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

• Published in: Journal of trace elements in medicine and biology Vol. 55; pp. 127 - 135
• Main Authors: Li, Kunqiang, Xia, Chao, Qiao, Yuqin, Liu, Xuanyong
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.09.2019
• Subjects: 3T3 Cells; Angiogenesis; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Cell Survival - drug effects; Copper; Copper - chemistry; Copper - pharmacology; Dose-response relationship; Dose-Response Relationship, Drug; Escherichia coli - drug effects; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Mice; Microbial Sensitivity Tests; Osteogenesis; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Angiogenesis; Antibacterial; Copper; Osteogenesis; Dose-response relationship
• ISSN: 0946-672X; 1878-3252
• DOI: 10.1016/j.jtemb.2019.06.015

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.