Improved myocardial performance in infarcted rat heart by co-injection of basic fibroblast growth factor with temperature-responsive chitosan hydrogel.
BACKGROUND
Basic fibroblast growth factor (bFGF) stimulates neoangiogenesis. The sustained release of bFGF by using biomaterials helped to enhance its angiogenic activity in vivo. In this study we investigated the effects of co-injection of bFGF with temperature-responsive chitosan hydrogel on myocardial performance in a rat model of infarction.


METHODS
Myocardial infarction was induced in rats using coronary artery ligation. Temperature-responsive chitosan hydrogel was prepared and injected intramyocardially into the left ventricular wall of rat infarction models alone or together with bFGF. Detailed histologic analysis and echocardiography were used to determine the structural and functional consequences 4 weeks after injection.


RESULTS
Heart function improved significantly in the chitosan+bFGF group compared with the phosphate-buffered saline (PBS)+bFGF group with regard to left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS) 4 weeks after transplantation (p < 0.05, n = 8 per group). In addition, arteriole densities within the infarcted area improved significantly (p < 0.01) in the chitosan+bFGF group (259 +/- 22/mm(2)) compared with the PBS+bFGF group (95 +/- 18/mm(2); n = 8 per group) at 4 weeks after transplantation. Infarct size and fibrotic area decreased significantly (p < 0.05) in the chitosan+bFGF group (39.64 +/- 1.75% and 25.09 +/- 3.31%, respectively) compared with the PBS+bFGF group (48.91 +/- 1.39% and 48.0 +/- 3.83%, respectively; n = 8 per group). No significant difference (p > 0.05) was noted between the PBS and PBS+bFGF groups.


CONCLUSIONS
Co-injection of bFGF with temperature-responsive chitosan hydrogels enhanced the effects of bFGF on arteriogenesis, ventricular remodeling and cardiac function. Our findings suggest a new approach to improve infarcted repairs in the prevention of adverse remodeling after myocardial infarction.
Wang
Haibin
H
Department of Tissue Engineering, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, PR China.
Zhang
Xuelian
X
Li
Yanmin
Y
Ma
Yitong
Y
Zhang
Ye
Y
Liu
Zhiqiang
Z
Zhou
Jin
J
Lin
Qiuxia
Q
Wang
Yanmeng
Y
Duan
Cuimi
C
Wang
Changyong
C
D000818:Animals; D048271:Chitosan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006490:Hemostatics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020100:Hydrogels; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D006490:Hemostatics; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D048271:Chitosan