Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway
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RESEARCH ARTICLE
Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway Zheng Xing1 · Chen Zhao2 · Chunchen Zhang3,4 · Yubo Fan1 · Haifeng Liu1 Received: 9 September 2020 / Accepted: 24 October 2020 © Zhejiang University Press 2020
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. Keywords Bilayer vascular grafts · Nicorandil · Sulfated silk fibroin · Endothelial cell function · PI3K/AKT/eNOS pathway
Introduction Cardiovascular disease (CVD) is still the primary cause of morbidity and mortality worldwide, and coronary artery disease (CAD) is the most extrusive form of CVD [1, 2]. Occlusion of blood vessels is the main reason of CVD, which impedes blood supply to crucial organs. Coronary artery bypass grafting (CABG) is commonly used in therapeutic
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Haifeng Liu [email protected]
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
strategies of CVD [3]. Surgeons often consider autologous vessels such as saphenous vein as their first choice for CABG. However, donor-site morbidity and autologous vascular deficiency l
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