Functional electrospun fibrous scaffolds with dextran-g-poly(l-lysine)-VAPG/microRNA-145 to specially modulate vascular SMCs.
Functional electrospun fibrous scaffolds with dextran-g-poly(l-lysine)-VAPG/microRNA-145 to specially modulate vascular SMCs.
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DOI：
10.1039/c7tb01755c
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发表时间：
2017-12
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影响因子：
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通讯作者：
Peiqiong Zhou;Fang Zhou;Bo Liu;Yunhui Zhao;Xiaoyan Yuan
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文献类型：
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作者：
Peiqiong Zhou;Fang Zhou;Bo Liu;Yunhui Zhao;Xiaoyan Yuan
通过microRNA（miRNAs）调控基因表达已成为科普心血管疾病的一种有前景的策略，而将功能性miRNAs靶向递送至特定的血管组织具有重要意义。通过引入Val-Ala-Pro-Gly（VAPG），一种特异性粘附于血管平滑肌细胞（SMC）的肽，将miRNAs局部递送至组织工程化血管移植物可能是一种流行的方法。本工作通过负载葡聚糖-g-聚赖氨酸-VAPG/miRNA-145（DPVm）复合物来调节SMC的表型和增殖，从而开发功能性电纺聚（丙交酯-共-乙交酯）（PLGA）膜。与血管内皮细胞相比，聚合物/miRNA-145复合物表现出轻微的细胞毒性、出色的血清稳定性和增强的SMC细胞摄取。将miRNA-145包封于电纺PLGA膜中，不仅具有良好的生物学活性，而且具有可控的释放特性。结果发现，静电纺丝膜能够支持SMCs的粘附和铺展。此外，在第3天，在基因和蛋白水平上检测到Krüppel样因子4表达的显著下调以及心肌蛋白和α-平滑肌肌动蛋白表达的上调。同时，由于miRNA-145的持续释放，SMCs以较低的增殖速率维持收缩表型。以聚（乙二醇）-b-聚（l-丙交酯-co-ε-己内酯）为内层、含DPVm复合物的PLGA为外层的功能性双层电纺支架替代兔颈动脉1个月，证明含miRNA-145的血管移植物也可有效地调节SMC表型。结果表明，将miRNA-145复合物包裹在小直径支架中可以作为防止血管组织再生过程中内膜增生的有效方法。
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.