We would like to thank the Division of Engineering, Mayo Clinic for their technical support. This study was financially supported by European Regional Development Fund - FNUSA-ICRC (No. CZ.1.05/1.100/02.0123), National Institutes of Health (T32 HL007111), American Heart Association Scientist Development Grant (AHA #06-35185N), and The Grainger Innovation Fund - Grainger Foundation.

1.聚氨酯静电的心轴收集<ol><li> 准备为芯棒静电 <ol><li>熔融约8ml生物相容的，食品级，水溶性载体材料在量筒（约9毫米直径和110毫米深）使用烘箱在155℃。 </li><li>蘸直径为3毫米，长100毫米的不锈钢心轴，得到心轴的表面上的支撑材料的涂层。之前浸渍，放置心轴在烘箱中在155℃约15分钟，以提高心轴表面，这有助于在表面与熔融载体材料润湿的温度。 </li><li>让浸渍芯棒冷却至约140℃，同时将熔融支撑材料凝固形成所述心轴表面上形成均匀的薄涂层。在冷却过程中，垂直悬挂的心轴，使得重力使过量支撑材料滴落。该涂料可轻松去除心轴成品支架 - 移植物的。 </li></ol></li><li> （见图1）的静电系统的心轴收集器的设置 <ol><li>水平对齐实验室混合器并连接一个塑料杆，这将在通风柜内的相对端保持在不锈钢心轴上。 </li><li>通过浸没仅心轴的前端在水中，以适应塑料支承杆在芯棒的端部溶解从心轴的前端的支撑材料。支持塑料支承杆在心轴的自由端，以协助在所述心轴收集器的均匀转动。 </li><li>使用在塑料支撑杆固定螺丝来固定不锈钢轴和避免静电过程中滑倒。 </li><li>由一个U形的地线附着到不锈钢心轴粉碎芯棒集电极。使用橡胶O形环以保持地线与心轴的两侧。 </li></ol></li><li> Setti纳克了静电系统的液体聚氨酯挤出系统<ol><li>混合，用25％（M / V）聚氨酯（PU）原液二甲基乙酰胺（DMA），以获得15％（M / V）的PU的DMA溶液（ 例如 ，加6毫升的DMA到毫升25 9％的PU溶液）。 警告！适当的个人防护设备通风橱内工作。 </li><li>装满钝端不锈钢针（喷丝板）15％PU液5毫升的玻璃注射器。 </li><li>编程注射器泵基于所述注射器的内直径为0.01毫升/分钟挤出。 </li><li>安装与上水平与针尖端从心轴收集约20cm注射泵喷丝头注射器。从注射器的导电部分绝缘注射泵用橡胶片，以避免产生电弧。 </li><li>高电压发生器连接到使用鳄鱼夹注射器的喷丝头。 </li></ol></li><li>以0.01毫升/分钟和轮状病毒运行注射器泵忒与实验室混合器以速度慢（ 例如 ，50rpm下）中运行的心轴。 </li><li>应用横跨喷丝头20千伏和集电极心轴的电压差。聚氨酯纳米纤维开始沉积在旋转的芯轴和薄层会在几分钟之内可见。确保通风柜被关闭，排气被关闭以避免纳米纤维的丧失。 </li></ol> 2.静电纺丝支架移植物<ol><li>上2小时的旋转心轴静电纺丝聚氨酯纳米纤维以产生均匀的管（如在步骤1中说明）。 </li><li>从连接到实验室混合器塑料杆移除心轴来安装裸金属支架。取出芯棒，以保证残留溶剂烟雾被删除之前，打开通风柜和开放排气。 </li><li>球囊可扩张不锈钢支架26上的静电管滑动到希望的位置。它可能需要稍微膨胀所述支架使其SLIPS上而不损坏静电管。 </li><li>卷曲的支架，以确保将支架紧紧地设置在管材料上的心轴，而不是足够松滑动。这也将有助于防止内层和外层的分层。 </li><li>再次装入管和支架芯轴上的实验室混合器的塑料杆为静电的支架移植物的外层。 </li><li>如步骤1中说明的3小时静电纺丝纳米纤维来制造支架移植物的外层。 </li><li>后静电外之后，沿圆周切断的PU材料从用手术刀在支架的端部大约为1毫米。 </li><li>泡与支架移植物的心轴在去离子水中，以从其中将来自心轴释放支架移植物的心轴溶解支撑材料。根据需要，以完全溶解载体材料用新鲜水替换。 </li><li>一旦支撑材料被溶解，轻轻取出从T支架移植他芯棒并晾干。考虑允许空气干燥之前浸泡在去离子水，以溶解任何残留的支撑材料去除的支架移植物。 </li></ol> 3.人造支架移植物的测试<ol><li>上滑动3毫米三折气球的支架移植物。 </li><li>压接支架移植使用上举行接工具手气球。 </li><li>检查使用均匀卷边和类似的覆盖材料的剥离或穿刺失败的由于支架变形任何其他标志显微镜卷曲支架 - 移植物。 </li><li>通过与充气装置和水加压三折球囊展开支架移植物，以3毫米的设计直径。再次，检查扩张的支架移植物的均匀膨胀和衰竭的迹象。 </li></ol>

