Arunkumar Pala, Dougherty Julie A, Weist Jessica, Kumar Naresh, Angelos Mark G, Powell Heather M, Khan Mahmood
Department of Emergency Medicine, College of Medicine, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Department of Materials Science and Engineering, Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.
Nanomaterials (Basel). 2019 Jul 20;9(7):1037. doi: 10.3390/nano9071037.
Coronary heart disease (CHD) is the leading cause of death in the Unites States and globally. The administration of growth factors to preserve cardiac function after myocardial infarction (MI) is currently being explored. Basic fibroblast growth factor (bFGF), a potent angiogenic factor has poor clinical efficacy due to its short biological half-life and low plasma stability. The goal of this study was to develop bFGF-loaded polycaprolactone (PCL) microspheres for sustained release of bFGF and to evaluate its angiogenic potential. The bFGF-PCL microspheres (bFGF-PCL-MS) were fabricated using the emulsion solvent-evaporation method and found to have spherical morphology with a mean size of 4.21 ± 1.28 µm. bFGF release studies showed a controlled release for up to 30 days. Treatment of HUVECs with bFGF-PCL-MS enhanced their cell proliferation and migration properties when compared to the untreated control group. Treatment of HUVECs with release media from bFGF-PCL-MS also significantly increased expression of angiogenic genes (bFGF and VEGFA) as compared to untreated cells. The angiogenic potential of these bFGF-PCL-MS was further confirmed in rats using a Matrigel plug assay with subsequent immunohistochemical staining showing increased expression of angiogenic markers. Overall, bFGF-PCL-MS could serve as a potential angiogenic agent to promote cell survival and angiogenesis following an acute myocardial infarction.
冠心病(CHD)是美国及全球范围内的主要死因。目前正在探索通过施用生长因子来在心肌梗死(MI)后维持心脏功能。碱性成纤维细胞生长因子(bFGF)是一种强效血管生成因子,但其生物学半衰期短且血浆稳定性低,导致临床疗效不佳。本研究的目的是开发负载bFGF的聚己内酯(PCL)微球以实现bFGF的持续释放,并评估其血管生成潜力。采用乳液溶剂蒸发法制备了bFGF-PCL微球(bFGF-PCL-MS),发现其具有球形形态,平均尺寸为4.21±1.28 µm。bFGF释放研究表明其可控制释放长达30天。与未处理的对照组相比,用bFGF-PCL-MS处理人脐静脉内皮细胞(HUVECs)可增强其细胞增殖和迁移特性。与未处理的细胞相比,用bFGF-PCL-MS的释放培养基处理HUVECs也显著增加了血管生成基因(bFGF和VEGFA)的表达。在大鼠中使用基质胶栓塞试验进一步证实了这些bFGF-PCL-MS的血管生成潜力,随后的免疫组织化学染色显示血管生成标志物的表达增加。总体而言,bFGF-PCL-MS可作为一种潜在的血管生成剂,在急性心肌梗死后促进细胞存活和血管生成。