Polyethylene Wear Particles Research Articles

Influence of surface profile of Co-28Cr-6Mo alloy on wear behaviour of ultra-high molecular weight polyethylene used in artificial joint

The influence of the surface profile of Co-28Cr-6Mo alloy (ASRM F75) on the wear behaviour of ultra-high molecular weight polyethylene (GUR1050) was investigated using pin-on-disc wear testing. The surface profile of Co-Cr-Mo alloy was designed to control not only the volume of wear of polyethylene but also the morphological features of the wear debris. The surface profile of Co-Cr-Mo alloy showed a surface roughness from the micrometre to nanometre scale, and a waviness curve with convex and concave parts of millimetres in size. The surface processing was conducted using micro slurry-jet erosion. The processed surface of Co-Cr-Mo alloy recorded the lowest wear rate of polyethylene in comparison with a conventional mirror finish surface. The equivalent circle diameter of the polyethylene wear particles from the processed surface was more than two-times larger than that using a conventional mirror finish surface. It was revealed that the larger debris group produced by the processed surface was able to reduce the secretion of IL-6 from macrophage activation during biochemistry tests. The results illustrate the possibility of controlling the major factors in the long-term osteolysis and loosening of artificial joints through the use of a surface modification of a Co-Cr-Mo alloy surface.

Particles and Ions Generated in Total Hip Joint Prostheses: In Vitro Wear Test Results of UHMWPE and XLPE Acetabular Components

The accurate and detailed characterization of wear particles and ions released from total hip joint prostheses is essential to understand the cause and development of osteolysis, aseptic loosening and hypersensitivity. In this in vitro research, the wear particles and ion release of 22 different test liquids from hip simulator studies were investigated. Wear particles generated from acetabular components made of ultra-high-molecular-weight polyethylene (UHMWPE) or cross-linked polyethylene containing vitamin E (XLPE) were compared using scanning electron microscopy (SEM) and laser diffraction. Additionally, the effect of running-in versus steady-state, accelerated ageing, head materials and calcium sulphate third-body particles on the morphology and size of the created debris was investigated. The Fe, Ni, Mn, Nb, Co, Mo and Al ions released from femoral heads made of stainless steel, CoCrMo and alumina ceramic were analysed using inductively coupled plasma mass spectrometry. The combination of SEM and laser diffraction to analyse both the morphology and the particle-size distributions of the polyethylene wear particles was very powerful. The wear particles were predominantly in the submicron range and globular, with occasional fibrils. The size distributions of the UHMWPE and XLPE particles were similar; however, more fibrils were observed among the UHMWPE particles. The average particle size decreased for most samples in the steady-state phase compared to the running-in. The accelerated ageing and the presence of third-body particles generally caused larger UHMWPE wear particles only. Increasing the size of the stainless steel femoral heads led to an increase in the ion level too.

A novel alginate-encapsulated system to study biological response to critical-sized wear particles of UHMWPE loaded with alendronate sodium

The aim of this study was to develop a novel alginate-encapsulated system (Alg beads) to investigate the cell response to critical-sized wear particles of ultra-high molecular weight polyethylene loaded with alendronate sodium (UHMWPE-ALN), one of the most effective drugs to treat bone resorption in clinic. The extrusion method was used to prepare Alg beads encapsulating rat calvarial osteoblasts (RCOs) and critical-sized UHMWPE-ALN wear particles with spherical morphology and uniform size. The morphology, permeability and stability of Alg beads were characterized. The proliferation, ALP activity, cell apoptosis and distribution of live/dead RCOs co-cultured with wear particles in Alg beads were evaluated. RCOs and critical-sized UHMWPE-ALN wear particles distributed evenly and contacted efficiently in Alg beads. Alg beads were both permeable to trypsin and BSA, while the smaller the molecular was, the larger the diffuse was. The proliferation of RCOs in Alg beads increased with time, which indicated that Alg beads provided suitable conditions for cell culture. The long-term stability of Alg beads indicated the possibility for the longer time of co-cultured cells with wear particles. Critical-sized UHMWPE-ALN and UHMWPE wear particles both inhibited the proliferation and differentiation of RCOs, and induced the apoptosis of RCOs encapsulated in Alg beads. However, these effects could be significantly alleviated by the ALN released from the critical-sized UHMWPE-ALN wear particles. The present results suggested that this novel-developed co-culture system was feasible to evaluate the cell response to critical-sized UHMWPE-ALN wear particles for a longer time.

