Osteolysis and periprosthetic bone loss have been a concern since Charnley’s original reports of metal on Teflon. Willart and Semlitch were the first investigators to propose a biologic mechanism for osteolysis associated with particulate wear debris. Harris in 1976 and Goldring 1983 describe the presence of macrophages and giant cells in the synovial membrane at the bone cement interface in loose THR. Initially it was associated with cement and it was called cement disease. Reports of resorption around cementless implants led to the realization that PE alone was good enough to create bone loss. Aetiology: Submicron wear particles are phagocytosed by macrophages resulting in release of various cellular mediators from these activated cells. Cellular mediators playing significant role in osteolysis are IL-1, IL-6, TNF-a, PGE2. These mediators lead to stimulation and differentiation of osteoclasts and inhibition of osteoblasts. These factors together assist in the dissolution of bone at the interface allowing for micromotion of the prosthesis that leads to further generation of wear debris. On top of the above there is release of collagenase, stromelysin, gelatinase which further destroy the bone. Another active area of research involves roles at Rank, Rank and osteoprotegerin. Recently there is extensive work done as far as it concerns the role of endotoxin in osteolysis and periprosthetic bone loss. It still remains a controversial issue. Other researchers have studied the effects of elevated periarticular hydrostatic pressure and fluid access in the development of osteolysis (effective joint space). Particles bioreactivity: It has been shown that the major determinants of particle bioreactivity are particle size, composition, shape, and concentration. Particles of submicron size are more stimulatory and there is a dose dependent response. Concerning the composition it has been found that UHMWPE, CoCr and stainless steel particles induce more severe reactions than Titanium and alumina ceramic. It also has been found that Al2O3 particles were more easily phagocytosed than UHMWPE at the same size and concentration but TNF-a release was higher with than UHMWPE with Al2O3. Concerning the metal to metal particles it has been found that the volumetric wear is less than M/P with smaller particles and less intensive tissue reaction but Shanbhag reported that bioreactivity of metal wear debris is a function of the total surface area and not the volume of wear debris and casts doubts at the theory that metal to metal wear particles produce a less intense biological response. Concerning the highly crosslinked PE it has been found that wear debris from gamma crossed –linked remelted PE contains very few fibrils after a dose of 5 Mrads and virtually none after 9.5 Mrads. Clinical Manifestations: The majority of patients with osteolysis are asymptomatic. Pain is caused mainly from a fracture.Ultimately periprosthetic bone loss results in aseptic loosening. Furthermore if the component becomes loose bone loss often progress more rapidly resulting in large bone defects that can lead to catastrophic failure or fracture. Radiographic manifestations: Characteristic radiographic patterns of osteolysis have been described on both the femoral and acetabular side with cemented and cementless components. Recent studies have suggested that plain radiographs often underestimate the extent of osteolysis and CT or MRI may be necessary to assess the true extent of the bone loss

Wear debris from metal on metal (M/M) hip resurfacing and metal on polyethylene (M/P) total hip replacements have different biocompatibilities. M/P wear particles have a foreign body effect. 1. M/M wear particles cause hypersensitivity. 2. , DNA damage. 3. ,. 4. and white blood cell suppression. 5. . M/P wear debris contains nickel and M/M wear debris contains cobalt. Nickel and cobalt are both heavy metals, required as trace elements for some bacteria but potentially toxic to bacteria in high concentrations. Cobalt kills Helicobacter Pylori at concentrations as low as 30 ppb. 6. , substantially lower than the concentration in prosthetic joints. Nickel/cobalt permease membrane transporters are found in a wide range of microorganisms. 7. including Staphylococcus Aureus and Coagulase Negative Staphylococci, which commonly infect prosthetic joints. The purpose was to investigate the effects of nanoparticulate wear debris and their heavy metal constituents on bacterial growth. Samples of Coagulase Negative Staphylococci (CNS), Staphylococcus Aureus and MRSA were cultivated to compare their growth in M/M wear debris, M/P wear debris, nickel, cobalt and control culture mediums over 48 hours. Nickel was toxic to CNS (p=0.006) and MRSA (p=0.048). Cobalt also retarded the growth of all three bacteria. M/M wear debris increased the growth of CNS 183 times at 48 hours (p=0.044), Staphylococcus Aureus and MRSA. M/P wear increased the growth of Staphylococcus Aureus 120 times at 48 hours (p=0.021), CNS and MRSA. M/M and M/P nanoparticulate wear debris accelerate the rate of growth of common organisms that infect prosthetic hip joints, the clinical significance of which is uncertain. In isolation, the heavy metals contained within wear debris retard bacterial growth, particularly nickel. Nanoparticulate wear debris does not possess the toxic effects of its constituent metals on bacteria. This reinforces the safety of wear debris but also shows the potential for anti-bacterial effects to be harnessed

Osteolysis induced by UHMWPE debris has historically been one of the major causes of long term failure of TJR. An increase in concentration of polyethylene particles in the peri-prostheic tissue has been linked to an increased incidence of osteolysis. The dual mobility hip bearing concept mates a femoral head into a polyethylene liner which has an unconstrained articulation into a metal shell. The wear mechanism of the dual mobility hip bearing is distinct from a constrained single articulation design, which may result in a difference in wear debris particles. The aim of this study is to evaluate wear debris generated from a dual mobility hip and compare it to a conventional single articulation design when both are manufactured from sequentially crosslinked and annealed polyethylene. The dual mobility hip (Restoration ADM) incorporated a 28mm CoCr femoral head into a polyethylene liner that articulates against a metal shell (48mm ID). The conventional hip (Trident®) mated a 28mm CoCr femoral head against a polyethylene liner. The polyethylene for all liners was sequentially crosslinked and annealed (X3). A hip joint simulator was used for testing at a rate of 1 Hz with cyclic Paul curve physiologic loading. A serum sample from each testing group was collected. Serum samples were protein digested following the published process by Scott et al. The digested serum was then filtered through a series of polycarbonate filter papers of decreasing size and sputter coated with gold for analysis using SEM. Image fields were randomized and wear debris was compared in terms of its length, width, aspect ration, and equivalent circular diameter (ECD). A total of 149 conventional hip particles and 114 dual mobility hip particles were imaged. Results show a majority of particles are of spherical nature and images do not indicate the presence of fibrillar or larger elongated polyethylene debris. Particle length between designs is not statistically different, while all other comparisons show statistical significance (p<0.05). It is hypothesized that the dual mobility hip system reduces the total amount of cross-shear motion on any one articulation, which aids in the reduction in wear. This design feature may be responsible for the slight difference in morphology of dual mobility wear debris when compared to the constrained hip design. The length of the particles was similar, simply indicating a different shape rather than a marked reduction in overall size. The debris generated is this study was from highly crosslinked polyethylene in two different designs, which produced a very significant decrease in quantity of particles when compared to the quantity of debris from conventional polyethylene. The wear debris was of similar length in both designs and so we do not expect any difference in biological response to debris from either device. The dual mobility design has also shown no effect of cup abduction angle on wear demonstrating forgiveness to implant positioning. This advantage, combined with the low wear rate and similar length wear particles, should lead to good clinical performance of dual mobility cups with sequentially irradiated and annealed polyethylene

Introduction. Currently, different techniques to evaluate biocompatibility of orthopaedic materials, including two-dimensional (2D) cell culture for metal and ceramic wear debris and floating 2D surfaces or three-dimensional (3D) agarose gels for UHMWPE wear debris, are used. We have developed a single method using 3D agarose gels that is suitable to test the biocompatibility of all three types of wear debris simultaneously. Moreover, stimulation of the cells by wear particles embedded in a 3D gel better mimics the in vivo environment. Materials and Methods. Clinically relevant sterile UHMWPE and CoCr wear particles were generated using methodologies described previously [1,2]. Commercially available nanoscale and micron-sized silicon nitride (Si. 3. N. 4. ) particles (<50 nm and <1 μm, Sigma UK) were sterilised by heat treatment for 4h at 180°C. Agarose-particle suspensions were prepared by mixing warm 2% (w/v) low-melting-point agarose solution with the particles dispersed by sonication in DMEM culture media. The suspensions were then allowed to set at room temperature for 10 min in 96 well culture plates. Sub-confluent L929 murine fibroblasts were cultured on the prepared gels for up to 6 days in 5% (v/v) CO. 2. at 37°C. After incubation, the viability of cells was measured using the ATP-lite assay. The results were expressed as mean ± 95% confidence limits and the data was analysed using one-way ANOVA and Tukey-Kramer post-hoc analysis. Results and Discussion. The gels were observed to ensure uniform distribution of particles and migration of cells into the gel. No significant reduction in viability was observed for nanoscale and micron-sized Si. 3. N. 4. particles at low doses (0.5 μm. 3. per cell) and high doses (50 μm. 3. per cell), or for UHMWPE wear debris at high doses (100 μm. 3. per cell) [Figure1]. Moreover, the viability was significantly reduced for high doses of CoCr wear debris (50 μm. 3. per cell) and the positive control, camptothecin (2 μg.ml. −1. ) at day 6 [Figure1]. These results are consistent with the literature [2,3] and therefore validate our 3D agarose cell culture method for comparing cytotoxicity of polymer, metal and ceramic particles in a single assay, simultaneously. Conclusion. Biocompatibility ofpolymer, metal and ceramic wear debris can be tested simultaneously by using 3D particle embedded agarose gels. Acknowledgements. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. GA-310477 LifeLongJoints

