Biodegradable Polymeric Stents

To overcome several problems of conventional metallic stents, there have been many attempts to manufacture stents made of biodegradable materials. Although some studies have noted various degrees of inflammatory responses after biodegradable stent implantation, stents made of poly-l-lactic acid (PLLA) showed high biocompatibility with minimal inflammatory response and neointimal formation in porcine coronary arteries. Therefore, PLLA materials are more likely to cover the specific need for human coronary arteries in terms of biodegradation period and scaffolding ability over 6 months. A clinical study of PLLA self-expanding stent implantation is underway in Japan. The initial and 6-month results are favorable and suggest the feasibility, safety, and efficacy of the PLLA biodegradable stent in humans. However, long-term follow-up with larger numbers of patients will be required to validate the long-term efficacy of PLLA stents.     

完全生物可降解支架与再内皮化策略

支架植入术是目前治疗冠心病的主要手段之一,药物支架的不断改进使再狭窄问题得到有效解决,但也存在诸多弊端,最突出的是晚期血栓形成,内皮损伤及内皮化障碍是其主要原因,诸多因素参与了这个过程,如支架涂层药物对正常内皮细胞的非特异性抑制、不可降解的支架材料导致的炎症反应等。由此导致的晚期血栓形成,是支架植入术面临的新矛盾。生物可降解支架,尤其是完全生物可降解支架,有望解决这一难题,是十分有前景的研究方向。     

生物及金属可降解支架在冠状动脉粥样硬化性心脏病介入治疗中的研究进展

冠状动脉粥样硬化性心脏病介入治疗已发展至药物洗脱支架时代,使血管再狭窄率降至10%以下,由于金属支架在体内长期留存可能会引发晚期不良反应。生物及金属可降解支架在置入早期对血管壁起到支撑作用,之后逐渐降解至消失,使血管的完整性和功能得以恢复,此类支架是未来支架的发展方向。现将重点阐述生物可降解支架及金属可吸收支架的研究进展。     

EXCEL可降解涂层雷帕霉素洗脱支架长期临床应用的安全性和有效性

目的:评估EXCEL可降解涂层雷帕霉素洗脱支架置入3年后的安全性和有效性。方法:连续入选我院100例冠心病住院患者,均单一置入EXCEL支架。术后接受双联抗血小板治疗(氯吡格雷和阿司匹林)6个月,随后单用阿司匹林。术后平均8个月实施造影随访及冠状动脉内超声检测。观察术后3年主要不良心脏事件(MACE)、全因死亡和血栓事件发生率。结果:100例患者均完成3年临床随访。1年时发生4例(4.0%)靶病变血运重建,无死亡和非致死性心肌梗死发生,1年MACE发生率为4.0%。3年随访时共6例(6.0%)MACE发生,包括靶病变血运重建4例(4.0%)和心性死亡2例(2.0%)。3年累计全因死亡率4%,包括心性死亡2例(2.0%),脑卒中和肺癌导致的非心性死亡各1例(2.0%),术后3年共发生支架内血栓事件2例(2.0%),其中很可能的支架内血栓事件仅1例(1.0%)。造影随访支架内再狭窄率3.6%(4/112),支架内晚期管腔丢失(0.12±0.34)mm。冠状动脉内超声检查共发现4处晚期支架贴壁不良(发生率6.3%,4/64),但随访期间无任何临床事件发生。结论:EXCEL支架置入术后患者的靶病变血运重建及MACE发生率一直处于较低水平,提示其早期临床获益可持续至术后3年。这一结论有待大规模、随机对照及随访期更长的临床研究证实。     

多聚物型可吸收冠状动脉支架的研究进展

新一代药物洗脱支架由可吸收多聚物为平台,具有与金属支架相当的的支撑力,以及良好的生物相容性.既可以暂时支撑管壁,抑制早期血栓形成及晚期新生内膜增生,还可作为良好的药物载体实现局部控制释放,达到有效防止支架置入后的血管急性闭塞和降低再狭窄率.     

Stent Coating Integrity of Durable and Biodegradable Coated Drug Eluting Stents

Background

Coatings consisting of a polymer and drug are widely used in drug‐eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub‐acute healing, and potentially trigger a chronic inflammatory response.

Objective

The aim of this study was to investigate the short‐term (7 and 28 days) and long‐term (90 and 180 days) coating integrity of the Xience Prime Everolimus‐Eluting Stent (EES), Resolute Zotarolimus‐Eluting Stent (ZES), Taxus Paclitaxel‐Eluting Stent (PES), and Nobori Biolimus A9‐Eluting Stent (BES) in a rabbit ilio‐femoral stent model.

