Localized angiogenesis induced by human vascular endothelial growth factor-activated PLGA sponge

Localized angiogenesis induced by human vascular endothelial growth factor-activated PLGA sponge
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DOI:
10.1089/ten.2006.12.959
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发表时间:
2006-04-01
期刊:
影响因子:
--
通讯作者:
Elcin, YM
Elcin, YM
中科院分区:
生物2区
文献类型:
--
作者:
Elcin, AE;Elcin, YM

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本研究旨在评价人血管内皮生长因子(VEGF)激活聚乳酸-羟基乙酸酯(PLGA)海绵的体外释放动力学和体内血管生成效应。将高孔海绵(每个3 × 4 × 4 mm(3))浸泡在VEGF溶液(2.5或5.0 μ g)中活化,然后冷冻干燥。通过竞争性酶免疫分析法研究其在PBS中的体外释放长达3周。在最初的3天内爆发型的初始释放,随后是一个更有控制的持续1 - 2周的释放。采用Wistar大鼠腹股沟筋膜皮下植入法评价VEGF海绵的血管生成潜能。组织形态学和扫描电镜证实,新生毛细血管从第一周开始渗入海绵孔隙,在第2周和第3周出现了明显的吻合。然而,植入对照海绵或接受VEGF注射的大鼠分别表现出更低或没有血管生成反应。透射电镜显示新生血管有一个单一的内皮层,周围是接种了大鼠循环的基质。结果表明,vegf激活的PLGA海绵可以作为建立组织工程应用的新血管化皮下移植位点的工具。
The objective of this study was to assess the in vitro release kinetics and the in vivo angiogenic effect of human vascular endothelial growth factor (VEGF)-activated poly(DL-lactide-co-glycolide) (PLGA) sponge. The highly porous sponges (each 3 x 4 x 4 mm(3)) were activated by soaking in a VEGF solution (2.5 or 5.0 mu g) and then freeze-drying. In vitro release in PBS was investigated by a competitive enzyme immunoassay for up to 3 weeks. The burst-type initial release within the first 3 days followed a more controlled one lasting for > 2 weeks. The angiogenic potential of the VEGF sponge was evaluated by subcutaneous implantation into the epigastric groin fascia of Wistar rats. Histomorphometry and SEM confirmed the formation of new capillaries infiltrating the sponge pores starting from the first week and the drastic anostomosis at weeks 2 and 3. However, the rats implanted with control sponges or receiving VEGF injection exhibited much lower or no angiogenic response, respectively. TEM revealed the neo-vessels had a single endothelial layer surrounded by the matrix inoculated with the rat circulation. The results indicate that VEGF-activated PLGA sponge can be considered as a tool to establish neovascularized subcutaneous transplantation sites for tissue-engineering applications.