Particulate wear debris from the UHMWPE component of implant prostheses typically causes inflammatory cascades leading to bone resorption and prosthesis loosening. Aseptic loosening is the leading cause of joint replacement failure. Green et al. have shown that the most biologically active polyethylene wear particles are in size range 0.3–10 micrometer, determined by filtration and Scanning Electron Microscopy. A new methodology based on radioisotope tracing is investigated which promises aseptic loosening is the leading cause of joint replacement failureto be more sensitive and may allow the characterization of wear debris shedding on the nanometer-scale. A constant force knee simulator has been designed and constructed at the University of New South Wales, to generate reproducible wear patterns. Atomic Force Microscopy is used to measure the wear particle dimensions. The constant axial force can be adjusted over a range of 0–1000 N, and flexion angles of 24°, 38°, 51° and 66° can be set. The UHMWPE wear surface is articulated at a rate of 1 cycle per second. It has been found that the simulator operates reliably over up to 2×10^6 cycles at various loads and flexion angles, and that wear debris can successfully be removed from the lubricant. For a walking cycle simulation, a wear rate of the order of 86 mg/10^6 cycles was measured using distilled water as lubricant. The debris particulates generated from the simulation have been characterized with Atomic Force Microscopy. In the nanometer range two characteristic types, clumps and fibrils, may be distinguished. A constant force knee simulator has been shown to operate reliably over up to 2×10^6 cycles at various loads and flexion angles, and that wear debris particulates can be obtained. It has also been shown that atomic force microscopy is well suited to characterize nanometre size UHMWPE particles. In parallel, the wear debris generated from the experiments is being tested for their bioirritant characteristics on osteoblast cells (in the TORU laboratory at the John Curtin School of Medical Research at ANU)

Major long-term complication of total hips is osteolysis in the more active patients. Osteolysis is a result of the biological response to the wear debris particles. This has resulted in the search for improved bearings such as metal and ceramic on polyethylene, all ceramic, and all metal total hips. Wear ranking of metal-polyethylene, ceramic-polyethylene, metal-metal, and ceramic-ceramic total hips has become clear at ratios of 1,000:500:10:1. However, wear debris from polyethylene, ceramic, and metal wear tests average about 0.6, 0.3, and 0.02 microns, respectively. From this information we can now deduce the number of particles librated is millions for ceramics, billions for polyethylene, and trillions for metal. In recent years, studies have revealed new information on the biological response to various types of wear debris. Factors such as number of particles, particle morphology (size and shape), and surface to volume ratio are becoming keys to a partial comprehension of this biological response and osteolysis. Recent studies have demonstrated that smaller particles (< 0.1 microns) may be more toxic to cells than larger particles (> 0.1 microns). Studies have shown that crosslinking of polyethylene reduces the size of the wear debris particles and that for gamma irradiated polyethylene this reduction in size is proportional to the radiation dose. It has also been shown that crosslinking results in a significant reduction in fibril particles. Therefore, large reductions in wear rate do not necessarily mean that the total joint will be more successful. Thus, two factors, which interact, are the volume rate of wear and the morphology of the wear debris particles. Some investigators have developed a biological ind

Summary Statement. The chemistry, amount, morphology, and size distribution of wear debris from silicon nitride coatings generated in the bearing surface can potentially reduce the negative biological response and increase the longevity compared to conventional materials in joint replacements. Introduction. Total hip implants have a high success rate at 15 years of implantation, but few survive over 25 years. At present, revisions are mostly due to aseptic loosening, believed to mainly be caused by the biological response to wear debris generated in the joint bearing. For the polymer liners the size of the wear debris determines the biological response, while for metal bearing surfaces a limitation is the metal ion release. When ceramics are used, the wear debris is in general small and mechanical factors may be the main cause for failure. A more recent, experimental alternative is to let the well-known metallic substrate serve as the soft, tough bulk, and additionally apply a hard and smooth ceramic coating. In this way a lower wear rate and reduced metal ion release could be obtained. Furthermore, the chosen composition, silicon nitride (SixNy), contains no detrimental ions, and silicon nitride debris has been shown to slowly dissolve in aqueous medium. Altogether, it can potentially increase the longevity of the implant. However, the debris from SixNy coatings has not yet been characterised. In this study, a wear model test was performed to generate wear debris from SixNy coatings. The debris was characterised using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) in combination with computational calculations. Methods. Silicon nitride coatings deposited on flat cobalt chromium alloy (ASTM F75) were worn in a reciprocating ball on disc setup in a 25% serum solution at 37°C against an alumina ball with a load of 1.5 N. Wear debris was separated using serum digestion with hydrochloric acid (ISO 17853:2011) and examined in SEM in combination with EDS. As reference polyethylene (PE) was used to verify that relevant particles sizes were achieved. The SEM images were processed using a modified MATLAB-script originating from Cervera Gontard et al. [1], identifying the particles and calculating their size. Results. Particles generated from SixNy coatings (n=62) a size distribution D50 [D10-D90] of 0.29 µm [0.16–0.69] and were round to oval in shape. The PE particles (n=70) had a size distribution of 0.29 µm [0.13–1.3], shaped similar to the SixNy particles or with a more elongated shape. Discussion and conclusions. PE wear debris has been reported to lie in the size range of nm up to several μm in vivo, with a large proportion within the critical size for macrophage activation (0.2 to 0.8 μm). The model test reports relevant sizes and shape of PE debris, confirming the validity of the method. Particles generated from the SixNy coatings showed a smaller size range than PE, however most particles were within the critical size range for biological activation. In conclusion, this model test could be used to generate what we believe are relevant sizes and shapes of PE and SixNy wear debris and to learn more at an early stage of prediction of wear debris. Further dissolution studies as well as studies on the in vitro and in vivo cell response to these types of particles will be performed. The authors thank the Swedish Foundation for Strategic Research (SSF) through MS2E and FP7 NMP project LifeLongJoints for financial support, as well as Linköping University for the coating facilities and expertise

Introduction:. Unicompartmental knee arthroplasty (UKA) has been used in the past decades to treat progressive cartilage degeneration in a single compartment. Concern has been raised over the rate of revision procedures for polyethylene wear and osteoarthritic progression into the adjacent compartment. Few studies have examined the pathology of cartilage degeneration in the setting of UKA. This study aims to investigate the viability of knee chondrocytes introduced to high and low concentrations of orthopaedic wear debris particulate. Methods:. Normal human articular chondrocytes (nHAC-Kn) were expanded in DMEM/F12 containing 10% FBS, 1% Penicillin/Streptomycin (Pen/Strp), and 50 μg/mL ascorbic acid (Asc). 24 hours prior to the start of the experiment, cells were seeded on 96-well plates at a density of 3500 cells/cm. 2. and exposed to DMEM/F12 containing 5% FBS, 1% Pen/Strp, and 50 μg/mL Asc. Particles (equivalent circle diameter range: 0.2–7 μm) at a low dose of 100: 1 (particles: cells) and high dose 1000: 1 (particles: cells) were introduced to treatment wells (n = 6). Control wells (n = 6) contained particles with no cells. Treatment groups included high and low doses of TiAl. 6. V. 4. alloy, 316L Stainless Steel, and Co-Cr-Mo alloy. At days 1, 3, 5, and 7, cells were assayed with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-dyphenyltetrazolium bromide (MTT) assay for determination of cell viability. Light microscopy was performed at each timepoint to assess change in cell morphology. Results:. All groups displayed a minor decrease in cell viability after 24 hours of exposure to particles. Similarly, a second distinct decrease in viability occurred at the day 3 timepoint. Days 5 and 7 yielded little change in cell viability. Results are displayed in Figure 1. Observations of light microscopy revealed cells may actively engulf particles over time. Images show particle concentrations at the same locations as chondrocytes with few particles present between cells. Conclusions:. Wear debris has been implicated as a contributing source to osteolysis and component loosening. A potential effect on the cellular level can ultimate lead to effects on the entire tissue and complications on the clinical level. A decrease in chondrocyte viability has been shown in response to the presence of particulate wear debris. Our results showed decreases in cell viability were most noticeable between 24 and 72 hours after introduction to particles. Chondrocyte death may contribute to progression of cartilage degeneration into healthy compartments of the knee. Continued experiments are underway further characterizing chondrocyte response to wear debris particulate with respect to protein and gene expression in an extended 7 day in vitro culture

