Recovery rate data for silicon nitride nanoparticle isolation using sodium polytungstate density gradients.

The average recovery rate of silicon nitride nanoparticles isolated from serum using the method detailed in previous article "A novel method for isolation and recovery of ceramic nanoparticles and metal wear debris from serum lubricants at ultra-low wear rate" (Lal et al., 2016) [1] was tested gravimetrically by weighing particles doped into serum before and after the isolation process. An average recovery rate of approximately 89.6% (± 7.1 SD) was achieved.

Development and optimisation data of a tissue digestion method for the isolation of orthopaedic wear particles.

The data contained within this article relate to several enzymatic tissue digestion experiments which were performed to produce an optimised protocol for the digestion of tissue samples. The digestion experiments involved a total of four different digestion protocols. The first protocol involved digestion with proteinase K, without the use of glycine. The second protocol involved digestion with proteinase K in the presence of glycine. The third protocol consisted of proteinase K digestion in the presence of glycine, with more frequent enzyme replenishment. The final protocol was similar to the third protocol but included a papain digestion stage prior to digestion with proteinase K. The data contained within this article are photographs of tissue samples which were captured at key stages of the four protocols and written descriptions based on visual observation of the tissue samples, which document the appearance of the tissue digests.

Validation of a novel particle isolation procedure using particle doped tissue samples.

A novel particle isolation method for tissue samples was developed and tested using particle-doped peri-articular tissues from ovine cadavers. This enabled sensitivity of the isolation technique to be established by doping tissue samples of 0.25 g with very low particle volumes of 2.5 µm3 per sample. Image analysis was used to verify that the method caused no changes to particle size or morphologies.

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method.

Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm3 of clinically relevant CoCrMo, Ti-6Al-4V or Si3N4 particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si3N4 particles before and after the recovery process (KS tests, p > 0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues. STATEMENT OF SIGNIFICANCE: This research presents a novel method for the isolation of wear particles from tissue. Methodology outlined in this work would be a valuable resource for future researchers wishing to isolate particles from tissues, either as part of preclinical testing, or from explants from patients for diagnostic purposes. It is increasingly recognised that analysis of wear particles is critical to evaluating the safety of an orthopaedic device.

Ultrahigh molecular weight polyethylene/graphene oxide nanocomposites: Wear characterization and biological response to wear particles.

In the field of total joint replacements, polymer nanocomposites are being investigated as alternatives to ultrahigh molecular weight polyethylene (UHMWPE) for acetabular cup bearings. The objective of this study was to investigate the wear performance and biocompatibility of UHMWPE/graphene oxide (GO) nanocomposites. This study revealed that low concentrations of GO nanoparticles (0.5 wt %) do not significantly alter the wear performance of UHMWPE. In contrast, the addition of higher concentrations (2 wt %) led to a significant reduction in wear. In terms of biocompatibility, UHMWPE/GO wear particles did not show any adverse effects on L929 fibroblast and PBMNC viability at any of the concentrations tested over time. Moreover, the addition of GO to a UHMWPE matrix did not significantly affect the inflammatory response to wear particles. Further work is required to optimize the manufacturing processes to improve the mechanical properties of the nanocomposites and additional biocompatibility testing should be performed to understand the potential clinical application of these materials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 183-190, 2018.

A novel method for isolation and recovery of ceramic nanoparticles and metal wear debris from serum lubricants at ultra-low wear rates.

