In vitro and in vivo evaluation of the pH-neutral bioactive glass as high performance bone grafts

Osteogenic and angiogenic properties are two most valued factors for bone grafting materials. Biomedical materials with synergistic promotion effects on these two properties would be highly desirable. In this study, we showed that a recently developed pH-neutral bioactive glass (PSC) possessed such characteristics. Compared to two classical biomaterials, 45S5 bioactive glass and beta-tricalcium phosphate (beta-TCP), PSC markedly improved BMSCs' proliferation, migration and mineralization as well as their osteogenic and angiogenic differentiation. In vivo, PSC showed better performance on inducing bone regeneration than both 45S5 and beta-TCP, as featured by elevated bone mineral density (BMD) and new bone areas. PSC also significantly promoted new blood vessels formation compared with those in control groups. Furthermore, we revealed that PSC induced osteogenic and angiogenic differentiation of BMSCs through the PI3K/Akt/HIF-1 alpha pathway, which had not been reported before. This synergistic effect of the PI3K/Akt/HIF-1 alpha pathway on osteogenesis and angiogenic differentiation of BMSCs suggested that biomedical materials may promote new bone formation through multiple signal pathways, thus shedding light on the future development of materials with better performance.