Name: tape: a biodegradable hemostatic glue inspired by a ubiquitous compound in plants for surgical application
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Description: Watch this Scientific Journal Video about TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application at JoVE.com

This study was supported by National Research Foundation of South Korea: Mid-career scientist grant (2014002855), and Ministry of Industry, Trade, and Natural Resources: World Premier Material Development Program. This work is also supported by in part by Center for Nature-inspired Technology (CNiT) in KAIST Institute for NanoCentury (KINC).

所有的动物护理和实验是按照由KAIST（科学与韩国高等科技学院）提供的道德协议IRB（伦理审查委员会）执行。 1. TAPE形成<ol><li>制备的TA溶液，放置在磁力搅拌器上4ml的大小的玻璃小瓶中，并加入1毫升蒸馏水有搅拌棒。 1克鞣酸加入到小瓶中，并通过温和搅拌以200rpm以上1小时溶解在水中。当TA完全溶解，该混合物变成透明的褐色。 </li><li>通过由涡旋几秒到使白色浆液将它们混合加入1g的PEG粉末（4-臂，10 kDa的，以及直链的，4.6 kDa的）至1毫升蒸馏水，随后制备的PEG溶液。保持在孵化该浆料在60℃下10分钟。直到白某变得完全清楚。 注:PEG的10 kDa的分子量的熔点为约55- 60℃，并在4 kDa的一个是53 - 58℃。熔化的PEG变成水混溶性，使得PEG的水高达1克高浓度/毫升，可以实现为透明的溶液。一旦明确PEG溶液在高温下形成的，该溶液仍然是冷却后在室温下是稳定的。 </li><li>添加PEG的329微升（4-臂，10 kDa）的溶液中制备1.2至671微升在步骤1.1中制备的TA溶液（在具有4.6 kDa的线性PEG的情况下，添加的PEG溶液的311微升至689微升在微型离心管中的TA溶液）。轻轻地融合与一个狭窄的铲两粘性和蜂蜜般的解决方案，它们均匀混合。 注意:这两种解决方案都相当粘稠，所以科学家必须缓慢而充分地拉起来 ​​，用微量的传输解决方案。 </li><li>旋在12300 xg离心在装有固定角转子的离心分离机，在步骤1.3制备3分钟的混合物。 </li><li>仔细REM奥雅纳尽可能多使用微量上清液尽可能的，并收集已定下来的产品是:这是完全形成胶带。后胶带的形成，它存放在冰箱（4 - 8℃）长达数周。注 :TAPE能够用γ射线或在外科应用在使用前的电子束处理来灭菌。 </li></ol> 2.带粘合强度的测量<ol><li>制备猪皮肤组织的两片由在皮肤上的组织去除所有脂肪后，用活检穿孔切割直径为6毫米。 注:从健康猪侧翼的皮肤得到的猪皮肤组织，并从位于大田的韩国当地肉类市场购买。 </li><li>适用的商业氰基丙烯酸酯胶的每个组织的外侧，并且组织附着到金属杆。 注:金属杆被用作补充手柄，使织物a重不直接由机器夹住。因此，它可以用下面的拉伸机的结构的其他材料来代替。 </li><li>应用带的压降（TAPE一滴大约为3 - 6毫克）于组织的一侧。然后，散布在胶带均匀地使用在其内两侧的两个组织之间的另一个组织，以便它们所连接， 如图2A所示 。 </li><li>然后，手动附加和分离组织双方几次混匀并最大限度地提高各组织和磁带之间的接口。 </li><li>用UTM，小心地夹住杆的每一侧。的粘接强度将通过分离附着有胶带两种组织所需的力来确定。首先，应用的20 N的力1分钟。接着，用机，以1mm /分的速度拉在相反方向上各棒。直至组织完全分离。 注意:数据将给出的力-距离由运动检测（FD）曲线的每个杆。 </li><li>除以在步骤2.5通过样品表面区域取得的FD曲线所示的最大力（kN）计算带的粘合强度，也就是3.14×（0.003米）2。 </li><li>对于在水的存在下监测的粘接强度，加入20微升的水在分离的区域两种组织之间，并立即附加它们。随着机，再次进行测试支队。 </li></ol> 3. 体外降解测试<ol><li>切微型离心管的盖子（D = 8 MM），并权衡帽将其定义为W C。 </li><li>装满150毫克磁带的帽子，再权衡所有一起将其设置为一个总的初始重量W 0。 注意:不要在帽超载TAPE。带的高度应该比盖的顶部低，因为它可以是一个物理屏障以在步骤3.4中孵育期间由搅拌过程中产生的PBS缓冲液的流。 </li><li&gt;把含有TAPE到细胞培养瓶的帽（75 平方厘米），并加入50毫升的PBS缓冲液（1×，pH 7.4）中，以细胞培养烧瓶，以便在盖的磁带完全浸入PBS缓冲液，如在图3A所示（N = 5）。 </li><li>孵育在步骤3.3中，在37℃，类似于生理条件的轨道摇动孵化器中制备的细胞培养瓶中，在温和搅拌下（50rpm）进行。 注意:保持搅拌条件以50rpm。更高的转速可能导致TAPE的崩溃。 </li><li>在每个时间点，采取与从细胞培养烧瓶TAPE帽，然后通过吹氮气干燥。称量装有剩余磁带上限。在每个时间点为W t将重量。再次更换新鲜的PBS，并在每个时间点测量W¯¯ 吨后再次摇晃。 </li><li>计算相对其余重量（％）在下面的等式。 相对剩余重量（％）=（W 吨 </suB&gt; - W C）/（W 0 - W C）×100％ </li></ol> 4.带止血能力 注:所有的动物实验应按照卫生和福利部韩国提供的准则和道德协议来完成。 <ol><li>为了评估在体内的止血功能，如参考文献24中描述审查出血鼠肝模型。 </li><li>麻醉15只小鼠（正常ICR小鼠，6周，30 - 35克，雄性）以替来他明 - 唑拉西泮（33.333毫克/千克）和赛拉嗪（7.773毫克/千克）的腹膜内注射（N =每组5只）。要确认正确的麻醉，轻轻一捏动物的爪子和观察运动，如抽出爪子等 ，没有动作表明，该动物是充分麻醉做手术。 </li><li>为防止动物的眼睛干涩，下充分而申请的兽医药膏眼睛感知。暴露经由中线腹部切口肝脏，并用18G的针以诱导出血刺肝脏。 </li><li>除去流动的血液用无菌纱布，并把100微升TAPE或纤维蛋白胶（阳性对照）的立即在出血部位。 注:在应用胶带后，需要因对伤口组织中的高血耐粘接性能没有进一步的缝合。为阴性对照，无处理发生在出血的部位。 </li><li>在每一种情况下，把一个滤纸与已知质量的肝脏下方，以收集来自损伤部位的血液。用新的，每30秒，4次（ 即 ，2分钟）更换纸张。 </li><li>测量所收集的每30秒每滤纸吸收血液的质量。动物实验后，通过牺牲二氧化碳窒息安乐死的老鼠。 </li></ol>

