Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase

Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase
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DOI:
10.1002/jbm.a.35670
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发表时间:
2016-06-01
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:
Sekiguchi, Hiroyuki;Uchida, Kentaro;Takaso, Masashi

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生长因子与动物源性胶原蛋白材料结合递送已被用于加速人类骨折患者的愈合。然而,将牛蛋白引入人体有人畜共患病和免疫并发症的风险。在这里,我们开发了一种基于胶原样多肽的骨形成系统,包括poly(pro - hy - gly)(10),它模拟胶原的三螺旋构象,碱性成纤维细胞生长因子(bFGF)融合到多囊肾病(PKD)结构域和溶组织梭菌胶原酶的胶原结合结构域(CBD)。圆二色光谱分析表明,当胃蛋白酶可溶性牛I型胶原在50℃下处理时,在220 nm处未检测到与胶原三螺旋相对应的阳性信号。相比之下,即使在80℃下处理,poly(pro - hy - gly)(10)仍保持220 nm的阳性峰。在小鼠骨折模型中,胶原结合-bFGF融合蛋白(bFGF- pkd - cbd)与poly(pro - hy - gly)(10)联合诱导的骨形成比单独的bFGF更大。综上所述,这些特性表明bFGF-PKD-CBD/poly(pro - hy - gly)(10)复合材料在临床环境中是一种很有前途的骨修复材料。(c) 2016 Wiley Periodicals, Inc.;[J]中国生物医学工程学报,2016,31(4):557 - 557。
Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)(10), which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50 degrees C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)(10) retained the 220-nm positive peak, even when treated at 80 degrees C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)(10) induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)(10) composite is a promising material for bone repair in the clinical setting. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016.