2种镁基材料的体内外生物相容性研究

Study on the biocompatibility of two kinds of magnesium based materials in vitro and in vivo

目的探讨高纯镁和镁-1钙合金2种镁基材料的体内外生物相容性,为其临床应用提供安全性数据。方法选择高纯镁和镁-1钙合金2种镁基材料,参照ISO 10993系列标准,开展细胞毒性、遗传毒性、皮内反应、致敏性、急性全身毒性和26w肌肉植入后组织反应的研究,探讨细胞活力的影响因素,评价其生物相容性。结果高纯镁和镁-1钙合金的细胞存活率分别为(70.5±5.7)%和(54.1±3.8)%,调节pH值为7.4后,2种材料的细胞存活率均有所增加。高纯镁和镁-1钙合金均未诱发鼠伤寒沙门氏菌的体外基因回复突变、未引起体外哺乳动物细胞L5178Y TK^+/-的TK基因突变和染色体诱变、未引起小鼠急性全身毒性反应、皮肤过敏和皮内反应;植入后26 w对局部肌肉组织均无明显的刺激作用。结论在本试验条件下,高纯镁的细胞存活率优于镁-1钙合金,Mg^2+的释放不是影响其细胞活力的单一因素,在一定的Mg^2+浓度范围内,细胞活力可能更依赖于其酸碱环境;2种镁基材料无遗传毒性、无急性全身毒性、无刺激性和致敏性,具有良好的组织相容性。

Objective The aim of this study was to investigate the biosafety of two kinds of magnesium based materials,pure Mg and Mg-1Ca alloy in vivo and in vitro,providing an important scientific basis for their clinical application.Methods According to the ISO 10993 standard,the cell viability genotoxicity,delayed type hypersensitivity,intracutaneous reactivity and acute systemic toxicity of pure Mg and Mg-1Ca alloy were evaluated in this study..Moreover,the factors affecting cell viability were also analyzed Compared with 316L medical stainless steel,the local surrounding tissue responses of two kinds of magnesium based materials were further investigated to evaluate the biocompatibility by implant test in muscles(26 w).Results The cell survival rate in the high purity magnesium group and Mg-1Ca alloy group was(70.5±5.7)%and(54.1±3.8)%,respectively,andthe cell survival rates in both groups were significantly increased after adjusting the pH value to 7.4.The pure Mg and Mg-1Ca alloy were considered to be non-mutagenic by the bacterial reverse mutation study and the L5178Y TK^+/-Mouse Lymphoma Mutagenesis Assay,and the result was also negative in the skin sensitization and irritation test,acute systemic toxicity test.At 26 w after implantation,the microscopic evaluation showed that both the pure Mg and Mg-1Ca alloy did not induce obvious local stimulation as compared to the 316L stainless steel.Conclusions Under the conditions of this study,the cell survival rate in thehigh purity magnesium group was better than that in the Mg-1Ca alloy group.The release of Mg^2+was not a single factor which affected the cell vitality and it may be more dependent on the pH environment within a certain range of Mg^2+concentration.Both magnesium-based materials showed a good histocompatibility with no genetic toxicity,no acute systemic toxicity,no irritation and sensitization.