Therapeutic angiogenesis using basic fibroblast growth factor in combination with a collagen matrix in chronic hindlimb ischemia.
Although therapeutic angiogenesis by angiogenic cytokines is a feasible strategy to improve regional blood flow in ischemic regions, the optimal delivery mode needs to be established. Here we designed a complex of collagen matrix (CM) and basic fibroblast growth factor (bFGF) and evaluated its proangiogenic effect in ischemic hindlimbs. The bFGF-CM was prepared using lyophilization. The morphology, porosity and toxicity of CM were examined. The bFGF releasing profile and bioactivity of released bFGF were assessed. bFGF-CM was intramuscularly implanted into the rabbit ischemic hindlimb model. Oxygen saturation parameters (OSP) of ischemic hindlimbs was measured to evaluate the extremity perfusion at intervals. Histological examination was performed to evaluate the level of angiogenesis. The CM and bFGF-CM were of identical multiporous structure lacking cytotoxicity. The releasing profile lasted 10 days and the released bFGF remained bioactive. OSP in bFGF-CM group was significantly higher than that in CM, bFGF and ischemic groups at 2 and 4 weeks. The number of capillaries and mature vessels in bFGF-CM group were significantly greater than that in untreated control, CM and bFGF groups. Therefore, bFGF-CM enables the safe and effective long-term release of bFGF with improved angiogenesis in ischemic hindlimbs compared with CM devoid of bFGF.
Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361001, China.
Jianyin
J
Zhou
Yilin
Y
Zhao
Jinling
J
Wang
Sheng
S
Zhang
Zhengjin
Z
Liu
Maochuan
M
Zhen
Yun
Y
Liu
Pingguo
P
Liu
Zhenyu
Z
Yin
Xiaomin
X
Wang
D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply*; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits
D016222:Fibroblast Growth Factor 2; D003094:Collagen; D010100:Oxygen