title: Hemolysis and cytotoxicity mechanisms of biodegradable magnesium and its alloys.
abstract: Good hemocompatibility and cell compatibility are essential requirements for coronary stents, especially for biodegradable magnesium alloy stents, which could change the in situ environment after implanted. In this work, the effects of magnesium ion concentration and pH value on the hemolysis and cytotoxicity have been evaluated. Solution with different Mg(2+) concentration gradients and pH values of normal saline and cell culture media DMEM adjusted by MgCl2 and NaOH respectively were tested for the hemolysis and cell viability. Results show that even when the concentration of Mg(2+) reaches 1000 μg/mL, it has little destructive effect on erythrocyte, and the high pH value over 11 caused by the degradation is the real reason for the high hemolysis ratio. Low concentrations of Mg(2+) (<100 μg/mL) cause no cytotoxicity to L929 cells, of which the cell viability is above 80%, while high concentrations of Mg(2+) (>300 μg/mL) could induce obvious death of the L929 cells. The pH of the extract plays a synergetic effect on cytotoxicity, due to the buffer action of the cell culture medium. To validate this conclusion, commercial pure Mg using normal saline and PBS as extract was tested with the measurement of pH and Mg(2+) concentration. Pure Mg leads to a higher hemolysis ratio in normal saline (47.76%) than in buffered solution (4.38%) with different pH values and low concentration of Mg(2+). The Mg extract culture media caused no cytotoxicity, with pH=8.44 and 47.80 μg/mL Mg(2+). It is suggested that buffered solution and dynamic condition should be adopted in the hemolysis evaluation.
authors.affiliation: Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhen
authors.affiliation: School of Material Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Materials Science and Engineering, State Key Laboratory for Turbulence and Complex System, College of Engineering, Peking University, Beijing 100871, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Biomedical Engineering Research Center, Shenzhen Institute, Peking University, Shenzhen 518057, China; Shenzhen Key Laboratory of Human Tissue Regeneration and Repair, Shenzhen Institute, Peking University, Shenzhen 518057, China. Electronic address: xitingfei@pku.edu.cn.
authors.forename: TingFei
authors.initials: T
authors.lastname: Xi
authors.affiliation: Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Department of Materials Science and Engineering, State Key Laboratory for Turbulence and Complex System, College of Engineering, Peking University, Beijing 100871, China; Shenzhen Key Laboratory of Human Tissue Regeneration and Repair, Shenzhen Institute, Peking University, Shenzhen 518057, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006461:Hemolysis; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D008274:Magnesium
keywords: Biodegradable magnesium; Hemolysis ratio; L929 cells; Magnesium ion concentration; pH values