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Bone regeneration with degradable hydrogels and genetically modified, recombinant human BMP-2 with two additional repeats of the heparin-binding domain.

使用可降解水凝胶和带有两个附加肝素结合结构域重复的转基因重组人 BMP-2 进行骨再生。

基本信息

批准号：
18592125
负责人：
NAWACHI Kumiko
金额：
$ 2.43万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592125/
关键词：
BMP-2 gelatin hydrogels bone regeneration implant periodontal disease carrier large animal Escherichia coli

项目摘要

A genetically modified, recombinant human bone morphogenetic proteirr2 with two additional repeats of the heparin-binding domain, derived from E coli (rhBMP-2 T4) has shown a stronger osteoinductivity than wild-type rhBMP-2. The aim of this study was to find a suitable carrier fix rhBMP-2 T4 in order to enhance bone regeneration. The in vitro and in vivo release profiles of^<125>I-labelled rhBMP-2 T4 incorporated into 6 kinds of gelatin hydrogels with different isoelectric point (IEP) were investigated. As a result, the higher the IEP was, the longer the rhBMP2 T4 radioactivity was preserved. To elucidate the osteoinductivity difference of the rhBMP2 T4/hydrogels composites, two high IEP gelatin hydrogels: a basic gelatin hydrogel (PI9) and a modified PI9 with spermine (SM), were implanted at critical-sized defects in the rat calvaria. The mean normalized radio-opacity against the surrounding intact bone in the PI9 group was significantly higher than those in the SM (p<0.001) and the control (without carrier) groups (p<0.001). The observed radio-opacity increase in the PI9 group was clearly related to the bone formation at the defect. Therefore, we concluded that PI9 is a suitable carrier for the rhBMP-2 T4 to enhance bone regeneration.

从大肠杆菌中提取的具有两个肝素结合结构域重复的基因修饰重组人骨形态发生蛋白2 （rhBMP-2 T4）显示出比野生型rhBMP-2更强的骨诱导能力。本研究的目的是寻找合适的载体固定rhBMP-2 T4以促进骨再生。研究了^<125> i标记的rhBMP-2 T4在6种不同等电点（IEP）明胶水凝胶中的体外和体内释放情况。结果表明，IEP越高，rhBMP2 T4的放射性保存时间越长。为了研究rhBMP2 T4/水凝胶复合材料的成骨性差异，我们将两种高IEP明胶水凝胶：碱性明胶水凝胶（PI9）和精胺修饰PI9 （SM）植入大鼠颅骨临界尺寸的缺损。PI9组对周围完整骨的平均标准化放射不透明度显著高于SM组（p<0.001）和对照组（p<0.001）。PI9组所观察到的放射不透明增加明显与缺损处的骨形成有关。因此，我们认为PI9是rhBMP-2 T4促进骨再生的合适载体。