<ol>
	<li>Leggat, P. A., Smith, D. R., Kedjarune, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+applications+of+cyanoacrylate+adhesives:+a+review+of+toxicity.">Surgical applications of cyanoacrylate adhesives: a review of toxicity.</a> ANZ J Surg. 77 (4), 209-213 (2007).</li><li>MacGillivray, T. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fibrin+Sealants+and+Glues.">Fibrin Sealants and Glues.</a> J Cardiac Surg. 18 (6), 480-485 (2003).</li><li>Radosevich, M., Goubran, H. A., Burnouf, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fibrin+sealant:+scientific+rationale,+production+methods,+properties+and+current+clinical+use.">Fibrin sealant: scientific rationale, production methods, properties and current clinical use.</a> Vox. Sang. 72 (3), 133-143 (1997).</li><li>Nomori, H., Horio, H., Suemasu, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+efficacy+and+side+effects+of+gelatin-resorcinol+formaldehyde-glutaraldehyde+(GRFG)+glue+for+preventing+and+sealing+pulmonary.">The efficacy and side effects of gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG) glue for preventing and sealing pulmonary.</a> Surg. Today. 30 (3), 244-248 (2000).</li><li>Duarte, A. P., Coelho, J. F., Bordado, J. C., Cidade, M. T., Gil, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+adhesives:+Systematic+review+of+the+main+types+and+development+forecast.">Surgical adhesives: Systematic review of the main types and development forecast.</a> Prog. Polym. Sci. 37 (8), 1031-1050 (2012).</li><li>Bhatia, S. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+injuries.">Traumatic injuries.</a> Biomaterials for clinical applications. , 213-258 (2010).</li><li>Bouten, P. J. 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=The+chemistry+of+tissue+adhesive+materials.">The chemistry of tissue adhesive materials.</a> Prog.Polym. Sci. 39 (7), 1375-1405 (2014).</li><li>Annabi, N., Tamayol, A., Shin, S. R., Ghaemmaghami, A. M., Peppas, N. A., Khademhosseini, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+materials:+Current+challenges+and+nano-enabled+solutions.">Surgical materials: Current challenges and nano-enabled solutions.</a> Nano Today. 9 (5), 574-589 (2014).</li><li>Strausberg, R. L., Link, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protein-based+medical+adhesives.">Protein-based medical adhesives.</a> Trends.Biotechnol. 8 (2), 53-57 (1990).</li><li>Bilic, 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=Injectable+candidate+sealants+for+fetal+membrane+repair:+bonding+and+toxicity+in+vitro.">Injectable candidate sealants for fetal membrane repair: bonding and toxicity in vitro.</a> Am J Obstet Gynecol. 202 (1), 1-9 (2010).</li><li>Mehdizadeh, M., Weng, H., Gyawali, D., Tang, L., Yang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Injectable+citrate-based+mussel-inspired+tissue+bioadhesives+with+high+wet+strength+for+sutureless+wound+closure.">Injectable citrate-based mussel-inspired tissue bioadhesives with high wet strength for sutureless wound closure.</a> Biomaterials. 33 (32), 7972-7980 (2012).</li><li>Ryu, J. H., Lee, Y., Kong, W. H., Kim, T. G., Park, T. G., Lee, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Catechol-functionalized+chitosan/pluronic+hydrogels+for+tissue+adhesives+and+hemostatic+materials.">Catechol-functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials.</a> Biomacromolecules. 12 (7), 2653-2660 (2011).</li><li>Mahdavi, 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=A+biodegradable+and+biocompatible+gecko-inspired+tissue+adhesive.">A biodegradable and biocompatible gecko-inspired tissue adhesive.</a> Proc Natl Acad Sci USA. 105 (7), 2307-2310 (2008).</li><li>Lee, H., Lee, B. P., Messersmith, P. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+reversible+wet/dry+adhesive+inspired+by+mussels+and+geckos.">A reversible wet/dry adhesive inspired by mussels and geckos.</a> Nature. 488, 338-341 (2007).</li><li>Yang, S. Y., 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=A+bio-inspired+swellable+microneedle+adhesive+for+mechanical+interlocking+with+tissue.">A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue.</a> Nature Commun. 4, 1702-1710 (2013).</li><li>Spotnitz, W. D., Burks, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemostats,+sealants,+and+adhesives:+components+of+the+surgical+toolbox.">Hemostats, sealants, and adhesives: components of the surgical toolbox.</a> Transfusion (Paris). 48 (7), 1502-1516 (2008).