Abstract:
The receptor activator of NF-κB ligand (RANKL)-binding peptide is known to accelerate bone morphogenetic protein (BMP)-2-induced bone formation. Cholesterol-bearing pullulan (CHP)-OA nanogel-crosslinked PEG gel (CHP-OA nanogel-hydrogel) was shown to release the RANKL-binding peptide sustainably; however, an appropriate scaffold for peptide-accelerated bone formation is not determined yet. This study compares the osteoconductivity of CHP-OA hydrogel and another CHP nanogel, CHP-A nanogel-crosslinked PEG gel (CHP-A nanogel-hydrogel), in the bone formation induced by BMP-2 and the peptide. A calvarial defect model was performed in 5-week-old male mice, and scaffolds were placed in the defect. In vivo μCT was performed every week. Radiological and histological analyses after 4 weeks of scaffold placement revealed that the calcified bone area and the bone formation activity at the defect site in the CHP-OA hydrogel were significantly lower than those in the CHP-A hydrogel when the scaffolds were impregnated with both BMP-2 and the RANKL-binding peptide. The amount of induced bone was similar in both CHP-A and CHP-OA hydrogels when impregnated with BMP-2 alone. In conclusion, CHP-A hydrogel could be an appropriate scaffold compared to the CHP-OA hydrogel when the local bone formation was induced by the combination of RANKL-binding peptide and BMP-2, but not by BMP-2 alone.
摘要:
已知NF-κB配体(RANKL)结合肽的受体激活剂可加速骨形态发生蛋白(BMP)-2诱导的骨形成。含胆固醇的支链淀粉(CHP)-OA纳米凝胶交联的PEG凝胶(CHP-OA纳米凝胶-水凝胶)显示可持续释放RANKL结合肽;然而,肽加速骨形成的合适支架尚未确定。这项研究比较了CHP-OA水凝胶和另一种CHP纳米凝胶的骨传导性,CHP-A纳米凝胶交联的PEG凝胶(CHP-A纳米凝胶-水凝胶),在BMP-2和肽诱导的骨形成中。在5周龄雄性小鼠中进行了颅骨缺损模型,并将支架放置在缺损处。每周进行体内μCT。支架放置4周后的放射学和组织学分析显示,当支架用BMP-2和RANKL结合肽浸渍时,CHP-OA水凝胶中的钙化骨面积和缺损部位的骨形成活性显著低于CHP-A水凝胶中的钙化骨面积和骨形成活性。当用单独的BMP-2浸渍时,在CHP-A和CHP-OA水凝胶中诱导的骨量相似。总之,当通过RANKL结合肽和BMP-2的组合而不是单独的BMP-2诱导局部骨形成时,与CHP-OA水凝胶相比,CHP-A水凝胶可以是合适的支架。