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To stimulate bone regeneration, the design of bioactive implants is a great challenge in current orthopedic research. We reasoned that implants should be suitable both to stimulate osteogenic differentiation of mesenchymal stem cells and prevent infections at the site of implantation. Therefore, we focus on copper ions, which are known to exert antimicrobial effects. On the other hand, copper is essential for the cell physiology, including the formation of the extracellular matrix. We studied the influence of copper ions on mesenchymal stem cells at various concentrations and identified the limits of copper concentrations for cell survival. Below the critical concentration for cell survival we analysed proliferation and osteogenic differentiation of the cells in the presence of copper ions. We found that copper stimulated the proliferation of the mesemchymal stem cells at 0.1 mM. Osteogenic differentiation decreased after 14 days at a concentration of 0.05 - 0.1 mM copper ions in osteogenic medium measured by the expression of osteogenic proteins, like alkaline phosphatase (ALP), bone sialoprotein (BSP) and collagen I (COL). We argue that at the implant surface a higher concentration of copper could prevent biofilm formation of bacteria and physiological concentrations in the vicinity of the implant would stimulate stem cell expansion. Together, copper is an interesting agent to control both bacteria and stem cells in the field of implant technology.

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