</li><li>Erel, I., Schlaad, H., Demirel, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+structural+isomerism+and+polymer+end+group+on+the+pH-stability+of+hydrogen-bonded+multilayers.">Effect of structural isomerism and polymer end group on the pH-stability of hydrogen-bonded multilayers.</a> J Colloid Interface Sci. 361 (2), 477-482 (2011).</li><li>Shutava, T. G., Prouty, M. D., Agabekov, V. E., Lvov, Y. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antioxidant+Properties+of+Layer-by-Layer+films+on+the+Basis+of+Tannic+Acid.">Antioxidant Properties of Layer-by-Layer films on the Basis of Tannic Acid.</a> Chem Lett. 35 (10), 1144-1145 (2006).</li><li>Schmidt, D. J., Hammond, P. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrochemically+erasable+hydrogen-bonded+thin+films.">Electrochemically erasable hydrogen-bonded thin films.</a> Chem Commun. 46 (39), 7358-7360 (2010).</li><li>Shutava, T., Prouty, M., Kommireddy, D., Lvov, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=pH+Responsive+Decomposable+Layer-by-Layer+Nanofilms+and+Capsules+on+the+Basis+of+Tannic+Acid.">pH Responsive Decomposable Layer-by-Layer Nanofilms and Capsules on the Basis of Tannic Acid.</a> Macromolecules. 38 (7), 2850-2858 (2005).</li><li>Erel, I., Zhu, Z., Zhuk, A., Sukhishvili, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hydrogen-bonded+layer-by-layer+films+of+block+copolymer+micelles+with+pH-responsive+cores.">Hydrogen-bonded layer-by-layer films of block copolymer micelles with pH-responsive cores.</a> J Colloid Interface Sci. 355 (1), 61-69 (2011).</li><li>Kim, B. -. S., Lee, H. -. I., Min, Y., Poon, Z., Hammond, P. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hydrogen-bonded+multilayer+of+pH-responsive+polymeric+micelles+with+tannic+acid+for+surface+drug+delivery.">Hydrogen-bonded multilayer of pH-responsive polymeric micelles with tannic acid for surface drug delivery.</a> Chem Commun. 45 (28), 4194-4196 (2009).</li><li>Murakami, Y., Yokoyama, M., Nishida, H., Tomizawa, Y., Kurosawa, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+hemostasis+model+for+the+quantitative+evaluation+of+hydrogel-based+local+hemostatic+biomaterials+on+tissue+surface.">A simple hemostasis model for the quantitative evaluation of hydrogel-based local hemostatic biomaterials on tissue surface.</a> Colloids Surf B Biointerfaces. 65 (2), 186-189 (2008).</li><li>Kim, 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=TAPE:+A+Medical+Adhesive+Inspired+by+a+Ubiquitous+Compound+in+Plants.">TAPE: A Medical Adhesive Inspired by a Ubiquitous Compound in Plants.</a> Adv Funct Mater. 25 (16), 2402-2410 (2015).</li><li>Suzuki, S., Ikada, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adhesion+of+cells+and+tissues+to+bioabsorbable+polymeric+materials:+scaffolds,+surgical+tissue+adhesives+and+anti-adhesive+materials.">Adhesion of cells and tissues to bioabsorbable polymeric materials: scaffolds, surgical tissue adhesives and anti-adhesive materials.</a> J Adhes. Sci. Technol. 24 (13), 2059-2077 (2010).</li><li>Lomova, M. V., 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=Multilayer+Capsules+of+Bovine+Serum+Albumin+and+Tannic+Acid+for+Controlled+Release+by+Enzymatic+Degradation.">Multilayer Capsules of Bovine Serum Albumin and Tannic Acid for Controlled Release by Enzymatic Degradation.</a> ACS Appl Mater Interfaces. 7 (22), 11732-11740 (2015).</li><li>Shin, M., Ryu, J. H., Park, J. P., Kim, K., Yang, J. W., Lee, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=DNA/Tannic+Acid+Hybrid+Gel+Exhibiting+Biodegradability,+Extensibility,+Tissue+Adhesiveness,+and+Hemostatic+Ability.">DNA/Tannic Acid Hybrid Gel Exhibiting Biodegradability, Extensibility, Tissue Adhesiveness, and Hemostatic Ability.</a> Adv Funct Mater. 25 (8), 1270-1278 (2015).</li><li>Kozlovskaya, V., Kharlampieva, E., Drachuk, I., Chenga, D., Tsukruk, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Responsive+microcapsule+reactors+based+on+hydrogen-bonded+tannic+acid+layer-by-layer+assemblies.">Responsive microcapsule reactors based on hydrogen-bonded tannic acid layer-by-layer assemblies.</a> Soft Matter. 6 (15), 3596-3608 (2010).</li><li>Oh, D. X., 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=A+rapid,+efficient,+and+facile+solution+for+dental+hypersensitivity:+The+tannin-iron+complex.">A rapid, efficient, and facile solution for dental hypersensitivity: The tannin-iron complex.</a> Sci Rep. 5, 10884 (2015).</li></ol>

