Modulation of gene expression via microRNAs (miRNAs) has been attractive as one of the promising strategies to cope with cardiovascular diseases, and the target-delivery of functional miRNAs to a specific vascular tissue is of importance. By the incorporation of Val-Ala-Pro-Gly (VAPG), a specific adhesive peptide to vascular smooth muscle cells (SMCs), local delivery of miRNAs to tissue-engineered vascular grafts could be a prevailing approach. In this work, functional electrospun poly(lactide-co-glycolide) (PLGA) membranes were developed by loading dextran-g-poly(l-lysine)-VAPG/miRNA-145 (DPVm) complexes to modulate the phenotype and proliferation of SMCs. The polymer/miRNA-145 complexes exhibited trivial cytotoxicity, excellent serum stability and enhanced cellular uptake by SMCs, over the vascular endothelial cells. When encapsulated into the electrospun PLGA membrane, miRNA-145 presented controlled release as well as good biological activity. It was found that the electrospun membranes were able to support the adhesion and spreading of SMCs. In addition, significant down-regulation of Krüppel-like factor 4 expression and up-regulation of myocardin and α-smooth muscle actin expression at both the gene and protein levels were detected on day 3. Meanwhile, due to the sustained release of miRNA-145, SMCs maintained the contractile phenotype at a slow proliferation rate compared with the negative control. One month of replacement of rabbit carotid artery by the functional bilayer electrospun scaffold, which was prepared with poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) as the inner layer and PLGA containing DPVm complexes as the outer layer, demonstrated that the vascular graft containing miRNA-145 could also be efficient for modulating the SMC phenotype in vivo. It was suggested that encapsulation of miRNA-145 complexes in small-diameter scaffolds could serve as an effective approach to prevent intimal hyperplasia during vascular tissue regeneration.

中文翻译：

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具有右旋糖酐-g-聚（1-赖氨酸）-VAPG / microRNA-145的功能性电纺纤维支架，可专门调节血管SMC。

作为应对心血管疾病的有前途的策略之一，通过microRNA（miRNA）调节基因表达已具有吸引力，并且功能性miRNA靶向递送至特定血管组织非常重要。通过掺入Val-Ala-Pro-Gly（VAPG）（一种特异性粘附肽到血管平滑肌细胞（SMC）），将miRNA局部递送到组织工程化的血管移植物中可能是一种流行的方法。在这项工作中，通过加载葡聚糖-g-聚（1-赖氨酸）-VAPG / miRNA-145（DPVm）复合物来调节SMCs的表型和增殖，开发了功能性电纺丙交酯-乙交酯共聚物（PLGA）膜。 。与血管内皮细胞相比，聚合物/ miRNA-145复合物表现出微不足道的细胞毒性，出色的血清稳定性和被SMC吸收的细胞。当封装到静电纺丝PLGA膜中时，miRNA-145表现出控制释放以及良好的生物学活性。发现电纺膜能够支持SMC的粘附和扩散。此外，在第3天检测到了Krüppel样因子4表达的显着下调以及基因和蛋白质水平的心肌素和α平滑肌肌动蛋白表达的上调。同时，由于miRNA- 145，与阴性对照相比，SMC以缓慢的增殖速率维持收缩表型。用双层功能性电纺丝支架置换兔颈动脉一个月，该双层电纺丝支架以聚（乙二醇）-b-聚（l-丙交酯-co-ε-己内酯）为内层，以含有DPVm配合物的PLGA为材料制备。外层 证明含miRNA-145的血管移植物也可有效调节体内SMC表型。有人提出，在小直径支架中封装miRNA-145复合物可以作为预防血管组织再生过程中内膜增生的有效方法。