Methods and Results

Stented arteries (n = 48) were harvested and the tissue surrounding the implanted stents digested away with an enzymatic solution. Results demonstrated that the majority of struts of EES were without any coating defects with a few struts showing minor defects. Similarly, for the ZES, most of the struts were without coating defects at all time points except at 180 days. The majority of PES demonstrated mostly webbing and uneven coating. In the BES group, the majority of strut coating showed polymer cracking.

Conclusion

Overall, the EES and ZES had fewer coating defects than the PES and BES. Coating defects, however increase over time for the ZES, whereas the percent of coating irregularities remained constant for the EES. These results provide, for the first time, a comparison of the long‐term durability of these drug‐eluting stent coatings in vivo.

     

Computational Analysis of Mechanical Performance for Composite Polymer Biodegradable Stents

Bioresorbable stents (BRS) represent the latest generation of vascular scaffolds used for minimally invasive interventions. They aim to overcome the shortcomings of established bare-metal stents (BMS) and drug-eluting stents (DES). Recent advances in the field of bioprinting offer the possibility of combining biodegradable polymers to produce a composite BRS. Evaluation of the mechanical performance of the novel composite BRS is the focus of this study, based on the idea that they are a promising solution to improve the strength and flexibility performance of single material BRS. Finite element analysis of stent crimping and expansion was performed. Polylactic acid (PLA) and polycaprolactone (PCL) formed a composite stent divided into four layers, resulting in sixteen unique combinations. A comparison of the mechanical performance of the different composite configurations was performed. The resulting stresses, strains, elastic recoil, and foreshortening were evaluated and compared to existing experimental results. Similar behaviour was observed for material configurations that included at least one PLA layer. A pure PCL stent showed significant elastic recoil and less shortening compared to PLA and composite structures. The volumetric ratio of the materials was found to have a more significant effect on recoil and foreshortening than the arrangement of the material layers. Composite BRS offer the possibility of customising the mechanical behaviour of scaffolds. They also have the potential to support the fabrication of personalised or plaque-specific stents.     

可降解聚合物涂层雷帕霉素洗脱支架在治疗冠状动脉弥漫性长病变中的临床研究

目的：评价重叠置入可降解聚合物涂层雷帕霉素洗脱支架（EXCEL支架）在治疗冠状动脉弥漫性长病变中（所需置入支架长度总和>60 mm）的安全性和有效性。
　　方法：回顾性选取2010-08至2012-05期间在我院接受经皮冠状动脉介入治疗（PCI）重叠置入EXCEL支架的冠状动脉弥漫性长病变患者71例,平均年龄为（62.85±10.26）岁,其中74.56%为男性患者。研究终点为住院期间和术后2年随访期间的主要不良心脏事件（MACE）。
　　结果：71例患者,平均每个靶病变置入支架（2.61±0.52）个,平均支架直径为（3.21±0.35）mm,平均每个病变总支架长度为（73.34±13.11）mm。住院期间MACE发生率为4.23%。院外2年随访期间的靶血管血运重建率和MACE发生率分别为9.86％和18.31%。Cox回归分析显示吸烟（风险比：12.102,95％可信区间1.460~100.309,P=0.021）、既往心肌梗死史（风险比：11.948,95％可信区间1.144~124.726,P=0.038）和既往PCI史（风险比：0.097,95％可信区间0.010~0.990,P=0.049）是影响院外MACE发生的独立危险因素。
　　结论：EXCEL支架在治疗冠状动脉弥漫性长病变中的应用是安全和有效的,但远期随访显示MACE和靶血管血运重建的发生率明显增高。     

Two-Step Geometry Design Method,Numerical Simulations and Experimental Studies of Bioresorbable Stents

