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Abstract: Rapid formation of a continuous endothelial cell (EC) monolayer with healthy endothelium function on the luminal surface of vascular implants is imperative to improve the longtime patency of small-diameter vascular implants. In the present study, we combined the contact guidance effects of aligned nanofibers, which enhance EC adhesion and proliferation because of its similar fiber scale with native vascular basement membranes, and aligned microfibers, which could induce EC elongation effectively and allow ECs infiltration. It was followed by successive immobilization of collagen IV and laminin to fabricate a biomimetic basement membrane (BBM) with structural and compositional biomimicry. The hemolysis assay and platelet adhesion results showed that the BBM exhibited excellent hemocompatibility. Meanwhile, the adhered human umbilical vein endothelial cells (HUVECs) onto the BBM aligned along the orientation of the microfibers with an elongated morphology, and the data demonstrated that the BBM showed favorable effects on EC attachment, proliferation, and viability. The oriented EC monolayer formed on the BBM exhibited improved antithrombotic capability as indicated by higher production of nitric oxide and prostacyclin (PGI2). Furthermore, fluorescence images indicated that HUVECs could infiltrate into the BBM, implying the BBM’s ability to enhance transmural endothelialization. Hence, the BBM possessed the properties to regulate EC behaviors and allow transmural ingrowth, demonstrating the potential to be applied as the luminal surface of small-diameter vascular implants for rapid endothelialization.

东华大学王璐、威斯康星大学麦迪逊分校Lih-Sheng Turng等 | 构建仿生血管基底膜促进血管移植物原位内皮化

本研究论文聚焦IV型胶原/层粘连蛋白修饰取向微/纳混合纤维构建仿生血管基底膜。远期通畅率不佳是限制小口径血管移植物临床应用转化的主要因素，促进其内表面的快速原位内皮化是解决此问题的理想方式。体内，内皮层粘附于血管基底膜。鉴于此，本文基于天然血管基底膜的拓扑结构和化学组成构建了一种取向微/纳混合纤维膜，并接枝引入IV型胶原和层粘连蛋白制备仿生血管基底膜，以期促进原位内皮化。微/纳混合纤维膜兼具取向纳米纤维和取向微米纤维对HUVECs的接触引导作用，其中直径为73 nm的取向PCL纳米纤维与天然血管基底膜的纤维尺度相近，直径为2.7 μm的取向PCL微米纤维的存在则可以有效引导HUVECs取向伸长。同时，IV型胶原/层粘连蛋白共接枝引入可以提升HUVECs的粘附、增殖、活性、一氧化氮和前列环素释放能力等。另一方面，此仿生血管基底膜整体结构松散，孔隙较大，允许HUVECs渗入迁移，这是跨壁毛细血管化发生的前提。综上所述，本文设计制备的仿生血管基底膜具有促进原位内皮化的潜力，可以作为小口径血管移植物的内层。