Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood.

The IONPs differentially affected the TLR ligand-induced cytokines, which has important implications for biomedical applications of IONPs.

The cemented Spectron EF stem in combination with the cemented non-crosslinked Reflection All-Poly cup showed a high rate of mid-term aseptic loosening. However, the failure mechanisms are not fully known. We assessed the inflammatory tissue reactions and wear particles in periprosthetic tissues, implant wear and blood metal ion levels in 28 patients with failed implants. Histological analysis showed a macrophage pre-dominant pattern with randomly distributed lymphocytes, with various amounts of neutrophils and giant cells. The number of different cell types in the tissue samples from patients in the cup group and in the stem group was similar. Wear particles, mainly ZrO 2 , CoCrMo, and polyethylene particles of different sizes and shapes, were associated with macrophages/giant cells, and total particle load/mm 2 was higher in cases of stem loosening. The Spectron EF stems were heavily worn, abraded, and polished. Stem abrasion correlated with metal ion concentrations in blood. The median polyethylene wear rate of the Reflection cups was 0.23 mm/year.The high proximal roughness of the Spectron EF stem resulted in excessive cement wear during loosening. The resulting inflammatory tissue responses to the degradation products both from the cup and the stem led to massive osteolysis and subsequent implant loosening.

The Nord-Trøndelag Health Study (The HUNT Study) is a large health survey population study in the county of Trøndelag, Norway. The survey has been repeated four times in about 10-year intervals. In the HUNT3 survey (2006–2008), we collected 28,000 samples for trace element analysis. Blood samples from 758 healthy persons without known occupational exposure were selected for multielement analysis of a small sample of blood (0.25 mL). The aim of the study was to determine the minimum blood volume that can be used for the analytical procedure and to compare our results with previously published results of similar surveys in healthy populations. Samples were digested and the concentration of selected trace elements was determined by ICP-MS. We report results on essential elements (B, Co, Cu, Mn, Se and Zn) as well as non-essential elements (As, Be, Br, Cd, Cs, In, La, Pb, Hg, Nd, Ni, Nb, Pd, Pt, Sm, Ta and Sn). Results are similar to previous studies on the HUNT3 population, and with a few exceptions, our data compares very well with results obtained in recent studies from other countries. We wanted to test a minimum volume of blood in a large-scale analytical program. For a number of nonessential elements, our results were below the limit of detection. We suggest that future studies using similar ICP-MS equipment as analytical tool should use at least 0.5 mL of blood.

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