Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues
Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues
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DOI：
10.1016/j.biomaterials.2009.09.039
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发表时间：
2010-01-01
期刊：
影响因子：
14
通讯作者：
Radisic, Milica
中科院分区：
文献类型：
--
作者：
Chiu, Loraine L. Y.;Radisic, Milica
本研究的目的是设计一种能够在体外和体内支持血管形成的生物材料。我们利用1-乙基-3-[3-二甲氨基丙基]碳二亚胺盐酸盐(EDC)化学方法将血管内皮生长因子(VEGF)和血管生成素-1(Ang1)共价固定在三维多孔胶原支架上。与未修饰支架和可溶性生长因子对照组相比，在体外培养3天和7天后，种子内皮细胞(ECs)在固定了血管内皮生长因子和/或血管内皮生长因子的支架上的增殖增加。值得注意的是，与添加生长因子的可溶性对照组相比，共固定化血管内皮生长因子和血管生成素1组在培养第3天的细胞数(P=0.0079)、总乳酸产量(P=0.0044)和总葡萄糖消耗率(P=0.0034)均显著高于其相应的可溶性对照组。培养到第7天，苏木精-伊红染色、活/死染色、CD31染色和von Willebrand因子染色均显示内皮细胞在含有共固定化生长因子的支架上培养时，促进了管状细胞的形成。有趣的是，与单独固定VEGF/Ang1的支架相比，共同固定的VEGF和Ang1支架在绒毛尿囊膜(CAM)检测中显示出更多的EC渗透。这项研究提出了一种促进血管结构形成的替代方法，即通过共价固定化血管生成生长因子，这些生长因子比可溶性生长因子更稳定，并且具有局部效应。(C)2009爱思唯尔有限公司。保留所有权利。
The aim of this study was to engineer a biomaterial capable of supporting vascularization in vitro and in vivo. We covalently immobilized vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang1) onto three-dimensional porous collagen scaffolds using 1-ethyl-3-[3-dimethylaminopropy]carbodiimide hydrochloride (EDC) chemistry. Over both 3 and 7 days in vitro, seeded endothelial cells (ECs) had increased proliferation on scaffolds with immobilized VEGF and/or Ang1 compared to unmodified scaffolds and soluble growth factor controls. Notably, the group with co-immobilized VEGF and Ang1 showed significantly higher cell number (P = 0.0079), higher overall lactate production rate (P = 0.0044) and higher overall glucose consumption rate (P = 0.0034) at Day 3, compared to its corresponding soluble control for which growth factors were added to culture medium. By Day 7, hematoxylin and eosin, live/dead, CD31, and von Willebrand factor staining all showed improved tube formation by ECs when cultivated on scaffolds with co-immobilized growth factors. Interestingly, scaffolds with co-immobilized VEGF and Ang1 showed increased EC infiltration in the chorioallantoic membrane (CAM) assay, compared to scaffolds with independently immobilized VEGF/Ang1. This study presents an alternative method for promoting the formation of vascular structures, via covalent immobilization of angiogenic growth factors that are more stable than soluble ones and have a localized effect. (C) 2009 Elsevier Ltd. All rights reserved.