Aims. This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys. Methods. Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment. Results. On stainless steel, both nonactivated and activated cell groups were shown to have a significant increase in metal ion release for Cr, Fe, and Ni (p < 0.001, p = 0.002, and p = 0.020 respectively) compared with medium only and showed macrophage-sized corrosive pits on the stainless steel surface. On titanium alloy discs there was a significant increase in aluminum (p < 0.001) among all groups compared with medium only. Conclusion. These results indicated that macrophages were able to attach to and affect the oxide surface of stainless steel and titanium alloy discs. Cite this article: Bone Joint J 2020;102-B(7 Supple B):116–121

Introduction. Metal alloys have been commonly used for surgical applications due to their suitable mechanical characteristics and relatively good biocompatibility. However, direct cellular corrosion of orthopaedic implants remains a controversial topic and is still not fully understood. This study aims to examine a possible aspect of this corrosion mechanism by determining if macrophages can attach and directly affect the surfaces of 316L stainless steel, Ti6Al4V, and CoCrMo by releasing components of the alloy oxide layer. Methods. IC-21 ATCC peritoneal macrophages were cultured with growth medium of RPMI 1640 with 10%FBS, L-glutamine, and gentamicin. Interferon Gamma (IFNy) and Lipopolysaccharide (LPS) were used to induce activation of macrophages. Stainless Steel, CoCr, and Titanium disks cut, polished, and placed into a 96 well plate. Stainless steel testing included 6 groups: standard medium, 20,000 cells, 40,000 cells, 20,000 activated cells, 40,000 activated cells. CoCr and Ti testing included the following: medium, 40,000 cells, 20,000 activated cells, cells, no disk + 20,000 cells, no disk + 40,000 cells. After cells were attached to the surface, culture media was replaced and collected every 24 hours for stainless steel and every 12 hours for Ti and CoCr. ICP-MS, conducted at Brooks Applied Labs (Bothell, WA), was used to determine metal concentrations found in the supernatant. Results. A Kurskal-Wallis test and Tukey test were used to compare the groups in Table 2 (medium only, IFNy/LPS 20K, medium 20K cells, medium 40K cells). On stainless steel, both non-activated and activated cell groups were shown to have a statistically significant increase in metal ion release for Cr, Fe, and Ni (p<0.05) compared to medium only. On Ti, there was a significant increase in Al (<0.001) and decrease in V (p=0.003) among all groups compared to medium. No differences were seen among disk groups on CoCr. No difference was seen among activated and non-activated cells placed on all three types of disks. Discussion. This study was successful in showing that macrophages are capable of affecting the oxide layer of stainless steel and Ti by releasing more components of the oxide surface within 30 days. A significant increase in Cr, Fe, and Ni ion release was realized when cells were cultured on the surface of stainless steel disks for 30 days. A previous study, also involving 316L stainless steel, has shown that osteoclasts cause a greater increase in Cr compared to Ni under similar conditions. Our results show that macrophages lead to a greater increase of Ni ions compared to Cr. This suggest that various cell types may effectively change metal ion release profiles in different ways. Surprisingly, V content decreased when cells were attached to Ti disks, possibly indicating uptake of the V particles into the cells instead of release into the supernatant. No differences where seen among CoCr disk groups, therefore we cannot determine if corrosion is occurring during the 30 period. To get a more accurate representation a longer testing time may be necessary. For any tables or figures, please contact the authors directly

