CoCrMo Wear Research Articles

Cobalt and Chromium Ions Impair Macrophage Response to Staphylococcus aureus Infection.

Cobalt-chromium-molybdenum (CoCrMo) alloys are routinely used in arthroplasty. CoCrMo wear particles and ions derived from arthroplasty implants lead to macrophage-driven adverse local tissue reactions, which have been linked to an increased risk of periprosthetic joint infection after revision arthroplasty. While metal-induced cytotoxicity is well characterized in human macrophages, direct effects on their functionality have remained elusive. Synchrotron radiation X-ray microtomography and X-ray fluorescence mapping indicated that peri-implant tissues harvested during aseptic revision of different arthroplasty implants are exposed to Co and Cr in situ. Confocal laser scanning microscopy revealed that macrophage influx is predominant in patient tissue. While in vitro exposure to Cr3+ had only minor effects on monocytes/macrophage phenotype, pathologic concentrations of Co2+ significantly impaired both, monocyte/macrophage phenotype and functionality. High concentrations of Co2+ led to a shift in macrophage subsets and loss of surface markers, including CD14 and CD16. Both Co2+ and Cr3+ impaired macrophage responses to Staphylococcus aureus infection, and particularly, Co2+-exposed macrophages showed decreased phagocytic activity. These findings demonstrate the immunosuppressive effects of locally elevated metal ions on the innate immune response and support further investigations, including studies exploring whether Co2+ and Cr3+ or CoCrMo alloys per se expose the patients to a higher risk of infections post-revision arthroplasty.

Translational characterization of macrophage responses to stable and non-stable CoCrMo wear and corrosion debris generated in-situ for total hip replacement

Metal wear and corrosion debris remain a limiting factor for long-term durability of total hip replacement (THR). Common wear particle production techniques for research differ from the actual tribocorrosion processes at the implant site, potentially causing loss of valuable information. The aim of this study was to investigate reactions to freshly generated and time-stabilized particles and ions released from CoCrMo-alloy using a bio-tribometer, which mimics conditions of the periprosthetic environment.THP-1 macrophages were challenged with freshly produced or time-stabilized wear debris. Wear generation took place in a custom-built bio-tribometer inside a CO2 incubator operating with a reciprocating rotation of an Al2O3 ball against a CoCrMo disc. Two different electrochemical conditions with increasingly forced corrosion rates were tested: +0.45 V (passive domain) and +0.67 V (transition to transpassive domain). Cell viability, proinflammatory cytokines, electrochemical measurements and ICP-MS metal ion content analyses were performed.Cobalt/ chromium concentrations were 6.6/ 1.6 ppm in the passive domain and almost doubled to 11.4/ 3.0 ppm in the passive-transpassive domain. Under those electrochemical conditions, freshly produced and time-stabilized CoCrMo wear decreased cell viability to the same extent. Secretion of proinflammatory cytokines were not significantly different for freshly produced and time-stabilized debris.This study suggests that freshly generated and time-stabilized metal particles/ions cause similar toxicity and inflammatory reactions in macrophages, indicating that standard practices for generating wear debris are valid methods to evaluate wear particle disease. Other cell types, materials, and corrosion potentials need to be studied in the future to solidify the conclusion.

Electrochemical Biosensor to Detect Implant-Derived Metal Ions: A Mice Model

Joint replacement surgeries are progressing at an increased rate in the USA, with around 1 million surgeries being performed annually. While these orthopedic implants provide a solution for a damaged joint, debris such as metal ions generated due to the wear and corrosion of the implants prove to be of considerable risk of systemic and local toxicity. As an effective diagnostic tool, there is a need to develop a patient-friendly, cost-effective, and rapid mode of metal ion detection in orthopedic patients with various implants. In this study, an electrochemical biosensor chip (Dropsens) is proposed as a diagnostic tool to detect metal ions through changes in impedance. In vivo studies were conducted using CoCrMo particles intraarticularly injected into mice. Then, blood was collected on 0th day, 14th day, and 28th day after injection and was centrifuged to obtain serum. The serum was subject to various electrochemical techniques, such as Electrochemical Impedance Spectroscopy (EIS) and cyclic voltammetry (CV). Additionally, standardization experiments were performed using different concentrations of CoCrMo wear particles suspended in PBS and mice serum. EIS results reveal a negative correlation between impedance (Rp) and the metal ion concentration in the standardization experiments. EIS and CV standardization data were used to obtain a regression equation which were later used to estimate the metal ion concentrations in experimental samples. Here, the positive control group shows the highest impedance at any frequency followed by the 28th-day experimental mice serum as seen on the bode plot. CV experimental data reveal a possible correlation between CV area and the metal ion concentrations. In this study, experimental mice models were established to mimic the possible diffusion of metal particles from implants. Dropsens electrochemical biosensors were efficiently employed to detect metal ions in serum through changes in impedance.

