Development of new Ti₅₀Zr₂₅Nb₂₀Cu_5–xAg_x high-entropy alloys with excellent antibacterial property, osteo-conductivity and biocompatibility in vitro and in vivo

A new series of medical antibacterial high-entropy alloys (HEAs) with composition Ti₅₀Zr₂₅Nb₂₀Cu_5–xAg_x (x = 0 at.%, 1 at.%, and 2.5 at.%) were developed by arc-melting the mixture of pure elements under a high-purity argon atmosphere. The cytotoxicity, osteo-conductivity, and antibacterial properties of these HEAs were systematically investigated in vitro, along with their in vivo biocompatibility and antibacterial properties. These HEAs, especially Ti₅₀Zr₂₅Nb₂₀Cu_2.5Ag_2.5, showed better antibacterial ability against Staphylococcus aureus than Ti–6Al–4V, which has a nearly 99% antibacterial rate in vitro. Moreover, ion release and cytotoxicity tests showed that these HEAs had excellent biosafety, similar to or better than that of Ti–6Al–4V. Osteoblasts were used to evaluate the osteogenic activity of these HEAs, and good osteo-conductivity was observed in vitro. In a Sprague-Dawley rat infection model, Ti₅₀Zr₂₅Nb₂₀Cu_2.5Ag_2.5 showed remarkable antibacterial properties compared to Ti–6Al–4V. The in vivo biocompatibility results showed that Ti₅₀Zr₂₅Nb₂₀Cu_2.5Ag_2.5 did not increase biotoxicity compared to Ti–6Al–4V. The excellent biocompatibility and antibacterial properties of the Ti–Zr–Nb–Cu–Ag HEAs are expected to enable the prevention of periprosthetic/peri-implant infections in the future.