Synergistic effects of immunoregulation and osteoinduction of ds-block elements on titanium surface

Ds-block elements have been gaining increasing attention in the field of biomaterials modification, owing to their excellent biological properties, such as antibiosis, osteogenesis, etc. However, their function mechanisms are not well understood and conflicting conclusions were drawn by previous studies on this issue, which are mainly resulted from the inconsistent experimental conditions. In this work, three most widely used ds-block elements, copper, zinc, and silver were introduced on titanium substrate by plasma immersion ion implantation method to investigate the rule of ds-block elements in the immune responses. Results showed that the implanted samples could decrease the inflammatory responses compared with Ti sample. The trend of anti-inflammatory effects of macrophages on samples was in correlation with cellular ROS levels, which was induced by the implanted biomaterials and positively correlated with the number of valence electrons of ds-block elements. The co-culture experiments of macrophages and bone marrow mesenchymal stem cells showed that these two kinds of cells could enhance the anti-inflammation and osteogenesis of samples by the paracrine manner of PGE2. In general, in their steady states on titanium substrate (Cu²⁺, Zn²⁺, Ag), the ds-block elements with more valence electrons exhibit better anti-inflammatory and osteogenic effects. Moreover, molecular biology experiments indicate that the PGE2-related signaling pathway may contribute to the desired immunoregulation and osteoinduction capability of ds-block elements. These findings suggest a correlation between the number of valence electrons of ds-block elements and the relevant biological responses, which provides new insight into the selection of implanted ions and surface design of biomaterials.