Quantitative in vivo biocompatibility of new ultralow-nickel cobalt–chromium–molybdenum alloys

Kazuaki Sonofuchi, Yoshihiro Hagiwara, Yuichiro Koizumi, Akihiko Chiba, Mitsuko Kawano, Masafumi Nakayama, Kouetsu Ogasawara, Yutaka Yabe, Eiji Itoi

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13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1505-1513
Number of pages9
JournalJournal of Orthopaedic Research
Issue number9
Publication statusPublished - 2016 Sept 1


  • cobalt–chromium–molybdenum alloy
  • metal ions
  • nickel


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