Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia.
Recently we have developed new sustained release system of basic fibroblast growth factor (bFGF) using gelatin hydrogel as a carrier. Using this system, we examined the effect of topical sustained release of bFGF on angiogenesis and tissue blood perfusion in a rabbit model of hind limb ischemia. Thirty-two rabbits underwent excision of right femoral artery under general anesthesia. Two weeks later the rabbits were randomized into four groups (n = 8 each): no treatment, intramuscular injection of gelatin hydrogel alone, and intramuscular injection of gelatin hydrogel incorporating 30 microg and 100 microg of bFGF. Four weeks after each treatment, selective angiography, tissue blood flowmetry using laser Doppler perfusion imaging, and histological examination of thigh muscle were performed. In groups treated with bFGF incorporating gelatin hydrogel, tissue blood flow, number of arterioles, and vascular density were significantly increased in a dose-dependent manner 4 weeks after the treatment. Serum concentrations of bFGF and vascular endothelial growth factor were not elevated 4 weeks after the treatment. In conclusion, sustained release of bFGF using gelatin hydrogel augmented angiogenesis and improved tissue blood flow after excision of the femoral artery.
Doi
Kazuhiko
K
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Shogoin, Kyoto 606-8507, Japan.
Ikeda
Tadashi
T
Marui
Akira
A
Kushibiki
Toshihiro
T
Arai
Yoshio
Y
Hirose
Keiichi
K
Soga
Yoshiharu
Y
Iwakura
Atsushi
A
Ueyama
Koji
K
Yamahara
Kenichi
K
Itoh
Hiroshi
H
Nishimura
Kazunobu
K
Tabata
Yasuhiko
Y
Komeda
Masashi
M
D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers; D005263:Femoral Artery; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005780:Gelatin; D006614:Hindlimb / Q000033:anatomy & histology / Q000098:blood supply* / Q000000981:diagnostic imaging; D020100:Hydrogels; D007273:Injections, Intramuscular; D007511:Ischemia; D017078:Laser-Doppler Flowmetry; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D011859:Radiography; D012039:Regional Blood Flow / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000097:blood
D004337:Drug Carriers; D020100:Hydrogels; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D005780:Gelatin