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

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31771058, 32071359, 11421202, 61227902 and 11120101001), National Key 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) and Fundamental Research Funds for the Central Universities.

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  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

    Zheng Xing, Yubo Fan & Haifeng Liu

  2. School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China

    Chen Zhao

  3. Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027, China

    Chunchen Zhang

  4. Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, 310027, China

    Chunchen Zhang

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  1. Zheng Xing
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Contributions

ZX and HFL took part in conceptualization; ZX, CCZ and HFL contributed to methodology; ZX and CZ carried out investigation; ZX wrote the original draft; all authors wrote, reviewed and edited the final manuscirpt; HFL acquired funding; YBF and HFL contributed to resources; and HFL conducted supervision.

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Correspondence to Haifeng Liu.

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Zheng Xing, Chen Zhao, Chunchen Zhang, Yubo Fan and Haifeng Liu declare that they have no conflict of interest.

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All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.

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Xing, Z., Zhao, C., Zhang, C. et al. Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway. Bio-des. Manuf. 4, 72–86 (2021). https://doi.org/10.1007/s42242-020-00107-2

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