Ultra-high Molecular Weight Polyethylene Particles Research Articles

Polyethylene Particle-Induced Bone Resorption in Substance P-Deficient Mice

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening.

Effect of bisphosphonates on the stimulation of macrophages by alumina ceramic particles: A comparison with ultra-high-molecular-weight polyethylene

Wear particle-induced osteolysis and loosening is a critical process that limits the longevity of total hip arthroplasty. Despite their potential value in the management of aseptic loosening, little is known about the cellular response to bisphosphonates (BPs) in the presence of particulate debris. In the present study, we compared the effect of pamidronate and clodronate, two structurally different bisphosphonates, on the induction of TNF-alpha release by alumina ceramic (Al(2)O(3)) and ultra-high-molecular-weight-polyethylene (UHMWPE) particles. We also looked, by Trypan blue exclusion, at the viability of J774 mouse macrophages incubated with Al(2)O(3) and UHMWPE particles in combination with pamidronate or clodronate. Results showed that pamidronate and clodronate can inhibit UHMWPE particle-induced TNF-alpha release while they had no effect on Al(2)O(3)-stimulated TNF-alpha release. The co-incubation of pamidronate or clodronate and Al(2)O(3) had no effect on the induction by Al(2)O(3) of poly(ADP-ribose)polymerase (PARP) proteolysis and DNA fragmentation. On the other hand, UHMWPE particles had no effect on these apoptotic markers. However, the co-incubation of pamidronate or clodronate with UHMWPE particles led to the appearance of these markers of apoptosis. Al(2)O(3) and UHMWPE particles had no effect on macrophage cell death or the number of macrophages at the end of experiments. Co-incubation of UHMWPE particles with pamidronate and clodronate led to a significant increase in cell death. Interestingly, the number of macrophages co-incubated with particles and pamidronate or clodronate significantly decreased. In conclusion, our results suggest that the effect of BPs on particle-stimulated macrophages is, at least in part, particle composition dependent.

Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses

The problems of osteolysis and late aseptic loosening associated with ultra-high molecular weight polyethylene (UHMWPE) particles has lead to a renewed interest in metal-on-metal prostheses. Wear particles generated by modern Co-Cr-on-Co-Cr prostheses are nanometre in size (range: 10-120 nm; mean: about 40 nm), an order of magnitude smaller than the size of UHMWPE known to be critical for activation of osteolytic cytokines by macrophages. Co-Cr wear particles will induce osteolytic cytokine production by human macrophages, but only at high volumetric concentrations. Unlike UHMWPE, Co-Cr particles are not inert. Co-Cr particles have the potential to release metal ions; they may be toxic to cells, induce deoxyribonucleic acid damage or cause host hypersensitivity. The nanometre size range of Co-Cr wear particles means that they may be disseminated widely in the body. The potential for metal-on-metal bearings to induce adverse effects clinically will be dependent upon the rate of wear. What constitutes a safe wear rate for modern metal-on-metal bearings is unknown. However, the wear of metal-on-metal prostheses is critically dependent upon the design and, in particular, the carbon content of the alloy, the radial clearance, and the head diameter. Thus, the potential for adverse biological reactions associated with metal-on-metal bearings can be reduced by selection of appropriately designed implants.

Characteristic modeling of the wear particle formation process from a tribological testing of polyethylene with controlled surface asperities

To study the ultra-high molecular weight polyethylene (UHMWPE) wear particles-induced osteolysis which leads to the failure of artificial joints, microfabricated surfaces with controlled asperities have been applied to generate narrowly distributed UHMWPE wear particles with various sizes and shapes. Our previous study further facilitated single wedge sliding tests to investigate the mechanism of the UHMWPE particle generation. In this study, the attempt was made to characterize the particle generation process into a mathematical model to predict particle volume with a given surface-texture dimensions and mechanical loading conditions. The particle-generation process is decomposed into two steps: (1) penetration of the cutting edge, and (2) lateral sliding of the cutting edge. By combining the indentation experimental data, the viscoelastic responses of UHMWPE was incorporated in the model. The effects of normal load, feature height, and cutting edge angle on the wear particle volume were illustrated from model predictions. Both experimental results and model predictions indicate the same trend of effects of surface-texture geometry and mechanical conditions on the volume of particles. The results of the model predictions are close to the experimental results of the particle generation. However, the particle volume predicted by the model is larger than the experimental results. It is believed that the reprocessing of the generated particles and viscoelastic recovery of UHMWPE in the experiments account for this difference. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 587–594, 2007

