Degradable PLGA scaffolds with basic fibroblast growth factor: experimental studies in myocardial revascularization.
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 (27.11% +/- 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.
Wang
Ying
Y
Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Peking Union Medical College, Tianjin 300457, People's Republic of China.
Liu
Xiao-Cheng
XC
Zhao
Jian
J
Kong
Xiang-Rong
XR
Shi
Rong-Fang
RF
Zhao
Xiao-Bin
XB
Song
Cun-Xian
CX
Liu
Tian-Jun
TJ
Lu
Feng
F
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D023921:Coronary Stenosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004343:Drug Implants; D004452:Echocardiography; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry*; D009200:Myocardial Contraction / Q000187:drug effects; D009204:Myocardial Revascularization / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D013556:Swine, Miniature; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid