Concentration-dependent osteogenic and angiogenic biological performances of calcium phosphate cement modified with copper ions

Development of multifunctional bone grafting biomaterials with both osteogenesis and angiogenesis properties have earned increasing interest in the field of regenerative medicine. In the present investigation, copper-doped beta-tricalcium phosphate (Cu-TCP) powders were successfully synthesized. And Cu-containing calcium phosphate cement (Cu-CPC) was acquired through uniformly mixing CPC and Cu-TCP powders, with Cu-TCP serving as the donor of Cu2+. Cu-CPC exhibited suitable setting time, and the incorporation of Cu-TCP aggregating into CPC exhibited positive effect on the compressive strength while Cu2+ was in lower concentration. Investigation results showed that Cu-CPC had relatively low releasing amount of Cu2+, which was attributed to the re-bonding of Cu2+ into the newly formed HA crystals on surface. In vitro osteogenesis and angiogenesis properties of Cu-CPC were systematically evaluated through co-culture with mouse bone marrow stromal cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs) respectively. The results indicated dose-dependent biological functions of Cu2+ in Cu-CPCs. The mBMSCs and HUVECs showed well activity and attachment morphology on TCP/CPC, 0.05 Cu-TCP/CPC, 0.1 Cu-TCP/CPC. The upregulated osteogenic-related genes expression and angiogenic-related genes expression were detected with lower Cu2+ content. Taken together, Cu-containing CPC is of great potential for the regeneration of vascularized new bone.