Enhanced osteogenesis and angiogenesis of calcium phosphate cement incorporated with zinc silicate by synergy effect of zinc and silicon ions

Calcium phosphate cement (CPC) with good injectability and osteoconductivity plays important roles in bone grafting application. Much attention has been paid to achieve multifunctionality through incorporating trace elements into CPC. Silicon and zinc can be used as additives to endow CPC with biological functions of osteogenesis, angiogenesis and anti-osteoclastogenesis. In this study, zinc and silicate ions were co-incorporated into CPC through mixing with submicron zinc silicate (Zn₂SiO₄, ZS) to obtain zinc silicate-modified CPCs (ZS/CPCs) with different contents. The results revealed that the addition of ZS increased the compressive strength, prolonged the setting time, and densified the structure of CPC. Low addition content of ZS facilitated the formation of surface apatite layer in the early mineralization stage. Incorporating ZS significantly induced osteogenesis of mouse bone marrow stromal cells (mBMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs), and moreover, restricted osteoclastogenesis of Raw 264.7 in vitro. Silicate and zinc ions could be steadily released from ZS/CPCs into the culture medium. With the synergistic effect of silicate and zinc ions, ZS/CPCs provided an appropriate microenvironment for the immune cells to facilitate the osteogenesis of mBMSCs and angiogenesis of HUVECs further. Taken together, it can be concluded that incorporating ZS is an effective way to endow CPC with multifunctionality and better bone regeneration for bone defect repair.