Introduction. In 2010, a widely used metal-on-metal hip implant was voluntarily recalled from the market by the manufacturer. Our lab performed detailed retrieval analysis of 548 of the explanted devices and 165 periprosthetic tissue specimens. We reported a high degree of variability in the multiple measurements that we performed on the components, including volumetric wear. Other studies using semi-quantitative tissue grading methods to describe the histology of the periprosthetic tissues from metal-on-metal hips have looked for relationships between component wear and histological features. Grammatopoulos et al found higher ALVAL scores in 45 hip resurfacing patients with pseudotumors compared to 11 without pseudotumors and a moderately positive correlation between wear and the histological rankings for tissue necrosis and lymphocytic response. We examined correlations between the component wear measurements from retrieval analysis and the tissue features in this large group of one metal-on-metal hip design. Materials and Methods. Tissues were processed routinely into paraffin sections, stained with H&E and characterized with light microscopic semi-quantitative scores for ALVAL features and for the number of macrophages and lymphocytes, extent of metal debris and the estimated percentage of necrosis per slide. Spearman correlation analysis was conducted to evaluate any correlations between retrieval wear measurements and histological findings. Results. The median combined cup and ball wear volume was 17.5mm3 in these 165 cases. The median tissue ALVAL score was 5.5 out of 10. Component total wear volume was not predictive of the ALVAL score (P = 0.09, R = −0.007) or the number of lymphocytes (P= 0.170, R= −0.077) but there was a positive correlation between wear volume and the ranking for macrophages in the tissues (P< 0.001, R=0.215). No other correlations were found for component wear. The median time to revision was 4.84 years. There was a negative correlation between tissue inflammation ranking (P=0.002, R=−0.183) and for lymphocyte ranking and time to revision (P=0.003, R=−0.173). There was a positive correlation between time to revision and the macrophage ranking (P=0.005, R=0.166). Conclusion. From this large-scale retrieval analysis of one design of metal-on-metal total hip, a high degree of variability was observed over the multiple analyses performed, including volumetric wear and tissue features. This likely reflects our previous observation that no single particular failure mechanism was predominant in this large cohort. Funded by DePuy Synthes Companies of Johnson & Johnson

Introduction. There are several potential biological mechanisms that may influence aseptic implant failure including excessive innate and adaptive immune responses to implant debris. We investigated the hypothesis that patients with painful total joint replacements will exhibit elevated levels of metal reactivity and inflammatory markers compared to patients with well-performing TJA. We evaluated this hypothesis by testing for metal hypersensitivity using in vitro LTT assay and analyzing serum levels of selected inflammatory markers. Methods. Subject Groups: Blinded de-identified data from patients with TJR referred for metal hypersensitivity testing using a lymphocyte transformation test (LTT) and serum markers of inflammation using Luminex Multi-Analyte Assay was approved by Rush University IRB and retrospectively reviewed. None of the patients had radiographically identifiable osteolysis. Two groups of TJA patients were tested: Group 1: Well-functioning implant (<3 yrs. post-op), with no self-reported pain, i.e. <1 on 0–10 VAS scale (n=8) and Group 2: Painful TJR (<3 yrs. post-op), with self-determined pain of >8 on a 0–10 VAS scale at the time of blood draw (n=25). Metal-LTT: Peripheral blood mononuclear cells (PBMCs) were collected from 30mL of peripheral blood by Ficoll gradient separation. PBMCs were cultured with NiCl2. 3H Thymidine was added at day 5 of culture and 3H thymidine incorporation was analyzed using a beta scintillation counter at day 6. A stimulation index (SI) of reactivity was calculated by dividing scintillation counts per minute (cpms) of Ni challenged cells by those of untreated controls. A SI of <2 was considered nonreactive, 2 to <4 was mildly reactive and 4 to <8 was reactive. Luminex Assay: Serum samples were collected from whole blood and were analyzed according to manufacturer's protocols. Statistical analysis: Statistical differences were determined using unpaired t-test with Welch's correction with statistical significance at p≤0.1 (90% confidence interval). Results. To test if differences in metal sensitization exist among individuals with joint pain following TJR vs. well-functioning TJR (no pain), we analyzed each person-specific PBMC SI of reactivity to NiCl2. Painful TJR group exhibited greater sensitivity as demonstrated by significantly higher in vitro metal SI level. In general, inflammatory markers measured in serum among patients with pain following TJR were significantly increased compared to patients with no pain following TJR. Specifically, inflammatory markers that are classified as prototypical markers of a M1 inflammatory macrophage i.e. GMCSF, IL-12, IL-18, IL-1β and TNFα were significantly greater in TJR patients with pain compared to TJR patients with no pain. Due to this increase in inflammatory markers, IL-4, an anti-inflammatory marker was also significantly greater in TJR patients with pain in order to combat/mitigate the inflammatory microenvironment. While VEGF was the only marker that was significantly greater in TJR patients with no pain and is characteristic of M2 anti-inflammatory macrophage phenotype. Discussion. Metal sensitivity reactivity and serum markers of inflammation demonstrated significant differences between groups of patients with painful TJRs vs. well-functioning TJR. Classical markers of M1 phenotype were significantly greater in painful TJR group. Our data suggests that patients with self-reported pain following a TJR demonstrate active innate and adaptive immune responses that are significantly higher than patients with a well-performing TJR and that these differences are associated with detectable serum inflammatory markers. An important limitation of this study however, is that group subject numbers were low and that statistical differences found in these groups suggests these inflammatory markers may be more marked than was anticipated

