In-vitro osteogenesis of synovium stem cells induced by controlled release of bisphosphate additives from microspherical mesoporous silica composite
In-vitro osteogenesis of synovium stem cells induced by controlled release of bisphosphate additives from microspherical mesoporous silica composite
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DOI：
10.1016/j.biomaterials.2009.04.021
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发表时间：
2009-08-01
期刊：
影响因子：
14
通讯作者：
Wang, Dong-An
中科院分区：
文献类型：
--
作者：
Shi, Xuetao;Wang, Yingjun;Wang, Dong-An
在这项研究中，在体外成功地诱导高度软骨形成滑膜间充质干细胞（SMSCs）的含氮双膦酸盐添加剂阿仑膦酸盐（AL）的控制释放介导的聚（乳酸-羟基乙酸）（PLGA）微球介导的介孔二氧化硅（MS）-羟基磷灰石（HA）复合物。这种基于微球的控释系统由三个层次的可降解结构构建：（1）首先将AL药物与HA纳米颗粒杂化;（2）通过原位自组装将HA-AL复合物填充到MS颗粒的介孔中;以及（3）在PLGA微球的本体中构建载有HA-AL的MS构建物（MSH-AL）。与任何单组分结构相比，该多组分系统的优越性来自两个方面的功能：（1）极亲水性药物-AL的显著更大的负载能力;和（2）AL释放的更好的控制曲线。基于这种新开发的PLGA/MSH-AL释放系统，作为受体的SMSCs，通常仅表现出高软骨形成，表现出强的成骨承诺。通过碱性磷酸酶（ALP）活性测定、钙分泌测定、真实的时间PCR和免疫组化分析对结果进行验证。考虑到SMSCs的可再生来源和高增殖特性，使用这种PLGA/MSH-AL控释系统实现工程化SMSCs成骨将为主要的骨修复和再生打开新的大门。(C)2009爱思唯尔有限公司保留所有权利。
In this study, in-vitro osteogenesis was successfully induced in the highly chondrogenic synovium mesenchymal stem cells (SMSCs) by controlled release of a nitrogenous bisphosphonate additive alendronate (AL) from a mesoporous silica (MS)-hydroxyapatite (HA) composite that was mediated in poly(lactic-co-glycolic acid) (PLGA) microspheres. This microspherical based controlled release system is constructed with three levels of degradable structures: (1) the AL drug was first hybridized with HA nanoparticles; (2) the HA-AL complexes were filled into the mesopores of MS particles by self-assembly in situ; and (3) the HA-AL-laden MS constructs (MSH-AL) were built in the bulk of PLGA microspheres. In comparison with any mono-component construct, the superiority of this multi-component system comes from two aspects of functionalities: (1) significantly greater loading capacity of the extremely hydrophilic drug-AL: and (2) better controlled profile of AL release. Based on this newly developed PLGA/MSH-AL releasing system, as recipients the SMSCs, which usually exhibit exclusively high chondrogenesis, demonstrated a strong osteogenic commitment. The results were verified by alkaline phosphatase (ALP) activity assay, calcium secretion assay, real time PCR and immunohistochemistry analysis. Considering the renewable source and high proliferative profile of SMSCs, the achievement of engineered SMSC osteogenesis with this PLGA/MSH-AL controlled release system would open a new door to major bony reparation and regeneration. (C) 2009 Elsevier Ltd. All rights reserved.