镁合金全降解血管支架研究进展

doi:10.11900/0412.1961.2017.00319

金属学报

2017, Vol. 53

Issue (10): 1153-1167 DOI: 10.11900/0412.1961.2017.00319

研究论文

本期目录 | 过刊浏览

镁合金全降解血管支架研究进展

奚廷斐^1,²(

), 魏利娜^1,³, 刘婧², 刘小丽⁴, 甄珍¹, 郑玉峰⁵

1 北京大学深圳研究院深圳 518057
2 北京大学前沿交叉学科研究院北京 100871
3 中国食品药品检定研究院北京 100050
4 河北科技大学材料科学与工程学院石家庄 050018
5 北京大学工学院材料科学与工程系北京 100871

Research Progress in Bioresorbable Magnesium Scaffolds

Tingfei XI^1,²(

), Lina WEI^1,³, Jing LIU², Xiaoli LIU⁴, Zhen ZHEN¹, Yufeng ZHENG⁵

1 Shenzhen Institute, Peking University, Shenzhen 518057, China
2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
3 National Institute for Food and Drug Control, Beijing 100050, China
4 College of Materials Science and Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China
5 Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China

引用本文:

奚廷斐, 魏利娜, 刘婧, 刘小丽, 甄珍, 郑玉峰. 镁合金全降解血管支架研究进展[J]. 金属学报, 2017, 53(10): 1153-1167.
Tingfei XI, Lina WEI, Jing LIU, Xiaoli LIU, Zhen ZHEN, Yufeng ZHENG. Research Progress in Bioresorbable Magnesium Scaffolds[J]. Acta Metall Sin, 2017, 53(10): 1153-1167.

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摘要:

全降解血管支架具有克服传统不可降解金属支架长期植入引起的慢性炎症、晚期支架血栓以及需长期服用抗血小板药物等问题的潜在优势,因此目前在世界范围内是介入医学工程领域研究开发的热点。镁合金全降解血管支架因兼具较高的支撑强度和生物可降解吸收特性,更是走在了全降解血管支架发展的前列。本文主要介绍国际上广泛关注的德国Biotronik公司镁合金全降解血管支架的研发历程,以及我国自主研发的AZ31、JDBM和MgZnYNd 3种镁合金全降解血管支架研发现状。国内外大量的动物和临床实验表明,镁合金血管支架在体内是安全有效的,但其降解速率比预期稍快。通过建立新型合金体系并改善支架的结构和涂层,镁合金全降解血管支架性能将逐渐完善,并在不久的将来在治疗心血管疾病等方面发挥其重大作用。

关键词 ：镁合金全降解血管支架, WE43镁合金, JDBM镁合金, MgZnYNd镁合金

Abstract：

Because the bioresorbable scaffold (BRS) could overcome the difficulties caused by traditional nondegradable stents including chronic inflammation, late stent thrombosis, and long-term antiplatelet therapy, BRS is the research focus of interventional medical engineering. Because of both the high supporting strength and bioresorbable feature, the bioresorbable magnesium scaffold (BMS) is the research focus of BRS. In this paper, development process of Biotronik serial magnesium stents along with research progress of our domestic AZ31, JDBM and MgZnYNd stents is reviewed. According to the results of extensive in vitro and in vivo studies, BMS is safe and effective in vivo although its degradation rate is faster than our expectation. Through developing novel alloy system and improving stents' structure, the performance of BMS will be better and it will play more important role on the therapy of cardiovascular disease.

Key words： bioresorbable magnesium scaffold WE43 magnesium alloy JDBM magnesium alloy MgZnYNd magnesium alloy

收稿日期: 2017-07-28

ZTFLH:

R318.08

基金资助:广东省自然科学基金项目Nos.2016A030310245和2016A030310244,中国博士后基金项目No.2016M591017和深圳市基础研究(自由探索)项目No.JCYJ20160427170611414

作者简介:

作者简介奚廷斐,男,1948年生,研究员

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图1 Biotronik公司系列镁合金支架示意图[14]