<ol>
	<li>Elsner, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+stent+grafts+covered+by+a+polytetrafluoroethylene+membrane.">Coronary stent grafts covered by a polytetrafluoroethylene membrane.</a> Am. J. Cardiol. 84 (3), 335-338 (1999).</li><li>St&#246;rger, H., Haase, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polytetrafluoroethylene-Covered+Stents:+Indications,+Advantages,+and+Limitations.">Polytetrafluoroethylene-Covered Stents: Indications, Advantages, and Limitations.</a> J. Interv. Cardiol. 12 (6), 451-456 (1999).</li><li>Moreno, P. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Macrophage+infiltration+predicts+restenosis+after+coronary+intervention+in+patients+with+unstable+angina.">Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina.</a> Circulation. 94 (12), 3098-3102 (1996).</li><li>Briguori, C., Sarais, C., Colombo, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+polytetrafluoroethylene-covered+stent:+a+device+with+multiple+potential+advantages.">The polytetrafluoroethylene-covered stent: a device with multiple potential advantages.</a> Int. J. Cardiovasc. Interv. 4 (3), 145-149 (2001).</li><li>Qureshi, M. A., Martin, Z., Greenberg, R. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endovascular+management+of+patients+with+Takayasu+arteritis:+stents+versus+stent+grafts.">Endovascular management of patients with Takayasu arteritis: stents versus stent grafts.</a> Semin. Vasc. Surg. 24 (1), 44-52 (2011).</li><li>Ahmadi, R., Schillinger, M., Maca, T., Minar, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Femoropopliteal+arteries:+immediate+and+long-term+results+with+a+Dacron-covered+stent-graft.">Femoropopliteal arteries: immediate and long-term results with a Dacron-covered stent-graft.</a> Radiology. 223 (2), 345-350 (2002).</li><li>Geremia, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+arteriovenous+fistulas:+treatment+with+silicone-covered+metallic+stents.">Experimental arteriovenous fistulas: treatment with silicone-covered metallic stents.</a> AJNR. Am. J. Neuroradiol. 18 (2), 271-277 (1997).</li><li>Saatci, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+internal+carotid+artery+aneurysms+with+a+covered+stent:+experience+in+24+patients+with+mid-term+follow-up+results.">Treatment of internal carotid artery aneurysms with a covered stent: experience in 24 patients with mid-term follow-up results.</a> AJNR. Am. J. Neuroradiol. 25 (10), 1742-1749 (2004).</li><li>Stefanadis, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stents+Wrapped+in+Autologous+Vein:+An+Experimental+Study1.">Stents Wrapped in Autologous Vein: An Experimental Study1.</a> J. Am. Coll. Cardiol. 28 (4), 1039-1046 (1996).</li><li>Palmaz, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review+of+polymeric+graft+materials+for+endovascular+applications.">Review of polymeric graft materials for endovascular applications.</a> J. Vasc. Interv. Radiol. 9, 7-13 (1998).</li><li>Bruckheimer, E., Dagan, T., Amir, G., Birk, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Covered+Cheatham-Platinum+stents+for+serial+dilation+of+severe+native+aortic+coarctation.">Covered Cheatham-Platinum stents for serial dilation of severe native aortic coarctation.</a> Catheter Cardiovasc. Interv. 74 (1), 117-123 (2009).</li><li>Tzifa, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Covered+Cheatham-platinum+stents+for+aortic+coarctation:+early+and+intermediate-term+results.">Covered Cheatham-platinum stents for aortic coarctation: early and intermediate-term results.</a> J. Am. Coll. Cardiol. 47 (7), 1457-1463 (2006).</li><li>Kuraishi, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+nanofiber-covered+stents+using+electrospinning:+in+vitro+and+acute+phase+in+vivo+experiments.">Development of nanofiber-covered stents using electrospinning: in vitro and acute phase in vivo experiments.</a> J. Biomed. Mater. Res. Part B Appl. Biomater. 88 (1), 230-239 (2009).</li><li>Pant, S., Bressloff, N. W., Limbert, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Geometry+parameterization+and+multidisciplinary+constrained+optimization+of+coronary+stents.">Geometry parameterization and multidisciplinary constrained optimization of coronary stents.</a> Biomech. Model Mechanobiol. 11 (1-2), 61-82 (2012).</li><li>Muller-Hulsbeck, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experience+on+endothelial+cell+adhesion+on+vascular+stents+and+stent-grafts:+first+in+vitro+results.">Experience on endothelial cell adhesion on vascular stents and stent-grafts: first in vitro results.