Heparin-Modified Small-Diameter Nanofibrous Vascular Grafts

Heparin-Modified Small-Diameter Nanofibrous Vascular Grafts
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DOI:
10.1109/tnb.2012.2188926
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发表时间:
2012-03-01
影响因子:
3.9
通讯作者:
Li, Song
Li, Song
中科院分区:
生物学3区
文献类型:
--
作者:
Janairo, Randall Raphael R.;Henry, Jeffrey J. D.;Li, Song

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由于血管旁路手术的高发生率,存在对合适的血管置换的未满足的需求,特别是对于小直径(<6mm)血管移植物。在这里,我们通过静电纺丝生产了直径为1 mm的具有纳米纤维结构的血管移植物,并通过使用二氨基聚乙二醇(PEG)作为连接体的肝素缀合成功地修饰了纳米纤维。这些肝素修饰的支架的抗血栓形成活性在体外得到证实。使用大鼠颈总动脉旁路模型植入1个月后,肝素修饰的移植物显示85.7%的通畅率,而PEG化移植物的通畅率为57.1%,未处理移植物的通畅率为42.9%。移植物的取出后分析显示管腔完全内皮化,移植物周围新生血管形成。周围新生组织中可见平滑肌细胞。此外,在肝素修饰的移植物中观察到更大的细胞浸润。这些发现表明肝素修饰可能在纳米纤维血管移植物的功能和重塑中发挥多种作用,通过预防血栓形成和保持通畅性,以及通过促进细胞浸润到三维纳米纤维结构中进行重塑。
Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter (< 6 mm)vascular grafts. Here we produced 1-mm diameter vascular grafts with nanofibrous structure via electrospinning, and successfully modified the nanofibers by the conjugation of heparin using di-amino-poly(ethylene glycol) (PEG) as a linker. Antithrombogenic activity of these heparin-modified scaffolds was confirmed in vitro. After 1 month implantation using a rat common carotid artery bypass model, heparin-modified grafts exhibited 85.7% patency, versus 57.1% patency of PEGylated grafts and 42.9% patency of untreated grafts. Post-explant analysis of patent grafts showed complete endothelialization of the lumen and neovascularization around the graft. Smooth muscle cells were found in the surrounding neo-tissue. In addition, greater cell infiltration was observed in heparin-modified grafts. These findings suggest heparin modification may play multiple roles in the function and remodeling of nanofibrous vascular grafts, by preventing thrombosis and maintaining patency, and by promoting cell infiltration into the three-dimensional nanofibrous structure for remodeling.