Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteloblasts in a dose-dependent manner

Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteloblasts in a dose-dependent manner
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DOI:
10.1073/pnas.202296599
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发表时间:
2002-10-01
影响因子:
11.1
通讯作者:
Mikos, AG
Mikos, AG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bancroft, GN;Sikavitsast, VI;Mikos, AG

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骨是由细胞和基质元素组成的复杂的高度结构化的机械活性3D组织。因此,骨细胞的真实生物环境源自经历机械力的响应性活性细胞与连续变化的3D矩阵结构之间的动态相互作用。为了在体外研究这种现象,将骨髓基质成骨细胞在3D支架上以不同流速进行流动灌注培养一段时间,以允许成骨细胞分化并产生大量基质和矿化。在所有的流动条件下,矿化基质的产生比静态培养的结构显著增加,培养的支架的总钙含量随着流速的增加而增加。流动灌注诱导从头组织建模与孔隙样结构的支架中的形成,并提高整个支架的细胞和基质的分布。这些结果代表了流体流动对初级分化成骨细胞的长期影响的报告,并表明流体流动对体外成骨细胞分化和表型表达具有深远的影响。流动灌注培养允许生成和研究的3D,积极建模,矿化基质,因此可以是一个有价值的工具,骨生物学和组织工程。
Bone is a complex highly structured mechanically active 3D tissue composed of cellular and matrix elements. The true biological environment of a bone cell is thus derived from a dynamic interaction between responsively active cells experiencing mechanical forces and a continuously changing 3D matrix architecture. To investigate this phenomenon in vitro, marrow stromal osteoblasts were cultured on 3D scaffolds under flow perfusion with different rates of flow for an extended period to permit osteoblast differentiation and significant matrix production and mineralization. With all flow conditions, mineralized matrix production was dramatically increased over statically cultured constructs with the total calcium content of the cultured scaffolds increasing with increasing flow rate. Flow perfusion induced de novo tissue modeling with the formation of pore-like structures in the scaffolds and enhanced the distribution of cells and matrix throughout the scaffolds. These results represent reporting of the long-term effects of fluid flow on primary differentiating osteoblasts and indicate that fluid flow has far-reaching effects on osteoblast differentiation and phenotypic expression in vitro. Flow perfusion culture permits the generation and study of a 3D, actively modeled, mineralized matrix and can therefore be a valuable tool for both bone biology and tissue engineering.