UNLABELLED: Ceramics have been used to deliver significant improvements in the wear properties of orthopaedic bearing materials, which has made it challenging to isolate wear debris from simulator lubricants. Ceramics such as silicon nitride, as well as ceramic-like surface coatings on metal substrates have been explored as potential alternatives to conventional implant materials. Current isolation methods were designed for isolating conventional metal, UHMWPE and ceramic wear debris. In this paper, we describe a methodology for isolation and recovery of ceramic or ceramic-like coating particles and metal wear particles from serum lubricants under ultra-low and low wear performance. Enzymatic digestion was used to digest the serum proteins and sodium polytungstate was used as a novel density gradient medium to isolate particles from proteins and other contaminants by ultracentrifugation. This method demonstrated over 80% recovery of particles and did not alter the size or morphology of ceramic and metal particles during the isolation process. STATEMENT OF SIGNIFICANCE: Improvements in resistance to wear and mechanical damage of the articulating surfaces have a large influence on longevity and reliability of joint replacement devices. Modern ceramics have demonstrated ultra-low wear rates for hard-on-hard total hip replacements. Generation of very low concentrations of wear debris in simulator lubricants has made it challenging to isolate the particles for characterisation and further analysis. We have introduced a novel method to isolate ceramic and metal particles from serum-based lubricants using enzymatic digestion and novel sodium polytungstate gradients. This is the first study to demonstrate the recovery of ceramic and metal particles from serum lubricants at lowest detectable in vitro wear rates reported in literature.

Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue.

Organ culture is an increasingly important tool in research, with advantages over monolayer cell culture due to the inherent natural environment of tissues. Successful organ cultures must retain cell viability. The aim of this study was to produce viable and non-viable osteochondral organ cultures, to assess the accumulation of soluble markers in the conditioned medium for predicting tissue viability. Porcine femoral osteochondral plugs were cultured for 20 days, with the addition of Triton X-100 on day 6 (to induce necrosis), camptothecin (to induce apoptosis) or no toxic additives. Tissue viability was assessed by the tissue destructive XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide tetrazolium salt) assay method and LIVE/DEAD® staining of the cartilage at days 0, 6 and 20. Tissue structure was assessed by histological evaluation using haematoxylin & eosin and safranin O. Conditioned medium was assessed every 3-4 days for glucose depletion, and levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP), glycosaminoglycans (GAGs), and matrix metalloproteinase (MMP)-2 and MMP-9. Necrotic cultures immediately showed a reduction in glucose consumption, and an immediate increase in LDH, GAG, MMP-2 and MMP-9 levels. Apoptotic cultures showed a delayed reduction in glucose consumption and delayed increase in LDH, a small rise in MMP-2 and MMP-9, but no significant effect on GAGs released into the conditioned medium. The data showed that tissue viability could be monitored by assessing the conditioned medium for the aforementioned markers, negating the need for tissue destructive assays. Physiologically relevant whole- or part-joint organ culture models, necessary for research and pre-clinical assessment of therapies, could be monitored this way, reducing the need to sacrifice tissues to determine viability, and hence reducing the sample numbers necessary.

Analysis of wear, wear particles, and reduced inflammatory potential of vitamin E ultrahigh-molecular-weight polyethylene for use in total joint replacement.

Vitamin E (VE) has been added to ultrahigh-molecular-weight polyethylene (UHMWPE) acetabular cups and tibial trays primarily to reduce oxidative damage to the polymer. The aim of this study was to investigate the relative wear rates of UHMWPE-containing VE compared with virgin UHMWPE. The ability of VE to reduce the amount of inflammatory cytokines produced from stimulated peripheral blood mononuclear cells (PBMNCs) was also investigated. Stimulation was achieved by exposure of PBMNCs to either lipoplysaccharide (LPS) or VE-containing UHMWPE (VE-UHMWPE). In the present study, results showed that the wear rates of UHMWPE with or without VE were not significantly different. Particles generated by UHMWPE with and without VE were not significantly different in size distribution. The production of osteolytic mediators, tumor necrosis factor-alpha, interleukin 1ß (IL-ß), IL-6, and IL-8 were significantly reduced in (PBMNCs) stimulated with either LPS + VE compared with LPS or VE-UHMWPE particles compared to virgin UHMWPE particles. This trend was also observed when VE was added as a liquid to UHMWPE wear particle-stimulated PBMNCs. The exact mechanism of how VE affects the release of inflammatory mediators from particle-stimulated macrophages is not yet understood. It is likely to involve the anti-inflammatory and/or antioxidant effects of VE.

In vitro analysis of the cytotoxic and anti-inflammatory effects of antioxidant compounds used as additives in ultra high-molecular weight polyethylene in total joint replacement components.

