Preparation of gelatin microspheres encapsulated with bFGF for therapeutic angiogenesis in a canine ischemic hind limb.
There is urgent need for the treatment of limb ischemia. In order to avoid the risk of genetic materials or injury in collection of implanted cells, a basic fibroblast growth factor (bFGF) sustained release system using cross-linked gelatin microspheres was developed for therapeutic angiogenesis. In this study, gelatin microspheres (MSs) and the complex of MSs and bFGF (MSs-bFGF) were prepared. MSs and MSs-bFGF were analyzed for morphology, particle size, in vitro bFGF release and the bioactivity of the released medium. MSs-bFGF was intramuscularly implanted into the ischemic hind limb of a dog and free bFGF, empty MSs and untreated animals were used as controls. Histological examination was performed for angiogenesis evaluation. After immersion in an aqueous solution, the un-cross-linked MSs became deformed and adhered together. The cross-linked MSs showed a more stable character both in vivo and in vitro. The bFGF released from MSs remained bioactive. The histological examination indicated that the densities of micro-vessels in the MSs-bFGF-treated hind limb muscle were significantly greater than that in the untreated control, free bFGF and empty MSs groups. The MSs-bFGF sustained release system was a simple, safe and effective way to achieve therapeutic angiogenesis in an ischemic limb.
Zhao
Yilin
Y
Department of Vascular Surgery, Zhongshan Hospital, Xiamen University, Xiamen, PR China.
Liu
Zhongchen
Z
Pan
Chao
C
Li
Zaohui
Z
Zhou
Jianyin
J
Wang
Jinling
J
Yin
Zhenyu
Z
Wang
Xiaomin
X
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D035002:Lower Extremity / Q000098:blood supply* / Q000473:pathology; D008422:Materials Testing; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010316:Particle Size
D001672:Biocompatible Materials; D004337:Drug Carriers; D016222:Fibroblast Growth Factor 2; D005780:Gelatin