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人血管内皮生长因子激活的聚乳酸-羟基乙酸共聚物海绵诱导的局部血管生成

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

作者信息

Elcin A Eser, Elcin Y Murat

机构信息

Tissue Engineering and Biomaterials Laboratory, Biotechnology Institute and Faculty of Science, Ankara University, Ankara, Turkey.

出版信息

Tissue Eng. 2006 Apr;12(4):959-68. doi: 10.1089/ten.2006.12.959.

DOI:10.1089/ten.2006.12.959
PMID:16674307
Abstract

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 microg) 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.

摘要

本研究的目的是评估人血管内皮生长因子(VEGF)激活的聚(DL-丙交酯-共-乙交酯)(PLGA)海绵的体外释放动力学和体内血管生成作用。将高度多孔的海绵(每块3×4×4 mm³)浸泡在VEGF溶液(2.5或5.0微克)中激活,然后冷冻干燥。通过竞争性酶免疫测定法研究其在PBS中的体外释放情况,长达3周。最初3天内的爆发式初始释放之后是持续超过2周的更可控的释放。通过皮下植入Wistar大鼠的腹股沟腹直肌筋膜来评估VEGF海绵的血管生成潜力。组织形态计量学和扫描电子显微镜证实,从第一周开始就有新的毛细血管长入海绵孔隙,在第2周和第3周出现大量吻合。然而,植入对照海绵或接受VEGF注射的大鼠分别表现出低得多的血管生成反应或无血管生成反应。透射电子显微镜显示,新生血管有单层内皮,周围是与大鼠循环相连的基质。结果表明,VEGF激活的PLGA海绵可被视为一种工具,用于为组织工程应用建立新血管化的皮下移植部位。

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