The methodology allows for the first time silver impregnation (as opposed to coating) of medical polymers and promises to lead to an antimicrobial biomaterial whose activity is not restricted by increasing antibiotic resistance.

High-aspect ratio ZnO nanowires have become one of the most promising products in the nanosciences within the past few years with a multitude of applications at the interface of optics and electronics. The interaction of zinc with cells and organisms is complex, with both deficiency and excess causing severe effects. The emerging significance of zinc for many cellular processes makes it imperative to investigate the biological safety of ZnO nanowires in order to guarantee their safe economic exploitation. In this study, ZnO nanowires were found to be toxic to human monocyte macrophages (HMMs) at similar concentrations as ZnCl(2). Confocal microscopy on live cells confirmed a rise in intracellular Zn(2+) concentrations prior to cell death. In vitro, ZnO nanowires dissolved very rapidly in a simulated body fluid of lysosomal pH, whereas they were comparatively stable at extracellular pH. Bright-field transmission electron microscopy (TEM) showed a rapid macrophage uptake of ZnO nanowire aggregates by phagocytosis. Nanowire dissolution occurred within membrane-bound compartments, triggered by the acidic pH of the lysosomes. ZnO nanowire dissolution was confirmed by scanning electron microscopy/energy-dispersive X-ray spectrometry. Deposition of electron-dense material throughout the ZnO nanowire structures observed by TEM could indicate adsorption of cellular components onto the wires or localized zinc-induced protein precipitation. Our study demonstrates that ZnO nanowire toxicity in HMMs is due to pH-triggered, intracellular release of ionic Zn(2+) rather than the high-aspect nature of the wires. Cell death had features of necrosis as well as apoptosis, with mitochondria displaying severe structural changes. The implications of these findings for the application of ZnO nanowires are discussed.

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Laboratory-defined T-cell lymphopenia was present in 13 patients (15%) (CD8(+) lymphopenia) and 11 patients (13%) (CD3(+) lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8(+) lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

A cup inclination angle greater than 45 degrees is associated with increased wear rates of metal on polyethylene (MOP) hip replacements. The same maybe true for metal on metal (MOM) hips yet this has not been clearly shown. We measured the acetabular inclination angle from plain radiographs, and whole blood metal ion levels using Inductively Coupled Plasma Mass Spectrometry of 26 patients (mean Harris Hip Score 94 and mean time post op of 22 months) with Birmingham Hip Resurfacings. We identified a threshold level of 50 degrees cup inclination. Below this threshold, the mean whole blood cobalt and chromium were 1.6 ppb and 1.88 ppb respectively; above this threshold, the mean blood cobalt and chromium were 4.45 ppb and 4.3 ppb respectively. These differences were significant cobalt (p<0.01) and chromium (p=0.01). All patients above the threshold had metal levels greater than any of the patients below the threshold. For 14 patients, who returned one year later for a repeat blood metal level measurement, cobalt and chromium levels were very similar. The effect of an acetabular inclination angle of greater than 50 degrees on wear rates of MOM hips, as measured through blood metal ion levels, appears to be similar to that seen with MOP hips. Additionally, our new analytical methods may allow blood metal levels to be used as a realistic biomarker of in vivo wear rate of MOM hips. The implication is that metal levels can be minimised with optimal orientation of the acetabular component.