The stent-implantation process during angioplasty procedures usually involves clamping the stent onto a catheter to a size that allows delivery to the place inside the artery. Finding the right geometrical form of the stent to ensure good functionality in the open form and to enable the clamping process is one of the key elements in the stent-design process. In the first part of the work, an original two-step procedure for stent-geometry design was proposed. This was due to the necessary selection of a geometry that would provide adequate support to the blood-vessel wall without causing damage to the vessel. Numerical simulations of the crimping and deployment processes were performed to verify the method. At the end of this stage, the optimal stent was selected for further testing. In addition, numerical simulations of selected experimental tests (catheter-crimping process, compression process) were used to verify the obtained geometrical forms. The results of experimental tests on stents produced by the microinjection method are presented. The digital image correlation (DIC) method was used to compare the results of numerical simulation and experimental tests. The two-step modeling approach was found to help select the appropriate geometry of the expanded stent, which is an extremely important step in the design of the crimping process. In the part of the paper where the results obtained by numerical simulation were compared with those gained by experiment and using the DIC method, a good compatibility of the displacement results can be observed. For both longitudinal and transverse (pinch) stent compression, the results practically coincide. The paper presents also the application of the DIC method which significantly expands the research possibilities, allowing for a detailed inspection of the deformation state and, above all, verification of local dangerous areas. This approach significantly increases the possibility of assessing the quality of the stents.     

Efficacy of Biodegradable Polydioxanone and Polylactic Acid Braided Biodegradable Biliary Stents for the Management of Benign Biliary Strictures

Background:Benign biliary strictures (BBS) are widely treated by endoscopic procedures involving temporary stent placement. Occasionally, stents are required to be removed, making the treatment process very painful as well as expensive. Until now, no effective biodegradable biliary stents (BDBS) have been available for clinical applications. This study aims to investigate the safety and efficacy of biodegradable polydioxanone (PDO) and polylactic acid (PLA) braided BDBS both in vitro and in vivo.Methods:Monofilaments of 3 different diameters, of PDO (0.30, 0.35, and 0.40 mm) and PLA (0.10, 0.15, and 0.20 mm) were braided to biliary stents and their mechanical properties were studied. The stents were placed in an ex vivo bile duct model perfused with porcine bile, taken out, and observed every week until they were completely degraded. After the bile duct stenosis model was established successfully in piglet, stents with appropriate mechanical properties were further examined under endoscopy; the changes in hematology, patency time, and pathology of the stents were observed for 8 months.Results:A total of 10 pigs were included (2 groups; 5 PDO, 5 PLA) in the study. The patency time of the stents in the PLA group was significantly longer than that in the PDO group (25.7 ± 5.6 weeks vs 11.3 ± 3.4 weeks, respectively).Conclusion:Our results project that biodegradable PLA and PDO braided biliary stents could be a better choice to treat BBS, with different rates of degradation.     

Effectiveness of Biodegradable Magnesium Alloy Stents in Coronary Artery and Femoral Artery

Objectives

To access the biocompatibility, effectiveness, and safety of biodegradable magnesium (Mg) alloy stent (BMAS) in the coronary artery and femoral artery.

Background

Atherosclerosis is a lesion of cardiovascular system, including the diseases in heart and blood vessels.

Methods

The aluminum (Al) and zinc (Zn)‐based BMAS was designed by cold drawing methods. Forty healthy immunized mongrel dogs were randomly divided into 8 groups. Five dogs who have not been treated with stent were included in control group. The other dogs were implanted with an absorbable magnesium (Mg) alloy in the coronary and/or femoral artery, and their artery angiography were observed at 7 time points (1, 3, 5, 7, 14, 21, and 28 days; n = 5) follow‐up. Dogs from each cohort were sacrificed following angiography for pathology assessment. The histological response including inflammatory response, thrombosis, and intimal hyperplasia were analyzed by hematoxylin‐eosin staining. Lumen area (La), intimal hyperplasia area (IHa), and the ratio of IHa were calculated by image analysis software.

Results

The thin‐walled BMAS were designed and produced by cold‐drawing technology. Fifty‐one devices were implanted into coronary artery of 35 dogs successfully. During the follow‐up days, the angiography of coronary artery and femoral artery had confirmed that the lumen was clear and there were no elastic recoil and thrombosis. The stents were completely disappeared at 7 days after implantation. Moderate intimal hyperplasia was found at 14 days after implantation.

Conclusion

The BMAS stent proved to be of good biocompatibility, safety, and effectiveness. (J Interven Cardiol 2015;XXXX:XX–XX)

     

可生物降解涂层药物洗脱支架介入治疗的近期疗效

目的 评估国产新型西罗莫司可生物降解涂层支架在急性心肌梗死患者介入治疗(percutaneous coronary intervention,PCI)中的疗效及安全性.方法 急性心肌梗死患者56例,其中ST段抬高性心肌梗死48例,非ST段抬高性心肌梗死8例,均置人西罗莫司可生物降解涂层洗脱支架,观察手术成功率、支架内血栓等并发症及主要不良心脏事件(main adverse coronary events,MACE)发生率,术后随访1～14个月,6～9个月行冠状动脉造影复查.结果 成功行PCI 55例,手术即刻成功率98%.82处病变共置入西罗莫司支架98枚,其中17枚(17.3%)为直接支架术.4例出现无复流现象,1例使用主动脉气囊反搏.1例术后6 h猝死,考虑急性支架内血栓.术中及住院期间无其他严重并发症发生.50例(89.3%)随访1～14个月,无晚期支架内血栓发生,无MACE;复查冠状动脉造影19例,1例发生支架内再狭窄,无需血运重建.结论 国产西罗莫司可生物降解涂层支架在急性心肌梗死患者行PCI治疗有较好疗效及安全性.     

