Sustained Release of Basic Fibroblast Growth Factor (bFGF) Encapsulated Polycaprolactone (PCL) Microspheres Promote Angiogenesis In Vivo

摘要

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. In vitro bFGF release studies showed a controlled release for up to 30 days. Treatment of HUVECs with bFGF-PCL-MS in vitro 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 in vivo 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.