Ultra high-molecular weight polyethylene (UHMWPE) remains the most commonly used material in modern joint replacement prostheses. However, UHMWPE wear particles, formed as the bearing articulates, are one of the main factors leading to joint replacement failure via the induction of osteolysis and subsequent aseptic loosening. Previous studies have shown that the addition of antioxidants such as vitamin E to UHMWPE can improve wear resistance of the polymer and reduce oxidative fatigue. However, little is known regarding the biological consequences of such antioxidant chemicals. This study investigated the cytotoxic and anti-inflammatory effects of a variety of antioxidant compounds currently being tested experimentally for use in hip and knee prostheses, including nitroxides, hindered phenols, and lanthanides on U937 human histocyte cells and human peripheral blood mononuclear cells (PBMNCs) in vitro. After addition of the compounds, cell viability was determined by dose response cytotoxicity studies. Anti-inflammatory effects were determined by quantitation of TNF-α release in lipopolysaccharide (LPS)-stimulated cells. This study has shown that many of these compounds were cytotoxic to U937 cells and PBMNCs, at relatively low concentrations (micromolar), specifically the hindered phenol 3,5-di-tert-butyl-4-hydroxyhydrocinnamate (HPAO1), and the nitroxide 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO). Lanthanides were only cytotoxic at very high concentrations and were well tolerated by the cells at lower concentrations. Cytotoxic compounds also showed reduced anti-inflammatory effects, particularly in PBMNCs. Careful consideration should therefore be given to the use of any of these compounds as potential additives to UHMWPE.

Wear and creep of highly crosslinked polyethylene against cobalt chrome and ceramic femoral heads.

The wear and creep characteristics of highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) articulating against large-diameter (36mm) ceramic and cobalt chrome femoral heads have been investigated in a physiological anatomical hip joint simulator for 10 million cycles. The crosslinked UHMWPE/ceramic combination showed higher volume deformation due to creep plus wear during the first 2 million cycles, and a steady-state wear rate 40 per cent lower than that of the crosslinked UHMWPE/cobalt chrome combination. Wear particles were isolated and characterized from the hip simulator lubricants. The wear particles were similar in size and morphology for both head materials. The particle isolation methodology used could not detect a statistically significant difference between the particles produced by the cobalt chrome and alumina ceramic femoral heads.

The effect of anterior-posterior shear load on the wear of ProDisc-L TDR.

The current wear-testing standard (ISO18192-1) for total disc replacement (TDR) requires only four degrees of freedom (DOF) inputs: axial load, flexion-extension, lateral bending and axial rotation. The study aim was to assess the effect of an additional DOF, anterior-posterior (AP) shear on the wear of the ProDisc-L TDR. A 5DOF simulator was used to test ProDisc-L implants under 4DOF and 5DOF conditions. The 4DOF conditions were defined by ISO18192-1 whilst the 5DOF used ISO18192-1 conditions with the addition of an AP load of +175 and -140 N (anterior and posterior, respectively), extrapolated from in vivo data. The implants were mounted such that the polyethylene insert could be removed for gravimetric measurements. Tests were run using bovine serum (15 g/l protein concentration) as a lubricant for five million cycles (MC), with measurements repeated every 1 MC. The mean wear rate in the 4DOF test was 12.7 +/- 2.1 mg/MC compared to 11.6 +/- 1.2 mg/MC in the 5DOF test. There were marked differences in the wear scars between 4DOF and 5DOF simulations. With 4DOF, wear scars were centralised on the dome of the insert, whilst 5DOF scars were larger, breaching the anterior rim of the dome causing deformation at the edge. The 4DOF wear test showed similar gravimetric wear rates to previously published ISO-tested TDRs. The addition of AP load was found to have no significant effect on the overall wear rate. However, there were pronounced differences in the respective wear scars, which highlights the need for more research in order to understand the factors that influence wear of TDR.

Identification of nanometre-sized ultra-high molecular weight polyethylene wear particles in samples retrieved in vivo.

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated. We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 microm to 0.99 microm size range. Particles in the 1.0 microm to 9.99 microm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles.

Wear and biological activity of highly crosslinked polyethylene in the hip under low serum protein concentrations.

