Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway  

作　　者：Zheng Xing Chen Zhao Chunchen Zhang Yubo Fan Haifeng Liu 

机构地区：[1]Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education,School of Biological Science and Medical Engineering,Beijing Advanced Innovation Centre for Biomedical Engineering,Beihang University,Xue Yuan Road No.37,Haidian District,Beijing 100191,China [2]School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China [3]Key Laboratory of Biomedical Engineering of Ministry of Education,Zhejiang University,Hangzhou 310027,China [4]Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal,Zhejiang University,Hangzhou 310027,China

出　　处：《Bio-Design and Manufacturing》2021年第1期72-86,共15页生物设计与制造（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(31771058,32071359,11421202,61227902 and 11120101001);NationalKey Technology R&D Program(2016YFC1100704,2016YFC1101101);International Joint Research Center of Aerospace Biotechnology and Medical Engineering from Ministry of Science and Technology of China;111 Project(B13003);Research Fund for the Doctoral Program of Higher Education of China(20131102130004);Fundamental Research Funds for the Central Universities.

摘　　要：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.

关 键 词：Bilayer vascular grafts NICORANDIL Sulfated silk fibroin Endothelial cell function PI3K/AKT/eNOS pathway 

分 类 号：TQ317[化学工程—高聚物工业] R318.08[医药卫生—生物医学工程]