The authors have nothing to disclose.

我们开发了一个全新的由植物衍生的多酚化合物，TA的抗水分子相互作用的启发止血胶粘剂命名的胶带。 TA是一个代表可水解单宁已显著受到关注，因为它的抗氧化，抗菌，抗诱变，和抗致癌特性。 使磁带的过程是非常简单的，可扩展和环境友好的，因为它仅仅是两种水溶液随后不经任何进一步的化学合成方法离心的一步法混合。 双组分混合协议是形成?...

在过去的十年中，已经进行了努力，以取代目前的手术缝合线和缝合钉关闭与生物可降解/生物可吸收的粘合剂伤口由于在外科手术处理它们在使用和低组织侵袭性的便利。市售的组织粘合剂分为四种类型:（1）氰基丙烯酸酯衍生物1，（2）通过酶转化从纤维蛋白原形成由凝血酶2,3至纤维蛋白聚合物的血纤维蛋白胶，（3）基于蛋白质的材料，如化学或物理交联的白蛋白和/或明胶4,5，和（4）为基础的聚合物合成的6。尽管它们已经在许多临床应用中使用，所有的粘合剂具有其自己固有的不足和缺陷，可以是它们的广泛使用的障碍。氰基丙烯酸酯系胶粘剂显示出高的粘合强度的组织，但它们的毒性副产物如氰基和甲醛降解过程中形成的，常会导致符号量占用度的炎症反应7。血纤维蛋白胶水和白蛋白或明胶基材料具有关于传染性成分，如动物来源的病毒的传输安全性的问题:人血浆纤维蛋白胶水和动物包括牛，鸡，猪和鱼明胶基胶水8。虽然一些基于合成聚合物的粘合剂已通过美国联邦药物管理局（FDA），由合成聚合物的大多数粘合剂继续在减少制造过程中的步骤和实现生物相容性9困难。最重要的是，所有的胶水贫困机械和粘接强度遭受湿纸巾10。近日，由贻贝11-13，14壁虎，壁虎与贻贝15和内寄生蠕虫启发16仿生组织粘合剂已经逐渐成为有前途的替代品，以目前的医疗胶由于其可调的机械和粘接性能与生物相容性。然而，到了今天，仍有待解决的问题，他们成为商业化产品17日之前。 在这里，我们报告一个称为胶带全新型医疗胶是由植物来源的粘附分子，单宁酸（TA）和一个生物惰性聚合物聚（乙二醇）（PEG）之间的分子间氢键制备正如其名称所示。 TA是植物的次生代谢过程中发现普遍存在的代表水解单宁。它已引起人们的关注，因为它的抗氧化剂，抗诱变，和抗致癌特性，并已被证明参与超分子相互作用与许多聚合物，如聚（N- -isopropylacrylamide）（PNIPAM）和聚（N -乙烯基吡咯烷酮）（PVPON），以形成层-层（LBL）膜18-20和药物释放的微胶囊21-23。在这项研究中，我们发现，TA可以作为一个有效的行动耐水粘接性官能基团，以形成医用粘合剂，胶带。通过用TA简单混合，非结垢聚合物PEG变得与超分子胶2.5倍与商业纤维蛋白胶相比增加粘合强度，并且此粘附保持在整个装卸的多达20个循环，甚至在水存在。其止血能力上的肝出血模型的体内测试，并显示出良好的止血能力以停止在几秒钟内出血。录像带的相关领域作为第一植物性粘合剂可以揭示新的洞察解决与生物启发方法目前存在的问题的弊端其显著的意义。我们也期望在各种医疗和药物应用如粘膜粘合剂，药物释放的补丁，伤口护理敷料以及其他的广泛使用磁带，由于其制备方法简单，可扩展性，可调谐的生物降解速率，以及高湿耐adhes离子的特性。

<table><tbody><tr><td>Tannic acid</td><td>Sigma-aldrich</td><td>403040</td><td></td></tr><tr><td>Poly(ethylene oxide), 4-arm, hydroxy terminated</td><td>Aldrich</td><td>565709</td><td>Averge Mn ~ 10,000</td></tr><tr><td>Poly(ethylene glycol)</td><td>Aldrich</td><td>373001</td><td>Average Mn 4,600</td></tr><tr><td>Biopsy punch</td><td>Miltex</td><td>33-36</td><td>Diameter = 6 mm</td></tr><tr><td>Aron Alpha</td><td>Toagosei Co., Ltd.</td><td></td><td>Instant glue</td></tr><tr><td>Universal testing machine (UTM)</td><td>Instron</td><td>5583</td><td></td></tr><tr><td>Microcentrifuge tubes</td><td>SPL life science</td><td>60015</td><td>1.5 ml</td></tr><tr><td>Petri dish</td><td>SPL life science</td><td>10090</td><td>90 x 15 mm</td></tr><tr><td>Sodium phosphate monobasic</td><td>Sigma</td><td>S5011</td><td>1x PBS ingredient</td></tr><tr><td>Sodium phosphate dibasic</td><td>Sigma</td><td>S5136</td><td>1x PBS ingredient</td></tr><tr><td>Sodium chloride</td><td>Duchefa biochemie</td><td>S0520.5000</td><td>1x PBS ingredient</td></tr><tr><td>Incubating shaker</td><td>Lab companion</td><td>SIF6000R</td><td></td></tr><tr><td>ICR mice</td><td>Orient bio</td><td>Normal ICR mouse</td><td>6 weeks, 30 - 35 g, male</td></tr><tr><td>Tiletamine-zolazepam (Zoletil 50)</td><td>Virbac</td><td></td><td></td></tr><tr><td>Zylazine (Rompun)</td><td>Bayer</td><td></td><td></td></tr><tr><td>PrecisionGlide&lt;sup&gt;TM&lt;/sup&gt; needle (18 G)</td><td>BD</td><td>302032</td><td>18 G</td></tr><tr><td>Filter paper</td><td>Whatman</td><td>1001 125</td><td>Diameter = 125 mm</td></tr><tr><td>Parafilm</td><td>Bemis Flexible Pakaging</td><td>PM996</td><td></td></tr></tbody></table>

tape: a biodegradable hemostatic glue inspired by a ubiquitous compound in plants for surgical application

