Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF2 and VEGF
Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF2 and VEGF
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DOI：
10.1016/j.biomaterials.2006.10.029
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发表时间：
2007-02-01
期刊：
影响因子：
14
通讯作者：
van Kuppevelt, Toin H.
中科院分区：
文献类型：
--
作者：
Nillesen, Suzan T. M.;Geutjes, Paul J.;van Kuppevelt, Toin H.
组织工程中的一个重要问题是植入结构的血管化，这通常需要几周时间。在体内，生长因子VEGF和FGF 2显示出对血管生成和血管成熟的组合作用。因此，我们假设这些生长因子加入到无细胞结构中会增加血管的形成和成熟。为了系统地评价每种支架组分对组织反应，特别是对血管形成的贡献，制备并表征了五种多孔支架，即：胶原、胶原与肝素、胶原与肝素加一种或两种生长因子（rrFGF 2和rrVEGF）。将支架皮下植入3月龄Wistar大鼠中。在所有测试的支架中，具有生长因子组合的支架显示出最高密度的血管（IV型胶原）和最成熟的血管（平滑肌肌动蛋白）。此外，在第7天和第21天在该支架中未发现缺氧细胞（缺氧诱导因子1-α）。这些结果表明，将FGF 2和VEGF两者添加到无细胞构建体中增强了早期成熟的脉管系统。这为缺血性心脏病或糖尿病溃疡等疾病的（无细胞）组织工程构建开辟了前景。(c)2006爱思唯尔有限公司保留所有权利。
An important issue in tissue engineering is the vascularisation of the implanted construct, which often takes several weeks. In vivo, the growth factors VEGF and FGF2 show a combined effect on both angiogenesis and maturation of blood vessels. Therefore, we hypothesise that the addition of these growth factors to an acellular construct increases blood vessel formation and maturation. To systematically evaluate the contribution of each scaffold component with respect to tissue response and in particular to blood vessel formation, five porous scaffolds were prepared and characterised, viz.: collagen, collagen with heparin, and collagen with heparin plus one or two growth factors (rrFGF2 and rrVEGF). Scaffolds were subcutaneously implanted in 3 months old Wistar rats. Of all scaffolds tested, the one with a combination of growth factors displayed the highest density of blood vessels (type IV collagen) and most mature blood vessels (smooth muscle actin). In addition, no hypoxic cells were found in this scaffold at day 7 and 21 (hypoxia inducible factor 1-alpha). These results indicate that the addition of both FGF2 and VEGF to an acellular construct enhances an early mature vasculature. This opens prospects for (acellular) tissue-engineered constructs in conditions as ischaemic heart disease or diabetic ulcers. (c) 2006 Elsevier Ltd. All rights reserved.