摘要
背景:研究已证实部分生物医用镁合金产品生物安全性及其他优势性能,但在其合金成分基础上改变制作工艺及产品形态制得的多孔支架材料生物安全性尚不明确。目的:探讨生物医用多孔镁合金支架材料的生物安全性能。方法:制取多孔镁合金支架材料浸提液,参照GB/T16886医疗器械生物学评价系列标准,进行体外细胞毒性实验、体外溶血实验、皮内反应实验、热源实验、急性全身毒性实验及遗传毒性实验,评估多孔镁合金支架材料浸提液对人骨髓间充质干细胞活性及血细胞胞膜结构完整性的影响,对动物皮内组织、体温、体质量、嗜多染红细胞染色体结构的影响;制备动物下颌骨缺损模型,将多孔镁合金材料植入缺损区,评估其对动物血清及尿液Mg2+浓度、血细胞数目和重要脏器等的影响。实验已通过北京大学医学部动物伦理委员会审核批准,批号为LA2017217。结果与结论:(1)多孔镁合金支架材料浸提液可促进骨髓间充质干细胞的增殖,细胞毒性为0级;(2)多孔镁合金支架材料浸提液的溶血率为0.94%,皮内刺激反应为0分,符合医疗器械溶血实验(<5%)及皮内反应实验(最终记分≤1.0)相关要求;(3)注射多孔镁合金浸提液后,所有动物体温升高均≤0.4℃,升高总度数≤0.8℃,符合医疗器械热源实验相关要求;(4)多孔镁合金浸提液未引起动物全身毒性反应,未破坏嗜多染红细胞染色体结构;(5)多孔镁合金支架材料植入动物骨缺损1个月内,动物血清及尿液Mg^2+浓度无明显变化,红细胞、白细胞、血小板处在正常范围,未引起心、肝、肾、脾组织明显的病理性改变;(6)结果表明,多孔镁合金支架材料具备优良的生物安全性能。
BACKGROUND: Biosafety and other advantages of biomedical magnesium alloy products have been confirmed, but the biosafety of porous scaffold materials prepared by changing the manufacturing process and product morphology based on the alloy composition is unclear.OBJECTIVE: To investigate the biosafety properties of a biomedical porous magnesium alloy scaffold.METHODS: Extracts of porous magnesium alloy scaffold materials were prepared, and in vitro cytotoxicity experiment, in vitro hemolysis experiment, intrauthelial reaction experiment, pyrogen experiment, acute systemic toxicity experiment and genetic toxicity experiment were conducted according to GB/T16886 biological evaluation series of medical devices. The effects of extracts of porous magnesium alloy scaffold materials on the activity of human bone marrow mesenchymal stem cells and the structural integrity of blood cell membrane, and the effects on the animal endothelial tissue, body temperature, body mass and chromosomal structure of polychromatic red blood cells were evaluated.Animal mandibular defect model was prepared, and porous magnesium alloy was implanted into the defect area to evaluate its influence on serum and urine Mg2+ concentration, blood cell number and important organs. The study was approved by the Experimental Animal Ethics Committee of Peking University Health Science Center(approval number: LA2017217).RESULTS AND CONCLUSION:(1) The extracts of porous magnesium alloy scaffolds could promote the proliferation of bone marrow mesenchymal stem cells, and the cytotoxicity was 0.(2) The hemolysis rate of the extracts of porous magnesium alloy scaffold material was0.94%, and the response to intradermal stimulation was 0, which met the requirements of medical device hemolysis experiment(< 5%) and intradermal reaction experiment(final score ≤ 1.0).(3) After the injection of porous magnesium alloy extract, the increased degree of body temperature was ≤ 0.4 oC and elevated total degree ≤ 0.8 oC in all animals, which conformed to the requirements of the medical equipment of heat experiment.(4) The porous magnesium alloy extract caused no systemic toxicity or damaged chromosomal structure of polychromatic erythrocytes.(5) Within 1 month after implantation of porous magnesium alloy scaffold material into the bone defect, there was no significant change in serum and urine Mg^2+ concentration, the red blood cells, white blood cells and platelets were in the normal range, and no obvious pathological changes were found in the heart, liver, kidney and spleen tissues.(6) These results imply that porous magnesium alloy scaffold has excellent biosafety property.
作者
王亮
郭玉兴
黄华
袁广银
张雷
Wang Liang;Guo Yuxing;Huang Hua;Yuan Guangyin;Zhang Lei(of Oral and Maxillofacial Surgery, Peking University Hospital of Stomatology, Beijing 100081,China;National Engineering Research Center of Light Alloys Net Forming and State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240,China)
出处
《中国组织工程研究》
CAS
北大核心
2019年第26期4121-4128,共8页
Chinese Journal of Tissue Engineering Research
基金
科技部重点研发计划子课题(2016YFC1102104),项目参与者:张雷
国家自然科学基金(51571143),项目负责人:袁广银
上海市卫生和计划生育委员会课题(201640281),项目参与者:袁广银~~
关键词
镁合金支架材料
多孔镁合金
生物安全性
生物降解性
颌骨缺损
体外细胞毒性实验
溶血实验
皮内反应实验
热源实验
急性全身毒性实验
遗传毒性实验
magnesium alloy scaffold materials
porous magnesium alloy
biosafety
biodegradable
jaw defect
in vitro cytotoxicity experiment
hemolysis experiment
intrauthelial reaction experiment
pyrogen experiment
acute systemic toxicity experiment
genetic toxicity experiment