Degradable PLGA Scaffolds with Basic Fibroblast Growth Factor Experimental Studies in Myocardial Revascularization

作者：Wang, Ying; Liu, Xiao-Cheng^*; Zhao, Jian; Kong, Xiang-Rong; Shi, Rong-Fang; Zhao, Xiao-Bin; Song, Cun-Xian; Liu, Tian-Jun; Lu, Feng

来源：TEXAS HEART INSTITUTE JOURNAL, 2009, 36(2): 89-97.

• Angiogenesis inducing agents/administration & dosage
• disease models, animal
• drug delivery systems/methods
• fibroblast growth factors/administration & dosage
• glycolates
• implants, experimental
• lactic acid
• myocardial infarction
• myocardial ischemia
• neovascularization, physiologic
• polyglycolic acid
• swine
• tissue engineering/methods

Our goal was to investigate the efficacy of degradable poly(D, L-lactic-coglycolic acid) (PLGA) scaffolds loaded with basic fibroblast growth factor (bFGF) in inducing cardiac neovascularization, increasing perfusion, and improving cardiac function.
For ease of scaffold implantation into the ventricular wall, we developed a channel producing device. Mini-swine, established as the animal model, were grouped as follows: channels-alone (control) group, channels and blank scaffolds (CBS) group, and channels and bFGF-incorporating scaffolds (CFS) group. Two scaffolds were implanted in each animal in the CBS and CFS groups. Six weeks postoperatively, endothelial cells were immunohistologically stained for von Willebrand factor and proliferating cells for Ki-67 antigen. The density of new vessels was counted by image-analysis software. Left ventricular function and myocardial perfusion were documented by echocardiography and nuclear scanning, respectively, before implantation and 6 weeks postoperatively.
The combined application of PLGA and bFGF ensured sustained release of growth factor in the target region. In the CFS group, Ki-67-positively stained cells, vascular density, and perfusion-defect percentage all showed significant improvement (P <0.001), compared with the control and CBS groups, which did not. Moreover, the left ventricular fractional shortening percentage in the CFS group (28.98% +/- 1.24%) showed a significant increase, compared with the control group (26.57% +/- 1.92%, P=0.009) and the CBS group (2711% +/- 0.71%, P=0.033), neither of which showed a difference (P=0.508).
The bFGF-incorporating PLGA scaffold can promote neovascular formation, enhance blood-flow perfusion, and improve myocardial function, although the original scaffold lumina were eventually occluded by inflammatory cells and scar tissue. (Tex Heart Inst J 2009,36(2):89-97)

• 出版日期2009-4
• 单位中国医学科学院北京协和医院; 泰达国际心血管病医院