Animal/clinical	Stent type	Implantation site	Follow up	Main result	Ref.
study (quantity)
Animal	Lekton	Coronary artery	4 and 12	Homogenous and rapid endothelialization	[15]
(Pig, 33)	Magic^?		Weeks	of the Mg alloy stent
Animal	Lekton	Coronary artery	3 d, 1 and	Mg alloy stents are safe and are associated with	[16]
(Pig, 17)	Magic^?		3 months	less neointima formation; however, reduced
				neointima did not result in larger lumen
Single case	Lekton	Left pulmonary	3 d, 1 and	Mg alloy stents are safe even in pediatric	[17]
	Magic^?	artery	4 months	patients; bioabsorbable stents with different
				diameters may be more helpful in vessel
				stenosis diseases
Single case	Lekton	Aorta	3 months	Mg alloy stents are safe and efficacy	[18]
	Magic^?
Single case	Lekton	Aortopulmonary	4 months	Mg alloy stents are safe and efficacy in	[19]
	Magic^?	collateral		children previously deemed unsuitable for
				stent placement
Clinical (20)	Lekton	Infrapopliteal	1 and 3	Mg alloy stents are safe and efficacy in the	[20]
	Magic^?	vessels	months	treatment of below-knee lesions after
				3 months based on the primary clinical
				patency and limb salvage rates
Clinical (117)	Lekton	Infrapopliteal	1 and 6	Mg alloy stents are safe, but it did not demonstrate	[21]
	Magic^?	vessels	months	efficacy in long-term patency over standard
				PTA¹ in the infrapopliteal vessels
Clinical (63)	Lekton	Coronary artery	4, 6 and	Mg alloy stents can achieve an immediate	[3]
	Magic^?		12 months	angiographic result similar to the result of
				other metal stents and can be safely degraded
				after 4 months
Clinical (63)	Lekton	Coronary artery	4, 12 and	IVUS² imaging supports the safety profile of Mg	[22]
	Magic^?		28 months	alloy stents with degradation at 4 months and
				maintains durability of the results without any
				early or late adverse findings
Clinical (63)	DREAMS	Coronary artery	1, 6 and	DREAMS (Mg alloy stents) is safe and efficacy,	[4]
			12 months	promising clinical and angiographic performance
				results up to 12 months
Clinical (63)	DREAMS	Coronary artery	24 and	DREAMS is safe and efficacy with no death and	[23]
			36 months	no scaffold thrombosis up to 3 years; stents could
				be absorbed completely within 6 months
Clinical (123)	DREAMS	Coronary artery	6 and 12	Implantation of the DREAMS 2G device in	[5]
	2G		months	de-novo coronary lesions is feasible, with
				favorable safety and performance outcomes at
				6 months. This novel absorbable metal scaffold
				could be an alternative to absorbable polymeric
				scaffolds for treatment of obstructive
				coronary disease

表1 Biotronik公司镁合金支架的动物及临床实验[3-5,15-23]

图2 不锈钢支架和镁合金支架植入28 d后的组织病理照片[16]

图3 JDBM、WE43和AZ31镁合金腐蚀形貌和腐蚀机理示意图[32]

图4 主动脉体内造影显示JDBM-2和316L不锈钢支架中均无急性和慢性血栓形成和支架内狭窄(从左到右分别为支架植入后1、2、4、6个月的结果)及JDBM-2和316L支架内IVUS结果[33]

图5 JDBM支架植入后不同时间点的支架段血管组织病理图及局部放大图[33]

图6 CCK-8法测MgZnYNd、2%PLGA-APTES-MgZnYNd、4%PLGA-APTES-MgZnYNd和4%PLGA-MgZnYNd样品表面培养的血管平滑肌细胞(VSMC)和人脐静脉内皮细胞(EA.hy926) 1、3、5天的细胞增殖率;细胞培养板作阴性对照,含10%二甲基亚砜的DMEM为阳性对照。组间差异采用One-way ANOVA统计比较方法,***代表p<0.001,*代表p<0.05[36]

图7 MgZnYNd药物洗脱冠状动脉支架显微镜及扫描电镜照片;“三点弯曲法”用于柔顺性测试;依据ASTM-F2394-07自行设计的血管通道模型(装配6F导管,导管内径1.98 mm)测试支架顺应性;支架在通道模型内进行推送和回撤过程以及顺应性实验后支架图像[36]

图8 MgZnYNd支架和BuMATM对照组植入6个月后的冠状血管造影(CAG)、光学相干断层扫描(OCT)和苏木精-伊红染色(HE)组织病理图像[36]

表2 MgZnYNd支架和BuMATM支架对照组术后1、3和6个月后体内定量血管造影结果[36]

表3 MgZnYNd支架和BuMATM对照组术后1、3和6个月体内OCT结果[36]

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