Wear mechanism and debris analysis of PEEK as an alternative to CoCrMo in the femoral component of total knee replacement

The polyetheretherketone (PEEK)-highly cross-linked polyethylene (XLPE), all-polymer knee prosthesis has excellent prospects for replacing the traditional metal/ceramic-polyethylene joint prosthesis, improving the service life of the joint prosthesis and the quality of patients’ life. The long-term wear mechanism of PEEK-XLPE knee joint prosthesis is comprehensively evaluated from wear amount, wear morphology, and wear debris compared to that of CoCrMo-XLPE joint prosthesis. After 5 million cycles of in vitro wear, the wear loss of XLPE in PEEK-XLPE (30.9±3.2 mg) is lower than that of XLPE in CoCrMo-XLPE (32.1±3.1 mg). Compared to the XLPE in CoCrMo-XLPE, the plastic deformation of XLPE in PEEK-XLPE is more severe in the early stage, and the adhesive peeling and adhesion are lighter in the later stage. The size distribution of XLPE wear debris in PEEK-XLPE is relatively dispersed, which in CoCrMo-XLPE is relatively concentrated. Wear debris is mainly flake and block debris, and the wear mechanism of XLPE was abrasive wear. The wear volume per unit area of PEEK femoral condyle (10.45×105 µm3/mm2) is higher than that of CoCrMo (8.32×105 µm3/mm2). The PEEK surface is mainly furrows and adhesions, while the CoCrMo surface is mainly furrows and corrosion spots. The PEEK wear debris is mainly in flakes and blocks, and the CoCrMo wear debris is mainly in the shape of rods and blocks. The wear mechanism of PEEK is abrasive wear and adhesion, and that of CoCrMo is abrasive wear and corrosion.

Separation and Extraction of Mixed Grinding Chips of Artificial Joints with Different Densities by Multiple Centrifugal Separations

Aseptic loosening caused by the wear and tear of the artificial joint prosthesis after implantation is one of the main causes of artificial joint failure. Therefore, it is important to investigate the wear debris generated due to wear when developing new artificial joint materials. Aseptic loosening is related to the size, number, and morphology of wear debris, and this study proposed the separation and extraction of mixed wear debris with different density ratios of artificial joints by centrifugation to study the characteristics of different artificial joint wear and wear debris extraction rates. The results showed that multiple centrifugations to separate the mixed wear debris were able to reintroduce the wear debris on the wall of the centrifuge tube into the solution and that the wear debris extraction rate was increased. Suspensions with different density ratios of artificially jointed mixed wear debris were effectively separated by this method. The total extraction rate of the three repeated extractions compared to the first extraction rate, the extraction rate of CoCrMo wear debris increased by 6.7%, ultra-high molecular weight polyethylene (UHMWPE) wear debris increased by 15.1–23.44%, ZrO2 wear debris increased by 10.91%, and that of polyether ether ketone (PEEK) wear debris increased by 9.95%. This method for separating and extracting wear debris from artificial joints can realize the separation of mixed wear debris from artificial joints and obtain a high extraction rate and high-quality wear debris images, investigate the wear mechanism of artificial joint implants, and provide valuable information on the wear performance of new artificial joint implants under investigation.

Icariin Alleviates Wear Particle-Induced Periprosthetic Osteolysis via Down-Regulation of the Estrogen Receptor α-mediated NF-κB Signaling Pathway in Macrophages.