</a> Invest. Radiol. 37 (6), 314-320 (2002).</li><li>Sarkar, S., Salacinski, H. J., Hamilton, G., Seifalian, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+mechanical+properties+of+infrainguinal+vascular+bypass+grafts:+their+role+in+influencing+patency.">The mechanical properties of infrainguinal vascular bypass grafts: their role in influencing patency.</a> Eur. J. Vasc. Endovasc. Surg. 31 (6), 627-636 (2006).</li><li>Shirota, T., Yasui, H., Shimokawa, H., Matsuda, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+of+endothelial+progenitor+cell+(EPC)-seeded+intravascular+stent+devices+and+in+vitro+endothelialization+on+hybrid+vascular+tissue.">Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hybrid vascular tissue.</a> Biomaterials. 24 (13), 2295-2302 (2003).</li><li>Grasl, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrospun+polyurethane+vascular+grafts:+in+vitro+mechanical+behavior+and+endothelial+adhesion+molecule+expression.">Electrospun polyurethane vascular grafts: in vitro mechanical behavior and endothelial adhesion molecule expression.</a> J. Biomed. Mater. Res. A. 93 (2), 716-723 (2010).</li><li>Kidoaki, S., Kwon, I. K., Matsuda, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Structural+features+and+mechanical+properties+of+in+situ-bonded+meshes+of+segmented+polyurethane+electrospun+from+mixed+solvents.">Structural features and mechanical properties of in situ-bonded meshes of segmented polyurethane electrospun from mixed solvents.</a> J. Biomed. Mater. Res. Part B Appl. Biomater. 76 (1), 219-229 (2006).</li><li>Stegemann, J. P., Kaszuba, S. N., Rowe, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review:+advances+in+vascular+tissue+engineering+using+protein-based+biomaterials.">Review: advances in vascular tissue engineering using protein-based biomaterials.</a> Tissue Eng. 13 (11), 2601-2613 (2007).</li><li>Sankaran, K. K., Subramanian, A., Krishnan, U. M., Sethuraman, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanoarchitecture+of+scaffolds+and+endothelial+cells+in+engineering+small+diameter+vascular+grafts.">Nanoarchitecture of scaffolds and endothelial cells in engineering small diameter vascular grafts.</a> Biotechnol. J. 10 (1), 96-108 (2015).</li><li>Gibson, P., Schreuder-Gibson, H., Rivin, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transport+properties+of+porous+membranes+based+on+electrospun+nanofibers.">Transport properties of porous membranes based on electrospun nanofibers.</a> Colloid Surf., A. 187, 469-481 (2001).</li><li>Zdrahala, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+caliber+vascular+grafts.+Part+II:+Polyurethanes+revisited.">Small caliber vascular grafts. Part II: Polyurethanes revisited.</a> J. Biomater. Appl. 11 (1), 37-61 (1996).</li><li>Uthamaraj, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+validation+of+a+novel+ferromagnetic+bare+metal+stent+capable+of+capturing+and+retaining+endothelial+cells.">Design and validation of a novel ferromagnetic bare metal stent capable of capturing and retaining endothelial cells.</a> Ann. Biomed. Eng. 42 (12), 2416-2424 (2014).</li><li>Tefft, B. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cell+Labeling+and+Targeting+with+Superparamagnetic+Iron+Oxide+Nanoparticles.">Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles.</a> J. Vis. Exp. (105), e53099 (2015).</li><li>Uthamaraj, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ferromagnetic+Bare+Metal+Stent+for+Endothelial+Cell+Capture+and+Retention.">Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention.</a> J. Vis. Exp. (103), e53100 (2015).</li><li>de Giovanni, J. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Covered+stents+in+the+treatment+of+aortic+coarctation.">Covered stents in the treatment of aortic coarctation.</a> J. Interv. Cardiol. 14 (2), 187-190 (2001).</li><li>Hans, F. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+wide-necked+aneurysms+with+balloon-expandable+polyurethane-covered+stentgrafts:+experience+in+an+animal+model.">Treatment of wide-necked aneurysms with balloon-expandable polyurethane-covered stentgrafts: experience in an animal model.</a> Acta. Neurochir. (Wien). 147 (8), 871-876 (2005).</li><li>Hasan, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrospun+scaffolds+for+tissue+engineering+of+vascular+grafts.">Electrospun scaffolds for tissue engineering of vascular grafts.</a> Acta. Biomater. 10 (1), 11-25 (2014).</li></ol>

