Department of Bioengineering, University of Pittsburgh, USA.
Biomaterials. 2013 Feb;34(6):1747-56. doi: 10.1016/j.biomaterials.2012.11.019. Epub 2012 Dec 2.
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.
外源性血管生成生长因子的有效传递可为缺血性疾病提供新的治疗方法。然而，生长因子疗法的临床转化面临多重挑战；其中最显著的一个是裸蛋白的半衰期短。我们使用肝素和一种无毒的多阳离子形成一种可注射的凝聚物，以保护生长因子并保持其生物活性。在这里，我们报告成纤维细胞生长因子 2（FGF2）凝聚物在减少小鼠心肌梗死模型中瘢痕负担的有效性。凝聚物为肝素结合蛋白的释放提供了时空控制。凝聚物处理的动物在梗死心肌中表现出较低水平的炎症、纤维化和心肌细胞死亡。组织学评估表明，FGF2 凝聚物显著增加了内皮细胞和壁细胞的数量，并导致稳定的毛细血管和小动脉至少在注射后 6 周。超声心动图评估表明，FGF2 凝聚物促进了心脏收缩力并抑制了心室扩张，表明组织水平的改善导致了更好的心脏功能。相比之下，相同剂量的游离 FGF2 在组织学或功能评估中与生理盐水或载体对照相比没有统计学差异。总体而言，FGF2 凝聚物的注射改善了心肌梗死后的缺血性损伤。在啮齿动物中令人鼓舞的数据表明，这项技术的临床转化具有进一步研究的潜力。
