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

Abstract

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 β-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.

Keywords: Angiogenesis; Calcium phosphate cement; Copper; Ion substitution; Osteogenesis.