Introduction. Wear debris generated by total hip replacements (THRs) may cause mechanical instability, inflammation, osteolysis and ultimately implant loosening, thus limiting the lifetime of such devices [1]. This has led to the development of biocompatible coatings for prostheses. Silicon nitride (SiN) coatings are highly wear resistant and any resultant wear debris are soluble, reducing the possibility of a chronic inflammatory reaction [2]. SiN wear debris produced from coatings have not been characterized in vivo. The aim of this research is to develop a sensitive method for isolating low volumes of SiN wear debris from periprosthetic tissue. Methods. Commercial silicon nitride particles of <50nm (Sigma Aldrich) were incubated with formalin fixed sheep synovium at a volume of 0.01mm. 3. /g of tissue (n=3). The tissue was digested with papain (1.56mg/ml) for 6h and subsequently proteinase K (1mg/ml) overnight. Proteinase K digestion was repeated for 6h and again overnight, after which samples appeared visibly homogeneous [Figure 1]. Samples were then subjected to density gradient ultracentrifugation using sodium polytungstate (SPT) [3]. The resulting protein band was removed from the pellet of particles. Control tissue samples, to which no particles were added, were also subjected to the procedure. Particles were washed with filtered water to remove residual SPT using ultracentrifugation and filtered onto 15nm polycarbonate filters. The filtered particles were imaged by cold field emission scanning electron microscopy (CFE-SEM) and positively identified by elemental analysis before and after the isolation procedure. To validate whether the isolation method affected particle size or morphology, imaging software (imageJ) was used to determine size distributions and morphological parameters of the particles. A Kolmogorov-Smirnov test was used to statistically analyse the particle morphology. Results. The appearance of particles was similar before and after the isolation procedure [Figure 2]. Scanning electron micrographs also demonstrated the complete removal of proteins and light impurities. Elemental analysis confirmed the identity of retrieved particles as SiN. The particle size distributions of isolated and non-isolated particles were similar [Figure 3]. Statistical analysis demonstrated that morphology in terms of roundness and aspect ratio was unchanged by the isolation procedure (P<0.05). Discussion. Results indicate that the particle isolation method effectively isolates low volumes of SiN particles whilst retaining particle characteristics and enabling particle characterisation. The method will therefore be validated for application to additional particle materials and applied to in vivo studies of novel SiN coated prostheses in a rabbit and sheep model

Between 1995 and 1998, eighty revision total knee arthroplasties were done for the primary reason of advanced polyethylene wear. The primary arthroplasties prosthesis that failed included thirty-four mobile bearing knees and forty-six fixed bearing knees. In thirty-four Low Contact Stress (LCS) mobile bearing knees, osteolysis was identified intraoperatively in sixteen knees (forty-seven per cent). There were varying of fixation methods included nine cemented, four cementless and three hybrids. In forty-six fixed bearing knees, osteolysis was identified intraoperatively in six knees (thirteen per cent). The fixation methods of prostheses included two cemented and four cementless. The incidence of osteolysis was statistically significant difference between the mobile bearing and fixed bearing knees (p< 0.02). Both scattering electron microscope (SEM) and light scattering analysis were used to examine the UHMWPE wear debris collected from tissue sample. The particle size analyzed by light-scattering is coincident with the measurement by SEM. The major type of wear debris extracted from failed knee prostheses is granular shape. There are more granular wear debris appear in the mobile bearing knees than in the fixed bearing knees. The particle size of UHMWPE wear debris with osteolysis was significantly smaller than that without osteolysis. The high rate of osteolytic lesions in mobile bearing knee (LCS) is well illustrated in our result that a lot of fine UHMWPE wear debris generated in the Low Contact Stress knee. The result also illustrates that there is no relationship between fixation methods and the third body wear that associate with osteolysis

Joint replacement implants, especially in their modular forms, are subjected to wear and corrosion at various sites in their articulation, such as the bearing surfaces, the undersurface of the insert, the femoral head-neck junction and the implant or polymethylmethacrylate-bone interface. Movement of the bearing surfaces is not the only cause, as faulty implant positioning can initiate wear through impingement between two parts of the articulation. These wear products of polyethelene or metal, in particulate form, are influential to the ultimate fate of the prostheses through the initiation of local and systemic immune reactions. These debris are phagocytised by macrophages and phagocytised proteins are partly degraded in intracellular vesicles, where they become associated with the major histocompatability complex molecule HLA-DR. This molecule when transported to the cell membrane, interacts with CD4+ lymphocytes to activate an immune response and initiate the production of interleukin1b, interleukin 6 and tumor necrosing factor a. These cytokines mediate the inflammatory response and activate osteoclasts causing periprosthetic osteolysis. Polyethelene and metal wear particles, in addition to their local effects, can be disseminated beyond the periprosthetic tissues and reach distant organs and regional lymphnodes. The concentrations of certain elements of metallic implants, such as iron, cobalt, chromium or titanium have been detected in lymphnodes, the liver and the spleen in levels a lot higher than normal, especially in patients with loose prostheses and, less so, in patients with stable prostheses. The reported values of metal ions in published series vary. Thus certain investigators (Brodner et al) have reported continuous systemic cobalt release during a five year follow-up period and in levels slightly above detection values, while others (Clarke et al, Lohtka et al) have reported consistently high levels of cobalt and chromium ions in metal on metal articulations. The diameter of the femoral head appears to be a significant factor. In surface hip replacements with large diameter heads the amount of detected metal ions was significantly higher compared with total hip replacements with use of 28mm diameter femoral heads. In that type of replacement the levels of cobalt was 50 times higher than normal and of chromium 100 times higher. Polyethelene particles, similarily have been detected in paraaortic lymphnodes in percentages similar to metal ions. However the detection of PE particles in the liver or the spleen was less, compared to metal ions, possibly due to the difficulty of modern methods to detect PE particles of submicrometre size. The relevance of the dissemination of metal ions and of PE wear debris in organs distal to the operated joint need to be carefully evaluated since certain of these elements are known carcinogens. Two studies have reported slight increase of haemopoeitic cancers in patients with cobalt alloy implants and in patients with metal on metal devices, while others have documented the development of malignant tumours in the vicinity of total hip replacements. Since prostheses with metal on metal bearing surfaces are used more and more frequently in younger patients, these patients require careful monitoring for longer periods

