The Effect of Gradations in Mineral Content, Matrix Alignment, and Applied Strain on Human Mesenchymal Stem Cell Morphology within Collagen Biomaterials.
The Effect of Gradations in Mineral Content, Matrix Alignment, and Applied Strain on Human Mesenchymal Stem Cell Morphology within Collagen Biomaterials.
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DOI：
10.1002/adhm.201600181
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发表时间：
2016-07
影响因子：
10
通讯作者：
Harley BA
中科院分区：
文献类型：
--
作者：
Mozdzen LC;Thorpe SD;Screen HR;Harley BA
腱骨连接（TBJ）是一个独特的、力学动态的、结构渐变的解剖区域，它在肌腱和骨骼之间传递拉伸载荷。当前的手术修复技术依赖于机械固定，可能导致较高的再次失败率。我们最近描述了一类新的胶原蛋白生物材料，它包含离散的矿化区域和结构排列区域，这些区域通过连续的界面连接，以模拟渐变的腱骨附着结构。在此我们报道了渐变的生物材料环境以及不断增加的施加应变水平（0 - 20%）对间充质干细胞（MSC）取向和排列的综合影响。在具有与天然腱骨界面特征相符的矿物质含量和结构排列相反梯度的腱骨支架中，MSC的细胞核和肌动蛋白排列最初由局部孔隙结构决定，而施加的拉伸应变则增强了细胞在应变方向上的排列。相比之下，在不包含任何结构排列线索的层状支架中，MSC在无应变条件下随机排列，然后在垂直于施加应变的方向上排列。这些发现初步揭示了支架结构如何在施加应变的情况下提供重要的、可能具有竞争性的反馈，从而影响MSC的取向，并为未来组织工程再生腱骨附着点的努力奠定了基础。
我们报道了三维胶原蛋白支架中孔隙各向异性和矿物质含量的变化对MSC在响应拉伸应变时排列的影响。MSC始终沿着局部孔隙结构的方向排列，尽管在各向同性支架中，细胞响应应变时会垂直于应变方向排列。支架孔隙结构在应变情况下为影响MSC取向提供了重要的结构反馈。
The tendon-bone junction (TBJ) is a unique, mechanically dynamic, structurally graded anatomical zone which transmits tensile loads between tendon and bone. Current surgical repair techniques rely on mechanical fixation and can result in high re-failure rates. We have recently described a new class of collagen biomaterial that contains discrete mineralized and structurally aligned regions linked by a continuous interface to mimic the graded osteotendinous insertion. Here we report the combined influence of graded biomaterial environment and increasing levels of applied strain (0 – 20%) on MSC orientation and alignment. In osteotendinous scaffolds, which contain opposing gradients of mineral content and structural alignment characteristic of the native osteotendinous interface, MSC nuclear and actin alignment was initially dictated by the local pore architecture, while applied tensile strain enhanced cell alignment in the direction of strain. Comparatively, in layered scaffolds that did not contain any structural alignment cues, MSCs were randomly oriented in the unstrained condition, then became oriented in a direction perpendicular to applied strain. These findings provide an initial understanding of how scaffold architecture can provide significant, potentially competitive, feedback influencing MSC orientation under applied strain, and forms the basis for future tissue engineering efforts to regenerate the osteotendinous enthesis. We report the effect of transitions in pore anisotropy and mineral content across three-dimensional collagen scaffolds on MSC alignment in response to tensile strain. MSCs align consistently in the direction of local pore architecture, though in response to strain cells in isotropic scaffolds orient perpendicular to strain. Scaffold pore architecture provides significant structural feedback influencing MSC orientation under strain.