作者宣称，他们没有竞争的经济利益。

We have developed a fabrication technique for a small caliber stent-graft which can be deployed using a standard percutaneous coronary intervention (PCI) procedure. Stent-grafts currently available are limited in their ability to maintain a low profile and flexibility for deployment. Bare metal stents developed by our group in our previous studies have proven to assist in rapid healing of the stented artery24,26. Various polymers have been electrospun by other groups and polyurethane has been proven biostable ...

冠状动脉介入治疗过程会由于斑块和血管壁的破坏显著血管壁损伤。这导致再狭窄，静脉移植物周围栓塞，冠状动脉管腔1-4的不连续性。为了避免这些并发症，一个有希望的战略将是覆盖了血管成形术的网站，这将潜在地抑制再狭窄，从血管腔的不连续性降低风险，防止周围栓塞血管表面。以前的研究已经比较裸金属支架，以支架移植物与支架移植5积极成果。研究人员已经使用了几种材料制造的膜，以覆盖支架。这包括合成的材料，如聚乙烯酯（PET），聚四氟乙烯（PTFE），聚氨酯（PU），以及硅或自体血管组织制造覆膜支架6-9。用于覆盖所述支架的理想移植材料应抗血栓的，非biodegradable，并应与没有过度增殖，炎症10天然组织整合。用于覆盖支架移植物材料还应促进支架移植物的愈合。 支架移植物被广泛用于主动脉缩窄，颈动脉的假性动脉瘤，动静脉瘘的治疗中，退化静脉移植，并大到巨型脑动脉瘤。但小口径支架移植物的发展是通过维持低轮廓和灵活性，这有助于在支架移植物11-14的部署的能力的限制。 PU为具有良好的机械强度，这是实现低轮廓和良好的柔韧性15,16所期望的性状的弹性体聚合物。除了具有良好的产能，支架移植还应促进快速愈合和内皮。 PU覆膜支架移植物表现出更好的生物相容性和增强的内皮17。研究者此前试图endothelialize PU与内皮细胞接种17它们覆盖支架移植物。聚氨酯的静电以创建纳米纤维基质已被证明是一种有价值的技术用于生产血管的移植物18,19。模仿天然细胞外基质的结构的纳米纤维的存在也是已知的，以促进内皮细胞增殖20,21。静电纺丝还允许在材料22的厚度的控制。制成的PU小口径血管移植已经研究了通过使用修饰如表面涂层，抗凝血剂，以及细胞增殖抑制剂，以促进愈合。所有这些修改都旨在调解主机接受和促进愈合的移植物23。 我们小组已经开发出可在动物模型24-26部署的球囊可扩张裸金属支架。电纺聚氨酯网格和球的组合OON扩张支架，使我们能够产生小口径球囊扩张支架移植物。大多数目前可用的支架移植物的经股动脉介入过程期间被引入，但只有少数商业覆膜支架可以引入1法国尺寸比为一个未膨胀的气球27需要更大。在这项研究中，我们通过包封静电聚氨酯的两层可被传递到一个经皮介入过程使用标准的8-9法国导向导管冠状动脉之间的球囊可扩张支架开发了小口径血管支架 - 移植物。

