Improved Hemocompatibility and Endothelialization of Vascular Grafts by Covalent Immobilization of Sulfated Silk Fibroin on Poly(lactic-co-glycolic acid) Scaffolds
Improved Hemocompatibility and Endothelialization of Vascular Grafts by Covalent Immobilization of Sulfated Silk Fibroin on Poly(lactic-co-glycolic acid) Scaffolds
复制标题
通过将硫酸化丝素蛋白共价固定在聚乳酸-乙醇酸支架上改善血管移植物的血液相容性和内皮化
DOI：
10.1021/bm200479f
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发表时间：
2011-08-01
影响因子：
6.2
通讯作者：
Fan, Yubo
中科院分区：
文献类型：
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作者：
Liu, Haifeng;Li, Xiaoming;Fan, Yubo
植入前血管移植物的内皮化已被广泛研究，以增强生物相容性和抗血栓形成性。人工血管的血栓形成通常是由于暴露于血液循环的剪切应力时内皮细胞脱离后血小板粘附和聚集引起的。因此，本研究旨在在内皮完全融合之前防止血小板粘附和聚集到生物材料上。我们报告了聚乳酸-乙醇酸 (PLGA) 支架的这种修饰，既可以赋予血液相容性，在内皮完全汇合之前防止血小板粘附和聚集，又可以支持 EC 生长以加速内皮化。该修饰是通过使用 γ 辐射将硫酸化丝素蛋白共价固定在 PLGA 支架上来实现的。使用磷酸盐缓冲盐水（PBS）作为老化介质，结果表明，γ辐照制备的支架对硫酸化丝素蛋白具有良好的保留作用。系统性体外血液相容性评价显示，硫酸化丝素蛋白共价固定PLGA（S-PLGA）支架可减少血小板粘附和活化，延长全血凝血时间、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）和凝血酶原时间（PT）。为了进一步评估支架的体外细胞相容性，我们将血管内皮细胞接种在支架上并培养2周。 ECs 在 S-PLGA 支架上附着和增殖良好，形成尺寸逐渐增大的细胞聚集体，并与相邻细胞聚集体融合，形成覆盖支架表面的单层。此外，通过基因转录水平和EC特异性标记物的蛋白表达表明，S-PLGA支架上的ECs的细胞功能比S-PLGA支架上的细胞功能得到了更好的保存。 PLGA 支架上的那些。因此，这项研究描述了血管移植物的产生，该血管移植物具有独特的能力，可以表现出优异的血液相容性，同时支持广泛的内皮化。
Endothelialization of vascular grafts prior to implantation has been investigated widely to enhance biocompatibility and antithrombogenicity. Thrombosis of artificial vessels is typically caused by platelet adhesion and agglomeration following endothelial cells detachment when exposed to the shear stress of blood circulation. The present study thus aimed at preventing platelet adhesion and aggregation onto biomaterials before the endothelial confluence is fully achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA) scaffolds, both to impart hemocompatibility to prevent platelet adhesion and aggregation before the endothelial confluence is fully achieved and to support EC growth to accelerate endothelialization. The modification was achieved by covalent immobilization of sulfated silk fibroin on PLGA scaffolds using gamma irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was demonstrated that the scaffolds prepared by gamma irradiation had a good retention of sulfated silk fibroin. The systematic in vitro hemocompatibility evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S-PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood clotting time, activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks. The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming cell aggregates that gradually increased in size and fused with adjacent cell aggregates to form a monolayer covering the scaffold surface. Moreover, it was demonstrated through the gene transcript levels and the protein expressions of EC-specific markers that the cell functions of ECs on S-PLGA scaffolds were better preserved than. those on PLGA scaffolds. Therefore, this study has described the generation of a vascular graft that possesses the unique ability to display excellent hemocompatibility while simultaneously supporting extensive endothelialization.