Bone and soft tissue reaction to Co(II)/Cr(III) ions stimulation in a murine calvaria model: A pioneering in vivo study

Metal ions released during wear and corrosion of the artificial knee/hip joints are considered to contribute to aseptic implant failure. However, there are few convincing in vivo studies that demonstrate the effects of metal ions on bone and soft tissue. This study examined the in vivo effects of Co(II)/Cr(III) ions on mouse calvaria and the supra-calvaria soft tissue in an original mouse model. With the implantation of a helmet-like structure, we set up a subcutaneous cavity on the calvaria in which Co(II) Chloride or Cr(III) Chloride solutions were administered respectively. A layer of interface membrane formed on the calvaria along with the implantation of the helmet. The administered Cr(III) ions accumulated in the interface membranes while Co(II) disseminated into the circulation. Accumulated Cr(III) and related products induced local massive macrophage infiltration and skewed the bone metabolic balance. At last, we revealed that lymphocyte aggregates, which are the pathologic hallmark of human periprosthetic tissue, could be caused by either Co(II) or Cr(III) stimulation. These in vivo results may shed light on the effects and pathogenic mechanism of the Co(II)/Cr(III) ions released from the joint prosthesis. STATEMENT OF SIGNIFICANCE: Macrophage infiltration and lymphocyte aggregates are hallmarks of human joint periprosthetic tissue. We chronically administered Co(II)/Cr(III) ions on mouse calvaria and reproduced these two histopathologic hallmarks on mouse tissue based on an implanted helmet-like structure. Our results reveal that Cr(III) ions are locally accumulated and are effective in inducing macrophage infiltration and they can be phagocytosed and stored. However, the lymphocytes aggregates could be induced by both Co(II), Cr(III) and other unspecific inflammatory stimuli.