<table><tbody><tr><td>Glass syringe</td><td>Air Tite</td><td>7.140-33</td><td>Syringe for spinneret</td></tr><tr><td>Graduated cylinder 5 ml</td><td>Fisher Scientific</td><td>08-552-4G</td><td>5 ml pyrex graduated cylinder about 9 mm diameter and 11 cm long</td></tr><tr><td>High voltage generator</td><td>Bertan Accociates, Inc.</td><td>205A-30P</td><td>Used to apply voltage difference across spinneret and collector</td></tr><tr><td>Laboratory mixer with rpm control</td><td>Scilogex</td><td>SCI-84010201</td><td>Available from various laboratory equipment suppliers</td></tr><tr><td>Polyurethane</td><td>DSM</td><td>BioSpan SPU</td><td>Biospan Segmented Polyurethane</td></tr><tr><td>Rubber sheet</td><td>McMaster Carr</td><td>1370N11</td><td>Used to insulate syringe during electrospinning</td></tr><tr><td>Stainless steel mandrel</td><td>N/A</td><td>N/A</td><td>Manufactured&amp;nbsp;</td></tr><tr><td>Stainless steel needle</td><td>Hamilton</td><td>91018</td><td>Used as spinneret in electrospinning</td></tr><tr><td>Support material</td><td>EnvisionTec</td><td>B04-HT-DEMOMAT</td><td>Biocompatible water soluble material</td></tr><tr><td>Syringe Pump</td><td>Harvard Apparatus</td><td>55-3333</td><td></td></tr></tbody></table>

fabrication of small caliber stent-grafts using electrospinning and balloon expandable bare metal stents

Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and perforations in vasculature. Such stent-grafts are manufactured by covering a stent with a polymer membrane. An ideal stent-graft should have a biocompatible stent covered by a porous, thromboresistant, and biocompatible polymer membrane which mimics the extracellular matrix thereby promoting injury site healing. The goal of this protocol is to manufacture a small caliber stent-graft by encapsulating a balloon expandable stent within two layers of electrospun polyurethane nanofibers. Electrospinning of polyurethane has been shown to assist in healing by mimicking native extracellular matrix, thereby promoting endothelialization. Electrospinning polyurethane nanofibers on a slowly rotating mandrel enabled us to precisely control the thickness of the nanofibrous membrane, which is essential to achieve a small caliber balloon expandable stent-graft. Mechanical validation by crimping and expansion of the stent-graft has shown that the nanofibrous polyurethane membrane is sufficiently flexible to crimp and expand while staying patent without showing any signs of tearing or delamination. Furthermore, stent-grafts fabricated using the methods described here are capable of being implanted using a coronary intervention procedure using standard size guide catheters.

<html>我们electrospinner设置（ 图1）导致了高品质的聚氨酯纳米纤维（ 图2）。的支架-移植物是通过电的聚氨酯的内层到心轴，在该层之上滑动裸金属支架，和静电聚氨酯第二外层（ 图3）制造的。聚氨酯纳米纤维以50微米/小时的速率，这导致在100μm的内层和150微米的支架移植物的外层电纺丝。用这里介绍的协议静电导致均匀的纳米纤维的聚氨酯的层（ 图4...

Watch this Scientific Journal Video about Fabrication of Small Caliber Stent-grafts Using Electrospinning and Balloon Expandable Bare Metal Stents at JoVE.com

Fabrication of Small Caliber Stent-grafts Using Electrospinning and Balloon Expandable Bare Metal Stents

In the protocol, we present a method to manufacture a small caliber stent-graft by sandwiching a balloon expandable stent between two electrospun nanofibrous polyurethane layers.

小口径支架移植物使用静电及球囊扩张裸金属支架的制作

Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and ...

fabrication-small-caliber-stent-grafts-using-electrospinning-balloon

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

8.9K 次观看.  Mayo Clinic. In the protocol, we present a method to manufacture a small caliber stent-graft by sandwiching a balloon expandable stent between two electrospun nanofibrous polyurethane layers.