此视频描述了制备可生物降解的手术胶水具有比商业组织粘合剂的有效的止血能力和更大的耐水粘合强度的最简单的协议。医用粘合剂已经由于其在使用方便与微创备受关注的潜在的替代工具，缝线和U形钉。虽然有几种协议制定组织粘合剂包括那些市售如纤维蛋白胶水和氰基丙烯酸酯基材料，主要是它们需要一系列的有机分子，或复杂的蛋白质纯化方法的化学合成的，在生物驱动材料的情况下（ 即纤维蛋白胶）。此外，手术胶水的发展显示出高的粘合性，同时维持生物降解性仍然是一个挑战，因为在实现本体的潮湿环境良好的性能的困难。我们说明了一种新的方法来准备医用胶，称为胶带，由植物来源的，湿耐粘合剂分子的物理混合后形成的水不混溶性的超分子聚集体的重量为基础的分离，T annic 的 CID（TA），以及公知的生物聚合物，聚（乙烯）乙二醇（PEG）。随着我们的做法，录像显示粘接强度高，比在有水存在的商业纤维蛋白胶的2.5倍。此外，磁带是在生理条件下可生物降解的，并且可以用作抗组织出血一种有效的止血胶水。我们预期在各种医疗环境和药物递送的应用中，广泛使用磁带的诸如用于粘膜粘附更为聚合物，药物贮藏和。

带是超分子聚集体离心含有TA（1微克/毫升蒸馏水中）和PEG（1微克/毫升的蒸馏水中）与2两种水溶液的混合物后稳定下来:1的体积比（ 图1A）。混合比是在实现高粘附强度的关键因素;当带通过一个2形成的:1混合比，20个单位在25个单位的TA的羟基（-OH）的与PEG各醚基（-O-）相互作用，导致最高的分子间氢键形成具有最大粘附性能。 -OH的其余五个单位似乎通过与TA?...

Watch this Scientific Journal Video about TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application at JoVE.com

TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application

我们描述制备生物可降解医用胶，有一个有效的止血能力的最简单的协议。带通过单宁酸的混合制备的水不混溶的超分子聚集体，一个无处不化合物在植物中发现，和聚（乙烯）乙二醇，与商业纤维蛋白胶相比，得到一个2.5倍的耐水附着性。

TAPE:一种生物可降解止血胶由无处不在的复方植物外科应用的启发

This video describes the simplest protocol for preparing biodegradable surgical glue that has an effective hemostatic ability and greater water-resistant ...

tape-biodegradable-hemostatic-glue-inspired-ubiquitous-compound

Universidad de Cartagena UDEC

Research

JoVE Journal

Bioengineering

14.1K 次观看.  Korea Advanced Institute of Science and Technology (KAIST). 我们描述制备生物可降解医用胶，有一个有效的止血能力的最简单的协议。带通过单宁酸的混合制备的水不混溶的超分子聚集体，一个无处不化合物在植物中发现，和聚（乙烯）乙二醇，与商业纤维蛋白胶相比，得到一个2.5倍的耐水附着性。 

视频: TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application

Engineering Biological-Based Vascular Grafts Using a Pulsatile Bioreactor

Much effort has been devoted to develop and advance the methodology to regenerate functional small-diameter arterial bypasses. In the physiological environment, both mechanical and chemical stimulation are required to maintain the proper development and functionality of arterial vessels1,2.
Bioreactor culture systems developed by our group are designed to support vessel regeneration within a precisely controlled chemo-mechanical environment mimicking that of native vessels. Our bioreactor assembly and maintenance procedures are fairly simple and highly repeatable3,4. Smooth muscle cells (SMCs) are seeded onto a tubular polyglycolic acid (PGA) mesh that is threaded over compliant silicone tubing and cultured in the bioreactor with or without pulsatile stimulation for up to 12 weeks. There are four main attributes that distinguish our bioreactor from some predecessors. 1) Unlike other culture systems that simulate only the biochemical surrounding of native blood vessels, our bioreactor also creates a physiological pulsatile environment by applying cyclic radial strain to the vessels in culture. 2) Multiple engineered vessels can be cultured simultaneously under different mechanical conditions within a controlled chemical environment. 3) The bioreactor allows a mono layer of endothelial cells (EC) to be easily coated onto the luminal side of engineered vessels for animal implantation models. 4) Our bioreactor can also culture engineered vessels with different diameter size ranged from 1 mm to 3 mm, saving the effort to tailor each individual bioreactor to fit a specific diameter size. 
The engineered vessels cultured in our bioreactor resemble native blood vessels histologically to some degree. Cells in the vessel walls express mature SMC contractile markers such as smooth muscle myosin heavy chain (SMMHC)3. A substantial amount of collagen is deposited within the extracellular matrix, which is responsible for ultimate mechanical strength of the engineered vessels5. Biochemical analysis also indicates that collagen content of engineered vessels is comparable to that of native arteries6. Importantly, the pulsatile bioreactor has consistently regenerated vessels that exhibit mechanical properties that permit successful implantation experiments in animal models3,7. Additionally, this bioreactor can be further modified to allow real-time assessment and tracking of collagen remodeling over time, non-invasively, using a non-linear optical microscopy (NLOM)8. To conclude, this bioreactor should serve as an excellent platform to study the fundamental mechanisms that regulate the regeneration of functional small-diameter vascular grafts.

Our group has developed a bioreactor culture system that mimics the physiological pulsatile stresses of the cardiovascular system to regenerate implantable small-diameter vascular grafts.

基于生物工程，人造血管使用脉动生物反应器

Much effort has been devoted to develop and advance the methodology to regenerate functional small-diameter arterial bypasses. In the physiological ...

科研

生物工程

A Chitosan Based, Laser Activated Thin Film Surgical Adhesive, 'SurgiLux': Preparation and Demonstration

Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound closure by virtue of their repair strength (~100 KPa). However, sutures can act as a nidus for infection and in many procedures are unable to effect wound repair or interfere with functional tissue regeneration.1 Surgical glues and adhesives, such as those based on fibrin and cyanoacrylates, have been developed as alternatives to sutures for the repair of such wounds. However, current commercial adhesives also have significant disadvantages, ranging from viral and prion transfer and a lack of repair strength as with the fibrin glues, to tissue toxicity and a lack of biocompatibility for the cyanoacrylate based adhesives. Furthermore, currently available surgical adhesives tend to be gel-based and can have extended curing times which limit their application.2 Similarly, the use of UV lasers to facilitate cross-linking mechanisms in protein-based or albumin 'solders' can lead to DNA damage while laser tissue welding (LTW) predisposes thermal damage to tissues.3 Despite their disadvantages, adhesives and LTW have captured approximately 30% of the wound closure market reported to be in excess of US $5 billion per annum, a significant testament to the need for sutureless technology.4
In the pursuit of sutureless technology we have utilized chitosan as a biomaterial for the development of a flexible, thin film, laser-activated surgical adhesive termed 'SurgiLux'. This novel bioadhesive uses a unique combination of biomaterials and photonics that are FDA approved and successfully used in a variety of biomedical applications and products. SurgiLux overcomes all the disadvantages associated with sutures and current surgical adhesives (see Table 1).
In this presentation we report the relatively simple protocol for the fabrication of SurgiLux and demonstrate its laser activation and tissue weld strength. SurgiLux films adhere to collagenous tissue without chemical modification such as cross-linking and through irradiation using a comparatively low-powered (120 mW) infrared laser instead of UV light. Chitosan films have a natural but weak adhesive attraction to collagen (~3 KPa), laser activation of the chitosan based SurgiLux films emphasizes the strength of this adhesion through polymer chain interactions as a consequence of transient thermal expansion.5 Without this 'activation' process, SurgiLux films are readily removed.6-9 SurgiLux has been tested both in vitro and in vivo on a variety of tissues including nerve, intestine, dura mater and cornea. In all cases it demonstrated good biocompatibility and negligible thermal damage as a consequence of irradiation.6-10

The fabrication of a novel, flexible thin film surgical adhesive from FDA approved ingredients, chitosan and indocyanine green is described. Bonding of this adhesive to collagenous tissue through a simple activation process with a low-powered infra-red laser is demonstrated.

基于几丁聚糖，激光激发薄膜手术胶粘剂，“SurgiLux的制备及示范

Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound closure by virtue of their repair strength (~100 KPa). However, sutures ...

Engineering a Bilayered Hydrogel to Control ASC Differentiation

Natural polymers over the years have gained more importance because of their host biocompatibility and ability to interact with cells in vitro and in vivo. An area of research that holds promise in regenerative medicine is the combinatorial use of novel biomaterials and stem cells. A fundamental strategy in the field of tissue engineering is the use of three-dimensional scaffold (e.g., decellularized extracellular matrix, hydrogels, micro/nano particles) for directing cell function. This technology has evolved from the discovery that cells need a substrate upon which they can adhere, proliferate, and express their differentiated cellular phenotype and function 2-3. More recently, it has also been determined that cells not only use these substrates for adherence, but also interact and take cues from the matrix substrate (e.g., extracellular matrix, ECM)4. Therefore, the cells and scaffolds have a reciprocal connection that serves to control tissue development, organization, and ultimate function. Adipose-derived stem cells (ASCs) are mesenchymal, non-hematopoetic stem cells present in adipose tissue that can exhibit multi-lineage differentiation and serve as a readily available source of cells (i.e. pre-vascular endothelia and pericytes). Our hypothesis is that adipose-derived stem cells can be directed toward differing phenotypes simultaneously by simply co-culturing them in bilayered matrices1. Our laboratory is focused on dermal wound healing. To this end, we created a single composite matrix from the natural biomaterials, fibrin, collagen, and chitosan that can mimic the characteristics and functions of a dermal-specific wound healing ECM environment.

This protocol focuses on utilizing the inherent ability of stem cells to take cue from their surrounding extracellular matrix and be induced to differentiate into multiple phenotypes. This methods manuscript extends our description and characterization of a model utilizing a bilayered hydrogel, composed of PEG-fibrin and collagen, to simultaneously co-differentiate adipose-derived stem cells1.

工程双层凝胶控制升序分化

Natural polymers over the years have gained more importance because of their host biocompatibility and ability to interact with cells in vitro and in ...

Fabrication and Application of Rose Bengal-chitosan Films in Laser Tissue Repair

Photochemical tissue bonding (PTB) is a sutureless technique for tissue repair, which is achieved by applying a solution of rose bengal (RB) between two tissue edges1,2. These are then irradiated by a laser that is selectively absorbed by the RB. The resulting photochemical reactions supposedly crosslink the collagen fibers in the tissue with minimal heat production3. In this report, RB has been incorporated in thin chitosan films to fabricate a novel tissue adhesive that is laser-activated. Adhesive films, based on chitosan and containing ~0.1 wt% RB, are fabricated and bonded to calf intestine and rat tibial nerves by a solid state laser (&lambda;=532 nm, Fluence~110 J/cm2, spot size~0.5 cm). A single-column tensiometer, interfaced with a personal computer, is used to test the bonding strength. The RB-chitosan adhesive bonds firmly to the intestine with a strength of 15 &plusmn; 6 kPa, (n=30). The adhesion strength drops to 2 &plusmn; 2 kPa (n=30) when the laser is not applied to the adhesive. The anastomosis of tibial nerves can be also completed without the use of sutures. A novel chitosan adhesive has been fabricated that bonds photochemically to tissue and does not require sutures.

Sutures are usually needed to repair tissue during surgical procedures. However, their application can be problematic as they are invasive and may damage tissue. The fabrication and application methods of a novel tissue adhesive are here reported. This adhesive film is laser-activated and does not require the use of sutures.

激光对生物组织的修复孟加拉玫瑰红壳聚糖膜的制备及应用

Photochemical tissue bonding (PTB) is a sutureless technique for tissue repair, which is achieved by applying a solution of rose bengal (RB) between two ...

Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair

Human induced pluripotent stem cells (hiPSCs) must be fully differentiated into specific cell types before administration, but conventional protocols for differentiating hiPSCs into cardiomyocytes (hiPSC-CMs), endothelial cells (hiPSC-ECs), and smooth muscle cells (SMCs) are often limited by low yield, purity, and/or poor phenotypic stability. Here, we present novel protocols for generating hiPSC-CMs, -ECs, and -SMCs that are substantially more efficient than conventional methods, as well as a method for combining cell injection with a cytokine-containing patch created over the site of administration. The patch improves both the retention of the injected cells, by sealing the needle track to prevent the cells from being squeezed out of the myocardium, and cell survival, by releasing insulin-like growth factor (IGF) over an extended period. In a swine model of myocardial ischemia-reperfusion injury, the rate of engraftment was more than two-fold greater when the cells were administered with the cytokine-containing patch comparing to the cells without patch, and treatment with both the cells and the patch, but not with the cells alone, was associated with significant improvements in cardiac function and infarct size.

We present three novel and more efficient protocols for differentiating human induced pluripotent stem cells into cardiomyocytes, endothelial cells, and smooth muscle cells and a delivery method that improves the engraftment of transplanted cells by combining cell injection with patch-mediated cytokine delivery.

多能干细胞衍生的心肌修复心肌细胞

Human induced pluripotent stem cells (hiPSCs) must be fully differentiated into specific cell types before administration, but conventional protocols for ...

发育生物学

Characterization of Leukocyte-platelet Rich Fibrin, A Novel Biomaterial

Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and have been extensively used in oral surgery. Unlike platelet rich plasma (PRP) that is a gel or a suspension, Leukocyte-Platelet Rich Fibrin (L-PRF) is a solid 3D fibrin membrane generated chair-side from whole blood containing no anti-coagulant. The membrane has a dense three dimensional fibrin matrix with enriched platelets and abundant growth factors. L-PRF is a popular adjunct in surgeries because of its superior handling characteristics as well as its suturability to the wound bed. The goal of the study is to demonstrate generation as well as provide detailed characterization of relevant properties of L-PRF that underlie its clinical success.

Leucocyte-Platelet Rich Fibrin (L-PRF) represents an FDA cleared preparation of autologous platelet concentrates that possesses unique fibrin architecture, enriched platelets and abundant growth factors. Here, we present a protocol for chair-side generation of L-PRF as well as evaluate its mechanical properties including uniaxial testing and suture retention strength testing.

白细胞 - 富血小板纤维蛋白，一种新型生物材料的表征

Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and have been extensively used in oral ...

Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery

During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone fusion. Large doses of highly potent biological agents are required due to growth factor instability as a result of rapid enzymatic degradation as well as carrier inefficiencies in localizing sufficient amounts of growth factor at implant sites. Hence, strategies that prolong the stability of growth factors such as BMP-2/NELL-1, and control their release could actually lower their efficacious dose and thus reduce the need for larger doses during future bone regeneration surgeries. This in turn will reduce side effects and growth factor costs. Self-assembled PECs have been fabricated to provide better control of BMP-2/NELL-1 delivery via heparin binding and further potentiate growth factor bioactivity by enhancing in vivo stability. Here we illustrate the simplicity of PEC fabrication which aids in the delivery of a variety of growth factors during reconstructive bone surgeries.

Self-assembled polyelectrolyte complexes (PEC) fabricated from heparin and protamine were deposited on alginate beads to entrap and regulate the release of osteogenic growth factors. This delivery strategy enables a 20-fold reduction of BMP-2 dose in spinal fusion applications. This article illustrates the benefits and fabrication of PECs.

聚电解质复合物肝素结合域成骨生长因子交货

During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone ...

A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.

