Effect of strontium substitution on functional activity of phosphate-based glass

Phosphate-based glass (PBG) is a bioactive agent, composed of a glass network with phosphate as the primary component and can be substituted with various therapeutic ions for functional enhancement. Strontium (Sr) has been shown to stimulate osteogenic activity and inhibit pro-inflammatory responses. Despite this potential, there are limited studies that focus on the proportion of Sr substituted and its impact on the functional activity of resulting Sr-substituted PBG (PSr). In this study, focusing on the cellular biological response we synthesized and investigated the functional activity of PSr by characterizing its properties and comparing the effect of Sr substitution on cellular bioactivity. Moreover, we benchmarked the optimal composition against 45S5 bioactive glass (BG). Our results showed that PSr groups exhibited a glass structure and phosphate network like that of PBG. The release of Sr and P was most stable for PSr6, which showed favorable cell viability. Furthermore, PSr6 elicited excellent early osteogenic marker expression and inhibition of pro-inflammatory cytokine expression, which was significant compared to BG. In addition, compared to BG, PSr6 had markedly higher expression of osteopontin in immunocytochemistry, higher ALP expression in osteogenic media, and denser alizarin red staining in vitro. We also observed a comparable in vivo regenerative response in a 4-week rabbit calvaria defect model. Therefore, based on the results of this study, PSr6 could be identified as the functionally optimized composition with the potential to be applied as a valuable bioactive component of existing biomaterials used for bone regeneration.