Magnesium phosphate ceramics incorporating a novel indene compound promote osteoblast differentiation in vitro and bone regeneration in vivo
Magnesium phosphate ceramics incorporating a novel indene compound promote osteoblast differentiation in vitro and bone regeneration in vivo
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DOI：
10.1016/j.biomaterials.2017.11.032
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发表时间：
2018-03-01
期刊：
影响因子：
14
通讯作者：
Park, Eui Kyun
中科院分区：
文献类型：
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作者：
Kim, Ju Ang;Yun, Hui-suk;Park, Eui Kyun
将生物活性分子植入合成陶瓷支架是一项挑战。在这项研究中，为了增强骨再生，将磷酸镁（MgP）陶瓷支架与新型茚化合物KR-34893结合。KR-34893诱导原代人骨髓间充质干细胞（BMSCs）和成骨细胞MC 3 T3-E1细胞系中矿物质沉积和成骨细胞标志物基因表达。对作用方式的分析表明，KR-34893诱导MAPK/细胞外信号调节激酶和细胞外信号调节激酶的磷酸化，随后诱导骨形态发生蛋白7的表达，伴随SMAD 1/5/8磷酸化。因此，将KR-34893掺入通过在室温下3D打印制备的MgP支架中，然后进行水泥反应。KR-34893掺入的MgP（KR-MgP）在体外诱导成骨细胞分化标志物基因的表达。在大鼠颅骨缺损模型中，通过显微计算机断层扫描和组织学分析评估，与MgP支架相比，KR-MgP支架增强了骨再生并增加了骨体积。总之，我们开发了一种用于生产骨诱导性MgP支架的方法，该支架包含生物活性有机化合物，而无需高温烧结。KR-MgP支架增强体外成骨细胞活化和体内骨再生。(C)2017爱思唯尔有限公司版权所有
Incorporating bioactive molecules into synthetic ceramic scaffolds is challenging. In this study, to enhance bone regeneration, a magnesium phosphate (MgP) ceramic scaffold was incorporated with a novel indene compound, KR-34893. KR-34893 induced the deposition of minerals and expression of osteoblast marker genes in primary human bone marrow mesenchymal stem cells (BMSCs) and a mouse osteoblastic MC3T3-E1 cell line. Analysis of the mode of action showed that KR-34893 induced the phosphorylation of MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase, and subsequently the expression of bone morphogenetic protein 7, accompanied by SMAD1/5/8 phosphorylation. Accordingly, KR-34893 was incorporated into an MgP scaffold prepared by 3D printing at room temperature, followed by cement reaction. KR-34893-incorporated MgP (KR-MgP) induced the expression of osteoblast differentiation marker genes in vitro. In a rat calvaria defect model, KR-MgP scaffolds enhanced bone regeneration and increased bone volume compared with MgP scaffolds, as assessed by micro-computed tomography and histological analyses. In conclusion, we developed a method for producing osteoinductive MgP scaffolds incorporating a bioactive organic compound, without high temperature sintering. The KR-MgP scaffolds enhanced osteoblast activation in vitro and bone regeneration in vivo. (C) 2017 Elsevier Ltd. All rights reserved.