The authors wished to determine if macrophage activation and the release of osteolytic cytokines in response to orthopaedic wear debris could be suppressed pharmacologically with the use of anti-inflammatory and anti-oxidant agents. The current long-term results of total joint arthroplasty are limited by mechanical wear of the implants with an associated immune mediated bone lysis with subsequent loosening and eventual failure. It has been demonstrated that the osteolysis seen in cases of aseptic loosening is mediated by the immune system both directly and indirectly by activated macrophages. Macrophages indirectly cause osteolysis through release of the osteoclast activating cytokines TNFα, IL-1 and PGE2. They also directly resorb bone in small amounts when activated by wear particles. We utilised established cell culture models of both peripherally derived monocyte/macrophages and lymphocyte enriched co-cultures and examined the effects of polymethylmethacrylate particles alone on the cells in culture. The effect of anti-inflammatory and anti-oxidant agents (dexamethasone, diclofenac and n-acetyl cysteine) in varying concentrations was then examined using ELISA of cytokine release and electron microscopy to examine ultra structural responses. Cell viability was also measured in cultures over 24 hour periods (at 6, 12 and 24 hours) using Trypan blue exclusion and Coulter counter, while cell type and morphology were determined cytologically, including-naphthyl acetate esterase cytochemical identification and electron microscopy. The use of N-acetyl cysteine was associated with very significant suppression of TNF, IL-1 and PGE2 in both macrophage and lymphocyte enriched co-culture with no effect on cell viability. While diclofenac was also associated with significant decreases in cytokine expression, it was associated with a decrease in cell viability that approached significance. Dexamethasone did not have a reliable effect on these cytokines. Ultra-structural electron microscopic examination of the cells also demonstrated signs of definite down-regulation of cytoplasmic and nuclear activation. Novel anti-oxidant therapies and possibly other immune modulating drugs can eliminate the activation of macrophages in response to periprosthetic wear particles without any associated decrease in cell viability and thus may provide a means of reducing the incidence of loosening and failure of total joint arthroplasty

The current long term results of total joint arthroplasty are limited by mechanical wear of the implants with an associated immune mediated bone lysis with subsequent loosening and eventual failure. It has been demonstrated that the osteolysis seen in cases of aseptic loosening is mediated by the immune system, particularly, both directly and indirectly, by activated macrophages. Macrophages indirectly cause osteolysis through release of the osteoclast activating cytokines: TNFα, IL-1 and PGE2 and also directly resorb bone in small amounts when activated by wear particles. We wished to determine if macrophage activation and the release of osteolytic cytokines in response to orthopaedic wear debris could be suppressed pharmacologically, with the use of anti-inflammatory and anti oxidant agents. We utilised established cell culture models of both peripherally derived monocyte/macrophages and lymphocyte enriched co-cultures and examined the effects of polymethylmethacrylate particles alone on the cells in culture. The effects of anti-inflammatory and anti-oxidant agents (dexamethasone, diclofenac and n-acetyl cysteine) in varying concentrations were then examined using ELISA of cytokine release and electron microscopy to examine ultra structural responses. Cell viability was also measured in cultures over 24 hour periods (at 6, 12 and 24 hours) using Trypan blue exclusion and Coulter counter, while cell type and morphology were determined cytologically, including α-naphthyl acetate esterase cytochemical identification and electron microscopy. The use of N-acetyl cysteine was associated with very significant suppression of TNFα, IL-1β and PGE2 in both macrophage and lymphocyte enriched co-culture with no effect on cell viability. While diclofenac was also associated with significant decreases in cytokine expression it was associated with a decrease in cell viability that approached significance. Dexamethasone did not have a reliable effect on these cytokines. Ultra-structural electron microscopic examination of the cells also demonstrated signs of definite down-regulation of cytoplasmic and nuclear activation. We have demonstrated, therefore, that novel anti-oxidant therapies and possibly other immune modulating drugs can eliminate the activation of macrophages in response to peri-prosthetic wear particles without any associated decrease in cell viability and thus may provide a means of reducing the incidence of loosening and failure of total joint arthroplasty