Electrostatic field may regulate proliferation and immune responses of macrophages induced by polyethylene wear particles

Abstract Effects of electrostatic field on the macrophage responses induced by ultra-high molecular weight polyethylene (UHMWPE) wear particles have been investigated in this study. An inverted cell culture system was applied to study the interactions between UHMWPE wear particles and macrophage cells. The electrostatic field induced device (EFID) was installed on the cell culture system. The high voltage and low current stimulations generated from EFID were first applied to the UHMWPE particles/macrophage co-culture system. The proliferation and tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1β cytokine expressions of J774A.1 macrophage cells were analyzed. The EFID applied voltage of 0.5 kV, 1.0 kV, 1.3 kV, and 1.6 kV were investigated. Our result indicated that the 0.5 kV and 1 kV voltages increased the proliferation of macrophage cells and activated the expression of related cytokines under the co-culture of UHMWPE wear particles. However, with the increasing applied voltage of 1.3 kV and 1.6 kV, the inhibition of the macrophage proliferation and expression of immunological cytokines were observed. There exists a critical applying EFID voltage to modulate the UHWMPE particle induced immune responses. The electrostatic field induced device presents a potential non-invasive therapy for particle induced bone resorption and osteolysis.

Sequentially annealed highly cross-linked polyethylene reduced in vivo wear particle generation in total knee arthroplasty.

Sequentially annealed highly cross-linked polyethylene (HXLPE) was recently introduced to reduce the wear in total knee arthroplasty (TKA). However, an in vivo advantage of sequentially annealed HXLPE on wear particle generation is still controversial. The purpose of this study is to compare the characteristics of in vivo wear particles between sequentially annealed HXLPE and conventional polyethylene after TKA. Synovial fluid was obtained from the eight knees with sequentially annealed HXLPE and from eight knees with conventional polyethylene 12 months after the operation. Polyethylene particles were isolated and examined using a scanning electron microscope and image analyzer. Total number of wear particles in each knee was 2.1 ± 1.0 × 107 with sequentially annealed HXLPE (mean ± standard deviation) and 4.9 ± 3.6 × 107 with conventional polyethylene ( p = 0.036). Particle size (equivalent circle diameter) was 1.01 ± 0.26 μm with sequentially annealed HXLPE and 1.02 ± 0.20 μm with conventional polyethylene ( p = 0.674). Aspect ratio was 1.33 ± 0.04 with sequentially annealed HXLPE and 1.39 ± 0.10 with conventional polyethylene ( p = 0.462). The sequentially annealed HXLPE reduced the in vivo polyethylene wear particles by 58% compared with conventional polyethylene without the significant change of particle size and shape.

Study on critical-sized ultra-high molecular weight polyethylene wear particles loaded with alendronate sodium: in vitro release and cell response.

The aim of this study was to investigate the in vitro release and the effect of RAW 264.7 macrophages of critical-sized wear particles of ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN), one of the most effective drugs to treat osteoporosis in clinic. The critical-sized UHMWPE-ALN 0.5 wt.% wear particles were prepared by vacuum gradient filtration combined with Pluronic F-68. In vitro release of ALN from critical-sized UHMWPE-ALN wear particles was investigated in phosphate buffered saline (PBS) at 37 °C with a shaker. Cell morphology, proliferation, lactate dehydrogenase (LDH) leakage and secretions of cytokines were evaluated after co-cultured with critical-sized UHMWPE-ALN wear particles in vitro. Results showed that ALN released from critical-sized UHMWPE-ALN wear particles included burst release and slow release in vitro. Macrophages would be chemotaxis and aggregated around the critical-sized UHMWPE-ALN or UHMWPE wear particle, which was phagocytosed with time. The proliferation of macrophages co-cultured with critical-sized UHMWPE-ALN wear particles was significantly decreased compared with that of critical-sized UHMWPE group. Meanwhile, the critical-sized UHMWPE-ALN wear particles significantly induced the LDH leakage of macrophages, which indicated the cell death. The death of macrophages induced by ALN was one of pathways to inhibit their proliferation. The secretions of cytokines (interleukin-6 and tumor necrosis factor-alpha) in critical-sized UHMWPE-ALN group were significantly lower than those in critical-sized UHMWPE group due to the released ALN. The present results suggested that UHMWPE-ALN had the potential application in clinic to treat osteolysis induced by wear particles.

Peri-Implant Distribution of Polyethylene Debris in Postmortem-Retrieved Knee Arthroplasties: Can Polyethylene Debris Explain Loss of Cement-Bone Interlock in Successful Total Knee Arthroplasties?