视频: Fabrication of Small Caliber Stent-grafts Using Electrospinning and Balloon Expandable Bare Metal Stents

Postproduction Processing of Electrospun Fibres for Tissue Engineering

Electrospinning is a commonly used and versatile method to produce scaffolds (often biodegradable) for 3D tissue engineering.1, 2, 3 Many tissues in vivo undergo biaxial distension to varying extents such as skin, bladder, pelvic floor and even the hard palate as children grow. In producing scaffolds for these purposes there is a need to develop scaffolds of appropriate biomechanical properties (whether achieved without or with cells) and which are sterile for clinical use. The focus of this paper is not how to establish basic electrospinning parameters (as there is extensive literature on electrospinning) but on how to modify spun scaffolds post production to make them fit for tissue engineering purposes - here thickness, mechanical properties and sterilisation (required for clinical use) are considered and we also describe how cells can be cultured on scaffolds and subjected to biaxial strain to condition them for specific applications.
Electrospinning tends to produce thin sheets; as the electrospinning collector becomes coated with insulating fibres it becomes a poor conductor such that fibres no longer deposit on it. Hence we describe approaches to produce thicker structures by heat or vapour annealing increasing the strength of scaffolds but not necessarily the elasticity. Sequential spinning of scaffolds of different polymers to achieve complex scaffolds is also described. Sterilisation methodologies can adversely affect strength and elasticity of scaffolds. We compare three methods for their effects on the biomechanical properties on electrospun scaffolds of poly lactic-co-glycolic acid (PLGA).
Imaging of cells on scaffolds and assessment of production of extracellular matrix (ECM) proteins by cells on scaffolds is described. Culturing cells on scaffolds in vitro can improve scaffold strength and elasticity but the tissue engineering literature shows that cells often fail to produce appropriate ECM when cultured under static conditions. There are few commercial systems available that allow one to culture cells on scaffolds under dynamic conditioning regimes - one example is the Bose Electroforce 3100 which can be used to exert a conditioning programme on cells in scaffolds held using mechanical grips within a media filled chamber.4 An approach to a budget cell culture bioreactor for controlled distortion in 2 dimensions is described. We show that cells can be induced to produce elastin under these conditions. Finally assessment of the biomechanical properties of processed scaffolds cultured with or without cells is described.

Electrospun scaffolds can be processed post production for tissue engineering applications. Here we describe methods for spinning complex scaffolds (by consecutive spinning), for making thicker scaffolds (by multi-layering using heat or vapour annealing), for achieving sterility (aseptic production or sterilisation post production) and for achieving appropriate biomechanical properties.

静电纤维组织工程的后期处理

Electrospinning is a commonly used and versatile method to produce  scaffolds (often biodegradable) for 3D tissue engineering.1, 2, 3 Many tissues in vivo ...

科研

生物工程

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.

颈动脉支架植入再狭窄的研究的小鼠模型

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

医学

Combination of Microstereolithography and Electrospinning to Produce Membranes Equipped with Niches for Corneal Regeneration

Corneal problems affect millions of people worldwide reducing their quality of life significantly. Corneal disease can be caused by illnesses such as Aniridia or Steven Johnson Syndrome as well as by external factors such as chemical burns or radiation. Current treatments are (i) the use of corneal grafts and (ii) the use of stem cell expanded in the laboratory and delivered on carriers (e.g., amniotic membrane); these treatments are relatively successful but unfortunately they can fail after 3-5 years. There is a need to design and manufacture new corneal biomaterial devices able to mimic in detail the physiological environment where stem cells reside in the cornea. Limbal stem cells are located in the limbus (circular area between cornea and sclera) in specific niches known as the Palisades of Vogt. In this work we have developed a new platform technology which combines two cutting-edge manufacturing techniques (microstereolithography and electrospinning) for the fabrication of corneal membranes that mimic to a certain extent the limbus. Our membranes contain artificial micropockets which aim to provide cells with protection as the Palisades of Vogt do in the eye.

We report a technique for the fabrication of micropockets within electrospun membranes in which to study cell behavior. Specifically, we describe a combination of microstereolithography and electrospinning for the production of PLGA (Poly(lactide-co-glycolide)) corneal biomaterial devices equipped with microfeatures.

Microstereolit​​hography和静电结合，以产生膜配备有利基的角膜再生

Corneal problems affect millions of people worldwide reducing their quality of life significantly. Corneal disease can be caused by illnesses such as ...

Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention

Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. The feasibility of using magnetic forces to capture and retain endothelial outgrowth cells (EOC) labeled with super paramagnetic iron oxide nanoparticles (SPION) has been shown previously. But this technique requires the development of a mechanically functional stent from a magnetic and biocompatible material followed by in-vitro and in-vivo testing to prove rapid endothelialization. We developed a weakly ferromagnetic stent from 2205 duplex stainless steel using computer aided design (CAD) and its design was further refined using finite element analysis (FEA). The final design of the stent exhibited a principal strain below the fracture limit of the material during mechanical crimping and expansion. One hundred stents were manufactured and a subset of them was used for mechanical testing, retained magnetic field measurements, in-vitro cell capture studies, and in-vivo implantation studies. Ten stents were tested for deployment to verify if they sustained crimping and expansion cycle without failure. Another 10 stents were magnetized using a strong neodymium magnet and their retained magnetic field was measured. The stents showed that the retained magnetism was sufficient to capture SPION-labeled EOC in our in-vitro studies. SPION-labeled EOC capture and retention was verified in large animal models by implanting 1 magnetized stent and 1 non-magnetized control stent in each of 4 pigs. The stented arteries were explanted after 7 days and analyzed histologically. The weakly magnetic stents developed in this study were capable of attracting and retaining SPION-labeled endothelial cells which can promote rapid healing.

Our goals were to design, manufacture and test ferromagnetic stents for endothelial cell capture. Ten stents were tested for fracture and 10 more stents were tested for retained magnetism. Finally, 10 stents were tested in-vitro and 8 more stents were implanted in 4 pigs to show cell capture and retention.

铁磁金属裸支架对血管内皮细胞捕获和保留

Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. ...

4D Printed Bifurcated Stents with Kirigami-Inspired Structures

Branched vessels, typically in the form of the letter &#34;Y,&#34;&#160;can be narrowed or blocked, resulting in serious health problems. Bifurcated stents, which are hollow in the interior and exteriorly shaped to the branched vessels, surgically inserted inside the branched vessels, act as a supporting structure so that bodily fluids can freely travel through the interior of the stents without being obstructed by the narrowed or blocked vessels. For a bifurcated stent to be deployed at the target site, it needs to be injected inside the vessel and travel within the vessel to reach the target site. The diameter of the vessel is much smaller than the bounding sphere of the bifurcated stent; thus, a technique is required so that the bifurcated stent remains small enough to travel through the vessel and expands at the targeted branched vessel. These two conflicting conditions, that is, small enough to pass through and large enough to structurally support narrowed passages, are extremely difficult to satisfy simultaneously. We use two techniques to fulfill the above requirements. First, on the material side, a shape memory polymer (SMP) is used to self-initiate shape changes from small to large, that is, being small when inserted and becoming large at the target site. Second, on the design side, a kirigami pattern is used to fold the branching tubes into a single tube with a smaller diameter. The presented techniques can be used to engineer structures that can be compacted during transportation and return to their functionally adept shape when activated. Although our work is targeted on medical stents, biocompatibility issues need to be solved before actual clinical use.

Using a 3D printer, a shape memory polymer filament is extruded to form a branched tubular structure. The structure is patterned and shaped such that it can contract into a compact form once folded and then return to its formed shape when heated.

4D 打印分叉支架与基里加米启发结构

Branched vessels, typically in the form of the letter &#34;Y,&#34;&#160;can be narrowed or blocked, resulting in serious health problems. Bifurcated ...

工程学

<meta charset="utf8"></head><body>使用牺牲铜夹具对 NiTi 线进行经济高效的形状设置

Rapid Formation and Testing of Self-expanding NiTi Frames with a Small Form Factor Suitable for Minimally Invasive Implants

NiTiNOL (commonly referred to as nitinol or NiTi) wires feature exceptional shape memory and super-elastic characteristics, while shape-setting is often a costly process. Among the steps in&#160;this process, heat treatment requires exposure to high temperatures for shape-setting. Traditionally, metal fixtures are used for this purpose.&#160;However, their manufacturing costs can be significant, which is unideal&#160;for iterating prototypes. This work demonstrates a recently introduced approach using sacrificial fixtures made of copper tubes, which eliminates the need for expensive fixtures. These copper tubes allow for the formation of complex geometries, and they offer a scaffold for various phases of the fabrication process. Moreover, ammonium persulfate is used&#160;for selective copper etching, which simplifies the production of NiTi frames. This work&#39;s findings confirm the effectiveness of this technique and&#160;demonstrate&#160;the successful shape-setting of NiTi wires for self-expanding frames. This methodology paves the way for future research, allowing for rapid prototyping of NiTi wireframes for various applications, especially those in medical devices.

