Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration.
Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration.
复制标题
介孔羟基磷灰石微球衍生的辛伐他汀缓释系统增强成骨和血管生成，实现卓越的骨再生。
DOI：
10.1038/srep44129
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发表时间：
2017-03-13
影响因子：
4.6
通讯作者：
He YH
中科院分区：
文献类型：
--
作者：
Yu WL;Sun TW;Qi C;Zhao HK;Ding ZY;Zhang ZW;Sun BB;Shen J;Chen F;Zhu YJ;Chen DY;He YH
同时具有良好的成骨和血管生成活性的生物材料是修复大量骨缺损的理想材料。本研究以1，6-二磷酸果糖三钠盐(FBP)为有机磷源，采用微波辅助水热法制备了具有成骨和血管生成活性的介孔羟基磷灰石微球(MHMS)。研究了辛伐他汀复合微球(S微球)对大鼠骨髓间充质干细胞(RBMSCs)成骨分化和EA.hy926细胞血管生成的影响。结果表明，S-MHMS不仅增强了rBMSCs成骨标志物的表达，而且还促进了EA.hy926细胞的迁移和管状形成。此外，将S-MHMS复合到胶原基质中，构建了一种新型的S-MHMS/胶原复合支架。在MHMS的辅助下，辛伐他汀不溶于水，均匀地结合到亲水性胶原基质中，并呈现出缓释特性。体内实验表明，S-MHMS/胶原支架同时促进了骨再生和新生血管的形成。这些结果表明，水不溶性辛伐他汀可以被整合到MHMS中并保持其生物活性，更重要的是，本研究制备的S-MHMS/胶原支架通过促进成骨和血管生成在骨缺损修复方面具有巨大的潜力。
Biomaterials with both excellent osteogenic and angiogenic activities are desirable to repair massive bone defects. In this study, simvastatin with both osteogenic and angiogenic activities was incorporated into the mesoporous hydroxyapatite microspheres (MHMs) synthesized through a microwave-assisted hydrothermal method using fructose 1,6-bisphosphate trisodium salt (FBP) as an organic phosphorous source. The effects of the simvastatin-loaded MHMs (S-MHMs) on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and angiogenesis in EA.hy926 cells were investigated. The results showed that the S-MHMs not only enhanced the expression of osteogenic markers in rBMSCs but also promoted the migration and tube formation of EA.hy926 cells. Furthermore, the S-MHMs were incorporated into collagen matrix to construct a novel S-MHMs/collagen composite scaffold. With the aid of MHMs, the water-insoluble simvastatin was homogenously incorporated into the hydrophilic collagen matrix and presented a sustained release profile. In vivo experiments showed that the S-MHMs/collagen scaffolds enhanced the bone regeneration and neovascularization simultaneously. These results demonstrated that the water-insoluble simvastatin could be incorporated into the MHMs and maintained its biological activities, more importantly, the S-MHMs/collagen scaffolds fabricated in this study are of immense potential in bone defect repair by enhancing osteogenesis and angiogenesis simultaneously.