Periprosthetic osteolysis is one of the major long-term complications following total joint replacement. Its cause is widely accepted to be wear particle-induced activation of inflammatory macrophages. No effective strategy for the prevention and treatment of periprosthetic osteolysis is yet available. Recently, considerable evidence has shown that icariin effectively protects against estrogen deficiency-related bone loss and bone deterioration. However, the molecular mechanism underlying the inhibitory effect of icariin on wear particle-induced periprosthetic osteolysis is not yet clear. In this study, nanoscale CoCrMo wear particles were obtained by high-vacuum three-electrode direct current from the femoral head implant of a patient diagnosed with aseptic loosening. The effects of icariin on wear particle-induced expression of proinflammatory factors, NF-κB signaling modulation, osteolysis, and estrogen receptor α (ERα) activation were evaluated in vitro and in vivo using bone marrow-derived macrophages and C57/BL6J mice, respectively. A possible link between ERα and the protective effect of icariin was further studied using an ERα antagonist and the ERα-siRNA interference. Chemical composition analysis showed that Cr and Co were the major metallic elements of the nanoscale particles, with a mean size of 150.2 ± 37.4 nm for the CoCrMo particles. Following icariin treatment, significant decreases were observed in CoCrMo wear particle-induced TNF-α and IL-6 mRNA expression in BMDMs, and osteolysis in mice calvaria. Marked decreases in the protein expression level of p-IKKβ, p-p65 and p-IκBα were also observed, together with significant decreases in the nuclear import of P65 and macrophage M1 polarization. RNA sequencing revealed that ERα was closely associated with TNF-α and IL-6 in wear particle-stimulated macrophages. Furthermore, marked increases in phospho-ERα Ser118 and phospho-ERα Ser167 protein expression and the nuclear import of ERα were also found in the icariin group. The protective effects of icariin on CoCrMo particle-induced mouse calvarial osteolysis and on the inflammation response in BMDMs were reversed by ERα antagonist and by ERα-siRNA interference. In conclusion, icariin attenuates wear particle-induced inflammation and osteolysis via down-regulation of the ERα-mediated NF-κB signaling pathway in macrophages. The potential application of icariin as a non-hormonal therapy for wear particle-induced periprosthetic osteolysis is worthy of further investigation.

Protein Content of Model Synovial Fluid and CoCrMo Wear

Wear of cobalt chromium molybdenum alloy in a reciprocating ball-on-plate test was measured for a series of model synovial fluid samples, where the effect of protein and phospholipid content was examined. The protein content (albumin and γ-globulin) was varied to replicate a range of healthy and diseased SF pathologies. The results showed reduced wear was strongly correlated with increasing protein content. The effect of phospholipid addition on wear was more complex. Limited evidence suggested phospholipids reduced wear for a high albumin/γ-globulin ratio (A/G) but increased wear for low A/G ratios. Post-test examination showed thick (~μm) insoluble “gel-like” films were deposited in, and around, the wear scar. Micro Infrared Reflection Absorption Spectroscopy analysis indicated the films were predominately denatured β-sheet proteins although in some cases lipids were also present. Similar films were found in tests with human synovial fluid samples. Scanning Electron Microscopy imaging showed an aggregated fibril “rope” structure typical of non-native β-sheet proteins. The gel film is a protein-rich viscous phase which is entrained intermittently to form a lubrication film which contributes to surface protection and reduction of wear. We also suggest the formation of gel deposits is comparable to the “boosted” lubrication model of proposed by Professor Duncan Dowson for articular cartilage. In the boosted model high-viscosity, concentrated protein films are formed in depressions on the cartilage surface. The tests indicate the chemistry of human synovial fluid, particularly the protein content, could affect CoCrMo wear and therefore the risk of implant failure.