BackgroundLoss of mechanical interlock between cement and bone with in vivo service has been recently quantified for functioning, nonrevised, cemented total knee arthroplasties (TKAs). The cause of interlocking trabecular resorption is not known. The goal of this study is to quantify the distribution of PE debris at the cement-bone interface and determine if polyethylene (PE) debris is locally associated with loss of interlock. MethodsFresh, nonrevised, postmortem-retrieved TKAs (n = 8) were obtained en bloc. Laboratory-prepared constructs (n = 2) served as negative controls. The intact cement-bone interface of each proximal tibia was embedded in Spurr’s resin, sectioned, and imaged under polarized light to identify birefringent PE particles. PE wear particle number density was quantified at the cement-bone interface and distal to the interface, and then compared with local loss of cement-bone interlock. ResultsThe average PE particle number density for postmortem-retrieved TKAs ranged from 8.6 (1.3) to 24.9 (3.1) particles/mm2 (standard error) but was weakly correlated with years in service. The average particle number density was twice as high as distal (>5mm) to the interface compared to at the interface. The local loss of interlock at the interface was not related to the presence, absence, or particle density of PE. ConclusionPE debris can migrate extensively along the cement-bone interface of well-fixed tibial components. However, the amount of local bone loss at the cement-bone interface was not correlated with the amount of PE debris at the interface, suggesting that the observed loss of trabecular interlock in these well-fixed TKAs may be due to alternative factors.

Histological Analysis of Early Osteolysis in Total Ankle Arthroplasty.

The purpose of this study was to perform a histological comparative analysis of tibiotalar joint samples taken from areas of osteolysis adjacent to total ankle arthroplasties vs control synovial specimens to determine the reaction to and presence of polyethylene (PE) particles. A total of 57 pathology samples were identified in the osteolysis group, while 11 were identified in the control group. For each sample, hematoxylin and eosin, Oil Red O (ORO), and macrophage marker CD163-stained slides were created. Polarized light and ORO stain were used to identify PE particles. The presence of metal particles and giant cell reaction to PE particles were also scored. Macrophages, PE particles, metallosis, and foreign body giant cell reaction scores were significantly higher in the osteolysis group compared with the control group. In the osteolysis group, ORO staining was positive in 93% (53/57), birefringent material was present in 96.5% (55/57), and macrophage infiltrates were present in 96.5% (55/57). Foreign body giant cell reaction with giant cells surrounding PE particles was present in 49.1% (28/57) of osteolytic specimens. The presence of foreign body giant cell reaction was associated with significantly higher macrophage, ORO, and polarizable material scores. The average time to surgery for osteolysis from the index ankle replacement was 6.0 (range, 0-15) years for the 57 patients in the osteolysis group. This study is the largest ankle arthroplasty histological analysis to show that areas of osteolysis consist of abundant polyethylene wear particles, present both intracellularly and extracellularly. Furthermore, these areas were associated with a CD163+ macrophage infiltrate and frequently a foreign body reaction with giant cells engulfing PE particles. It is likely that implant wear particles play a significant role in osteolysis based on the histopathology. Level III, retrospective comparative series.

NF-κB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model

Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3–6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. Statement of SignificanceTotal joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone-resorbing cells), and osteoblasts (bone-forming cells) could potentially mitigate this disease. Here we demonstrated that local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) mitigated ultra-high molecular weight polyethylene (UHMWPE) wear particle induced bone loss in a clinically relevant murine model. The protective effects of decoy ODN was associated with reduced macrophage infiltration and osteoclast activation, but had no significant effects on osteoblast numbers. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced bone loss.

Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis

Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis

Effect of particle size on biological response by human monocyte-derived macrophages

Abstract Ultra-high molecular weight polyethylene (UHMWPE) wear particles from artificial joints induce osteolysis and the subsequent loosening of implants. Studies have reported that particles in the size range of 0.1–10 μm are the most biologically active in macrophage immune response. To develop prosthetic joints with greater longevity and durability, it is crucial to understand the deleterious effects of wear particles. In this study, to evaluate the effects of particle size on the activities of human monocyte-derived macrophages (HMDMs), seven differently sized particles of polymethylmethacrylate (PMMA), in the range of 0.1–20 μm, were prepared. Viability and the secretion of cytokines were evaluated after phagocytosis of each size particles by HMDMs. Differences in the viability of HMDMs after phagocytosis of particles sized 0.16–9.6 μm were statistically significant. Proinflammatory cytokine production of both tumor necrosis factor-α and interleukin-6 by HMDMs was strongly induced by 0.8 μm PMMA particles. Consistent with the fact that macrophages are known to respond to pathogens measuring approximately 1.0 μm in size, in this study, PMMA particles measuring 0.8 μm in size induced an immune response. This work provides fundamental data for the designing of surface profiles of prosthetic joints, Which may expect the lower incidence of immune response.

Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis

Periprosthetic osteolysis (PO) leading to aseptic loosening, is the most common cause of failure of total hip replacement (THR) in the mid- to long-term. Polyethylene (PE) particulates from the wear of prosthesis liners are bioactive and are implicated in the initiation and or progression of osteolysis. Evidence exists that cells of the osteoblast/osteocyte lineage are affected by PE particles and contribute to the catabolic response by promoting osteoclastic bone resorption. In this study, we hypothesised that osteocytes contribute directly to PO by removing bone from their perilacunar matrix. Osteocyte responses to ultra-high molecular weight PE (UHMWPE) particles were examined in vitro in human primary osteocyte-like cultures, in vivo in the mouse calvarial osteolysis model, and in the acetabulum of patients undergoing revision total hip replacement (THR) surgery for PO. Osteocytes exposed to UHMWPE particles showed upregulated expression of catabolic markers, MMP-13, carbonic anhydrase 2 (CA2), cathepsin K (CTSK) and tartrate resistant acid phosphatase (TRAP), with no effect on cell viability, as assessed by Caspase 3 activity. Consistent with this catabolic activity causing perilacunar bone loss, histological analysis of calvarial sections from mice exposed to UHMWPE revealed a significant (p<0.001) increase in osteocyte lacunar area (Lac.Ar) compared to sham-operated animals. Furthermore, acetabular biopsies from patients with PO also showed significantly (p<0.001) increased osteocyte lacunar size in trabecular bone adjacent to PE particles, compared with osteocyte lacunar size in bone from primary THR patients. Together, these findings suggest a previously unrecognised action of UHMWPE wear particles on osteocytes, which directly results in a loss of osteocyte perilacunar bone. This action may exacerbate the indirect pro-osteoclastic action of UHMWPE-affected osteocytes, previously shown to contribute to aseptic loosening of orthopaedic implants. Statement of SignificanceThis study addresses the clinical problem of periprosthetic osteolysis, bone loss in response to polyethylene wear particles derived from materials used in orthopaedic implants. Periprosthetic osteolysis has been thought to be due largely to wear particles stimulating the activity of bone resorbing osteoclasts. However, in this study we demonstrate for the first time that polyethylene particles stimulate another type of bone loss, mediated by the direct activity of bone mineral embedded osteocytes, termed osteocytic osteolysis or osteocyte perilacunar remodelling. This study provides new mechanistic insight into wear-particle mediated bone loss and represents a new paradigm for the way in which bone cells, namely osteocytes, the key controlling cell type in bone, react to biomaterials.

Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo.

Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.

Adverse local tissue reaction (ALTR) associated with corrosion products in metal-on-metal and dual modular neck total hip replacements is associated with upregulation of interferon gamma-mediated chemokine signaling.

Adverse local tissue reactions (ALTR) associated with tribocorrosion following total hip arthroplasty (THA) have become a significant clinical concern in recent years. In particular, implants featuring metal-on-metal bearing surfaces and modular femoral stems have been reported to result in elevated rates of ALTR. These tribocorrosion-related tissue reactions are characterized by marked necrosis and lymphocytic infiltration, which contrasts sharply with the macrophagic and foreign body giant cell inflammation associated with polyethylene wear particle induced peri-implant osteolysis. In this study, we characterize tribocorrosion-associated ALTR at a molecular level. Gene expression profiling of peri-implant tissue around failing implants identifies upregulation of numerous inflammatory mediators in ALTR, including several interferon gamma inducible factors, most notably the chemokines MIG/CXCL9 and IP-10/CXCL10. This expression profile is distinct from that associated with polyethylene wear induced osteolysis, which is characterized by induction of markers of alternative macrophage activation, such as chitotriosidase (CHIT-1). Importantly, MIG/CXCL9 and IP-10/CXCL10 are also elevated at the protein level in the synovial fluid and, albeit more moderately, the serum, of ALTR patients, raising the possibility that these factors may serve as circulating biomarkers for the early detection of ALTR in at-risk patients.

Experimental testing of total knee replacements with UHMW-PE inserts: impact of severe wear test conditions.

Aseptic implant loosening due to inflammatory reactions to wear debris is the main reason for the revision of total knee replacements (TKR). Hence, the decrease in polyethylene wear particle generation from the articulating surfaces is aimed at improving implant design and material. For preclinical testing of new TKR systems standardized wear tests are required. However, these wear tests do not reproduce the entire in vivo situation, since the pattern and amount of wear and subsequent implant failure are underestimated. Therefore, daily activity, kinematics, implant aging and position, third-body-wear and surface properties have to be considered to estimate the wear of implant components in vivo. Hence, severe test conditions are in demand for a better reproduction of the in vivo situation of TKR. In the present article an overview of different experimental wear test scenarios considering clinically relevant polyethylene wear situations using severe test conditions is presented.

