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

一种遗传修饰的重组人骨形态发生蛋白2（rhBMP-2 T4）具有两个额外的肝素结合结构域重复序列，来源于大肠杆菌，已显示出比野生型rhBMP-2更强的骨诱导性。本研究的目的是寻找一种合适的载体固定rhBMP-2 T4，以促进骨再生。研究<125>了6种不同等电点（IEP）的明胶水凝胶对~（131）I标记的rhBMP-2 T4的体内外释药特性。结果表明，IEP越高，rhBMP 2 T4的放射性保留时间越长。为了阐明rhBMP 2 T4/水凝胶复合物的骨诱导性差异，将两种高IEP明胶水凝胶：碱性明胶水凝胶（PI 9）和含精胺（SM）的改性PI 9植入大鼠颅骨的临界尺寸缺损处。PI 9组中相对于周围完整骨的平均标准化射线不透性显著高于SM（p&lt;0.001）和对照（无载体）组（p&lt;0.001）。在PI 9组中观察到的射线不透性增加与缺损处的骨形成明显相关。因此，我们得出结论，PI 9是rhBMP-2 T4促进骨再生的合适载体。

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.