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Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants and potential gene expression mechanisms for new vessel growth

机译：载有细胞因子的透明质酸水凝胶植入物刺激体内血管生成和新血管生长的潜在基因表达机制

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As a first step to developing cytokine-impregnated hydrogels capable of promoting desired physiologic responses, we have tested in vivo angiogenesis in a mouse model. Hyaluronic acid (HA) hydrogel samples pre-loaded with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) were surgically implanted in an ear pocket in the mouse. The implants were then retrieved at 7 and 14 days post surgery, and the number of ingrowing microvessels evaluated by direct counting. As compared to contralateral controls, we show that released degrading hyaluronan alone is itself an effective stimulus for new vessel growth. Pre-loading of the gel with VEGF, however, dramatically augments the rate of new microvessel growth, resulting in a 2.3-fold increase in neovascularization over the sum of the rates produced by HA and VEGF individually. In contrast, although bFGF alone greatly augments vessel growth, no such potentiation effect was observed between bFGF and HA. We present physiologic data demonstrating vessel growth and correlate those data with gene expression changes measured by microarray analysis. The results show that HA-cytokine combinations can be designed to optimize angiogenesis, and suggest potential mechanisms by which angiogenic vessel proliferation may occur.
机译：作为开发能够促进所需生理反应的细胞因子浸渍水凝胶的第一步，我们已经在小鼠模型中测试了体内血管生成。将预先装有血管内皮生长因子（VEGF）或碱性成纤维细胞生长因子（bFGF）的透明质酸（HA）水凝胶样品通过手术植入小鼠的耳袋中。然后在术后7天和14天取回植入物，并通过直接计数评估向内生长的微血管数量。与对侧对照相比，我们显示仅释放降解的透明质酸本身就是对新血管生长的有效刺激。但是，用VEGF预加载凝胶会显着增加新的微血管生长速率，从而导致新血管形成比HA和VEGF单独产生的速率总和增加2.3倍。相反，尽管单独使用bFGF可以大大促进血管生长，但在bFGF和HA之间未观察到这种增强作用。我们提供了表明血管生长的生理数据，并将这些数据与通过微阵列分析测量的基因表达变化相关联。结果表明，可以设计HA细胞因子组合以优化血管生成，并提示可能发生血管生成血管增殖的潜在机制。

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