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Microbiological and cellular evaluation of fluorine-phosphorus doped titanium alloy: A novel antibacterial and osteostimulatory biomaterial with potential applications in orthopedic surgery.

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both of which are associated with high morbidity and substantial costs for patients and health systems. The development of a biomaterial that is capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. We report antibacterial and osteostimulatory effects in a novel F-P-doped TiO2 oxide film grown on Ti-6Al-4V alloy with a nanostructure of bottle-shape nanotubes -bNT samples-using five bacterial species ( Staphylococcus aureus , S. epidermidis , Escherichia coli , Pseudomonas aeruginosa , and Stenotrophomonas malthophilia ) and MCT3T3-E1 osteoblastic cells. The interaction between the bacteria and bNT Ti-6Al-4V was complex, as the adhesion of four bacterial species decreased (staphylococci, E. coli , and S. maltophilia ), and the viability of staphylococci and S. maltophilia also decreased because of the aluminium (Al) released by bNT Ti-6Al-4V. This released Al can be recruited by the bacteria through siderophores and retained only by the Gram-negative bacteria tested. P. aeruginosa showed higher adhesion on bNT Ti-6Al-4V compared to chemically polished samples of Ti-6Al-4Valloy -CP samples- and an ability to mobilize Al from bNT Ti-6Al-4V. The cell adhesion and proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 and 168 h, as did the matrix mineralization of these cells and the gene expression of three of the most important markers related to bone differentiation. According to our results, the bNT Ti-6Al-4V alloy could have clinical application, preventing infection and stimulating bone growth, thus preventing the two main causes of joint prosthesis failure. Importance: This work evaluates F-P doped bNT Ti-6Al-4V from a microbiological and cellular approach. The bacterial results highlight that antibacterial ability of bNTc Ti-6Al-4V is the result of a combination of antiadhesive and bactericidal effect exerted by Al released from the alloy. The cell results highlight that F-P bNT Ti-6Al-4V alloy increases osseointegration due to the chemical composition modification of the alloy due to P incorporation and not due to the nanostructure as was reported previously. A key finding was the detection of Al release from the inner of the bNT Ti-6Al-4V alloy, result of the nanostructure growth during anodizing process and responsible of its part of its bactericidal effect.

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