Objectives. This study aimed to characterise and qualitatively grade the severity of the corrosion particles released into the hip joint following taper corrosion. Methods. The 26 cases examined were CoC/ABG Modular (n = 13) and ASR/SROM (n = 13). Blood serum metal ion levels were collected before and after revision surgery. The haematoxylin and eosin tissue sections were graded on the presence of fibrin exudates, necrosis, inflammatory cells and corrosion products. The corrosion products were identified based on visible observation and graded on abundance. Two independent observers blinded to the clinical patient findings scored all cases. Elemental analysis was performed on corrosion products within tissue sections. X-Ray diffraction was used to identify crystalline structures present in taper debris. Results. The CoC/ABG Modular patients had a mean age of 64.6 years (49.4 to 76.5) and ASR/SROM patients had a mean age of 58.2 years (33.3 to 85.6). The mean time in situ for CoC/ABG was 4.9 years (2 to 6.4) and ASR/SROM was 6.1 years (2.5 to 8.1). The blood serum metal ion concentrations reduced following revision surgery with the exception of Cr levels within CoC/ABG. The grading of tissue sections showed that the macrophage response and metal debris were significantly higher for the ASR/SROM patients (p < 0.001). The brown/red particles were significantly higher for ASR/SROM (p < 0.001). The taper debris contained traces of titanium oxide, chromium oxide and aluminium nitride. Conclusion. This study characterised and qualitatively graded the severity of the corrosion particles released into the hip joint from tapers that had corrosion damage. Cite this article: S. Munir, R. A. Oliver, B. Zicat, W. L. Walter, W. K. Walter, W. R. Walsh. The histological and elemental characterisation of corrosion particles from taper junctions. Bone Joint Res 2016;5:370–378. DOI: 10.1302/2046-3758.59.2000507

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response. . Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). . The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. . 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. . Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. . These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. Cite this article: Bone Joint J 2015;97-B:917–23

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. . These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172–7

Aims

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings.

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Total hip arthroplasties are known to corrode predominantly at the taper junctions between Cobalt Chromium Molybedenum (CoCrMo) and Titanium (Ti) alloy components. We aimed to understand the modes underlying clinically significant tissue reactions to metals from corroded implants by determining: (1) what type of metal is present in the tissues, (2) which cells contain the metal species and (3) how this compares with results from metal-on-metal (MOM) hip resurfacings (HRs). This study involved periprosthetic tissue from patients that had undergone revision surgery due to adverse reactions to metal debris (ARMD) from dual-taper prostheses consisting of Ti-based alloy stems paired with CoCrMo necks. We used Synchrotron micro X-ray Fluorescence Spectroscopy (µXRF) and micro X-ray Absorption Near Edge Spectroscopy (µXANES) for detection of Co, Cr and Ti, and determination of their oxidation state. Synchrotron radiation has shown that the chromium in tissues is Cr. 2. O. 3. when derived from corroded CoCrMo/Ti junctions beside the CrPO. 4. species found when hip implants release CoCrMo nanoparticles from their bearing surfaces (MoM HRs). Presence of Cr. 2. O. 3. was associated with titanium oxide TiO. 2. This may be the outcome of the chemical interaction between the two species. Histological examination showed corrosion products present within viable macrophages and in the extracellular connective tissue, Figure 1. Understanding corrosion at taper junctions and the pathogenesis of the biological response is of significant clinical importance. This is the first study to co-register histology and metal distribution maps and to explore the potential synergy effect of CoCrMo with Ti alloy. This study provides guidance for toxicological studies on wear/corrosion particles, how they stimulate the host response and the cellular mechanisms involved in the pathogenesis of ARMD. For any figures or tables, please contact the authors directly by clicking on ‘Info & Metrics’ above to access author contact details

