Gradient nanofibrous chitosan/poly ε-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering
Gradient nanofibrous chitosan/poly ε-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering
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DOI：
10.1016/j.biomaterials.2011.10.037
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发表时间：
2012-01-01
期刊：
影响因子：
14
通讯作者：
Zhang, Yuanyuan
中科院分区：
文献类型：
--
作者：
Du, Fengyi;Wang, Hao;Zhang, Yuanyuan
组织工程化小直径血管的主要挑战之一是由血栓形成引起的再狭窄。本研究的目的是开发一种三维梯度肝素化纳米纤维支架，帮助内皮细胞排列在血管腔上，以防止血栓形成。以壳聚糖和聚己内酯（PCL）为原料，采用连续定量梯度共静电纺丝法制备了垂直梯度壳聚糖/聚己内酯（CS/PCL）纳米纤维血管支架。为了模拟天然血管微环境，我们在梯度CS/PCL中肝素化并固定血管内皮生长因子（VEGF），肝素化壳聚糖纳米纤维在梯度CS/PCL血管壁中从外膜到管腔表面逐渐增加。在梯度CS/PCL中，比在均匀CS/PCL纳米纤维支架中，更多的肝素与壳聚糖交联反应。通过活化部分凝血活酶时间和血小板粘附测定，这些支架的肝素化增强了支架的抗血栓形成性能。与均匀CS/PCL支架相比，梯度CS/PCL支架的VEGF释放更加稳定和持续，在最初的12 h内VEGF的突释减少了约42.5%。人脐静脉内皮细胞（HUVEC）在梯度CS/PCL支架上的粘附和增殖能力增强。此外。HUVEC生长并在梯度CS/PCL支架的顶侧上形成完整的单层。因此，使用垂直梯度肝素化CS/PCL纳米纤维支架可以提供一种方法来创建具有哺乳动物血管的抗凝和快速诱导再内皮化的固有特性的小直径血管移植物。(C)2011爱思唯尔有限公司保留所有权利。
One of the major challenges of tissue-engineered small-diameter blood vessels is restenosis caused by thrombopoiesis. The goal of this study was to develop a 3D gradient heparinized nanofibrous scaffold, aiding endothelial cells lined on the lumen of blood vessel to prevent thrombosis. The vertical graded chitosan/poly epsilon-caprolactone (CS/PCL) nanofibrous vessel scaffolds were fabricated with chitosan and PCL by sequential quantity grading co-electrospinning. To mimic the natural blood vessel microenvironment, we used heparinization and immobilization of vascular endothelial growth factor (VEGF) in the gradient CS/PCL The quantity of heparinized chitosan nanofibers increased gradually from the tunica adventitia to the lumen surfaces in the gradient CS/PCL wall of tissue engineered vessel. More heparin reacted to chitosan nanofiber in gradient CS/PCL than in uniform CS/PCL nanofibrous scaffolds. Antithrombogenic properties of the scaffolds were enhanced by the heparinization of these scaffolds, as shown by activated partial thromboplastin time and platelet adhesion assay. Compared to the uniform CS/PCL scaffold, the release of VEGF from the gradient CS/PCL was more stable and sustained, and the burst release of VEGF was reduced approximately 42.5% within the initial 12 h. The adhesion and proliferation of human umbilical vein endothelial cells (HUVEC) were enhanced on the gradient CS/PCL scaffold. Furthermore. HUVEC grew and formed an entire monolayer on the top side of the gradient CS/PCL scaffold. Therefore, use of vertical gradient heparinized CS/PCL nanofibrous scaffolds could provide an approach to create small-diameter blood vessel grafts with innate properties of mammalian vessels of anticoagulation and rapid induction of re-endothelialization. (C) 2011 Elsevier Ltd. All rights reserved.