To　optimize　mesenchymal　stem　cell　differentiation　and　antibacterial　properties　of　titanium　(Ti),　nano-sized　zinc　oxide　(ZnO)　particles　with　tunable　concentrations　were　incorporated　into　TiO2　nanotubes　(TNTs)　using　a　facile　hydrothermal　strategy.　It　is　revealed　here　for　the　first　time　that　the　TNTs　incorporated　with　ZnO　nanoparticles　exhibited　better　biocompatibility　compared　with　pure　Ti　samples　(controls)　and　that　the　amount　of　ZnO　(tailored　by　the　concentration　of　Zn(NO3)(2)　in　the　precursor)　introduced　into　TNTs　played　a　crucial　role　on　their　osteogenic　properties.　Not　only　was　the　alkaline　phosphatase　activity　improved　to　about　13.8　U/g　protein,　but　the　osterix,　collagen-I,　and　osteocalcin　gene　expressions　was　improved　from　mesenchymal　stem　cells　compared　to　controls.　To　further　explore　the　mechanism　of　TNTs　decorated　with　ZnO　on　cell　functions,　a　response　surface　mathematical　model　was　used　to　optimize　the　concentration　of　ZnO　incorporation　into　the　Ti　nanotubes　for　stem　cell　differentiation　and　antibacterial　properties　for　the　first　time.　Both　experimental　and　modeling　results　confirmed　(R-2　values　of　0.8873-0.9138　and　0.9596-0.9941,　respectively)　that　Ti　incorporated　with　appropriate　concentrations　(with　an　initial　concentration　of　Zn(NO3)(2)　at　0.015　M)　of　ZnO　can　provide　exceptional　osteogenic　properties　for　stem　cell　differentiation　in　bone　cells　with　strong　antibacterial　effects,　properties　important　for　improving　dental　and　orthopedic　implant　efficacy.