Therapeutic bioactive microcarriers: Co-delivery of growth factors and stem cells for bone tissue engineering
Therapeutic bioactive microcarriers: Co-delivery of growth factors and stem cells for bone tissue engineering
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DOI：
10.1016/j.actbio.2013.09.042
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发表时间：
2014-01-01
影响因子：
9.7
通讯作者：
Kim, H. -W.
中科院分区：
文献类型：
--
作者：
Perez, R. A.;El-Fiqi, A.;Kim, H. -W.
以溶胶-凝胶法制备的生物活性玻璃为载体，可有效地将治疗分子导入骨组织工程干细胞的培养中。具有不同浓度的Ca（0-30摩尔%）的硅溶胶在优化条件下配制成200 - 300 μ m的微球。形成了高度介孔结构，介孔尺寸为2.5-63 nm，比表面积为420-710 m2/g，这高度依赖于Ca浓度。在微球配制过程中，治疗分子可以有效地负载在介孔微载体中。细胞色素C（cyt C），用作释放研究的模型蛋白质，以高度可持续的方式释放，在几个月的时间内几乎为零级动力学;释放量在9天时接近2%，在40天时接近15%。在含Ca的微载体中观察到释放速率略有增加，这与溶解速率和孔径有关。Ca的存在加速了微载体表面羟基磷灰石的形成。在生物活性微载体上培养的细胞贴壁分布良好，增殖活跃，证实了微载体的三维基质作用。在大鼠皮下模型中进行的体内研究表明，所制备的微球具有令人满意的生物相容性。将碱性成纤维细胞生长因子（bFGF）作为治疗靶分子掺入微载体中。观察到bFGF类似于cyt C的缓慢释放模式。细胞粘附和增殖到显着更高的水平上的bEGF加载的微载体，证明了bFGF在细胞增殖潜力的有效作用。据信，开发的介孔生物活性玻璃微球代表了一类新的治疗性细胞递送载体，潜在地可用于可持续递送治疗性分子如生长因子，以及支持骨组织工程的干细胞增殖和成骨。(C)2013 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Novel microcarriers made of sol-gel-derived bioactive glasses were developed for delivering therapeutic molecules effectively while cultivating stem cells for bone tissue engineering. Silica sols with varying concentration of Ca (0-30 mol.%) were formulated into microspheres ranging from 200 to 300 mu m under optimized conditions. A highly mesoporous structure was created, with mesopore sizes of 2.5-63 nm and specific surface areas of 420-710 m(2) g(-1), which was highly dependent on the Ca concentration. Therapeutic molecules could be effectively loaded within the mesoporous microcarriers during microsphere formulation. Cytochrome C (cyt C), used as a model protein for the release study, was released in a highly sustainable manner, with an almost zero-order kinetics over a period of months; the amount released was similar to 2% at 9 days, and 15% at 40 days A slight increase in the release rate was observed in the-microcarrier containing Ca, which was related to the dissolution rate and pore size. The presence of Ca accelerated the formation of hydroxyapatite on the surface of the microcarriers. Cells cultured on the bioactive microcarriers were well adhered and distributed, and proliferated actively, confirming the three-dimensional substrate role of the microcarriers. An in vivo study performed in a rat subcutaneous model demonstrated the satisfactory biocompatibility of the prepared microspheres. As a therapeutic target molecule, basic fibroblast growth factor (bFGF) was incorporated into the microcarriers. A slow release pattern similar to that of cyt C was observed for bFGF. Cells adhered and proliferated to significantly higher levels on the bEGF-loaded microcarriers, demonstrating the effective role of bFGF in cell proliferative potential. It is believed that the developed mesoporous bioactive glass microspheres represent a new class of therapeutic cell delivery carrier, potentially useful in the sustainable delivery of therapeutic molecules such as growth factors, as well as in the support of stem cell proliferation and osteogenesis for bone tissue engineering. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.