Controlled release of FGF-2 using fragmin/protamine microparticles and effect on neovascularization
Controlled release of FGF-2 using fragmin/protamine microparticles and effect on neovascularization
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DOI：
10.1002/jbm.a.32265
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发表时间：
2009-12-01
影响因子：
4.9
通讯作者：
Ishihara, Masayuki
中科院分区：
文献类型：
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作者：
Nakamura, Shingo;Kanatani, Yasuhiro;Ishihara, Masayuki
约0.5-1.通过简单地混合低分子量肝素（法安明）和鱼精蛋白制备直径为10 μ m的肝素。我们研究了这些微粒抑制成纤维细胞生长因子（FGF）-2、保护FGF-2免于降解、增强FGF-2活性和促进FGF-2的控释的能力。FGF-2以高亲和力（Kd = 2.08 × 10（-9）M）结合到fragmin/鱼精蛋白微粒上，并且FGF-2活性的半衰期通过FGF-2与微粒的结合，通过保护FGF-2免受热和蛋白水解的失活而被显著延长。在皮下注射到小鼠背部后，fragmin/鱼精蛋白微粒经历生物降解并在约2周内消失。类似地注射含FGF-2的微粒导致1周后注射部位附近显著的新血管形成和纤维组织形成。这些结果表明，生物活性FGF-2的控释通过微粒的缓慢扩散和生物降解，随后诱导新血管形成。(C)2008 Wiley Periodicals，Inc. J Biomed Mater Res 91A：814-823，2009
Water-insoluble fragmin/protamine microparticles of about 0.5-1. mu m in diameter were prepared by simple mixing of low-molecular-weight heparin (fragmin) with protamine. We investigated the capability of these microparticles to immobilize fibroblast growth factor (FGF)-2, to protect FGF-2 against degradation, to enhance FGF-2 activity, and to facilitate controlled release of FGF-2. FGF-2 bound to the fragmin/protamine microparticles with high affinity (Kd = 2.08 x 10(-9) M) and the half-life of FGF-2-activity was prolonged Substantially through binding of FGF-2 to the microparticles, by protection of FGF-2 from inactivation by heat and proteolysis. After Subcutaneous injection into the back of mice, the fragmin/protamine microparticles underwent biodegradation and disappeared in about 2 weeks. A similar injection of FGF-2-containing microparticles resulted in significant neovascularization and fibrous tissue formation near the injection site after 1 week. These results indicate that controlled release of biologically active FGF-2 Occurs through both slow diffusion and biodegradation of the microparticles, with subsequent induction of neovascularization. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91A: 814-823, 2009