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Abstract: 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.

北航刘海峰等 | 负载尼可地尔的聚己内酯/磺酸化丝素蛋白双层小口径人工血管的构建及对内皮功能的影响

本研究论文聚焦负载尼可地尔的聚己内酯/磺酸化丝素蛋白双层小口径人工血管的构建及对内皮功能的影响。冠状动脉旁路移植术是目前临床上治疗心血管疾病（CVD）的常规治疗手段之一，但目前临床上常用的小口径人工血管在移植后往往面临着难以自发内皮化和急性血栓形成的问题，最终导致人工血管再狭窄，远期通畅率不理想。因此，开发兼具抗凝活性与促内皮化活性的小口径人工血管来提高患者旁路移植后的远期通畅率具有重要意义。针对这一问题，本研究基于仿生策略使用聚己内酯和磺酸化丝素蛋白两种生物材料开发出了一种负载尼可地尔（NIC）的双层小口径人工血管（BLVG）。结果表明，NIC的加入在提高了BLVG内表面亲水性的同时没有影响其整体的力学性能。负载NIC的BLVG具有多种生物活性，有利于人工血管在移植后的自发内皮化，抑制急性血栓形成。而发挥这些活性的潜在生物学机制可能与BLVG能够激活内皮细胞中PI3K/Akt/eNOS信号通路有关。

（论文的第一作者为北京航空航天大学博士研究生邢正；清华大学博士研究生肇晨也对本研究做出了重要贡献；北京航空航天大学生物与医学工程学院刘海峰教授为该文章的通讯作者）