Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway
Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway
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双层负载尼可地尔的小直径血管移植物通过 PI3K/AKT/eNOS 途径改善内皮细胞功能
DOI：
10.1007/s42242-020-00107-2
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发表时间：
2021-03
影响因子：
7.9
通讯作者：
Liu Haifeng
中科院分区：
文献类型：
--
作者：
Xing Zheng;Zhao Chen;Zhang Chunchen;Fan Yubo;Liu Haifeng
对于心血管疾病（CVD）的外科治疗，在开发小直径（直径<6 mm）血管移植物方面存在明确且未满足的需求。硫酸化丝素蛋白（SF）具有良好的细胞相容性和血液相容性，在我们的前期工作中已被成功制备，成为制备血管移植物的潜在候选材料。然而，单层血管移植物难以适应复杂的内环境。本研究以聚己内酯（PCL）和硫酸化丝素纤维（SF）为原料，模拟天然血管结构，制备双层血管移植物（BVG）。为了增强BVG的生物活性，将FDA批准的具有多种生物活性的药物尼可地尔（NIC）负载到BVG中，以制备负载NIC的BVG。对镍基复合材料的形貌、化学组成和力学性能进行了研究。结果表明，载镍BVG的双层结构使其具有双相释药行为。体外研究表明，负载镍离子的BVG能显著增强内皮细胞的增殖、迁移和抗氧化能力。此外，我们还发现其潜在的生物学机制是PI 3 K/AKT/eNOS信号通路的激活。总体而言，结果有效地证明了负载NIC的BVG作为功能性小直径血管移植物具有有希望的体外性能。
For the surgical treatment of cardiovascular disease (CVD), there is a clear and unmet need in developing small-diameter (diameter<6 mm) vascular grafts. In our previous work, sulfated silk fibroin (SF) was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility. However, vascular graft with single layer is difficult to adapt to the complex internal environment. In this work, polycaprolactone (PCL) and sulfated SF were used to fabricate bilayer vascular graft (BLVG) to mimic the structure of natural blood vessels. To enhance the biological activity of BLVG, nicorandil (NIC), an FDA-approved drug with multi-bioactivity, was loaded in the BLVG to fabricate NIC-loaded BLVG. The morphology, chemical composition and mechanical properties of NIC-loaded BLVG were assessed. The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior. The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation, migration and antioxidation capability of endothelial cells (ECs). Moreover, we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway. Overall, the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
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