The role of copper ions in bone regeneration

Introduction Bone injuries caused by fractures, diseases, tumor surgery, and congenital anomalies are increasing worldwide. Current treatments include allografts or autografts have several limitations. Thus, tissue engineering was proposed to develop alternative methods. Researchers try to overcome bone graft limitations using cell, scaffold, and biological molecules. Bone regeneration is a consistent process in which angiogenesis and osteogenesis are closely related and the presence of a vascular network is essential to a successful bone formation. One of the strategies to improve the angiogenesis is incorporating copper ions within tissue engineering constructs. Objectives The aim of present study was to review the role of copper ions in angiogenesis and osteogenesis in bone defects. Methods Web of science, PubMed, Scopus, and Science direct databases were explored based on pre- defined key words. Related original articles were investigated from 2015 to 2018. Results Copper ions improve the angiogenesis by inducing hypoxia, followed by the activation of hypoxia-sensitive genes, including vascular endothelial growth factor. Also, copper ions increase in vitro proliferation of endothelial cells in a dose-dependent manner. Recently osteostimulatory effect of copper ions was suggested. Conclusion It seems that copper ions improve the angiogenesis significantly. Also, they have the ability to stimulate new bone formation. Despite the role of copper ions in bone regeneration, it seems that high concentration of copper ions may be toxic to cells and has a negative effect on bone regeneration and new bone formation. So it is necessary to study this aspect much better

Keywords:

Bone injuries , Tissue engineering , Osteogenesis , Angiogenesis , Copper ions