The dosage dependence of VEGF stimulation on scaffold neovascularisation
The dosage dependence of VEGF stimulation on scaffold neovascularisation
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DOI：
10.1016/j.biomaterials.2008.05.007
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发表时间：
2008-09-01
期刊：
影响因子：
14
通讯作者：
Zilla, Peter
中科院分区：
文献类型：
--
作者：
Davies, Neil;Dobner, Stephan;Zilla, Peter
生长因子通常用于组织再生以刺激聚合物支架的血管形成，血管内皮生长因子（VEGF）已被广泛研究用于短期血管向内生长。因此，我们评估了不同浓度的VEGF对多孔支架血管化的影响，在短期，中期和长期，通过渗透泵输送15，150和1500 ng VEGF/天聚氨酯支架长达6周。在终止VEGF递送后数月，仅在150 ng/天时实现增加的血管形成（46%，p < 0.05）。该剂量始终显示血管化水平升高（第10、20、30和42天分别比PBS对照高出144、125、160和60%，p < 0.05），而最高剂量诱导的血管，尽管最初最大程度升高（在10和20天时为265和270%，p < 0.05）在VEGF递送20天后趋于消退。最高剂量组在20天时周细胞覆盖率降低（30%，p < 0.05）。凝集素灌注证明支架内的血管在所有时间点都连接到宿主脉管系统，并且在第20天通过VEGF递送显著提高灌注。这些结果表明VEGF的浓度在组织再生支架中形成的脉管系统的性质和持久性中起关键作用。(c)2008爱思唯尔有限公司保留所有权利。
Growth factors are often used in tissue regeneration to stimulate vascularisation of polymeric scaffolds, with vascular endothelial growth factor (VEGF) having been extensively studied for short-term vessel ingrowth. We have therefore evaluated the effect of different concentrations of VEGF on the vascularisation of a porous scaffold in the short-, intermediate- and long-term, by delivering 15, 150 and 1500 ng VEGF/ day to polyurethane scaffolds by osmotic pumps for up to 6 weeks. An increased vascularisation months after termination of VEGF delivery was only achieved with 150 ng/day (46%, p < 0.05). This dosage consistently showed elevated levels of vascularisation (144, 125 160 and 60% above PBS controls at 10, 20, 30 and 42 days, respectively, p < 0.05), whilst the vessels induced by the highest dosage, though initially maximally elevated (265 and 270% at 10 and 20 days, p < 0.05) tended to regress after 20 days of VEGF delivery. Pericyte coverage was decreased at 20 days for the highest dosage (30%, p < 0.05). Lectin perfusion demonstrated that vessels within the scaffold were connected to the host vasculature at all time points and perfusion was substantially raised by VEGF delivery at day 20. These results suggest concentration of VEGF plays a critical role in the nature and persistence of vasculature formed in a tissue regenerative scaffold. (c) 2008 Elsevier Ltd. All rights reserved.