Novel Biodegradable Stents for Benign Esophageal Strictures Following Endoscopic Submucosal Dissection

The application of metallic stents for benign stenosis is limited due to long-term complications. We report here the results of the implantation of a novel biodegradable poly-l-lactic acid (PLLA) esophageal stent in two patients with benign esophageal stenosis after endoscopic submucosal dissection (ESD). Case 1 was a 64-year-old man who received ESD for an early squamous esophageal cancer in the middle esophagus. The mucosal defect was seven-eighths of the circumference, and the distal margin of the resection scar formed the stenosis. After balloon dilatation, the PLLA esophageal stent was endoscopically placed; for 6 months, he has not experienced any symptoms of re-stenosis. Case 2 consisted of a 62-year-old man who developed an early squamous esophageal cancer in the middle esophagus. The lesion was resected by ESD, and the mucosal defect was seven-eighths of the circumference. The resection scar formed the stenosis, and the PLLA esophageal stent was endoscopically placed. He also has not experienced any symptoms of re-stenosis for 6 months. In conclusion, the PLLA esophageal stent provides a new possibility for the management of benign esophageal strictures after ESD. Due to the biodegradable features of this stent, longer term studies are necessary to investigate the relationship between the expected disappearance of the stent and the patency of the stricture.     

Biodegradable Polymer Drug-Eluting Stents Versus Second-Generation Drug-Eluting Stents for Patients With Coronary Artery Disease: An Update Meta-Analysis

Objective

Permanent polymer drug-eluting stents (DES) are associated with a higher risk of late and very late stent thrombosis (ST); biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, their benefits are not completely clear.

Method

We undertook a meta-analysis of randomized studies identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Eligible studies were those that compared BP-DES with second-generation permanent polymer DES in patients undergoing percutaneous coronary intervention.

Results

Five studies (8,740 patients) with a mean follow-up of 19.2 months were included. Overall, BP-DES were associated with a broadly equivalent risk of definite and probable ST (odds ratio [OR], 1.07; 95 % confidence interval [CI], 0.67 to 1.71; P?=?0.76; I ²?=?5.0 %), target vessel revascularization (OR, 1.04; 95 % CI, 0.87 to 1.24; P?=?0.68; I ²?=?38.0 %), all-cause mortality (OR, 1.10; 95 % CI, 0.87 to 1.41; P?=?0.42; I ²?=?0.0 %), and major adverse cardiac events (OR, 1.03; 95 % CI, 0.88 to 1.20; P?=?0.74; I ²?=?0.0 %) when compared with second-generation DES. However, BP-DES significantly decreased in-stent late luminal loss (standard mean difference [SMD], ?0.01; 95 % CI, ?0.12 to 0.11; P?=?0.93; I ²?=?0.0 %) and in-segment late luminal loss (SMD, ?0.06; 95 % CI, ?0.17 to 0.05; P?=?0.27; I ²?=?0.0 %) compared with second-generation DES.

Conclusions

Compared with second-generation permanent polymer DES, biodegradable stents appear to have equivalent short- to medium-term clinical benefits, and it remains unclear whether they reduce the incidence of very late ST.     

新型生物可降解聚合物雷帕霉素靶向洗脱支架预防支架内狭窄的动物实验研究

目的:评价新型的生物可降解聚合物雷帕霉素靶向洗脱支架—Firehawk在小型猪冠状动脉模型预防支架内狭窄的疗效。方法:将Firehawk支架(Firehawk组,n=10)和采用永久聚合物涂层雷帕霉素洗脱支架Firebird 2(Firebird 2组,n=8)置入健康小型猪冠状动脉。术后4周时测定两组支架血管段的平均内膜厚度、新生内膜面积、面积狭窄百分比等参数,以比较其内膜增生的情况。结果:术后4周,Firehawk组和Firebird 2组平均内膜厚度分别为(0.15±0.10)mm和(0.14±0.06)mm,新生内膜面积分别为(1.12±0.57)mm2和(1.04±0.36)mm2,面积狭窄百分比分别为(24.58±14.85)%和(26.80±10.64)%,差异均无统计学意义(P均>0.05)。两组均无支架内狭窄发生。结论:Firehawk支架可有效抑制支架置入后4周时的内膜增生,预防冠状动脉实验性支架内狭窄,效果与传统的永久聚合物涂层药物洗脱支架相当。长期效果有待进一步观察。     

