Dose-response relationships between copper and its biocompatibility/antibacterial activities

Copper has already been widely used in the modification of biomaterials because it possesses multifunctional biological effects like osteogenic, angiogenic and antibacterial activities. However, it is still not clear how different cell lines and bacteria will respond to different concentrations of Cu2+, which is very critical to the application of copper-doped implants.This study aimed to explore the dose-response relationships of Cu2+ and its biological effects in vitro. Rat bone marrow mesenchymal stem cell (rBMSCs), mouse osteoblastic cell line (MC3T3-E1), and human umbilical vein endothelial cells (HUVECs) were used to evaluate cellular behaviors. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were used to evaluate bacterial behaviors.Results showed that the HUVECs exhibited significantly higher tolerance to copper ions than MC3T3-E1 and rBMSCs. The IC50 values of copper for HUVECs, MC3T3-E1 and HUVECs were approximated to 327.9 μM, 134.6 μM, and 0.7 μM, respectively. Besides, the threshold concentration of copper for effective inhibition against bacteria growth is 37 μM. When the concentration exceeded the threshold value, antibacterial activity could increase dramatically.These results altogether establish a technological foundation for the application of copper-doped biomaterials in bone growth and remodeling.