Research Progress in Bioresorbable Magnesium Scaffolds

doi:10.11900/0412.1961.2017.00319

Acta Metall Sin

2017, Vol. 53

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

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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

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Tingfei XI, Lina WEI, Jing LIU, Xiaoli LIU, Zhen ZHEN, Yufeng ZHENG. Research Progress in Bioresorbable Magnesium Scaffolds. Acta Metall Sin, 2017, 53(10): 1153-1167.

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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

Received: 28 July 2017

ZTFLH:

R318.08

Fund: Supported by Natural Science Foundation of Guangdong Province (Nos.2016A030310245 and 2016A030310244), China Postdoctoral Science Foundation (No.2016M591017) and Shenzhen Fundamental Research (No.JCYJ20160427170611414)

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https://www.ams.org.cn/EN/10.11900/0412.1961.2017.00319 OR https://www.ams.org.cn/EN/Y2017/V53/I10/1153

Fig.1 Schematic cross-sectional profile of magnesium scaffolds struts of uncoated, non-eluting, AMS-1 with 80 μm×165 μm (a); DREAMS 1st generation (DREAMS 1G) with 130 μm×120 μm struts (b) and DREAMS 2nd generation (2G) with 150 μm×140 μm struts (c)^[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

Table 1 Animal and clinical studies of Biotronik absorbable Mg-alloy stents^[3-5,15-23]

Fig.2 Low (a, c) and high (b, d) magnified representative photomicrographs of hematoxylin-eosin (HE) stained sections of porcine coronary arteries 28 d after stainless steel stent (a, b) and magnesium alloy stent (c, d) implantation^[16]

Fig.3 Surface morphologies (a, c, e) and the schematics (b, d, f) of the corresponding degradation mechanism of JDBM (a, b), WE43 (c, d) and AZ31 (e, f) alloys^[32]

Fig.4 The in vivo aortic angiographies showing no acute and late thrombogenesis as well as in-stent restenosis in the JDBM-2 (a) and 316L stainless steel (c) stents after stenting for 1 month, 2 months, 4 months and 6 months (from left to right). The corresponding follow-up IVUS images illustrating the longitudinal reconstruction of the abdominal aorta after the JDBM-2 (b) and 316L stainless steel (d) stents implantation^[33]

Fig.5 HE staining images of the stented arteries showing compromised foreign body reaction and neointimal coverage on the JDBM-2 struts in the period of 1 month (a), 2 months (b), 4 months (c) and 6 months (d) implantation (Inset in each image showing detailed view of the stented artery)^[33]

Fig.6 Cell viabilities cultured on bare MgZnYNd, 2%PLGA-APTES-MgZnYNd, 4%PLGA-APTES-MgZnYNd, and 4%PLGA-MgZnYNd samples over 5 d of incubation by the CCK-8 assay; DMEM with serum worked as negative control, DMEM with 10% dimethyl sulfoxide as positive control. Data presented were statistically analyzed by using a one-way ANOVA, *** represents p<0.001, * represents p<0.05^[36]
a) VSMC (b) EA. hy926

Fig.7 Microscope (a~c) and SEM (d, e) images of MgZnYNd stent: (a) before crimping onto balloon, (b) after crimping onto balloon, (c, d) after expanding at nominal pressure (6 bar), the outer diameter under the three conditions were (2.00±0.03) mm, (1.58±0.04) mm and (3.00±0.06) mm (n=6), respectively, (e) integrity of PLGA coating was maintained after plastic deformation with no obvious peeling detected, while visible regional nanosized cracking (with no exposure of the underlying strut) was observed as a result of stress accommodation only in locations of larger plastic deformation, (f) flexibility test was performed through “three-point blending” method, (g) self-designed simulated vascular channel model equipped with 6F catheter (internal diameter: 1.98 mm) according to the guidance in ASTM-F2394-07 to test stent compliance, (h) stents conducting push and withdrawal process in the channel model, and (i) the postexperiment stent image^[36]

Fig.8 CAG (a), OCT (b) and H&E staining images (c) after MgZnYNd stent and control group BuMA^TM stent implantation for a period of six months (The red arrows in Figs.8a and b signify the outline and remnants of the stent struts of MgZnYNd stent, and the enlarged insets in Fig.8c showed the more detailed morphologies)^[36]

Table 2 Coronary angiography results of MgZnYNd stent and BuMA^TM stent post-implantation for a period of 1, 3 and 6 months, respectively^[36]

Table 3 Optical coherence tomography results of MgZnYNd stent and BuMA^TM stent post-implantation for a period of 1, 3, and 6 months, respectively^[36]

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