Study on the osteogenesis of rat mesenchymal stem cells and the long-term antibacterial activity of Staphylococcus epidermidis on the surface of silver-rich TiN/Ag modified titanium alloy

J Biomed Mater Res B Appl Biomater. 2020 Oct;108(7):3008-3021. doi: 10.1002/jbm.b.34630. Epub 2020 May 9.


The main causes of failure of orthopedic implants are infection and poor bone ingrowth. Surface modification of the implants to allow for long-term antibacterial and osteogenic functions is an effective solution to prevent failure of the implants. We developed silver-rich TiN/Ag nano-multilayers on the surface of titanium alloy with different doses of Ag+ . The antibacterial stability and osteogenesis of the silver-rich surface were determined by evaluating the adhesion and proliferation of Staphylococcus epidermidis, and the adhesion, proliferation, alkaline phosphatase activity, extracellular matrix mineralization, and the expression level of genes involved in osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). The results demonstrated that the antibacterial rates (Ra) of 5 × 1016 -Ag, 1 × 1017 -Ag, 5 × 1017 -Ag, and 1 × 1018 -Ag were respectively 46.21%, 85.66%, 94.99%, 98.48%, and 99.99%. After subcutaneous implantation in rats or immersion in phosphate buffered saline for up to 12 weeks, the silver-rich surface of the titanium alloy showed long-term stable inhibition of Staphylococcus epidermidis. Furthermore, in vitro and in vivo studies indicated that the Ag-implanted titanium did not show apparent cytotoxicity and that lower Ag+ implanted groups (5 × 1016 -Ag, 1 × 1017 -Ag) had better viability and biological safety when compared with higher Ag+ implanted groups. In addition, when compared with the Ti6Al4V-group, all Ag-implanted groups exhibited enhanced osteogenic indicators in rat BMSCs. Regarding osteogenic indicators, the surfaces of the 5 × 1017 -Ag group had better osteogenic effects than those of other groups. Therefore, the proper dose of Ag+ implanted TiN/Ag nano-multilayers may be one of the options for the hard tissue replacement materials with antibacterial activity and osteogenic functions.

Keywords: Nano-multilayers; Staphylococcus epidermidis; antibacterial activity; mesenchymal stem cells; titanium alloys.

Publication types

  • Research Support, Non-U.S. Gov't