Summary. We report the first use of synchrotron xray spectroscopy to characterize and compare the chemical form and distribution of metals found in tissues surrounding patients with metal-on-metal hip replacements that failed with (Ultima hips) or without (current generation, large diameter hips) corrosion. Introduction. The commonest clinical category of failure of metal-on-metal (MOM) hip replacements is “unexplained” and commonly involved a soft tissue inflammatory response. The mechanism of failure of the Ultima MOM total hip replacement includes severe corrosion of the metal stem and was severe enough to be removed from clinical use. Corrosion is not a feature that we have found in the currently used MOM bearings. To better understand the biological response to MOM wear debris we hypothesized that tissue from failed hips with implant corrosion contained a different type of metal species when compared to those without corrosion. Method. Tissue from patients with two types of MOM hip arthroplasty were analysed: Ultima that failed with severely corroded femoral stems (n=12); and large diameter, current generation MOM hips that failed without visible corrosion (n=7). Comparison was also made to samples of cobalt, chromium and molybedanum standards. We used a high energy synchrotron xray beam to map and characterise the type of metal within the tissues. This enabled us to analyse the type of chemical in a situation that is as realistic as possible: without staining; without the use of a vacuum; and the use of fresh frozen tissue sections with metals at relatively low concentrations. This could not have been achieved without a synchrotron. Results. Comparison with standards revealed the chemical form of the chromium in the tissues surrounding metal-on-metal hip replacements was chromium (III). This was similar for both corroded (Ultima MOM) and non-corroded (large diameter, current generation MOM) hips. This was chromium (III) phosphate in the non-corroded hips but because the concentration of chromium was lower in the corroded hips it was difficult to differentiate chromium phosphate from oxide. There was some evidence of localistaion of cobalt and chromium, both in metallic form. One sample from corroded hips contained chromium (VI). Conclusion. Chromium (III) phosphate was the predominant metallic species in the tissues surrounding metal-on-metal hip replacements. This may have arisen from corrosion, wear or a combination of both

Background. Wear particles are considered to be the major culprit for the aseptic loosening. Their characterization is thus crucial for the understanding of their bioreactivity and contribution to the development of aseptic loosening. Methods. Metal wear debris particles were analyzed directly in periprosthetic tissue resins by scanning electron microscopy (SEM) combined with back-scattered electron imaging (BSE) and energy dispersive X-ray spectroscopy (EDS). Four groups of tissue samples retrieved at revision operations of loosened hip implants with different bearing surfaces (metal-on-metal, ceramic-on-polyethylene and metal-on-polyethylene), and different material of the femoral stem (Ti alloy, CoCrMo and polymer combined with stainless steel) were investigated. Tissue samples were first analyzed histologicaly. Sections from the same paraffin blocks were then carbon coated and analyzed using SEM/BSE/EDS method. Results. Metal particles were detected in all samples. Their composition corresponded to the composition of the implant components. The gradation of metal particles ranged from +1 to +3. A considerable number of big metal particles were actually agglomerates of submicron particles visible only at higher magnification. The clustering of particles was observed primarily for CoCrMo and, to a lesser extent, for stainless steels particles. The median sizes of CoCrMo clusters in two groups of samples were 2.9 1.8 m (range, 0.5 to 7.6 m) and 3.2 1.0 m (range, 1.9 to 5.4 m). The effect of clustering was not observed for Ti particles. The median sizes of individual Ti particles determined in two groups of samples were 2.5 3.6 m (range, 0.4 to 17.3 m) and 4.3 2.8 m (range, 0.8 to 11.0 m). Conclusion. Scanning electron microscopy combined with back-scattered electron imaging is an appropriate and selective method to recognize metal particles in tissue sections, without being destructive to specimens. When the size of the particles is considered, however, it should be differed between the size of individual particles and size of clusters of particles. Besides its benefits, this study has some limitations: the detection of particles smaller than 0.4 m is difficult, and this method cannot be used to identify polyethylene particles