Crosslinked ultra-high molecular weight polyethylene (UHMWPE) has been developed and introduced into clinical practice in order to reduce wear in the hip. Zero wear of highly crosslinked UHMWPE in vitro has been reported by some groups using lubricants with high concentrations of serum proteins in hip simulators. In contrast, some clinical studies have reported finite wear rates. The aim of this study was to compare the wear rates, wear surfaces, and wear debris produced by UHMWPE with different levels of crosslinking in a hip joint simulator, with lower, more physiologically relevant concentrations of protein in the lubricant. The UHMWPEs were tested in the Leeds ProSim hip joint simulator against cobalt-chromium (CoCr) femoral heads. The wear particles were isolated and imaged using a field emission gun scanning electron microscope (FEGSEM) at high resolution. The highly crosslinked UHMWPEs had significantly lower wear volumes than the non-crosslinked UHMWPEs. No significant difference was found in the percentage number and percentage volume of the particles in different size ranges from any of the materials. They had similar values of specific biological activity. The functional biological activity (FBA), which takes into account the wear volume and specific biological activity, showed that the highly crosslinked UHMWPEs had lower FBAs due to their lower wear volume.

Isolation and characterization of UHMWPE wear particles down to ten nanometers in size from in vitro hip and knee joint simulators.

There is currently considerable interest in the wear debris and osteolytic potential of different types of bearings used in total joint replacements. The biological activity of the wear debris is dependent on the size and volume of the particles produced. Wear volume also plays an important role in the functional biological activity of a joint replacement. In vitro studies have shown that crosslinking of ultra high molecular weight polyethylene (UHMWPE) acetabular cups and tibial trays produces a reduction in wear volume, and crosslinking has now been introduced clinically for both types of prostheses. Previous studies have identified both micron and submicron-sized polyethylene wear particles. The aim of this study was to characterize the wear and wear particles generated from moderately crosslinked GUR 1,020 GVF UHMWPE acetabular cups and tibial trays in hip and knee joint wear simulators down to 10 nanometers in size. The wear rates of the two prosthesis types were very similar at 25.6 +/- 5.3 mm(3) per million cycles for the hip prostheses and 22.75 +/- 5.95 mm(3) per million cycles for the knee prostheses. Nanometer-sized wear particles were isolated and characterized from both hip and knee simulator lubricants for the first time. Significantly higher numbers (p < 0.05) of particles in the nanometer (<0.1 microm) size range were produced by the hip prostheses compared to the knee prostheses. The knee prostheses produced larger particles, with the mode of particle size in the 0.1-1.0 microm size range, compared to <0.1 microm size range for the hip prostheses. In addition, the knee prostheses produced a greater volumetric concentration of wear particles in the 1.0-10 microm size range, and consequently lower specific biological activity and functional biological activity indices. These results indicated that the knee prostheses had a lower osteolytic potential compared to the hip prostheses.

Wear of surface engineered metal-on-metal hip prostheses.

The wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/million cycles) is much lower than the more widely used polyethylene-on-metal bearings (30-100 mm3/million cycles). However, there remain some potential concerns about the toxicity of metal wear particles and elevated metal ion levels, both locally and systemically in the human body. The aim of this study was to investigate the wear, wear debris and ion release of fully coated surface engineered MOM bearings for hip prostheses. Using a physiological anatomical hip joint simulator, five different bearing systems involving three thick (8-12 microm) coatings, TiN, CrN and CrCN, and one thin (2 microm) coating diamond like carbon (DLC) were evaluated and compared to a clinically used MOM cobalt chrome alloy bearing couple. The overall wear rates of the surface engineered prostheses were at least 18-fold lower than the traditional MOM prostheses after 2 million cycles and 36-fold lower after 5 million cycles. Consequently, the volume of wear debris and the ion levels in the lubricants were substantially lower. These parameters were also much lower than in half coated (femoral heads only) systems that have been reported previously. The extremely low volume of wear debris and concentration of metal ions released by these surface engineered systems, especially with CrN and CrCN coatings, have considerable potential for the clinical application of this technology.

