首页> 外文期刊>Acta biomaterialia >Reduced hydraulic permeability of three-dimensional collagen scaffolds attenuates gel contraction and promotes the growth and differentiation of mesenchymal stem cells.
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Reduced hydraulic permeability of three-dimensional collagen scaffolds attenuates gel contraction and promotes the growth and differentiation of mesenchymal stem cells.

机译:三维胶原蛋白支架的水力渗透性降低,会减弱凝胶收缩并促进间充质干细胞的生长和分化。

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摘要

Optimal scaffold characteristics are essential for the therapeutic application of engineered tissues. Hydraulic permeability (k) affects many properties of collagen gels, such as mechanical properties, cell-scaffold interactions within three dimensions (3D), oxygen flow and nutrient diffusion. However, the cellular response to 3D gel scaffolds of defined k values has not been investigated. In this study, unconfined plastic compression under increasing load was used to produce collagen gels with increasing solid volume fractions. The Happel model was used to calculate the resulting permeability values in order to study the interaction of k with gel mechanical properties and mesenchymal stem cell (MSC)-induced gel contraction, metabolism and differentiation in both non-osteogenic (basal medium) and osteogenic medium for up to 3 weeks. Collagen gels of fibrillar densities ranging from 0.3 to >4.1 wt.% gave corresponding k values that ranged from 1.00 to 0.03 microm(2). Mechanical testing under compression showed that the collagen scaffold modulus increased with collagen fibrillar density and a decrease in k value. MSC-induced gel contraction decreased as a direct function of decreasing k value. Relative to osteogenic conditions, non-osteogenic MSC cultures exhibited a more than 2-fold increase in gel contraction. MSC metabolic activity increased similarly under both osteogenic and non-osteogenic culture conditions for all levels of plastic compression. Under osteogenic conditions MSC differentiation and mineralization, as indicated by alkaline phosphatase activity and von Kossa staining, respectively, increased in response to an elevation in collagen fibrillar density and decreased gel permeability. In this study, gel scaffolds with higher collagen fibrillar densities and corresponding lower k values provided a greater potential for MSC differentiation and appear most promising for bone grafting purposes. Thus, cell-scaffold interactions can be optimized by defining the 3D properties of collagen scaffolds through k adjustment.
机译:最佳的支架特性对于工程组织的治疗应用至关重要。水力渗透率(k)影响胶原蛋白凝胶的许多特性,例如机械特性,三维空间内的细胞-支架相互作用(3D),氧气流量和营养物扩散。但是,尚未研究对定义的k值的3D凝胶支架的细胞反应。在这项研究中,在增加的载荷下无限制的塑料压缩被用于生产具有增加的固体体积分数的胶原蛋白凝胶。为了研究k与凝胶力学性质和间充质干细胞(MSC)诱导的在非成骨性(基础培养基)和成骨性培养基中的凝胶收缩,代谢和分化的相互作用,使用Happel模型来计算最终的渗透率值长达3周。原纤维密度范围为0.3至> 4.1 wt。%的胶原蛋白凝胶产生的相应k值范围为1.00至0.03 microm(2)。压缩下的机械测试表明,胶原支架模量随胶原原纤维密度的增加和k值的降低而增加。 MSC引起的凝胶收缩是降低k值的直接函数。相对于成骨条件,非成骨MSC培养物的凝胶收缩增加了2倍以上。在所有水平的塑性压缩下,在成骨和非成骨培养条件下,MSC代谢活性均类似增加。在成骨条件下,分别通过碱性磷酸酶活性和von Kossa染色表明,MSC分化和矿化响应胶原纤维密度的增加和凝胶渗透性的降低而增加。在这项研究中,具有较高胶原纤维密度和相应较低k值的凝胶支架为MSC分化提供了更大的潜力,并且似乎最有希望用于骨移植。因此,可以通过k调节来定义胶原蛋白支架的3D特性来优化细胞-支架相互作用。

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