Alliance Of Gallium And Strontium Potently Mediates The Osteoclastic And Osteogenic Activities Of Beta-Tricalcium Phosphate Bioceramic Scaffolds

Systemic administration of gallium (Ga) nitrate and strontium (Sr) ranelate, which are metal ion-based drugs, has been approved to treat the diseases associated with accelerated bone resorption. In the present study, Ga and Srcontaining phosphate glasses (PGs) were used to modify the ?-tricalcium phosphate (?-TCP), and the ?-TCP-based bioceramic (TCP/PGs) scaffolds were fabricated employing an extrusion-microdrilling method. The TCP/PGs scaffolds were characterized by channel-like round and square macropores, fully 3D interconnection and distinctively improved compressive strength. The TCP/PGs scaffolds with single Ga promoted cell proliferation, and markedly inhibited in vitro osteogenic differentiation and osteoclastic activities; by contrast, the combination of Sr and Ga enabled the TCP/PGs to achieve remarkably enhanced cell proliferation and osteogenic differentiation while maintaining the inhibitory effect on the osteoclastic activities. In vivo assessment results demonstrated that the TCP/PGs with single Ga significantly inhibited bone resorption, and did not have better bone formation; the TCP/PGs with Ga and Sr not only suppressed bone resorption but also effectively promoted bone regeneration after implantation in the defects of rabbit femora. This study elucidated the combinatory effect of Ga and Sr on mediating the osteogenic and osteoclastic activities, and the TCP/PGs containing Ga and Sr are expected to efficiently repair the bone defects in the pathological state of accelerated bone resorption.