The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates

Development of biomedical titanium implants with high osteogenic ability for fast and good osseointegration under normal as well as osteoporotic conditions is hotly pursued. Strontium (Sr) loaded nanotubular structures (NT-Sr) that allow controlled and long-term Sr release are expected to yield favorable osteogenic effects and properties. NT-Sr structures with different tube diameters are fabricated by hydrothermal treatment of titania nanotubes formed at 10 and 40 V (NT10 and NT40). The loaded Sr amounts are regulated by the hydrothermal treatment time of 1 and 3 h (samples NT10-Sr1, NT10-Sr3, NT40-Sr1 and NT40-Sr3) in the Sr(OH)2 solution. Long lasting and controllable Sr release is observed from the NT-Sr samples with no cytotoxicity. The samples NT10 and NT10-Sr have multiple nanocues, comprising bundles of nanotubes of less than or equal to 30 nm with bundle diameters between 100 and 400 nm separated by about 80 nm. Sr incorporation enhances proliferation of rat mesenchymal stem cells (MSCs) on the NT structure, especially NT10-Sr which promotes the spread of the MSCs into a polygonal osteoblastic shape. Both the NT and NT-Sr samples promote osteogenesis to varying degrees as indicated by gene expression and among the various samples, samples NT10-Sr3 and NT40-Sr significantly up-regulate the expressions of the osteogenesis related genes in the absence of an extra osteogenic agent. Samples NT10 and NT10-Sr generate big nodular alkaline phosphatase (ALP) products and induce extracellular matrix (ECM) mineralization, and the effects on NT10-Sr3 are most obvious due to the multiple scaled nanostructure and proper amount of incorporated Sr. In comparison, less ALP products and failure to induce ECM mineralization are observed from sample NT40-Sr, possibly due to cell function impairment by the uneven protein distribution. NT10-Sr3 which shows excellent osteogenic properties is very attractive and has large clinical potential.