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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 XI1,2(), Lina WEI1,3, 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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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)

Cite this article: 

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.

URL: 

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 BuMATM 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]
Implantation duration Stent type RLD MLD DSR
month mm mm %
1 MgZnYNd (n=3) 2.62±0.20 2.09±0.33 20.67±9.07
BuMATM (n=3) 2.59±0.65 2.15±0.41 15.67±5.86
p value 0.67 0.88 0.56
3 MgZnYNd (n=3) 2.42±0.16 2.03±0.80 15.67±8.14
BuMATM (n=3) 2.03±0.18 1.51±0.13 15.67±5.86
p value 0.22 0.04 0.11
6 MgZnYNd (n=3) 2.75±0.26 2.30±0.49 15.33±22.23
BuMATM (n=3) 2.65±0.80 2.05±0.31 22.33±14.15
p value 0.11 0.62 0.13
Table 2  Coronary angiography results of MgZnYNd stent and BuMATM stent post-implantation for a period of 1, 3 and 6 months, respectively[36]
Implantation Stent type Stent length DRVA PRVA MLA MSA
duration / month mm mm2 mm2 mm2 mm2
1 MgZnYNd (n=3) 14.30±1.27 2.56±2.87 2.72±2.80 2.02±1.84 2.62±1.94
BuMATM (n=3) 14.70±2.08 2.84±0.83 3.68±0.93 2.49±0.37 4.97±1.10
3 MgZnYNd (n=3) 14.80±0.97 4.51±1.37 6.36±2.16 3.87±1.85 5.52±2.10
BuMATM (n=3) 14.25±4.45 2.58±0.19 4.09±1.24 2.32±0.05 5.22±0.61
6 MgZnYNd (n=3) 14.13±0.95 3.92±0.79 3.94±0.78 2.93±0.58 4.52±1.08
BuMATM (n=3) 14.40±2.78 5.58±2.43 5.89±1.66 3.03±1.09 6.03±1.90
Table 3  Optical coherence tomography results of MgZnYNd stent and BuMATM stent post-implantation for a period of 1, 3, and 6 months, respectively[36]
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