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Therapeutic bioactive microcarriers: Co-delivery of growth factors and stem cells for bone tissue engineering

机译:治疗性生物活性微载体:骨组织工程中生长因子和干细胞的共同递送

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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 μm under optimized conditions. A highly mesoporous structure was created, with mesopore sizes of 2.5-6.3 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 ~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 bFGF-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.
机译:开发了由溶胶-凝胶衍生的生物活性玻璃制成的新型微载体,可有效地输送治疗分子,同时培养用于骨组织工程的干细胞。在优化的条件下,将具有不同浓度的Ca(0-30 mol。%)的硅溶胶配制为200至300μm的微球。产生了高度介孔的结构,介孔尺寸为2.5-6.3 nm,比表面积为420-710 m 2 g-1,这高度依赖于Ca的浓度。在微球配制过程中,治疗分子可以有效地负载在中孔微载体中。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,在几个月的时间内动力学几乎为零。 9天释放量约为2%,40天释放量为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的存在促进了微载体表面上羟基磷灰石的形成。在生物活性微载体上培养的细胞被很好地粘附和分布,并活跃地增殖,从而证实了微载体的三维底物作用。在大鼠皮下模型中进行的体内研究表明,制备的微球具有令人满意的生物相容性。作为治疗靶分子,将碱性成纤维细胞生长因子(bFGF)掺入到微载体中。对于bFGF,观察到类似于cyt C的缓慢释放模式。在粘附有bFGF的微载体上,细胞粘附并增殖到明显更高的水平,证明bFGF在细胞增殖潜力中的有效作用。据信,已开发的中孔生物活性玻璃微球代表了一类新型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(例如生长因子)以及支持干细胞增殖和骨生成以用于骨组织工程。

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