Acceleration of periosteal bone formation by human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase.

Acceleration of periosteal bone formation by human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase.
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DOI:
10.1002/jbm.a.34841
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发表时间:
2014-06
影响因子:
4.9
通讯作者:
Takaso, Masashi
Takaso, Masashi
中科院分区:
工程技术3区
文献类型:
--
作者:
Uchida, Kentaro;Matsushita, Osamu;Naruse, Kouji;Mima, Takehiko;Nishi, Nozomu;Hattori, Shunji;Ogura, Takayuki;Inoue, Gen;Tanaka, Keisuke;Takaso, Masashi

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碱性成纤维细胞生长因子2(bFGF)是间充质细胞的一种有效的有丝分裂原,局部应用重组bFGF可加速骨愈合和缺损修复。然而,需要重复给药以获得持续的治疗效果,因为bFGF的功效在其从骨缺损部位扩散后迅速降低。在这里,我们试图开发一种基于胶原的骨形成系统,使用融合蛋白(胶原结合bFGF,CB-bFGF)组成的bFGF和胶原结合结构域(CBD)的溶组织梭菌胶原酶。CBD加入bFGF并没有改变其天然的生物活性,如融合蛋白促进骨膜间充质细胞体外增殖的能力所示。融合蛋白对胶原和脱矿骨基质(DBM)的亲和力也通过胶原结合试验证实。此外,在体内骨膜骨形成试验表明,CB-bFGF与胶原蛋白片的组合诱导骨膜骨形成的蛋白质浓度低于单独的bFGF所需的浓度。此外,与单独施用相同浓度的bFGF相比,负载CB-bFGF的DBM移植物加速了大鼠股骨中的新骨形成。综上所述,这些性能表明,CB-bFGF/胶原复合材料是一种有前途的材料,在临床上的骨修复。© 2013 Wiley Periodicals,Inc. J Biomed Mater Res Part A:102A:1737-1743,2014.
Basic fibroblast growth factor 2 (bFGF) is a potent mitogen for mesenchymal cells, and the local application of recombinant bFGF accelerates bone union and defect repair. However, repeated dosing is required for sustained therapeutic effect as the efficacy of bFGF decreases rapidly following its diffusion from bone defect sites. Here, we attempted to develop a collagen-based bone formation system using a fusion protein (collagen binding-bFGF, CB-bFGF) consisting of bFGF and the collagen-binding domain (CBD) of Clostridium histolyticum collagenase. The addition of the CBD to bFGF did not modify its native biological activity, as shown by the capacity of the fusion protein to promote the in vitro proliferation of periosteal mesenchymal cells. The affinity of the fusion protein towards collagen and demineralized bone matrix (DBM) was also confirmed by collagen-binding assays. Moreover, in vivo periosteal bone formation assays showed that the combination of CB-bFGF with a collagen sheet induced periosteal bone formation at protein concentrations lower than those required for bFGF alone. In addition, grafts of DBM loaded with CB-bFGF accelerated new bone formation in rat femurs compared to the same concentration of bFGF administered alone. Taken together, these properties suggest that the CB-bFGF/collagen composite is a promising material for bone repair in the clinical setting. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1737–1743, 2014.
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发表时间: 2007-04-01
影响因子: 2.8
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