Small-diameter vascular grafts hold great promise as potential substitutes for coronary and peripheral arteries. However, their clinical availability is hindered by thrombogenicity and intimal hyperplasia. Herein, bilayer vascular grafts with enhanced antithrombogenicity and endothelialization were developed by two-step electrospinning technology. First, the well-designed recombinant human type III collagen (rhCOLIII), featuring numerous triplets that promote cell adhesion while excluding sequences prone to platelet adhesion and activation, was composited with poly(L-lactide-co-ε-caprolactone) (PLCL) to create a bioactive inner layer. Afterward, a pure PLCL outer layer with exceptional elasticity was constructed to provide mechanical support. In vitro antiplatelet and cytocompatibility experiments revealed that the graft containing 60% rhCOLIII exhibited almost no platelet adhesion, while the number of adhered endothelial cells increased approximately 20 times compared to pure PLCL. Furthermore, Beagle dog femoral artery implantation models demonstrated that the rhCOLIII-modified grafts underwent endothelialization within three months, contributing to the patency of grafts. The potential mechanism for enhanced endothelialization by rhCOLIII was investigated through transcriptome sequencing and verified by an integrated analysis of gene and protein expression. The cell-affinity units, Gly-Glu-Arg (GER) and Gly-Glu-Lys (GEK) triplets, present in rhCOLIII contribute to initial adhesion of endothelial cells. Following adhesion, they may upregulate the expression of integrins αVβ8 on the cell surface, thereby further enhancing cell adhesion. Subsequently, the FAK/PI3K/AKT pathway within endothelial cells may also be activated to promote cell proliferation.

中文翻译：

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优化小直径血管移植物：利用重组人 III 型胶原 (rhCOLIII) 的力量来增强抗血小板和内皮化性能


小直径血管移植物作为冠状动脉和外周动脉的潜在替代品具有广阔的前景。然而，它们的临床可用性受到血栓形成和内膜增生的阻碍。在此，通过两步静电纺丝技术开发了具有增强的抗血栓形成和内皮化能力的双层血管移植物。首先，精心设计的重组人 III 型胶原 (rhCOLIII) 与聚 (L-丙交酯 - ε - 己内酯) (PLCL) 复合，具有许多促进细胞粘附的三联体，同时排除了容易血小板粘附和激活的序列。创建生物活性内层。随后，构建了具有卓越弹性的纯 PLCL 外层以提供机械支撑。体外抗血小板和细胞相容性实验表明，含有60% rhCOLIII的移植物几乎没有血小板粘附，而粘附的内皮细胞数量比纯PLCL增加了约20倍。此外，Beagle 犬股动脉植入模型表明，rhCOLIII 修饰的移植物在三个月内经历了内皮化，有助于移植物的通畅。通过转录组测序研究了 rhCOLIII 增强内皮化的潜在机制，并通过基因和蛋白质表达的综合分析进行验证。 rhCOLIII 中存在的细胞亲和单位 Gly-Glu-Arg (GER) 和 Gly-Glu-Lys (GEK) 三联体有助于内皮细胞的初始粘附。粘附后，它们可能上调细胞表面整合素αVβ8的表达，从而进一步增强细胞粘附。随后，内皮细胞内的FAK/PI3K/AKT通路也可能被激活，促进细胞增殖。