Zelldifferenzierung einer humanen Knochenmarkzellkultur unter dem Einfluss von UHMW-PE Abriebpartikeln

The purpose of the present study was to evaluate the influence of ultra-high-molecular-weight polyethylene (UHMW-PE), which is the major constituent of the material debris formed as a result of orthopaedic implant wear, on the cellular differentiation in a modified in vitro model. UHMW-PE particles (Ø < or = 7.5 microm) were suspended in soluble collagen type I and subsequently solidified in different concentrations (10(5), 10(6) and 10(7) particles per well) on the bottom of the wells. Human bone marrow cells in a concentration of 3 x 10(6) cells per well were seeded on the collagen-particle substrate and maintained for up to 72 h. The response of the cells to the particles was examined by light microscopy, scanning electron microscopy and FACS analysis compared to cells on control collagen surfaces without any particles. Light and scanning microscopic evaluation revealed that the UHMW-PE particles, which had built large conglomerates (Ø 7.5 microm), were mainly surrounded by the cells and less phagocytosed. The results of the FACS analysis revealed significant differences in CD3/CD4 positive, CD14 positive and CD19 positive cells (p < 0.05). A significant elevation of CD3/CD4 positive and CD14 positive cells (p < 0.05) was observed after the period of culture (72 h) whereas a significant decrease could be detected in the case of CD19 positive cells. The results demonstrate that the particle-induced response by UHMW-PE limits itself not only to the particle macrophage contact but influences also the differentiation of the bone marrow. Moreover, the results confirm that the present method is useful to evaluate the in vitro effects of UHMW-PE wear particles with direct particle cell contact. Although the particles built large conglomerates, it could be shown that a change of the immune-competent cells also occurred.

Correlating subjective and objective descriptors of ultra high molecular weight wear particles from total joint prostheses

A total of 750 images of individual ultra-high molecular weight polyethylene (UHMWPE) particles isolated from periprosthetic failed hip, knee, and shoulder arthroplasties were extracted from archival scanning electron micrographs. Particle size and morphology was subsequently analyzed using computerized image analysis software utilizing five descriptors found in ASTM F1877-98, a standard for quantitative description of wear debris. An online survey application was developed to display particle images, and allowed ten respondents to classify particle morphologies according to commonly used terminology as fibers, flakes, or granules. Particles were categorized based on a simple majority of responses. All descriptors were evaluated using a one-way ANOVA and Tukey–Kramer test for all-pairs comparison among each class of particles. A logistic regression model using half of the particles included in the survey was then used to develop a mathematical scheme to predict whether a given particle should be classified as a fiber, flake, or granule based on its quantitative measurements. The validity of the model was then assessed using the other half of the survey particles and compared with human responses. Comparison of the quantitative measurements of isolated particles showed that the morphologies of each particle type classified by respondents were statistically different from one another ( p < 0.05 ). The average agreement between mathematical prediction and human respondents was 83.5% (standard error 0.16%). These data suggest that computerized descriptors can be feasibly correlated with subjective terminology, thus providing a basis for a common vocabulary for particle description which can be translated into quantitative dimensions.

Analysis of polyethylene particles isolated from periprosthetic tissue of loosened hip arthroplasty and comparison with radiographic appearance

Aseptic loosening is the major problem associated with joint arthroplasty, but little is known about the precise mechanism of osteolysis. To elucidate this mechanism we analyzed polyethylene particles retrieved from granulation tissue around the stem of loosened hip arthroplasties. Granulation tissue was obtained from 35 patients at revision surgery for a loosened hip and digested with papain, followed by ultracentrifugation. The isolated particles were identified with ultra-high molecular weight polyethylene particles by Fourier transform infrared spectroscopy. The morphology and number of particles were analyzed by scanning electron microscopy. Most of the particles were granular, with 87.9% being less than 1 μm in equivalent circle diameter (mean 0.83 ± 0.45 μm). The mean number of particles per gram of tissue was 1.48 × 109 (range 7.59 × 107 to 1.15 × 1010). We compared these data to the radiological appearance and found that focal-type osteolysis contained more particles than the linear type. The amount of submicron-sized particles is related to the development of osteolysis.

The inhibition of neutrophil antibacterial activity by ultra-high molecular weight polyethylene particles

Following infection, bacterial killing by polymorphonuclear leukocytes (neutrophils) is the main host defense against bacteria. Our hypothesis is that particles of ultra-high molecular weight polyethylene (UHMWP) may impair local neutrophil function and consequently reduce neutrophil bacterial killing. To determine how the in vitro phagocytic–bactericidal activity of neutrophils was affected by exposure to wear particles, tests were run comparing the effects of different particle composition, and different concentrations and sizes of UHMWP particles. There was a significant correlation between the number of particles and the decrease in neutrophil bactericidal activity ( p < 0.01 ), and the greatest effect was obtained with a concentration of 10 7 UHMWP/ml. There was a significant decrease in neutrophil bactericidal activity by incubation with particles of 0.1–5 μm ( p < 0.01 ), but not with larger size. The results suggest that neutrophil functional defects triggered by the presence of UHMWP particles may potentially contribute to the susceptibility of loose implants to bacterial infections.

Preventive and Mitigative Effects of Alendronate on Osteolysis induced by Particulate Debris: Quantitative and Comparative Analysis Using Mouse Calvarial Model

Purpose: Wear particle induced osteolysis is a serious complication in total joint arthroplasty. The purpose of this study was to compare the preventive and mitigative effects of alendronate on particle induced osteolysis among particles using mouse calvarial model. Materials and Methods: Seventy-two mice were randomized into sham group, Ti6Al4V group, CoCr-Mo group and Ultra High Molecular Weight Polyethylene (UHMWPE) group according to the particles treated to the calvarial tissues. Each group was divided into control subgroup which received no alendronate, preventive subgroup which received alendronate for 4 weeks after particle distribution and therapeutic subgroup which received alendronate for 3 weeks after 1 week delay from particle distribution. We evaluated the effects quantitatively using histomorphometry. Number of osteoclast, fibrous thickness, eroded bone surface area, bone thickness and bone volume were measured and compared. Results: Alendronate showed significant preventive and mitigative effects on osteolysis induced by Ti6Al4V particles and showed significant preventive and somewhat less mitigative effect on osteolysis by CoCrMo particles. On UHMWPE particles, alendronate showed no preventive and mitigative effects. Conclusion: Alendronate may be useful in preventing osteolysis induced by metal particles but had no effect on ostelysis induced by UHMWPE particles.

Zytokinprofil einer humanen Knochenmarkzellkultur unter dem Einfluss von UHMW-PE Abriebpartikeln / Cytokine profile of a human bone marrow cell culture under the influence of UHMW-PE wear particles

There is considerable evidence that orthopaedic wear debris plays a crucial role in the pathology of aseptic loosening of joint prostheses. The purpose of the present study was to evaluate the influence of ultra-high-molecular-weight polyethylene (UHMW-PE) on the cytokine response in a modified in vitro model. UHMW-PE particles (psi < 7.5 microm) were suspended in soluble collagen type I and subsequently solidified in different concentrations (105,106 and 107 particles per well) on the bottom of the wells. Human bone marrow cells in a concentration of 3 x 106 cells per well were seeded on the collagen-particle substrata and maintained for up to 12 days. The cytokine response (IL-1_, IL-6 and TNF-_) of the cells to the particles were examined by ELISA compared to cells on control collagen surfaces without any particles. Assays for viability using LDH activity were done immediately. Light and scanning microscopic evaluation revealed that the UHMWPE particles, which have built large conglomerates (psi7.5_m), were mainly surrounded by the cells and less phagocytosed. The results of the cytokine release revealed significant differences in interleukin (IL)6, tumor necrosis factor (TNF)- _ and IL-1beta. The cell viability was not affected by the UHMW-PE particles. The results demonstrate that the particle induced cytokine response by UHMW-PE is mainly by the release of Interleukin 6 and TNF- _. Moreover the results confirm that the present method is useful to evaluate the in vitro effects of UHMW-PE wear particles with direct particle cell contact.

UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease

Background We examined the effects of ultra-high molecular weight polyethylene (UHMWPE) particles on mononuclear cell proinflammatory gene expression in a novel murine model. We hypothesized that mononuclear cell gene trainscription of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1) would be upregulated by the addition of polyethylene particles in this murine intramedullary rod model.Material and methods The model involved a stainless steel Kirschner wire inserted retrograde with a line-to-line fit in bilateral femora of C57bl/6 mice. Additionally, the right femora were injected with 3 × 109 UHMWPE particles. Mononuclear marrow cells were isolated by bone marrow aspiration and Ficoll-Paque centrifugation at 2, 4 and 10 weeks post-surgery. Total RNA was isolated and real-time RT-PCR was performed to quantify gene expression. Histological specimens of explanted femora were also analyzed to track the changes in periprosthetic tissue.Results UHMWPE particles stimulated gene transcription in mononuclear cells when examined at 2, 4 and 10 weeks post-surgery, compared to the rod-only group. Relative levels of IL-1βand MCP-1 mRNA increased in a linear fashion over the 10-week time-course. IL-6 mRNA showed increased expression which peaked at 4 weeks. TNF-αmRNA expression was variable and reached a minimum at 4 weeks. The addition of UHMWPE particles stimulated ingress of macrophages and multinuclear cells of macrophage origin to the bone-implant interface.Interpretation In this model, a single bolus of UHMWPE particles had a long-term effect on gene transcription in mononuclear cells which perpetuated a chronic inflammatory state. This murine model of intramedullary particle-induced inflammation simulates periprosthetic events associated with implant wear in humans, and may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.

Opsonization of polyethylene wear particles regulates macrophage and osteoblast responses in vitro.

The cellular reaction to wear debris may result in the failure of an artificial joint's fixation to the skeleton. The influence of debris opsinization on cell activity has received little attention. This study seeks to establish whether different proteinaceous culture environments may invoke variant cellular responses to debris challenge. Consideration of the zeta potential of a low density polyethylene particle group and an ex vitro ultrahigh molecular weight polyethylene particle group revealed that the nature of the protein adsorbants is related to the concentration of the proteins in solution. Furthermore, the composition of the adsorbed layer was shown to vary with the spectra of proteins in solution. In standard cell culture conditions zeta potential approached zero, indicating the high probability of particle agglomeration. Cell challenge studies with U937 macrophages showed that BSA and FCS protein adsorption mediated increased cell adhesion, while bovine IgG showed little change over control values. No changes in behavior of osteoblastic cells were observed in similar experiments.

The influence of alumina and ultra-high molecular weight polyethylene particles on osteoblast–osteoclast cooperation

Particle-induced macrophage activation, mainly by UHMWPE wear, has been recognized as the biological mechanism leading to periprosthetic bone resorption, which is responsible for the loosening of the total hip replacements (THR). Ceramic-on-ceramic implants have been advocated as a means of reducing wear products. Many studies investigated the effect of alumina (Al 2O 3) particles on monocytes/macrophages, but only limited information are available on their participation to bone turnover. An in vitro model was performed to investigate how Al 2O 3 and UHMWPE particles may influence the osteoblast–osteoclast interaction: human osteoblasts (HOB) were obtained from trabecular bone, while osteoclasts were derived from peripheral blood mononuclear cells (PBMC) of healthy donors. The amount of IL6, TNF α, GM-CSF, and other factors acting on the bone turnover, i.e. the ‘receptor activator of NFkB’ ligand (RANKL) and osteoprotegerin (OPG), was detected in culture medium of particle-challenged HOB (HOB-CM). The Al 2O 3 and UHMWPE particles did not affect either cell viability or TNF and GM-CSF release, while the increase in IL6 release seemed to be dependent on the particle concentration. UHMWPE increased the release of RANKL from HOB, while OPG and OPG-to-RANKL ratio were significantly inhibited. The ability of HOB-CM to promote osteoclastogenesis was tested via osteoblast/monocyte cooperation: after seven days of culture UHMWPE HOB-CM induced a large amount of multinucleated TRAP-positive giant cells, as well as significantly reduced the amount of IL6, GM-CSF and RANKL in the supernatant. With regard to the inductive effect on the osteoclastogenesis, our results show that the Al 2O 3 wear debris are less active.

The effect of COX-2 inhibitors on periprosthetic osteolysis

We aimed to test the hypothesis that COX(cyclooxygenase)-2 inhibitors suppress periprosthetic osteolysis in a rabbit model. Porous coated titanium bar was inserted into distal femur of 24 skeletally mature New Zealand white rabbits. The rabbits were randomized into 3 groups. Group I (8 rabbits) was the control group. In Group II (8 rabbits), 5 mg of ultrahigh molecular weight polyethylene particles was inserted along with prosthesis. In Group III (8 rabbits), the same procedure as in Group II was done and a COX-2 inhibitor (celecoxib, Pharmacia: 10 mg/day) was administered for 7 weeks. Rabbits were sacrificed after 8 weeks of implantation. Gross, radiological, histological, and immunohistochemical assessments were done. Gross examination showed that one implant in Group II was loose. In radiological evaluation, focal osteolysis was found in 2 rabbits of Group II and 1 rabbit of Group III. Linear osteolysis was found in 2 rabbits of Group II and 1 rabbit of Group III. On histological examination, focal area of granulation tissue laden with macrophages was observed in 6 rabbits of Group II and 6 rabbits of Group III. The mean number of osteoclasts as demonstrated by tartarate positive acid phosphatase staining was 0.5±0.5 in Group I, 6.5±2.7 in Group II, 3.6±2.6 in Group III ( p<0.05). Immunohistochemical staining for inducible nitric acid synthase and COX-2 did not show significant difference between Groups II and III. The overall results of this study suggest that COX-2 inhibitors in the therapeutic dose may have a place in suppressing the process of periprosthetic osteolysis.

Distinct gene expression of receptor activator of nuclear factor-κB and rank ligand in the inflammatory response to variant morphologies of UHMWPE particles

Recent studies have examined the role of wear debris-induced bone resorption in the aseptic loosening of orthopedic prostheses. Research has shown that inflammation depends not only on the amount of particulate debris, but also the shape and size of the accumulated wear particles. Our previous studies have demonstrated that variant shapes of ultra-high molecular weight polyethylene (UHMWPE) particles induce diverse cellular and apoptotic responses in a murine inflammation model. Since enhanced osteoclastogenesis is recognized as a hallmark of bone loss in prosthetic loosening, we have now investigated the gene expression of receptor activator of nuclear factor-κB (RANK) and receptor activator of nuclear factor-κB ligand (RANKL) during the inflammatory response to different shapes of UHMWPE particles. Two shapes of UHMWPE particles (globular or elongated) were implanted in established air pouches on BALB/c mice, and pouches harvested 7 days after stimulation with UHMWPE particles. Gene levels of RANK, RANKL, TNF α, IL-1 β, and cathepsin K (CK) were quantified by real time RT-PCR, and TRAP staining of pouch membrane was used to evaluate osteoclastogenesis. We found that (i) elongated particles generated significantly higher RANK and RANKL gene expression than globular particles in pouch tissue; (ii) elongated particles provoked significantly higher IL-1 β and TNF α gene expression; (iii) a positive association was found between tissue inflammation status and the gene level of RANK/RANKL; and (iv) elongated particles stimulated significantly higher CK gene expression in comparison with globular particles. Histology revealed that clusters of TRAP+ cells were located in regions in contact with elongated particles. Overall, these data suggest that the morphology of wear debris may be a critical factor in the pathogenesis of prosthetic loosening.

Local infusion of FGF-2 enhances bone ingrowth in rabbit chambers in the presence of polyethylene particles.

Osseointegration of porous-coated implants during revision arthroplasty procedures is often impeded due to the presence of residual granuloma, particulate debris, and a sclerotic, dysvascular bone bed. We hypothesized that local infusion of recombinant fibroblast growth factor (FGF-2) would increase bone ingrowth in an in vivo model of tissue differentiation in the rabbit tibia in the presence of phagocytosable polyethylene particles. A drug test chamber (DTC) was implanted in the proximal medial tibial metaphysis of mature rabbits unilaterally. The chamber contained a 1x 1 x 5-mm tunnel for tissue ingrowth, and was connected to an osmotic diffusion pump. FGF-2 was infused at dosages of 0, 0.5, 5, 50, or 500 ng/day for a 3-week period, with subsequent harvesting of the ingrown tissue after each 3-week treatment. The effects of ultrahigh molecular weight polyethylene particles (0.5-microm diameter) on tissue ingrowth were determined by adding particles to the chamber at concentrations of 5.8 x 10(11) (low dose) or 1.7 x 10(12) (high dose) particles/mL, with and without infusion of 50 ng/day of FGF for 3 weeks. The tissue forming in the chamber was harvested after each treatment for histologic processing and morphometric analysis of bone ingrowth. Statistical analysis was performed using parametric tests (ANOVA), nonparametric tests (Kruskal-Wallis test) and post hoc tests. In the absence of particles, infusion of 50 ng FGF-2 per day yielded the greatest amount of bone ingrowth. The high dose of particles suppressed bone ingrowth into the chamber, but the low dose particles did not (p = 0.0002, 95% confidence limits = 9.19-18.80). Infusion of 50 ng FGF-2 per day significantly increased net bone formation in the presence of high-dose UHMWPE particles (p = 0.039, 95% confidence limits = 1.41-6.79). There was a trend for decreased numbers of vitronectin-receptor positive (osteoclast-like) cells with the addition of FGF-2, compared to particles alone (p = 0.08). Local delivery of FGF-2 may prove useful in mitigating the adverse effects of wear debris (e.g., in treating early osteolytic lesions), and facilitating osseointegration of revision total joint replacements in situations where the bone bed is suboptimal and residual particles and granulomatous tissue are present.

Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles.

Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

Diverse cellular and apoptotic responses to variant shapes of UHMWPE particles in a murine model of inflammation

The wear of orthopaedic prostheses results in the release of a markedly heterogeneous assortment of particulate debris, with respect to both size and shape. Although particle size has been extensively examined, the role of particle shape in adverse inflammatory reactions to debris remains unclear. Using an in vivo murine model of inflammation, we assessed tissue responses to globular and to elongated ultra-high molecular weight polyethylene (UHMWPE) particles with a similar surface area, and investigated whether inflammation and cellular apoptosis varied with particle shape in the debris–tissue interaction. Histological changes of UHMWPE-stimulated pouch membrane were assessed using a computerized image analysis system. Quantitative real time PCR and ELISA were performed to assess mRNA expression and protein level of the cytokines, and TUNEL assays were conducted to quantify apoptotic cells. The data revealed that elongated particles generated more active inflammatory air pouches, stimulated more severe membrane proliferation and the inflammatory cellular infiltration compared to globular particles. Increased levels of IL-1 β and TNF α were detected in the lavage and homogenate of pouches stimulated with elongated particles in comparison to pouches with globular particles, and the apoptotic assay indicated more severe apoptotic changes within the inflammatory membrane provoked with elongated particles. Our results suggest that cellular responses to UHMWPE wear debris are dependent on the shape of the particles.

Nitric oxide and prostaglandin E2 production in response to ultra-high molecular weight polyethylene particles depends on osteoblast maturation state.

Recent studies have shown that osteoblast-like cells respond directly to ultra-high molecular weight polyethylene particles in culture, suggesting that they may be involved in aseptic loosening of endoprostheses. We tested the hypothesis that the state of cell maturation plays a role in the response of osteogenic cells to ultra-high molecular weight polyethylene particles. MG63 cells (immature osteoblast-like cells), OCT-1 cells (mature secretory osteoblast-like cells), and MLO-Y4 cells (osteocyte-like cells) were treated for twenty-four hours with commercial ultra-high molecular weight polyethylene particles with an average diameter of 1 mm. The effect of particle treatment on cell proliferation was assessed by measuring the number of cells, whereas the effects on differentiation and local factor production were assessed by measuring the production of osteocalcin, prostaglandin E2, and nitric oxide. The effect of particles on apoptosis was also evaluated. The addition of ultra-high molecular weight polyethylene particles increased the number of MG63 cells, did not affect the number of OCT-1 cells, and led to a decrease in the number of MLO-Y4 cells. The observed changes in cell number were not due to programmed cell death, as no more than 3% of the cells in cultures treated with the highest concentration of particles were undergoing apoptosis. Osteocalcin production was not affected by the addition of particles. Prostaglandin E2 production was increased in all three types of cultures, but the effect was greatest in OCT-1 cell cultures, as was the absolute amount of prostaglandin E2 produced. Nitric oxide production was unaffected in MG63 cell cultures, but it was stimulated in OCT-1 and MLO-Y4 cell cultures. The results of the present study support the hypothesis that osteoblast cell maturation state plays an important role in the response to ultra-high molecular weight polyethylene particles and that the terminally differentiated osteocyte may be involved in the bone response to wear debris in vivo.

Electrical properties of polyethylene and carbon black particle blends prepared by gelation/crystallization from solution

Composite materials based on low molecular weight polyethylene (LMWPE), ultra-high molecular weight polyethylene (UHMWPE) and carbon black (CB) particles were prepared by gelation/crystallization from solution. The positive temperature coefficient (PTC) intensity for the 90/10 (LMWPE/UHMWPE) composition exceeded five orders of magnitude for the specimens heat-treated at a suitable temperature, which was almost equal to that observed with LMWPE–CB blends prepared by a kneading method. In comparison with LMWPE–CB blends, much promoted reproducibility of PTC effect and inhibition of the negative temperature coefficient (NTC) effect were achieved.