Strontium delivery on topographical titanium to enhance bioactivity and osseointegration in osteoporotic rats

Osseointegration remains a major clinical challenge in osteoporotic patients. Strontium (Sr) has been shown to be a significant therapy to favor bone growth by both increasing new bone formation and reducing bone resorption. In this study, we attempt to chemically functionalize Ti implants by micro-arc oxidation, alkali treatment and ion exchange. This functionalized Ti surface possessed a hierarchical topography with Sr incorporation, which can release Sr ions at a slow rate. To our knowledge, this work is the first to use this type of Sr-doped Ti surface to address osteoporotic bone mesenchymal stem cells (BMSCs) in the dual directions of bone regeneration, bone formation and bone resorption. The modified surface was demonstrated to remarkably enhance the adhesion, spreading, and osteogenic differentiation of BMSCs in vitro. The effect of the wash-out solution from various groups on osteoporotic BMSCs was also investigated. The Sr-doped group can improve the ALP activity and osteogenic gene expression. Moreover, the Sr-doped group and the wash-out solution show the most inhibition in osteoclast formation and maturation. Furthermore, the increased bioactivity of the hierarchical structure was also confirmed with the ovariectomized rat femur model in vivo. The outcome of fluorescence labeling, histology and histomorphometric analysis demonstrated a significant promotion of osseointegration in ovariectomized rats. Altogether, the experimental data indicate that the fabrication of a Sr-doped hierarchical Ti surface is a meaningful attempt to incorporate the Sr nutrient element into Ti-based implants, and it is expected to be exploited in developing better osseointegration for osteoporotic patients.