The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of treatments in vivo1. The traditional, established protocol has been further fine-tuned to minimize the damage to the animal. Notably, the pectoral muscle layers are teased away rather than simply cut, and the thoracotomy is approached intercostally as opposed to breaking the ribs in a sternotomy, preserving the integrity of the ribcage. With these changes, the overall stress on the animal is decreased. 
Stem cell therapies aimed to alleviate the damage caused by MIs have shown promise over the years for their pro-angiogenic and anti-apoptotic benefits. Current approaches of delivering cells to the heart surface typically involve the injection of the cells either near the damaged site, within a coronary artery, or into the peripheral blood stream2-4. While the cells have proven to home to the damaged myocardium, functionality is limited by their poor engraftment at the site of injury, resulting in diffusion into the blood stream5. This manuscript highlights a procedure that overcomes this obstacle with the use of a cell-encapsulated hydrogel patch. The patch is fabricated prior to the surgical procedure and is placed on the injured myocardium immediately following the occlusion of the left coronary artery. To adhere the patch in place, biocompatible external fibrin glue is placed directly on top of the patch, allowing for it to dry to both the patch and the heart surface. This approach provides a novel adhesion method for the application of a delicate cell-encapsulating therapeutic construct.

This protocol aims to alleviate the limitation of poor cell engraftment for stem cell treatment of myocardial infarctions through the use of a hydrogel system and a fibrin-based glue. With this approach, cell-to-tissue contact post-infarction can be maintained, increasing the therapeutic potential of beneficial agents at the site of injury.

水凝胶构造和纤维蛋白基胶方法来提供治疗的小鼠心肌梗死模型。

The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of ...

医学

Synthesis of Strong Adhesive Hydrogel, Gelatin O-Nitrosobenzaldehyde

Adhesive materials have become popular biomaterials in the field of biomedical and tissue engineering. In our previous work, we presented a new material - gelatin o-nitrosobenzaldehyde (gelatin-NB) - which is mainly used for tissue regeneration and has been validated in animal models of corneal injury and inflammatory bowel disease. This is a novel hydrogel formed by modifying biological gelatin with o-nitrosobenzaldehyde (NB). Gelatin-NB was synthesized by activating the carboxyl group of NB-COOH and reacting with gelatin through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The obtained compound was purified to generate the final product, which can be stably stored for at least 18 months. NB has a strong adhesion to -NH2 on the tissue, which can form many C = N bonds, thus increasing the adhesion of gelatin-NB to the tissue interface. The preparation process comprises steps for the synthesis of the NB-COOH group, modification of the group, synthesis of gelatin-NB, and purification of the compound. The goal is to describe the specific synthesis process of gelatin-NB in detail and to demonstrate the application of gelatin-NB to damage repair. Moreover, the protocol is presented to further strengthen and expand the nature of the material produced by the scientific community for more applicable scenarios.

The protocol presented here shows the synthesis of a strong adhesive hydrogel gelatin o-nitrosobenzaldehyde (gelatin-NB). Gelatin-NB has rapid and efficient tissue adhesion ability, which can form a strong physical barrier to protect wound surfaces, so it is expected to be applied to the field of injury repair biotechnology.

强粘性水凝胶明胶O-亚硝基苯甲醛的合成

Adhesive materials have become popular biomaterials in the field of biomedical and tissue engineering. In our previous work, we presented a new material - ...

Occlusion of the Great and Small Saphenous Vein Using Copolymeric Glue Based on N-Butyl Cyanoacrylate and Methacryloxy Sulfolane

We present the preliminary results of a longitudinal observational study aimed at evaluating the effectiveness and safety at different short- and long-term follow-ups of vascular occlusion of the great saphenous vein (GSV) and small saphenous vein (SSV) affected by severe pathological reflux, using an innovative modified cyanoacrylate surgical glue composed of N-butyl cyanoacrylate and methacryloxy sulfolane (NBCA+MS). Ninety patients, prospectively recruited for 1 year, underwent the study with EcoColor-Doppler (ECD) to evaluate the maximum diameters of the GSV and SSV in the orthostatic position and the reflux time (RT). An RT greater than 0.5 s was considered pathologic. Clinical, etiology, anatomy, and pathophysiology (CEAP) assessment was used for the complete evaluation of each patient in the study. All the patients were treated by NBCA+MS glue to obtain vein occlusion and observed before treatment (baseline; T0), within 6 h after treatment (T1), 1 month after treatment (T2), 3 months after treatment (T3), 6 months after treatment (T4), and 1 year after treatment (T5). Chi-square (&#967;) analysis was performed to evaluate the effectiveness and safety of the treatment. All the patients participated in the entire duration of the study. Complete occlusion was maintained in 100% of patients at T1, 98.9% at T2 and T3, and 97.8% at T4 and T5 (p &lt; 0.001). None of the patients suffered from post-surgical thrombosis. No blue hyperpigmentation, or paresthesia was observed during the entire observation period. Immediately after treatment, 7.7% of patients needed painkillers; 1 week after treatment, 100% of patients returned to normal life. Vascular occlusion of the great or small saphenous vein using NBCA+MS glue is a safe procedure with persistent benefits after a 1 year follow-up. This procedure can be performed with local anesthesia, allowing a quick return to normal life. Thanks to its low invasiveness, the treatment is not painful.

Here, we present a protocol to treat the great saphenous vein (GSV) and the small saphenous vein (SSV) affected by severe pathological reflux, using an original sclerosing and embolizing cyanoacrylate-based glue composed of N-butyl cyanoacrylate and methacryloxy sulfolane (NBCA+MS).