Stimulation of proangiogenesis by calcium silicate bioactive ceramic

Angiogenesis is critical for bone tissue engineering. Stimulating proangiogenesis in an engineered bone construct using bioglass or bioceramic is now attracting much attention. However, the specific ion that plays important roles in the stimulation of proangiogenesis has not yet been elucidated. In this study, calcium silicate (CS), an osteogenic bioceramic containing only Ca and Si ions, significantly stimulated proangiogenesis of human umbilical vein endothelial cells (HUVECs). The determination of the ionic dissolution product indicates that Si ion concentrations of the CS extracts were significantly higher than that of the calcium phosphate ceramic extracts and control medium. However, the concentrations of Ca and P ions of both ceramic extracts and normal medium were at the same level. With the specific Si ion and its effective concentrations, CS extracts stimulated the proliferation of HUVECs, up-regulated the expression of vascular endothelial growth factor, basic fibroblast growth factor and their receptors, and finally stimulated the proangiogenesis. As the Si ion played an important role in osteogenesis stimulated by Si-containing bioceramics, confirmation of the Si ion's specific role and its effective ion concentrations in CS-induced angiogenesis may be extremely useful in designing osteogenic and angiogenic bioactive materials for bone tissue engineering.