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Nickel (Ni) eluted from metallic biomaterials is widely accepted as a major cause of allergies and inflammation. To improve the safety of cobalt-chromium-molybdenum (Co-Cr-Mo) alloy implants, new ultralow-Ni Co-Cr-Mo alloys with and without zirconium (Zr) have been developed, with Ni contents of less than 0.01%. In the present study, we investigated the biocompatibility of these new alloys in vivo by subcutaneously implanting pure Ni, conventional Co-Cr-Mo, ultralow-Ni Co-Cr-Mo, and ultralow-Ni Co-Cr-Mo with Zr wires into the dorsal sides of mice. After 3 and 7 days, tissues around the wire were excised, and inflammation; the expression of IL-1β, IL-6, and TNF-α; and Ni, Co, Cr, and Mo ion release were analyzed using histological analyses, qRT-PCR, and inductively coupled plasma mass spectrometry (ICP-MS), respectively. Significantly larger amounts of Ni eluted from pure Ni wires than from the other wires, and the degree of inflammation depended on the amount of eluted Ni. Although no significant differences in inflammatory reactions were identified among new alloys and conventional Co-Cr-Mo alloys in histological and qRT-PCR analyses, ICP-MS analysis revealed that Ni ion elution from ultralow-Ni Co-Cr-Mo alloys with and without Zr was significantly lower than from conventional Co-Cr-Mo alloys. Our study, suggests that the present ultralow-Ni Co-Cr-Mo alloys with and without Zr have greater safety and utility than conventional Co-Cr-Mo alloys. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1505-1513, 2016.

Environmental contamination from landfill leachate has been linked to disturbances in human health. Often, however, only global parameters, such as dissolved organic content, chemical oxygen demand, and 5-d biological oxygen demand, are used to evaluate wastewater quality. In the present study, we determined leachate cytotoxicity and stress response of leachate-treated mammalian cells using in vitro bioassays and other molecular techniques. The modified E-screen assay using human breast cancer MCF-7 cells was used to determine the estrogenic potential and/or cytotoxicity of water samples from two solid-waste landfills in Tunisia. The cytotoxicity mechanism of the leachate was determined by DNA fragmentation and lactate dehydrogenase assays. The stress response of heat shock protein (HSP) 47-positive Chinese hamster ovary cells treated with leachate also was determined. Proteomics analyses and real-time reverse transcription-polymerase chain reaction were used to determine and confirm the enhanced expressions of certain stress-related proteins. Results showed that the leachate samples generally did not have estrogenic activity. Instead, they were cytotoxic toward MCF-7 cells, and the cytotoxicity was by necrosis during the early stages of incubation. Leachate also enhanced the expression of HSP and various stress-related proteins, such as heterogeneous nuclear ribonucleoprotein E1, phosphoglycerate mutase, and nuclear matrix protein 200, in MCF-7 cells. These can be considered as survival mechanisms against leachate-induced cytotoxicity.