and low wear could extend the life of TJRs. A novel acetabular cup design using polyurethane (PU) as a compliant layer (to mimic the natural joint) has been developed. This study describes a series of friction tests that have been used to select the most appropriate material, optimize the design parameters, and fine-tune the manufacturing processes of these joints. To determine accurately the mode of lubrication under which these joints operate, a synthetic lubricant was used in all these tests. Friction tests were carried out to assess the lubrication of four PU bearing materials. Corethane 80A was the preferred material and was subjected to subsequent testing. Friction tests conducted on acetabular cups, manufactured using Corethane 80A articulating against standard, commercially available femoral heads, demonstrated friction factors approaching those for full-fluid-film lubrication with only approximately 1 per cent asperity contact. As the joint produces these low friction factors within less than half a walking cycle after prolonged periods of loading, start-up friction was not considered to be a critical factor. Cups performed well across the full range of femoral head sizes, but a number of samples manufactured with reduced radial clearances performed with higher than expected friction. This was caused by the femoral head being gripped around the equator by the low clearance cup. To avoid this, the cup design was modified by increasing the flare at the rim. In addition to this the radial clearance was increased. As the material is incompressible, a radial clearance of 0.08 mm was too small for a cup diameter of 32 mm. A clearance of between 0.10 and 0.25 mm produced a performance approaching full-fluid-film lubrication. This series of tests acted as a step towards the optimization of the design of these joints, which has now led to an in vivo ovine model.