The effect of cross-linking of collagen matrices on their angiogenic capability
The effect of cross-linking of collagen matrices on their angiogenic capability
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DOI：
10.1016/j.biomaterials.2007.08.049
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发表时间：
2008-01-01
期刊：
影响因子：
14
通讯作者：
Steffens, Guy
中科院分区：
文献类型：
--
作者：
Yao, Chang;Markowicz, Marta;Steffens, Guy
细胞侵袭后基质血管成形率差被认为是组织工程中使用的支架的主要缺点之一。在过去的十年里，人们一直致力于提高生物材料的血管生成潜力。大量的研究报道了通过固定血管生成因子，如血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子-2 （FGF-2）来增强血管形成。我们还试图通过将肝素共价掺入到胶原基质中并装载VEGF来修饰胶原基质来实现这一目标。我们和其他人已经观察到，将血管生成因子装载到肝素化的材料上显著增加血管生成能力。在本文中，我们还研究了仅交联的胶原基质的血管生成特性，即在缺乏肝素的情况下。利用绒毛膜尿囊膜测定法评价修饰后基质的血管生成能力。血管生成潜能的差异是通过对绒毛膜和尿囊膜的宏观和微观分析以及干重变化推断出来的。仅交联的基质和既交联又肝素化的基质似乎比未修饰的基质显示出更大的血管生成潜力。如前所述，将VEGF加载到这些基质中进一步增强了血管生成的潜力。令人惊讶的是，交联对血管生成潜力有重大影响。就量级而言，这种效果与将VEGF加载到肝素化基质的效果相似。这两种修饰过程都导致胶原基质内平均孔径的增加，这一观察结果可能解释了小鼠成纤维细胞更快地侵入交联和肝素化基质。在体内接触过程中也监测了植入物的形态变化：与未修饰的基质相比，交联和肝素化的基质表现出更好的抗收缩能力。将绒毛膜尿囊膜实验结果与大鼠模型实验数据进行比较，证实了绒毛膜尿囊膜实验的结果。这个相对简单的实验再次被证明对评估和预测生物材料在组织工程和伤口愈合中的血管生成能力非常有帮助。(c) 2007 Elsevier Ltd.版权所有。
The poor vascularization rate of matrices following cell invasion is considered to be one of the main shortcomings of scaffolds used in tissue engineering. In the past decade much effort has been directed towards enhancing the angiogenic potential of biomaterials. A great many studies have appeared reporting about enhancement of vascularization by immobilizing angiogenic factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor-2 (FGF-2). We have also tried to achieve this goal by modifying collagen matrices by covalent incorporation of heparin into the matrices and loading them with VEGF. We and others have observed that loading angiogenic factors to heparinized materials markedly increases angiogenic capacity. In the present paper we also investigated the angiogenic properties of collagen matrices which were only cross-linked, i.e. in the absence of heparin. The angiogenic capacity of the modified matrices was evaluated using the chorioallantoic membrane assay. Differences in angiogenic potential were deduced from macroscopic and microscopic analyses of the chorioallantoic membrane, as well as from dry weight changes. Cross-linked only matrices and matrices both cross-linked and heparinized appeared to show a significantly larger angiogenic potential than unmodified matrices. As previously observed, loading VEGF to these matrices further stepped up angiogenic potential. Quite surprisingly, cross-linking had a substantial impact on angiogenic potential. In terms of magnitude, this effect was similar to the effect of loading VEGF to heparinized matrices. Both modification procedures resulted in an increase of average pore size within the collagen matrices, and this observation may explain the more rapid invasion of mouse fibroblasts into cross-linked and heparinized matrices. Form changes of the implants were also monitored during the in vivo contacts: cross-linked and heparinized matrices showed far better resistance against contraction, as compared to unmodified matrices.Results from the chorioallantoic membrane assay experiments were compared with data obtained from rat model experiments, which confirmed the results from the chorioallantoic membrane assay. This relatively simple assay was again shown to be extremely helpful in evaluating and predicting the angiogenic capabilities of biomaterials for use in tissue engineering and wound healing. (c) 2007 Elsevier Ltd. All rights reserved.