Statement of Purpose:. The wear rate of Ultra High Molecular Weight Polyethylene (UHMWPE) in joint replacements has been correlated to both contact area and contact stress in the literature, [1], [2]. In both publications and our experiment, UHMWPE articulated with a polished surface of cobalt-chromium alloy was evaluated using a Pin-On-Disk (POD) apparatus (AMTI) implementing bi-directional movement. In publication [1], volumetric wear was independent of normal load and dependent upon increasing contact area. The results demonstrated that increasing contact stress decreased wear rates twofold. In publication [2], at maximum cross-shear, wear was proportional to nominal contact area and wear factors normalized to area are more appropriate than load based wear factors. In both studies, the contact surface areas of the POD pins were reduced by decreasing the diameters of the POD Pins. In our experiment, the contact area was dependent on textured POD Pin 390 (T390) which had low wear [3]. T390 reduced the normal POD contact area from 71 mm. 2. to 8.26 mm. 2. Hydroxylapatite (HA) particles were introduced to the serum to simulate third body wear debris. We hypothesized that the normal POD Pins would have greater wear rates than the textured POD Pins. A measurement of 0.14 mg HA particles per 250 mL of serum was used for each test 0.33 million cycles. Methods:. The GUR 1020 resin XLK POD Pins were gamma irradiated to 50 kGy in a vacuum package and then remelted. Three (3) T390 POD pins and nine (9) untextured XLK POD Pins were used. Three untextured XLK POD Pins were tested against three T390 POD pins. The other six (6) untextured XLK POD Pins were used as soak controls. Each pin articulated against a polished, high carbon wrought CoCr metal alloy counterface (ASTM F1537; diameter = 38.1 mm; thickness = 12.7 mm). Wear rate tests were for 1.98 million cycles. In order to perform the t-test analysis, the wear rates for each pin were given by the slope of the linear regression line through the individual data points (cycle count, cumulative wear), excluding the (0, 0) point. Results:. The probability for the means between the T390 POD pins and the untextured XLK POD Pins was *p = 0.009. T390 wear rates were statistically significant as compared to the untextured XLK POD Pin wear rates. The T390 POD Pin is illustrated in Figure 1. Figures 2 and 3 summarize the wear rates between T390 POD Pins and the untextured POD Pins with and without HA particles. Conclusions:. The wear rates between T390 and untextured POD pins did not take into account that the POD pins were not cleaned using a solution to remove potentially embedded HA particles. The follow-on experiment will use a special cleaning method to remove all HA particles after each test cycle

There have been numerous reports regarding “pseudotumor” associated with hip arthroplasty. We present two reports in which main etiology in the pseudotumor formation was titanium (Ti), but not cobalt-chromium (Co-Cr). We should keep in mind that Ti analysis is essential in some cases.

(Case 1) A 68-year-old male presented to our institution because of right hip pain and lower extremity swelling four years after a bipolar hemiarthroplasty. MRI predicted a cystic pseudotumor. However, revision surgical findings showed no apparent cause of ARMD previously described in the literatures. Postoperative analysis showed that the metal debris mainly originated from the Ti alloy itself. (Case reports in Orthopedics, vol.2014, Article ID 209461, 4 pages)

(Case 2) A 77-year-old female presented to our institution because of right hip pain and swelling six years after a total hip arthroplasty using a cable trochanteric reattchment. Plain radiographs demonstrated evidences of severe osteolysis and multiple fragments of the broken cable. However, MRI predicted a psudotumor(See Figure 1). Postoperative analysis clarified that main etiology in the pseudotumor formation was the stem mede of Ti, but not the cable made of Co-Cr.

Introduction

Silicon nitride (SiN) is a recently introduced bearing material for THR that has shown potential in its bulk form and as a coating material on cobalt-chromium (CoCr) substrates. Previous studies have shown that SiN has low friction characteristics, low wear rates and high mechanical strength. Moreover, it has been shown to have osseointegration properties. However, there is limited evidence to support its biocompatibility as an implant material. The aim of this study was to investigate the responses of peripheral blood mononuclear cells (PBMNCs) isolated from healthy human volunteers and U937 human histiocytes (U937s) to SiN nanoparticles and CoCr wear particles.

The generation of wear particles at the primary articulating interface of total hip arthroplasty is well documented. Particles may also be generated at the stem/cement interface in cemented prostheses. An investigation of explanted Capital femoral stems demonstrated that wear at the stem/cement interface had contributed to their early failure. This study compared the wear particle generated by stems of three different materials and with three different surface finishes. Three femoral stems were chosen as ‘templates’, one with a smooth surface,(the Exeter), one with a slightly roughened surface (the charnley) and one with a very rough surface (the capital). Their surfaces were measured and plates were manufactured with comparable surfaces in each of three materials in use for femoral stems, stainless steel, cobalt chrome and titanium alloy.

The plates were opposed to cement pins in a laboratory wear simulator. The volume of cement lost from the pins was measured and the debris generated was examined under the scanning electron microscope.

Analysis of the results demonstrated that for each of the materials tested, volume of wear particles generated increased as the roughness of the surface increased. When comparing similar surfaces in different materials it was also demonstrated that softer materials produced greater volumes of wear than harder materials.

The analysis of the debris demonstrated that material affected debris size; harder materials produced smaller cement particles than softer materials independent of surface finish.

Particles size and number of particles have been demonstrated to influence macrophage activity. The results of this study would suggest that softer materials should not be used for cemented stems with a rough surface finish.

Orthopaedic cobalt chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition.

Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts.

The assessment of reproductive risk from maternal exposure to biomaterials, especially those liberated by orthopaedic implants, is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.