1D24 人工関節用ポリエチレン摩耗粉からの生体反応を抑制する摩擦面加工方法(OS10:ヒトや環境に適用可能なマテリアルテクノロジ)

1D24 人工関節用ポリエチレン摩耗粉からの生体反応を抑制する摩擦面加工方法(OS10:ヒトや環境に適用可能なマテリアルテクノロジ)

The result of revision total hip arthroplasty in patients with metallosis following a catastrophic failure of a polyethylene liner.

BackgroundWear cannot be completely prevented after total hip arthroplasty. If severe polyethylene (PE) liner wear develops, the so-called catastrophic failure occurs and metallosis develops. We postulated that longevity of the new implant may be affected after revision surgery for metallosis following a catastrophic failure of a PE liner due to the substantial amount of PE wear particles and infiltration of the metal particles in this catastrophic condition.MethodsTwenty-three hips of 23 patients were identified because they showed metallosis during revision total hip arthroplasties performed in Seoul National University Hospital between January 1996 and August 2004. They were followed for at least 6.5 years after the index revision total hip arthroplasty. The clinical and radiological results of revision total hip arthroplasties in these patients were evaluated.ResultsThe median Harris hip score increased from 60 points before revision total hip arthroplasties to 90 points at the final follow-up. Osteolysis was detected at an average of 9.3 years after revision total hip arthroplasties in 13 hips and acetabular cup loosening at average 9.8 years after revision total hip arthroplasties in 9 hips. With radiographic evidence of osteolysis and loosening as the end points, the 15-year survival rates were 28.2% and 56.0%, respectively.ConclusionsThe survival rate of revision total hip arthroplasty in patients with metallosis following a catastrophic failure of a PE liner was low.

Wear rates of highly cross-linked polyethylene humeral liners subjected to alternating cycles of glenohumeral flexion and abduction

Although short-term outcomes of reverse total shoulder arthroplasty have been promising, long-term success may be limited due to device-specific complications, including scapular notching. Scapular notching has been explained primarily as mechanical erosion; however, the generation of wear debris may lead to further biologic changes contributing to the severity of scapular notching. A 12-station hip simulator was converted to a reverse total shoulder arthroplasty wear simulator subjecting conventional and highly cross-linked ultra-high-molecular-weight polyethylene humeral liners to 5 million cycles of alternating abduction-adduction and flexion-extension loading profiles. Highly cross-linked polyethylene liners (36.5±10.0mm(3)/million cycle) exhibited significantly lower volumetric wear rates compared with conventional polyethylene liners (83.6±20.6mm(3)/million cycle; P<.001). The flexion-extension loading profile exhibited significantly higher wear rates for conventional (P<.001) and highly cross-linked polyethylene (P<.001) compared with the abduction-adduction loading profile. Highly cross-linked wear particles had an equivalent circle diameter significantly smaller than wear particles from conventional polyethylene (P<.001). Highly cross-linked polyethylene liners significantly reduced polyethylene wear and subsequent particle generation. More favorable wear properties with the use of highly cross-linked polyethylene may lead to increased device longevity and fewer complications but must be weighed against the effect of reduced mechanical properties.

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: A preliminary report

Total joint replacement (TJR) is very cost-effective surgery for end-stage arthritis. One important goal is to decrease the revision rate, mainly because TJR has been extended to younger patients. Continuous production of ultra-high molecular weight polyethylene (UHMWPE) wear particles induces macrophage infiltration and chronic inflammation, which can lead to periprosthetic osteolysis. Targeting individual pro-inflammatory cytokines directly has not reversed the osteolytic process in clinical trials, owing to compensatory up-regulation of other pro-inflammatory factors. It is hypothesized that targeting the important transcription factor NF-κB could mitigate the inflammatory response to wear particles, potentially diminishing osteolysis. In the current study, NF-κB activity in mouse RAW 264.7 and human THP1 macrophage cell lines, as well as primary mouse and human macrophages, was suppressed via competitive binding with double strand decoy oligodeoxynucleotide (ODN) containing an NF-κB binding element. It was found that macrophage exposure to UHMWPE particles induced multiple pro-inflammatory cytokine and chemokine expression, including TNF-α, MCP1, MIP1α and others. Importantly, the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages, and resulted in suppression of macrophage recruitment. The strategic use of decoy NF-κB ODN, delivered locally, could potentially diminish particle-induced periprosthetic osteolysis.

Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies.