Efficacy of photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2 in a rabbit model of chronic myocardial infarction.
BACKGROUND
Therapeutic angiogenesis in ischemic myocardium has been shown to be an effective strategy to improve regional blood flow and myocardial function. However, no effective delivery system for growth factor administration is yet known to induce important therapeutic angiogenic responses in ischemic myocardium.


METHODS
FGF-2-incorporated chitosan (FGF-2/chitosan) hydrogels were immobilized on the surface of ischemic myocardium of rabbit models of chronic myocardial infarction by UV-irradiation. After 4 weeks, cardiac functional analyses by noradrenalin challenge and histopathological analyses were performed to evaluate the efficacy of a controlled release of FGF-2 from FGF-2/chitosan hydrogel immobilized on the surface of ischemic myocardium.


RESULTS
Significant improvement by application of FGF-2/chitosan hydrogels was found in systolic pressure at the left ventricle, +dp/dt maximum, and -dp/dt maximum during noradrenalin challenge at a dose of 1 microg/kg/min. Histological observations showed that a significantly larger amount of viable myocardium and CD 31 immunostained blood vessels were found in the FGF-2/chitosan hydrogel-applied group than only the chitosan-applied and control groups.


CONCLUSIONS
These preliminary results indicate that the controlled release of biologically active FGF-2 molecules from FGF-2/chitosan hydrogel induces angiogenesis and possibly collateral circulation in ischemic myocardium, thereby protecting the myocardium.
Fujita
Masanori
M
Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. BXB01424@nifty.ne.jp
Ishihara
Masayuki
M
Morimoto
Yuji
Y
Simizu
Masafumi
M
Saito
Yoshio
Y
Yura
Hirofumi
H
Matsui
Takemi
T
Takase
Bonpei
B
Hattori
Hidemi
H
Kanatani
Yasuhiro
Y
Kikuchi
Makoto
M
Maehara
Tadaaki
T
D000818:Animals; D048271:Chitosan / Q000008:administration & dosage*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D020100:Hydrogels / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D011817:Rabbits
D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D048271:Chitosan