Surface-modified bioresorbable electrospun scaffolds for improving hemocompatibility of vascular grafts

Surface-modified bioresorbable electrospun scaffolds for improving hemocompatibility of vascular grafts
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DOI:
10.1016/j.msec.2017.02.151
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发表时间:
2017-06-01
影响因子:
7.9
通讯作者:
Alvarez-Lorenzo, Carmen
Alvarez-Lorenzo, Carmen
中科院分区:
工程技术1区
文献类型:
--
作者:
Caracciolo, Pablo C.;Isabel Rial-Hermida, Maria;Alvarez-Lorenzo, Carmen

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小直径血管的替代是组织工程中的主要挑战之一。此外,小直径血管移植物(SDVG)的表面修饰是治疗成功的关键因素,因为它们由于缺乏功能性内皮而增加了血栓形成能力和感染易感性。本工作以聚乳酸-L(PLLA)和链段聚氨酯(PHD)共混物为原料,制备了具有SDVG内层性能的电纺支架。然后,按照两种不同的策略成功地用肝素对支架进行表面修饰,这两种策略依赖于将肝素嫁接到PLLA或PHD官能团上。这两种方法都提供了较高的肝素密度,对于乌拉坦方法学来说更高。功能化支架未引起溶血,并在很大程度上抑制了血小板的黏附。然而,通过乌拉坦方法获得的溶菌酶/肝素功能化支架获得了最高的血小板黏附抑制。表面功能化纳米结构的亲水性和吸水率的增加有利于人脂肪干细胞的黏附和增殖。与溶菌酶结合的肝素化表面表现出依赖于肝素含量的微生物水解活性。总体而言,氨基甲酸酯改性支架的性能更好,再加上氨基甲酸酯法不涉及断链,使后者成为PLLA/PHD 50/50电纺支架表面改性的最佳选择。通过这种途径功能化的支架可以作为适用于血管组织工程的SDVG的高级组件,表现出仿生行为,避免血栓形成,并提供抗菌功能。(C)2017爱思唯尔B.V.保留所有权利。
The replacement of small-diameter vessels is one of the main challenges in tissue engineering. Moreover, the surface modification of small-diameter vascular grafts (SDVG) is a key factor in the success of the therapy due to their increased thrombogenicity and infection susceptibility caused by the lack of a functional endothelium. In this work, electrospun scaffolds were prepared from blends of poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) with a composition designed to perform as SDVG inner layer. The scaffolds were then successfully surface-modified with heparin following two different strategies that rely on grafting of heparin to either PLLA or PHD functional groups. Both strategies afforded high heparin density, being higher for urethane methodology. The functionalized scaffolds did not cause hemolysis and inhibited platelet adhesion to a large extent. However, lysozyme/heparin-functionalized scaffolds obtained through urethane methodology achieved the highest platelet attachment inhibition. The increase in hydrophilicity and water absorption of the surfacefunctionalized nanostructures favored adhesion and proliferation of human adipose-derived stem cells. Heparinized surfaces conjugated with lysozyme presented microbial hydrolysis activity dependent on heparin content. Overall, a better performance obtained for urethane-modified scaffold, added to the fact that no chain scission is involved in urethane methodology, makes the latter the best choice for surface modification of PLLA/PHD 50/50 electrospun scaffolds. Scaffolds functionalized by this route may perform as advanced components of SDVG suitable for vascular tissue engineering, exhibiting biomimetic behavior, avoiding thrombi formation and providing antimicrobial features. (C) 2017 Elsevier B.V. All rights reserved.