Improved osteogenesis and angiogenesis of a novel copper ions doped calcium phosphate cement

Improving the angio1genesis potential of bone-repairing materials is vital for the repair of cancerous bone defects. It can further facilitate the delivery of active substances with osteogenesis and anti-tumor functions, ultimately promoting the formation of new bone tissues. Copper ions (Cu²⁺) have been proved to be beneficial to angiogenesis. This study developed a new type of Cu-containing calcium phosphate cement (Cu-CPC) by incorporating with copper phosphate (CuP) nanoparticles with a photothermal anti-tumor effect. The results revealed that the main phases of all hydrated CPCs were hydroxyapatite, unreacted tricalcium phosphate and calcium carbonate. But the hydration products of CPC became thinner after the incorporation of Cu²⁺. With the increase of CuP concentration, the setting time of CPC was prolonged while the injectability and the compressive strength were increased. The release concentration of Cu²⁺in vitro was among 0.01 to 0.74 mg/mL, which showed a positive relation with CuP content. Mouse bone marrow stromal cells (mBMSCs) displayed higher adhesion activity, proliferation performance and expression of osteogenic genes and proteins on CPC with 0.01 wt% CuP (0.01Cu-CPC) and 0.05 wt% CuP (0.05Cu-CPC). When human umbilical vein endothelial cells were co-cultured with 0.01Cu-CPC and 0.05Cu-CPC extracts, the proliferation and angiogenesis-related gene and protein expression were significantly increased, and the in vitro tube formation capacity was promoted. However, higher CuP content inhibited the proliferation of mBMSCs. In conclusion, CPC with 0.01 wt% and 0.05 wt% CuP nanoparticles has the potential to promote bone formation around cancerous bone defects, which would be promising for bone regeneration and treatment of bone tumors.