Site-specific delivery of acidic fibroblast growth factor stimulates angiogenic and osteogenic responses in vivo
Site-specific delivery of acidic fibroblast growth factor stimulates angiogenic and osteogenic responses in vivo
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DOI：
10.1002/jbm.a.30163
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发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Thompson, JA
中科院分区：
文献类型：
--
作者：
Kelpke, SS;Zinn, KR;Thompson, JA
骨不连的愈合是骨科临床上的一个主要问题。这种骨修复过程的局限性包括血管生成和矿化不足。将适当的生物材料与伤口部位的部位特异性新血管形成和骨生成相结合一直是几种临床相关治疗策略的焦点。酸性成纤维细胞生长因子（FGF-1）作为一种细胞外蛋白，诱导、协调和维持与血管生成和骨生成相关的位点特异性分子反应。为了建立这种生长因子在体内协调骨再生过程的能力，评价了包埋在纤维蛋白/羟基磷灰石复合物中的FGF-1的位点特异性递送。体内动力学分析表明，生物复合材料能够提供生物活性FGF-1。释放动力学显示，在前20小时内，活性FGF-1的初始递送为87.5 ng/h，随后在接下来的20小时内递送减少至28 ng/h。原位免疫组织学分析表明，含有FGF-1的植入物诱导血管生成增加和表达成骨相关标志物（即，骨桥蛋白、骨钙素）。总的来说，这些努力支持纤维蛋白/羟基磷灰石复合材料中活性FGF-1的位点特异性递送不仅能够诱导血管生成，还能够诱导成骨细胞反应。(C)2004 Wiley Periodicals，Inc.
A major clinical problem in orthopedics is the healing of nonunion fractures. Limitations of this bone repair process include insufficient angiogenesis and mineralization. Integrating appropriate biomaterials with site-specific neovascularization and osteogenesis at the wound site has been the focus of several clinically relevant therapeutic strategies. As an extracellular protein, acidic fibroblast growth factor (FGF-1) induces, coordinates, and sustains site-specific molecular responses associated with angiogenesis and osteogenesis. To establish the ability of this growth factor to coordinate bone regenerative process in vivo, site-specific delivery of FGF-1, entrapped in a fibrin/hydroxyapatite composite, was evaluated. Kinetic analysis in vivo revealed the biocomposite was capable of delivering biologically active FGF-1. Release kinetics revealed an initial delivery of 87.5 ng/h of active FGF-1 in the first 20 h, followed by a reduced delivery of 28 ng/h during the next 20 h. In situ immunohistological analyses demonstrated that FGF-1-containing implants induced increased angiogenesis and infiltration of cells expressing osteogenic related markers (i.e., osteopontin, osteocalcin). Collectively, these efforts support that site-specific delivery of active FGF-1 in a fibrin/hydroxyapatite composite is competent to induce not only angiogenesis but also osteogenic cellular responses. (C) 2004 Wiley Periodicals, Inc.