In vitro analysis of the wear, wear debris and biological activity of surface-engineered coatings for use in metal-on-metal total hip replacements.

Extremely low wear rates have been reported for metal-on-metal total hip replacements, but concerns remain about the effects of metal ion release, dissolution rates and toxicity. Surface-engineered coatings have the potential to improve wear resistance and reduce the biological activity of the wear debris produced. The aim of this study was to examine the wear and wear debris generation from surface-engineered coatings: titanium nitride (TiN), chromium nitride (CrN) and chromium carbon nitride (CrCN) applied to a cobalt-chrome alloy (CoCr) substrate. The coatings were articulated against themselves in a simple geometry model. The wear particles generated were characterized and the cytotoxic effect on U937 macrophages and L929 fibroblasts assessed. The CrN and CrCN coatings showed a decrease in wear compared to the CoCr bearings and produced small (less than 40 nm in length) wear particles. The wear particles released from the surface engineered bearings also showed a decreased cytotoxic effect on cells compared to the CoCr alloy debris. The reduced wear volumes coupled with the reduced cytotoxicity per unit volume of wear indicate the potential for the clinical application of this technology.

An in vitro study of the reduction in wear of metal-on-metal hip prostheses using surface-engineered femoral heads.

Although the wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/10(6) cycles) is much lower than the more widely used polyethylene-on-metal bearings, there are concerns about the toxicity of metal wear particles and elevated metal ion levels, both locally and systemically, in the human body. The aim of this study was to investigate the possibility of reducing the volume of wear, the concentration of metal debris and the level of metal ion release through using surface-engineered femoral heads. Three thick (8-12 microm) coatings (TiN, CrN and CrCN) and one thin (2 microm) coating (diamond-like carbon, DLC), were evaluated on the femoral heads when articulating against high carbon content cobalt-chromium alloy acetabular inserts (HC CoCrMo) and compared with a clinically used MOM cobalt-chromium alloy bearing couple using a physiological anatomical hip joint simulator (Leeds Mark II). This study showed that CrN, CrCN and DLC coatings produced substantially lower wear volumes for both the coated femoral heads and the HC CoCrMo inserts. The TiN coating itself had little wear, but it caused relatively high wear of the HC CoCrMo inserts compared with the other coatings. The majority of the wear debris for all half-coated couples comprised small, 30 nm or less, CoCrMo metal particles. The Co, Cr and Mo ion concentrations released from the bearing couples of CrN-, CrCN- and DLC-coated heads articulating against HC CoCrMo inserts were at least 7 times lower than those released from the clinical MOM prostheses. These surface-engineered femoral heads articulating on HC CoCrMo acetabular inserts produced significantly lower wear volumes and rates, and hence lower volumetric concentrations of wear particles, compared with the clinical MOM prosthesis. The substantially lower ion concentration released by these surface-engineered components provides important evidence to support the clinical application of this technology.

Alumina-alumina artificial hip joints. Part II: characterisation of the wear debris from in vitro hip joint simulations.

Until recently it was not possible to reproduce clinically relevant wear rates and wear patterns in in vitro hip joint simulators for alumina ceramic-on-ceramic hip prostheses. The introduction of microseparation of the prosthesis components into in vitro wear simulations produced clinically relevant wear rates and wear patterns for the first time. The aim of this study was to characterise the wear particles generated from standard simulator testing and microseparation simulator testing of hot isostatically pressed (HIPed) and non-HIPed alumina ceramic-on-ceramic hip prostheses, and compare these particles to those generated in vivo. Standard simulation conditions produced wear rates of approximately 0.1 mm3 per million cycles for both material types. No change in surface roughness was detected and very few wear features were observed. In contrast, when microseparation was introduced into the wear simulation, wear rates of between 1.24 (HIPed) and 1.74 mm3 per million cycles (non-HIPed) were produced. Surface roughness increased and a wear stripe often observed clinically on retrieved femoral heads was also reproduced. Under standard simulation conditions only nanometre-sized wear particles (2-27.5 nm) were observed by TEM, and it was thought likely that these particles resulted from relief polishing of the alumina ceramic. However, when microseparation of the prosthesis components was introduced into the simulation, a bi-modal distribution of particle sizes was observed. The nanometre-sized particles produced by relief polishing were present (1-35nm). however, larger micrometre-sized particles were also observed by both transmission electron microscopy (TEM) (0.021 microm) and scanning electron microscopy (SEM) (0.05-->10 microm). These larger particles were thought to originate from the wear stripe and were produced by trans-granular fracture of the alumina ceramic. In Part I of this study, alumina ceramic wear particles were isolated from the periprosthetic tissues from around Mittelmeier ceramic-on-ceramic hip prostheses. Characterisation of the particles by TEM and SEM revealed a bi-modal size distribution. SEM analysis revealed particles in the 0.05-3.2 microm size range. and TEM revealed particles in the 5-90 nm size range, indicating that microseparation of the prosthesis components may be a common event in vivo. This study (Part II) has revealed that the introduction of microseparation of the prosthesis components during the swing phase of the wear simulation reproduced clinically relevant wear rates, wear patterns and wear particles in in vitro hip joint simulators.

