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

A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system and ultimately clinical infections. The hypothesis of the current study was that a change in microbiome and/or breach in GI epithelial barrier could be partially responsible for development of periprosthetic joint infections (PJI). Multiple biomarkers of gut barrier disruption were tested in parallel in plasma samples collected as part of a prospective cohort study of patients undergoing revision arthroplasty for aseptic failures or PJI (As defined by the 2018 ICM criteria). All blood samples were collected before any antibiotic was administered. Samples were tested for Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) using commercially available enzyme-linked immunosorbent assays. Statistical analysis consisted of descriptive statistics, Mann-Whitney t-test, and Kruskal-Wallis test. A total of 134 patients were consented and included in the study. 44 were classified as PJI (30 chronic and 14 acute), and 90 as aseptic failures (26 primaries and 64 aseptic revisions). Both Zonulin and sCD14, but not LPS, were found to be significantly increased in the PJI group compared to non-infected cases (p<0.001; p=0.003). Higher levels of Zonulin were found in acute infections compared to chronic PJI (p=0.005. This prospective ongoing study reveals a possible link between gut permeability and the ‘gut-immune-joint axis’ in PJI. If this association continues to be born out with larger cohort recruitment and more in-depth analysis, it would have an immense implication in managing patients with PJI. In addition to administering antimicrobials, patients with PJI and other orthopedic infections may require gastrointestinal modulators such as pro and prebiotics

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

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

Aims

Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH.

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.

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.