Wear particles induce a new macrophage phenotype with the potential to accelerate material corrosion within total hip replacement interfaces

Evidence that macrophages can play a role in accelerating corrosion in CoCrMo alloy in total hip replacement (THR) interfaces leads to questions regarding the underlying cellular mechanisms and immunological responses. Hence, we evaluated the role of macrophages in corrosion processes using the cell culture supernatant from different conditions and the effect of wear particles on macrophage dynamics. Monocytes were exposed to CoCrMo wear particles and their effect on macrophage differentiation was investigated by comparisons with M1 and M2 macrophage differentiation. Corrosion associated macrophages (MCA macrophages) exhibited upregulation of TNF-α, iNOS, STAT-6, and PPARG and down-regulation of CD86 and ARG, when compared to M1 and M2 macrophages. MCA cells also secreted higher levels of IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70 than M1 macrophages and/or M2 macrophages. Our findings revealed variation in macrophage phenotype (MCA) induced by CoCrMo wear particles in generating a chemical environment that induces cell-accelerated corrosion of CoCrMo alloy at THR modular interfaces. Statement of SignificanceFretting wear and corrosion within the implant's modular taper junction are prominent causes of implant failure, as they promote the release of corrosion products and subsequent development of adverse local tissue reactions. Being a multifactorial process, several in vitro models have been developed to recreate the in vivo corrosion process, often summarized as mechanically-assisted crevice corrosion. Considering the excellent corrosion properties of CoCrMo alloy, the severity of chemically-generated damage observed at the modular interface has been surprising and poorly understood. The aim of the current study is to provide a better understanding of macrophages and their plasticity at the THR taper interface when they encounter wear debris from CoCrMo alloy. This is a preliminary study along the path towards determining the mechanism(s) of CAC.

In Vitro Evidence for Cell-Accelerated Corrosion Within Modular Junctions of Total Hip Replacements.

Corrosion at modular junctions of total hip replacement (THR) remains a major concern today. Multiple types of damage modes have been identified at modular junctions, correlated with different corrosion characteristics that may eventually lead to implant failure. Recently, within the head-taper region of the CoCrMo retrieval implants, cell-like features and trails of etching patterns were observed that could potentially be linked to the involvement of cells of the periprosthetic region. However, there is no experimental evidence to corroborate this phenomenon. Therefore, we aimed to study the potential role of periprosthetic cell types on corrosion of CoCrMo alloy under different culture conditions, including the presence of CoCrMo wear debris. Cells were incubated with and without CoCrMo wear debris (obtained from a hip simulator) with an average particle size of 119 ± 138 nm. Electrochemical impedance spectroscopy (EIS) was used to evaluate the corrosion tendency, corrosion rate, and corrosion kinetics using the media after 24 h of cell culture as the electrolyte. Results of the study showed that there was lower corrosion resistance (p < 0.02) and higher capacitance (p < 0.05) within cell media from macrophages challenged with particles when compared with the other media conditions studied. The potentiodynamic results were also in agreement with the EIS values, showing significantly higher corrosion tendency (low Ecorr ) (p < 0.0001) and high Icorr (p < 0.05) in media from challenged macrophages compared with media with H2 O2 solution. Overall, the study provides in vitro experimental evidence for the possible role of macrophages in altering the chemical environment within the crevice and thereby accelerating corrosion of CoCrMo alloy. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:393-404, 2020.

Chemical Evolution of CoCrMo Wear Particles: An in Situ Characterization Study

The unexpected high failure rates of CoCrMo hip implants are associated with the release of a large number of inflammatory wear particles. CoCrMo is nominally a stable material; however, previous chemical speciation studies on CoCrMo wear particles obtained from periprosthetic tissue revealed only trace amounts of Co remaining despite Co being the major component of the alloy. The unexpected high levels of Co dissolution in vivo raised significant clinical concerns particularly related to the Cr speciation in the dissolution process. At high electrochemical potentials, the alloy’s Cr-rich passive film breaks down (transpassive polarization), facilitating alloy dissolution. The potential release of the carcinogenic Cr(VI) species in vivo has been a subject of debate. While the large-scale Co dissolution observed on in vivo produced particles could indicate a highly oxidizing in vivo environment, Cr(VI) species were not previously detected in periprosthetic tissue samples (except in the specific case of pos...

Understanding the In Vivo Reactivity of Metal-on-Metal Implants

CoCrMo-based hip implants experienced high failure rates despite the high wear and corrosion resistance of the bulk material. Although they exhibit a lower volumetric wear compared to other implant materials, CoCrMo-based implants produced a significantly larger number of smaller wear particles. Simulation studies show that up to one trillion wear particles could be produced in one patient annually.1 Implant wear particles can trigger an immune system inflammatory response2,3 which is associated with eventual failure of the implants. In light of these failures, many devices have been retracted from the market, and class-action lawsuits were filed in the US. Additionally, one of the largest product liability hearings is currently ongoing in the UK as patients sue implant manufacturers. CoCrMo is nominally an extremely stable material with high Cr content providing passivity. However, despite the Co:Cr ratio in the original alloy being 2:1; chemical analyses of wear particles from periprosthetic tissue have found the particles to be composed predominately of Cr species, with only trace amounts of Co remaining.4 The immune system’s inflammatory response leads to a rise in local electrochemical potential via the production of reactive oxygen/nitrogen species by activated macrophages as well as local acidification. However, the mechanism eliciting the inflammatory response is uncertain. In this work, the dissolution of CoCrMo in bulk, thin film and nanoparticle form was studied in a simulated biological environment. Electrochemical potentials were applied to simulate the increasingly oxidising environment found within the macrophage cells. A multimodal in situ spectroscopy and microscopy approach was used, at high chemical and spatial resolution, to elucidate the dissolution mechanism. The results reveal that CoCrMo dissolution occurs via a non-stoichiometric, geometrically inhomogeneous mechanism similar to de-alloying, and previously unreported for this material. Taken together, the results suggest that the in vivo dissolution of CoCrMo wear debris can be understood in terms of the local environment and specific corrosion mechanisms that come into play under these conditions: not observed in conventional testing for implant safety. I. Catelas, J. D. Bobyn, J. B. Medley, J. J. Krygier, D. J. Zukor and O. L. Huk. J. Biomed. Mater. Res. A, 2003, 67, 312–327D. J. Langton, T. J. Joyce, S. S. Jameson, J. Lord, M. Van Orsouw, J. P. Holland, A. V. F. Nargol and K. A. De Smet. J. Bone Jt. Surgery, Br. Vol., 2011, 93, 164–171Y.-M. Kwon, S. Glyn-Jones, D. J. Simpson, A. Kamali, P. McLardy-Smith, H. S. Gill and D. W. Murray. J. Bone Jt. Surgery, Br. Vol., 2010, 92, 356–361A. E. Goode, J. M. Perkins, A. Sandison, C. Karunakaran, H. Cheng, D. Wall, J. a. Skinner, A. J. Hart, A. E. Porter, D. W. McComb and M. P. Ryan. Chem. Commun., 2012, 48, 8335

Release of metal ions from nano CoCrMo wear debris generated from tribo-corrosion processes in artificial hip implants

CoCrMo alloys have been widely used in metal-on-metal (MoM) hip replacements due to their superior wear and corrosion resistance properties. However, metal ions like Co2+ and Cr3+, or even Cr6+ released from CoCrMo hip prostheses can induce macrophage apoptotic vs. necrotic mortality and damage the surrounding tissues. Simultaneously, osteolysis induced by the wear debris can be a cause of failure. Nano wear debris is more active than the bulk material, due to its small size. In this study, to accurately analyse the fresh wear debris retrieved from the hip simulator and the interaction between the particles and tribocorrosion of CoCrMo, wear debris was observed without protein digest, using a combined experimental approach involving the employment of TEM and ICP-MS. The results suggest that nanoscale wear debris generated from a hip simulator in bovine serum albumin (BSA) lubrication was Cr-rich, containing crystalline and amorphous structures; meanwhile, without any proteins, the wear particles mostly had an hcp-Co crystalline structure.

The effect of contact load on CoCrMo wear and the formation and retention of tribofilms

Tribochemical reactions in a protein lubricated metal-on-metal (MoM) sliding contact may play a significant role for its wear performance. Such reactions lead to the formation of a carbonaceous ‘tribofilm’, which can act as a protective layer against corrosion and wear. The purpose of this study was to determine the effect of contact load on wear and the formation and retention of tribofilms.Wear tests were performed in a custom-made ball-on-flat testing apparatus that incorporated an electrochemical cell. A ceramic ball was used to articulate against low-carbon wrought CoCrMo alloy pins in bovine serum. Using a range of contact loads at a single potentiostatic condition (close to free potential), weight loss and changes in surface properties were evaluated.We determined that wear was influenced by the loading condition. As expected, wear increased with load, but the association between applied load and measured weight loss was not linear. In the intermediate load region, in the range of 32–48N (~58–80MPa), there was more than an order of magnitude drop in the wear per unit load, and the wear versus load data suggested an inflexion point at 49N. Regression analyses yielded a cubic model (R2=0.991; p=0.0002), where the cubic term, which represents the inflexion, was highly significant (p=0.0021). This model is supported by the observations that the minimum in the friction versus load curve is at 52N and the highest relative increase in polarization resistance occurred at 49N. Scanning electron microscopy and Raman spectroscopy indicated the absence of a tribofilm for the low and within the contact area of the high load cases. Synergistic interactions of wear and corrosion seem to play an important role.

In vivo production of nanosized metal wear debris formed by tribochemical reaction as confirmed by high‐resolution TEM and XPS analyses

High-resolution transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were used to establish the link between particles isolated from periprosthetic tissue of metal-on-metal (MOM) bearing and the solid deposit at the surface of retrieved MOM hip components. The high resolution of TEM made it possible to identify individual CoCrMo wear particles. Two shapes were observed. Needle-shaped particles ranged from 40 to 120 nm and contained both Co and Cr. Globular particles ranged up to 90 nm and contained high levels of Cr and no Co. Ti- and Ca-based particles were also identified. XPS analysis of the areas of thick solid deposit on the retrieved femoral head showed that the base alloy was covered by up to nearly 1-microm thick layer containing carbon, nitrogen, and oxygen. This layer was organic in nature, presumably protein-related. In areas with a thinner deposit, an organic-related layer was mixed with layers of metal oxides, the latter being much thinner than the extensive organic, carbon-rich layer. Outside the area of the deposit, the passive oxidized chromium layer was thinner, less than 20 nm, and carbon was bound to nonorganic oxygen.

Metal wear particle characterization from metal on metal total hip replacements: Transmission electron microscopy study of periprosthetic tissues and isolated particles

The less intense tissue reaction around metal on metal total hip replacements (THRs) compared to metal on polyethylene (PE) THRs may be explained by the differences in the characteristics of metal wear particles. In this study, transmission electron microscopy was used to study metal wear particles that were either in situ in cells or had been extracted from the cells by a new technique based on enzymatic tissue digestion. The tissues were obtained from 13 patients undergoing revision of metal on metal THRs with cobalt-chromium-molybdenum (CoCrMo) bearing couples. Most of the CoCrMo wear particles were smaller than 50 nm (range 6–834 nm) and round to oval in shape with irregular boundaries. This size range is considerably smaller than that reported for PE particles. While even a small volume of metal wear will produce high numbers of particles, the apparently less severe local tissue reaction to metal particles may be due to the possibility that corrosion, dissolution, and dissemination of metal particles may result in fewer local biological effects than the long-term retention of PE particles in the periprosthetic tissues. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 42, 103–111, 1998.

Metal wear particle characterization from metal on metal total hip replacements: transmission electron microscopy study of periprosthetic tissues and isolated particles.

The less intense tissue reaction around metal on metal total hip replacements (THRs) compared to metal on polyethylene (PE) THRs may be explained by the differences in the characteristics of metal wear particles. In this study, transmission electron microscopy was used to study metal wear particles that were either in situ in cells or had been extracted from the cells by a new technique based on enzymatic tissue digestion. The tissues were obtained from 13 patients undergoing revision of metal on metal THRs with cobalt-chromium-molybdenum (CoCrMo) bearing couples. Most of the CoCrMo wear particles were smaller than 50 nm (range 6-834 nm) and round to oval in shape with irregular boundaries. This size range is considerably smaller than that reported for PE particles. While even a small volume of metal wear will produce high numbers of particles, the apparently less severe local tissue reaction to metal particles may be due to the possibility that corrosion, dissolution, and dissemination of metal particles may result in fewer local biological effects than the long-term retention of PE particles in the periprosthetic tissues.