Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds.
Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds.
复制标题
通过加载 BMP-2 释放壳聚糖/藻酸盐/羟基磷灰石支架上的 MSC 来增强大鼠颅骨缺损的愈合。
DOI：
10.1371/journal.pone.0104061
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
He X;Liu Y;Yuan X;Lu L
本研究设计了一种壳聚糖/藻酸盐/羟基磷灰石复合支架作为重组BMP-2（CAH/B2）的载体，并对BMP-2的释放动力学进行了评价。通过扫描电镜、MTS、碱性磷酸酶（ALP）测定、茜素红染色和qRT-PCR等方法评价CAH/B2支架对骨髓间充质干细胞（MSCs）活力和分化的影响。此外，将MSC接种在支架上并用于8 mm大鼠颅骨缺损模型中。术后12周通过放射学、苏木精和伊红染色评估新骨形成。我们发现，与广泛用于BMP-2递送的胶原凝胶相比，CAH/B2支架中BMP-2的释放动力学延迟。从支架释放的BMP-2增加了MSC分化，并且没有显示出任何细胞毒性。MSCs表现出更高的ALP活性以及更强的钙矿物质沉积，骨相关标志物Col 1 α、骨桥蛋白和骨钙素上调。体内骨形成的分析表明，CAH/B2支架比其他组诱导更多的骨形成。这项研究表明，CAH/B2支架可能是有用的提供成骨BMP-2蛋白，并提出了一个有前途的骨再生策略。
In this study, we designed a chitosan/alginate/hydroxyapatite scaffold as a carrier for recombinant BMP-2 (CAH/B2), and evaluated the release kinetics of BMP-2. We evaluated the effect of the CAH/B2 scaffold on the viability and differentiation of bone marrow mesenchymal stem cells (MSCs) by scanning electron microscopy, MTS, ALP assay, alizarin-red staining and qRT-PCR. Moreover, MSCs were seeded on scaffolds and used in a 8 mm rat calvarial defect model. New bone formation was assessed by radiology, hematoxylin and eosin staining 12 weeks postoperatively. We found the release kinetics of BMP-2 from the CAH/B2 scaffold were delayed compared with those from collagen gel, which is widely used for BMP-2 delivery. The BMP-2 released from the scaffold increased MSC differentiation and did not show any cytotoxicity. MSCs exhibited greater ALP activity as well as stronger calcium mineral deposition, and the bone-related markers Col1α, osteopontin, and osteocalcin were upregulated. Analysis of in vivo bone formation showed that the CAH/B2 scaffold induced more bone formation than other groups. This study demonstrates that CAH/B2 scaffolds might be useful for delivering osteogenic BMP-2 protein and present a promising bone regeneration strategy.