Quantitative analysis of UHMWPE wear debris isolated from the periprosthetic femoral tissues from a series of Charnley total hip arthroplasties.

Submicrometer and micrometer-sized UHMWPE wear particles have been associated with osteolysis and failure of total hip replacements. A previous study by Tipper et al. examined the wear debris isolated from the acetabular periprosthetic tissues from 18 Charnley total hip replacements, and compared this data to the tribological variables of the prostheses. The present study aimed to isolate the UHMWPE wear debris from the femoral periprosthetic tissues from 10 of the same cohort of patients, and compare it with the debris isolated from the corresponding acetabular tissues. A variety of particle morphologies were observed, discrete submicrometer particles, along with flakes and fibrils. The particle size distributions ranged from 0.1 to >250 microm, however, the largest particles were only found in samples when the femoral head damage was characterised as low (R(pm) < 0.2 microm). The mode of the frequency distribution of particles was in the range of 0.1-0.5 microm for all the femoral tissues. Considerable variations were found in the mass distributions of the wear particles as a function of size for different patients. The net mass of debris isolated from the femoral tissues was significantly lower (p < 0.05, Student's t-test) than from the corresponding acetabular tissues. This along with considerable spatial variation in the net mass of debris isolated from the different regions of the same sample of acetabular tissue, indicates that the transportation of the debris has a marked effect on the net mass of debris accumulated in different tissues.

Comparison of wear, wear debris and functional biological activity of moderately crosslinked and non-crosslinked polyethylenes in hip prostheses.

The wear, wear debris and functional biological activity of non-crosslinked and moderately crosslinked ultrahigh molecular weight polyethylene (UHMWPE) acetabular cups have been com pared when articulating against smooth and intentionally scratched femoral heads. Volumetric wear rates were determined in a hip joint simulator and the debris was isolated from the lubricant and characterized by the percentage number and volumetric concentration as a function of particle size. The volumetric concentration was integrated with the biological activity function determined from in vitro cell culture studies to predict an index of specific biological activity (SBA). The product of specific biological activity and volumetric wear rate was used to determine the index of functional biological activity (FBA). On smooth femoral heads the crosslinked UHMWPE had a 30 per cent lower wear rate, but it had a greater percentage volume of smaller, more biologically active particles, which resulted in a similar index of FBA compared with the non-crosslinked material. On the scratched femoral heads the volumetric wear rate was three times higher for the moderately crosslinked UHMWPE and two times higher for the non-crosslinked UHMWPE compared with the smooth femoral heads. This resulted in a higher wear rate for the moderately crosslinked material on the scratched femoral heads. All the differences in wear rate were statistically significant. There were only small differences in particle volume concentration distributions, and this resulted in similar indices of FBA which were approximately twice the values of those found on the smooth femoral heads. Both materials showed lower wear and FBA than for previously studied aged and oxidized UHMWPE gamma irradiated in air. However, this study did not reveal any advantage in terms of predicted FBA for moderately crosslinked UHMWPE compared with non-crosslinked UHMWPE.