Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts.

Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts.
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DOI:
10.1016/j.actbio.2014.07.031
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发表时间:
2014-11
期刊:
影响因子:
9.7
通讯作者:
Hong, Yi
Hong, Yi
中科院分区:
工程技术1区
文献类型:
--
作者:
Punnakitikashem, Primana;Danh Truong;Menon, Jyothi U.;Nguyen, Kytai T.;Hong, Yi

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脱细胞生物可降解小直径血管移植物(SDVG)需要抗血栓形成、抑制内膜增生和快速内皮化以提高移植物的通畅性。然而,目前的抗血栓形成和抗增殖方法往往与SDVG上的内皮细胞层形成相冲突。为了解决这一限制,将可生物降解的弹性聚氨酯脲(BPU)和药物双嘧达莫(DPA)混合,然后静电纺丝成可生物降解的纤维支架。BPU将提供适当的机械支撑,而支架中的DPA将提供上述所需的生物功能。我们发现所得到的支架具有与人冠状动脉相当的拉伸强度和应变。支架中的DPA在37 °C下在磷酸盐缓冲溶液中连续释放长达91天,在前3天内具有低突释。与单独的BPU相比,负载DPA的BPU支架的改善的非血栓形成性被证明具有延长的人凝血时间、较低达特复合物浓度、较低的溶血和减少的人血小板沉积。DPA含量较高(5%和10%)的支架对人主动脉平滑肌细胞的增殖有明显的抑制作用。此外,DPA负载的支架对人主动脉内皮细胞的生长没有不利影响,但它促进了它们的增殖。DPA负载的BPU支架具有吸引人的机械性能和生物功能,表明其作为血管替代物的脱细胞生物降解SDVG的潜力。
Acellular biodegradable small diameter vascular grafts (SDVGs) require antithrombosis, intimal hyperplasia inhibition and rapid endothelialization to improve the graft patency. However, current antithrombosis and antiproliferation approaches often conflict with endothelial cell layer formation on SDVGs. To address this limitation, biodegradable elastic polyurethane urea (BPU) and the drug dipyridamole (DPA) were mixed and then electrospun into a biodegradable fibrous scaffold. The BPU would provide the appropriate mechanical support, while the DPA in the scaffold would offer biofunctions as required above. We found that the resulting scaffolds had tensile strengths and strains comparable with human coronary artery. The DPA in the scaffolds was continuously released up to 91 days in phosphate buffer solution at 37 °C, with a low burst release within the first 3 days. Compared to BPU alone, improved non-thrombogenicity of the DPA-loaded BPU scaffolds was evidenced with extended human blood clotting time, lower TAT complex concentration, lower hemolysis and reduced human platelet deposition. The scaffolds with a higher DPA content (5 and 10%) inhibited proliferation of human aortic smooth muscle cell significantly. Furthermore, the DPA-loaded scaffolds had no adverse effect on human aortic endothelial cell growth, yet it improved their proliferation. The attractive mechanical properties and biofunctions of the DPA-loaded BPU scaffold indicate its potential as an acellular biodegradable SDVG for vascular replacement.
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