Local Delivery of Dual miRNAs in Trilayered Electrospun Grafts for Vascular Regeneration.
Local Delivery of Dual miRNAs in Trilayered Electrospun Grafts for Vascular Regeneration.
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在三层电纺移植物中局部递送双 miRNA 以实现血管再生。
DOI：
10.1021/acsami.9b19452
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Yuan Xiaoyan
中科院分区：
文献类型：
--
作者：
Wen Meiling;Zhi Dengke;Wang Lina;Cui Ce;Huang Ziqi;Zhao Yunhui;Wang Kai;Kong Deling;Yuan Xiaoyan
全球日益严重的心血管疾病问题导致对合成血管移植物的相当大的需求。对于小口径人工血管，实现快速内皮化、抑制内膜增生、防止钙化是保持通畅的关键。为了调节血管再生，本文中，我们开发了生物活性三层组织工程化血管移植物，其分别在纤维内层和中间层中包封miRNA-126和miRNA-145。体外细胞活性研究表明，三层电纺膜具有明显的生物学优势，可促进血管内皮细胞的生长和细胞内一氧化氮的产生，调节血管平滑肌细胞（SMC）的表型，并通过快速释放miRNA-126和缓慢释放miRNA-145抑制钙沉积。在大鼠腹主动脉间置模型中体内植入的组织学和免疫荧光分析表明，双miRNA负载的三层电纺移植物对加速内皮化、改善收缩性SMC再生和促进正常细胞外基质形成具有积极作用。同时，miRNA-126和miRNA-145在三层血管移植物中的局部生物活性可能通过促进巨噬细胞转化为抗炎M2表型来调节炎症和抑制钙化。这些结果表明，通过局部递送双miRNA的三层电纺移植物可能用作人工小口径血管替代物的生物活性替代物。
Globally growing problems in cardiovascular diseases lead to a considerable need of synthetic vascular grafts. For small-caliber vascular prosthesis, it remains essential to fulfill rapid endothelialization, inhibit intimal hyperplasia and prevent calcification for keeping patency. To modulate vascular regeneration, herein, we developed a bioactive trilayered tissue-engineered vascular graft encapsulating both miRNA-126 and miRNA-145 in the fibrous inner and middle layers, respectively. In vitro cell activities demonstrated that the trilayered electrospun membranes had significantly biological advantages in enhanced growth and intracellular nitric oxide production of vascular endothelial cells, modulation of phenotypes of vascular smooth muscle cells (SMCs) and restraint of calcium deposition through fast-releasing miRNA-126 and slow-releasing miRNA-145. Histological and immunofluorescent analyses of in vivo implantation in a rat abdominal aorta interposition model suggested that the dual-miRNA-loading trilayered electrospun graft exerted a positive effect on accelerating endothelialization, improving contractile SMC regeneration, and promoting normal extracellular matrix formation. Meanwhile, the local bioactivity of miRNA-126 and miRNA-145 in the trilayered vascular graft could regulate inflammation and depress calcification possibly by facilitating transformation of macrophages into the anti-inflammatory M2 phenotype. These findings indicated that the trilayered electrospun graft by local delivery of dual miRNAs could be possibly used as a bioactive substitute for replacement of artificial small-caliber blood vessels.
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DOI：
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发表时间：
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期刊：
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影响因子：
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