Effect of alkyl chain length on the interfacial strength of surgical sealants composed of hydrophobically-modified Alaska-pollock-derived gelatins and poly(ethylene)glycol-based four-armed crosslinker

Effect of alkyl chain length on the interfacial strength of surgical sealants composed of hydrophobically-modified Alaska-pollock-derived gelatins and poly(ethylene)glycol-based four-armed crosslinker
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DOI:
10.1016/j.colsurfb.2016.06.017
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发表时间:
2016-10-01
影响因子:
5.8
通讯作者:
Taguchi, Tetsushi
Taguchi, Tetsushi
中科院分区:
工程技术2区
文献类型:
--
作者:
Mizuta, Ryo;Ito, Temmei;Taguchi, Tetsushi

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外科封闭剂在临床上有着广泛的应用。纤维蛋白密封胶是一种常用的密封胶,但在手术中潮湿的条件下效果不佳。在这项研究中,我们开发了由疏水修饰的阿拉斯加鳕鱼衍生明胶(Hm-ApGltns)和聚乙二醇基四臂交联剂(4S-PEG)组成的手术密封剂。用新鲜的猪血管对hM-ApGltns密封胶的破裂强度进行了评价,发现当ApGltn的氨基取代率约为10mol%时,随着烷基链长的增加,该密封剂的破裂强度从167+/-22增加到299+/-43 mm Hg。硬脂酰基改性的ApGltn(Ste-ApGltn)/4S-PEG型密封胶的耐爆强度最高,是原来的ApGltn(Org-ApGltn)/4S-PEG型密封胶的3倍,是商品纤维蛋白密封胶的10倍。StE-ApGltn/4S-PEG型封闭剂在8周内在大鼠皮下组织内降解,无严重炎症反应。通过表面等离子体共振的分子相互作用分析,发现Ste-ApGltn与纤维连接蛋白的结合常数是Org-ApGltn的9倍。因此,所研制的密封胶,特别是STE-ApGltn/4S-PEG基密封胶,在心血管外科和胸科手术领域具有潜在的应用前景。(C)2016爱思唯尔B.V.保留所有权利。
Surgical sealants are widely used clinically. Fibrin sealant is a commonly used sealant, but is ineffective under wet conditions during surgery. In this study, we developed surgical sealants composed of hydrophobically modified Alaska-pollock-derived gelatins (hm-ApGltns) with different alkyl chain lengths from C3 to C18 and a poly(ethylene)glycol-based 4-armed crosslinker (4S-PEG). The burst strength of the hm-ApGltns-based sealant was evaluated using a fresh porcine blood vessel and was found to increase with increasing alkyl chain length from 167 +/- 22 to 299 +/- 43 mmHg when the substitution ratio of amino groups of ApGltn was around 10 mol%. The maximum burst strength was observed when stearoyl-group modified ApGltn (Ste-ApGltn)/4S-PEG-based sealant was used, displaying 3-fold higher burst strength than the original ApGltn (Org-ApGltn)/4S-PEG sealant, and 10-fold higher than the commercial fibrin sealant. Ste-ApGltn/4S-PEG-based sealant was biodegraded in rat subcutaneous tissue within 8 weeks without severe inflammation. By molecular interaction analysis using surface plasmon resonance, the binding constant of Ste-ApGltn to fibronectin was found to be 9-fold higher than that of Org-ApGltn. Therefore, the developed sealant, in particular the Ste-ApGltn/4S-PEG-based sealant, has potential applications in the field of cardiovascular surgery as well as thoracic surgery. (C) 2016 Elsevier B.V. All rights reserved.