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The adverse effects of nickel ions being released into the human body have prompted the development of high-nitrogen nickel-free austenitic stainless steels for medical applications. Nitrogen not only replaces nickel for austenitic structure stability but also much improves steel properties. Here we review the harmful effects associated with nickel in medical stainless steels, the advantages of nitrogen in stainless steels, and emphatically, the development of high-nitrogen nickel-free stainless steels for medical applications. By combining the benefits of stable austenitic structure, high strength and good plasticity, better corrosion and wear resistances, and superior biocompatibility compared to the currently used 316L stainless steel, the newly developed high-nitrogen nickel-free stainless steel is a reliable substitute for the conventional medical stainless steels.

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The antibacterial mechanism of the Cu-containing materials has not been fully understood although such understanding is crucial for the sustained clinical use of Cu-containing antibacterial materials such as bone implants. The aim of this study is to investigate the molecular mechanisms by which the Gram-positive Staphylococcus aureus (S.aureus) is inactivated through Cu-bearing titanium alloys (Ti6Al4V5Cu). Cu ions released from the alloys were found to contribute to lethal damage of bacteria. They destroyed the permeability of the bacterial membranes, resulting in the leakage of reducing sugars and proteins from the cells. They also promoted the generation of bacteria-killing reactive oxygen species (ROS). The ROS production was confirmed by several assays including fluorescent staining of intracellular oxidative stress, detection of respiratory chain activity, and measurement of the levels of lipid peroxidation, catalase and glutathione. Furthermore, the released Cu ions showed obvious genetic toxicity by interfering the replication of nuc (species-specific) and 16SrRNA genes, but with no effect on the genome integrity. All of these effects lead to the antibacterial effect of Ti6Al4V5Cu. Collectively, our work reconciles the conflicting antibacterial mechanisms of Cu-bearing metallic materials or nanoparticles reported in the literature, as well as highlight the potential use of Ti6Al4V5Cu alloys in inhibiting bacterial infections.