Aims

Dual mobility implants in total hip arthroplasty are designed to increase the functional head size, thus decreasing the potential for dislocation. Modular dual mobility (MDM) implants incorporate a metal liner (e.g. cobalt-chromium alloy) in a metal shell (e.g. titanium alloy), raising concern for mechanically assisted crevice corrosion at the modular liner-shell connection. We sought to examine fretting and corrosion on MDM liners, to analyze the corrosion products, and to examine histologically the periprosthetic tissues.

Introduction. The biological pathways responsible for adverse reactions to metal debris (ARMD) are unknown. Necrotic and inflammatory changes in response to Co-Cr nanoparticles in periprosthetic tissues may involve both a cytotoxic response and a type IV delayed hypersensitivity response. Our aim was to establish whether differences in biological cascade activation exists in tissues of patients with end-stage OA compared to those with aseptic loosening of a metal on polyethylene (MoP) THR and those with ARMD from metal-on-metal (MoM) THR. Patients & Methods. A microarray experiment (Illumina HT12-v4) was performed to identify the range of differential gene expression between 24 patients across 3 phenotypes: Primary OA (n=8), revision for aseptic loosening of MoP THR (n=8) and ARMD associated with MoM THR (n=8). Results were validated using Taqman Low Density Array (TLDA) selecting the top 36 genes in terms of fold-change (FC)>2 and a significant difference (p<0.05) on ANOVA. Pathways of cellular interaction were explored using Ingenuity IPA software. Results. There is a similar pattern of gene expression between MoP and MoM phenotypes versus primary OA across 33,777 genes. One hundred and thirty significantly differentially expressed genes across 3 phenotypes were identified. Fifteen pathways were associated with differentially expressed genes between MoP and MoM phenotypes. TLDA demonstrated qualitative mirroring of the expression pattern observed in the microarray and consistency in the direction of change for individual genes. Discussion. There were no signature pathways in which multiple genes are differentially expressed such that inferences between the contributions of innate macrophage and adaptive T-cell responses can be made. TIMP3 & MMP12 were consistently identified in 15 pathways that were associated with differential gene expression between MoP and MoM phenotypes. Conclusion. Analyses of the expression of individual genes such as PRG4 (lubricin) have demonstrated patterns that may provide avenues for further research into biomarkers for periprosthetic osteolysis and ARMD

Aims

Adverse local tissue reactions associated with abnormal wear considerably slowed down the general use of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), now limited to a few specialized centres. In this study, we provide the clinical results of 400 consecutive MoM HRAs implanted more than 20 years ago in one such centre.

Aims

We aimed to evaluate the long-term outcome of highly cross-linked polyethylene (HXLPE) cemented acetabular components and assess whether any radiolucent lines (RLLs) which arose were progressive.

Aims

Although there is increasing legalization of the use of cannabis in the USA, few well-powered studies have evaluated the association between cannabis use disorder and outcomes following primary total hip arthroplasty (THA). Thus, the aim of this study was to determine whether patients who use cannabis and undergo primary THA have higher rates of in-hospital length of stay (LOS), medical complications, implant-related complications, and costs.

Aims

The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

Aims

The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components.

Objectives

The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI.