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用硅烷化生物墨水功能化的生物功能注入润滑剂的血管移植物可抑制凝血酶生成并促进内皮化。

Biofunctional Lubricant-Infused Vascular Grafts Functionalized with Silanized Bio-Inks Suppress Thrombin Generation and Promote Endothelialization.

作者信息

Badv Maryam, Alonso-Cantu Claudia, Shakeri Amid, Hosseinidoust Zeinab, Weitz Jeffrey I, Didar Tohid F

机构信息

Thrombosis & Atherosclerosis Research Institute (TaARI), 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

出版信息

ACS Biomater Sci Eng. 2019 Dec 9;5(12):6485-6496. doi: 10.1021/acsbiomaterials.9b01062. Epub 2019 Nov 8.

DOI:10.1021/acsbiomaterials.9b01062
PMID:33417801
Abstract

The ongoing problem with the thrombogenicity and poor tissue integration of synthetic vascular grafts demands the design of new surfaces that simultaneously suppress thrombosis and promote endothelialization. Lubricant-infused surfaces have shown outstanding results in preventing clot formation; however, their innate ability to completely block the surface, averts targeted binding of desired biomolecules. We report a new class of expanded polytetrafluoroethylene (ePTFE) vascular grafts that prevent blood coagulation and concurrently promote endothelial cell adhesion. This is made possible by direct silanization of anti-CD34 antibody with the coupling agent and subsequent conjugation of the silanized antibody to the ePTFE surface. In contrast to the conventional methods, we eliminated the need to chemically modify the ePTFE substrate for attaching the capturing ligand, and as a result preserved the innate surface properties of the ePTFE substrate. This is crucial for infiltrating the fluorine-based ePTFE substrate with a biocompatible perfluorocarbon-based lubricant and ultimately creating a functional and stable lubricant-infused layer. Compared to commercially available ePTFE vascular grafts and the ones coated using conventional methods, our developed ePTFE grafts significantly attenuate thrombin generation and blood clot formation and specifically capture endothelial cells from human whole blood while preventing nonspecific adhesion of undesirable proteins and cells. The developed technology can be applied to other biomarkers and biomaterials and can be tailored toward different biomedical applications where biofunctionality and targeted binding are of importance.

摘要

合成血管移植物的血栓形成性和较差的组织整合性这一持续存在的问题,要求设计出能同时抑制血栓形成并促进内皮化的新表面。注入润滑剂的表面在防止血栓形成方面已显示出卓越成效;然而,其完全封闭表面的固有能力,阻碍了所需生物分子的靶向结合。我们报告了一类新型的膨体聚四氟乙烯(ePTFE)血管移植物,它能防止血液凝固并同时促进内皮细胞黏附。这是通过用偶联剂对抗CD34抗体进行直接硅烷化,然后将硅烷化抗体与ePTFE表面共轭来实现的。与传统方法相比,我们无需对ePTFE基质进行化学修饰以连接捕获配体,从而保留了ePTFE基质的固有表面特性。这对于用生物相容性全氟碳基润滑剂渗透含氟的ePTFE基质并最终形成功能稳定的注入润滑剂层至关重要。与市售的ePTFE血管移植物以及用传统方法涂层的移植物相比,我们开发的ePTFE移植物能显著减弱凝血酶生成和血凝块形成,并能从人全血中特异性捕获内皮细胞,同时防止不需要的蛋白质和细胞的非特异性黏附。所开发的技术可应用于其他生物标志物和生物材料,并可针对生物功能和靶向结合至关重要的不同生物医学应用进行定制。

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