Practical Clinical Evaluation of Stents

This article discusses the clinical issues pertaining to an optimal stenting result and analyzes relevant stent structures and functions. There are five components of optimal stenting: favorable clinical features, easy stent delivery, ideal scaffolding, low stent thrombosis, and low restenosis. In straightforward cases, such as stenting in the mid-right coronary artery with a straight proximal segment, procedural success can be achieved with any stent. In vessels with curved, tortuous proximal segments, a highly flexible stent is needed for a smooth and successful delivery. For ostial, protected left main, or aortoanastomotic lesions, stents with sufficient radial strength and good visibility are needed. The two major concerns of an interventional cardiologist choosing a stent are excellent trackability for fast delivery and low long-term restenosis rate. In all situations, the procedural success depends on the operator's manual dexterity, experience with a particular stent design, and critical evaluation of different structural stent features to maximize benefits. Any new stent with high longitudinal flexibility, excellent scaffolding and radial strength, adequate radiopacity, complete deployment after one inflation, and that is easily recrossed and provides a good symmetrical conduit for a smooth coronary flow resulting in little tendency for thrombosis or restenosis would be today's stent of choice.     

An Enhanced Device for Transluminal Retrieval of Vascular Stents Without Surgical Procedures: Experimental Studies

Background: Although efforts have been focused on developing endovascular procedures by which intravascular devices such as stents could be effectively deployed, few data exist regarding devices for the nonsurgical retrieval of deployed stents. Therefore, we designed to enable retrieval of deployed stents without a surgical procedure. Methods: The device consisted of four components: ultra‐low profile forceps with 2.0 mm in diameter, conducting shaft with 1.8 mm in diameter, control handle by which the forceps is opened or closed, and a covering sheath. This device was designed to advance into the vessel lumen along a 0.014‐inch guidewire by over the wire fashion. Results: The forceps could firmly catch nonexpanded as well as expanded tubular‐type stents with open cells in an in vitro model that was 4.0 mm in diameter. Then, we used this device in porcine renal arteries with 2.5–5.0 mm in diameter. At first, a fragmented 0.014‐inch guidewire could be safely removed without vessel damage that was confirmed by intravascular ultrasound. This device could successfully remove four of five inappropriately and 11 of 14 appropriately deployed stents. Under these conditions, intravascular ultrasound demonstrated minor vessel wall dissection in two‐third of cases. Conclusions: These results demonstrate that the present device can be used for transluminal removal of foreign bodies such as nonexpanded as well as expanded stents in acute phase. Further miniaturization may enable using this type of device in the renal as well as coronary arteries. (J Interven Cardiol 2010;23:264–270)     

药物洗脱支架的临床研究

目的:观察药物洗脱支架治疗冠状动脉(冠脉)病变的可行性和安全性.方法:对我院78例冠心病患者,置入药物洗脱支架(Cypher支架),治疗病变84处,A型病变4处,B型病变38处,C型病变42处.靶病变长度(19.89±10.61)mn,术前靶病变狭窄程度(86.00±10.01)%;目标血管直径(2.95±0.11)mm.其中长度＞20 mm的病变26处.68例支架在行球囊预扩张后置入,10例为支架直接置入.术前、术后常规使用抗血小板药物及治疗冠心病药物.观察药物洗脱支架置入的手术成功率、术中并发症、住院期间及短期临床随访期间的心脏事件.随访术后6个月时的再狭窄发生率.结果:78例患者84处病变共置入Cypher支架100枚,手术即刻成功率100%,术后冠脉造影提示病变残余狭窄(5.0±6.8)%.1例术后38小时因胸痛冠脉造影证实为支架内血栓形成.临床随访16～188天,平均(94.0±10.9)天,无一例心肌梗死或猝死发生.25例(32.05%)患者术后6个月随访冠脉造影未发现支架再狭窄.结论:药物洗脱支架置入时手术成功率高,未见术中并发症,部分病例短期随访效果令人鼓舞.