Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency.
Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency.
复制标题
肝素键合 P(LLA-CL) 复合纳米纤维制备小直径血管支架以改善移植物通畅
DOI：
10.2147/ijn.s44956
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发表时间：
2013
影响因子：
8
通讯作者：
Qiu LJ
中科院分区：
文献类型：
--
作者：
Wang S;Mo XM;Jiang BJ;Gao CJ;Wang HS;Zhuang YG;Qiu LJ
迄今为止，小直径血管移植术后通畅率低仍然是影响人工血管广泛临床应用的主要障碍。我们之前的研究发现，静电纺丝聚（l -乳酸-co-epsilon-己内酯）（P[la - cl]）纳米纤维促进内皮细胞（EC）的附着和生长，并且P（la - cl）纳米纤维中的肝素能够以可控的方式释放。因此，我们假设肝素结合P（la - cl）血管支架与自体EC预内皮化可以显著提高移植物的通畅率。为了构建小直径血管支架，内层采用肝素结合P（LLA-CL）纳米纤维同轴静电纺丝制备，外层采用纯P（LLA-CL）纳米纤维编织。除了动态顺应性（5.4 1.7 vs 12.8 2.4 × 10−4/mmHg, P < 0.05）、最大抗拉强度、破裂压力和缝线保留度外，复合材料支架与犬股动脉支架相当。体外研究表明，该支架可以连续释放肝素至少12周，并通过动态孵育获得理想的内皮化，EC活力和增殖实验及扫描电镜证实了这一点。此外，体内研究表明，与肝素负荷相比，自体内皮细胞预内皮化对移植物的通畅率有更好的影响，并且在犬股动脉置换术模型中，预内皮化和肝素负荷联合应用可显著提高P（LLA-CL）支架24周的通畅率（88.9%，对照组12.5%,P < 0.05）。这些结果表明肝素结合P（la - cl）支架具有与天然动脉相似的生物力学特性，并且具有多孔和生物相容性表面，可以在体外实现令人满意的内皮化。自体EC预内皮化的肝素结合P（la - cl）支架在计划血管搭桥手术中有可能成为天然小直径血管的替代品。
The poor patency rate following small-diameter vascular grafting remains a major hurdle for the widespread clinical application of artificial blood vessels to date. Our previous studies found that electrospun poly(L-lactide-co-epsilon-caprolactone) (P[LLA-CL]) nanofibers facilitated the attachment and growth of endothelial cells (EC), and heparin incorporated into P(LLA-CL) nanofibers was able to release in a controlled manner. Hence, we hypothesized that heparin-bonded P(LLA-CL) vascular scaffolds with autologous EC pre-endothelialization could significantly promote the graft patency rate. To construct a small-diameter vascular scaffold, the inner layer was fabricated by heparin-bonded P(LLA-CL) nanofibers through coaxial electrospinning, while the outer layer was woven by pure P(LLA-CL) nanofibers. Except dynamic compliance (5.4 1.7 versus 12.8 2.4 × 10−4/mmHg, P < 0.05), maximal tensile strength, burst pressure, and suture retention of the composite, scaffolds were comparable to those of canine femoral arteries. In vitro studies indicated that the scaffolds can continuously release heparin for at least 12 weeks and obtain desirable endothelialization through dynamic incubation, which was confirmed by EC viability and proliferation assay and scanning electronic microscopy. Furthermore, in vivo studies demonstrated that pre-endothelialization by autologous ECs provided a better effect on graft patency rate in comparison with heparin loading, and the united application of pre-endothelialization and heparin loading markedly promoted the 24 weeks patency rate of P(LLA-CL) scaffolds (88.9% versus 12.5% in the control group, P < 0.05) in the canine femoral artery replacement model. These results suggest that heparin-bonded P(LLA-CL) scaffolds have similar biomechanical properties to those of native arteries and possess a multiporous and biocompatible surface to achieve satisfactory endothelialization in vitro. Heparin-bonded P(LLA-CL) scaffolds with autologous EC pre-endothelialization have the potential to be substitutes for natural small-diameter vessels in planned vascular bypass surgery.