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首页> 外文期刊>Biomaterials >The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium
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The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium

机译：基于肝素的成纤维细胞生长因子-2凝聚层对梗死心肌瘢痕形成的影响

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Effective delivery of exogenous angiogenic growth factors can provide a new therapy for ischemic diseases. However, clinical translation of growth factor therapies faces multiples challenges; the most significant one is the short half-life of the naked protein. We use heparin and a nontoxic polycation to form an injectable coacervate that protects growth factors and preserves their bioactivities. Here we report the effectiveness of fibroblast growth factor-2 (FGF2) coacervate in reducing scar burden in a mouse myocardial infarction model. The coacervate provides spatial and temporal control of the release of heparin-binding proteins. Coacervate treated animals show lower level of inflammation, fibrosis and cardiomyocyte death in the infarcted myocardium. Histological evaluation indicates that FGF2 coacervate significantly increases the number of endothelial and mural cells and results in stable capillaries and arterioles to at least 6 weeks post injection. Echocardiographic assessment shows that FGF2 coacervate promotes cardiac contractibility and inhibits ventricular dilation, suggesting that the improvement at the tissue level leads to better cardiac functions. On the contrary, identical dosage of free FGF2 shows no statistical difference from saline or vehicle control in histological or functional assessment. Overall, injection of FGF2 coacervate ameliorated the ischemic injury caused by myocardial infarction. The promising data in rodent warrant further examination of the potential of clinical translation of this technology.
机译：有效递送外源性血管生成生长因子可以为缺血性疾病提供一种新的疗法。然而，生长因子疗法的临床翻译面临多重挑战。最重要的是裸蛋白的半衰期短。我们使用肝素和无毒的聚阳离子形成可注射的凝聚层，以保护生长因子并保留其生物活性。在这里，我们报告成纤维细胞生长因子2（FGF2）凝聚减少小鼠心肌梗塞模型中的疤痕负担的有效性。凝聚层提供了肝素结合蛋白释放的空间和时间控制。凝聚治疗的动物在梗死的心肌中显示出较低水平的炎症，纤维化和心肌细胞死亡。组织学评估表明，FGF2凝聚层显着增加了内皮和壁细胞的数量，并导致至少在注射后6周内稳定的毛细血管和小动脉。超声心动图评估显示，FGF2凝聚层可促进心脏收缩并抑制心室扩张，提示组织水平的改善可改善心脏功能。相反，相同剂量的游离FGF2在组织学或功能评估中与生理盐水或溶媒对照无统计学差异。总体而言，注射FGF2凝聚层可改善由心肌梗塞引起的缺血性损伤。啮齿动物中有希望的数据值得进一步检查该技术的临床翻译潜力。

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