<meta charset="utf8"></head><body>作者聚焦：用于经导管植入式器械的自膨胀镍钛合金框架的快速原型设计和测试

This work illustrates a low-cost fabrication technique for shape-setting nitinol wires/frames with a small form factor using sacrificial fixtures. The technique is demonstrated for the fabrication of self-expanding frames designed for minimally invasive implants with complex shapes.

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

NiTiNOL (commonly referred to as nitinol or NiTi) wires feature exceptional shape memory and super-elastic characteristics, while shape-setting is often a ...

Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model.
Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing &#62;500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique.
Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 &#177; 22 min, 26 &#177; 6 min and 11 &#177; 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis).
The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.

Reproducable experimental animal models are needed for the testing of novel embolization materials, which have been designed to treat endovascular occlusion of intracranial aneurysms (IA). The present study aims to develop a safe and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model.

生物可降解镁支架治疗大鼠囊动脉瘤的实验研究--手术技术介绍

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable ...

神经科学

Combining 3D-Printing and Electrospinning to Manufacture Biomimetic Heart Valve Leaflets

Electrospinning has become a widely used technique in cardiovascular tissue engineering as it offers the possibility to create (micro-)fibrous scaffolds with adjustable properties. The aim of this study was to create multilayered scaffolds mimicking the architectural fiber characteristics of human heart valve leaflets using conductive 3D-printed collectors.
Models of aortic valve cusps were created using commercial computer-aided design (CAD) software. Conductive polylactic acid was used to fabricate 3D-printed leaflet templates. These cusp negatives were integrated into a specifically designed, rotating electrospinning mandrel. Three layers of polyurethane were spun onto the collector, mimicking the fiber orientation of human heart valves. Surface and fiber structure was assessed with a scanning electron microscope (SEM). The application of fluorescent dye additionally permitted the microscopic visualization of the multilayered fiber structure. Tensile testing was performed to assess the biomechanical properties of the scaffolds.
3D-printing of essential parts for the electrospinning rig was possible in a short time for a low budget. The aortic valve cusps created following this protocol were three-layered, with a fiber diameter of 4.1 &#177; 1.6 &#181;m. SEM imaging revealed an even distribution of fibers. Fluorescence microscopy revealed individual layers with differently aligned fibers, with each layer precisely reaching the desired fiber configuration. The produced scaffolds showed high tensile strength, especially along the direction of alignment. The printing files for the different collectors are available as Supplemental File 1, Supplemental File 2, Supplemental File 3, Supplemental File 4, and Supplemental File 5.
With a highly specialized setup and workflow protocol, it is possible to mimic tissues with complex fiber structures over multiple layers. Spinning directly on 3D-printed collectors creates considerable flexibility in manufacturing 3D shapes at low production costs.

The presented method offers an innovative way for engineering biomimetic fiber structures in three-dimensional (3D) scaffolds (e.g., heart valve leaflets). 3D-printed, conductive geometries were used to determine shape and dimensions. Fiber orientation and characteristics were individually adjustable for each layer. Multiple samples could be manufactured in one setup.

结合3D打印和静电纺丝来制造仿生心脏瓣膜传单

Electrospinning has become a widely used technique in cardiovascular tissue engineering as it offers the possibility to create (micro-)fibrous scaffolds ...

小口径支架移植物使用静电及球囊扩张裸金属支架的制作

摘要

探索更多视频

静电纤维组织工程的后期处理

颈动脉支架植入再狭窄的研究的小鼠模型

Microstereolithography和静电结合，以产生膜配备有利基的角膜再生

铁磁金属裸支架对血管内皮细胞捕获和保留

4D 打印分叉支架与基里加米启发结构

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

生物可降解镁支架治疗大鼠囊动脉瘤的实验研究--手术技术介绍

结合3D打印和静电纺丝来制造仿生心脏瓣膜传单

小口径支架移植物使用静电及球囊扩张裸金属支架的制作

摘要

探索更多视频

静电纤维组织工程的后期处理

颈动脉支架植入再狭窄的研究的小鼠模型

Microstereolit​​hography和静电结合，以产生膜配备有利基的角膜再生

铁磁金属裸支架对血管内皮细胞捕获和保留

4D 打印分叉支架与基里加米启发结构

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

快速形成和测试适用于微创植入物的小尺寸自膨胀 NiTi 框架

生物可降解镁支架治疗大鼠囊动脉瘤的实验研究--手术技术介绍

结合3D打印和静电纺丝来制造仿生心脏瓣膜传单

Microstereolithography和静电结合，以产生膜配备有利基的角膜再生