Strontium modulates osteogenic activity of bone cement composed of bioactive borosilicate glass particles by activating Wnt/β-catenin signaling pathway

There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery. Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo. However, the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined. In this study, bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr (0 mol% to 12 mol% SrO) were created and evaluated in vitro and in vivo. The setting time of the cement increased with Sr substitution of the glass. Upon immersion in PBS, the cement degraded and converted more slowly to HA (hydroxyapatite) with increasing Sr substitution. The released Sr(2+) modulated the proliferation, differentiation, and mineralization of hBMSCs (human bone marrow mesenchymal stem cells) in vitro. Osteogenic characteristics were optimally enhanced with cement (designated BG6Sr) composed of particles substituted with 6mol% SrO. When implanted in rabbit femoral condyle defects, BG6Sr cement supported better peri-implant bone formation and bone-implant contact, comparing to cements substituted with 0mol% or 9mol% SrO. The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs. These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.