Modulation of 3D fibrin matrix stiffness by intrinsic fibrinogen-thrombin compositions and by extrinsic cellular activity.
Modulation of 3D fibrin matrix stiffness by intrinsic fibrinogen-thrombin compositions and by extrinsic cellular activity.
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DOI：
10.1089/ten.tea.2008.0319
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发表时间：
2009-07
影响因子：
--
通讯作者：
Tawil B
中科院分区：
文献类型：
--
作者：
Duong H;Wu B;Tawil B
纤维蛋白是由凝血成分：纤维蛋白原和凝血酶催化转化而形成的物质。这两种成分的动力学决定了纤维蛋白结构的结构特性。我们之前已经表明，改变纤维蛋白原和凝血酶浓度在最终的三维（3D）纤维蛋白基质影响细胞增殖和分化。在这项研究中，我们进一步研究了纤维蛋白原和凝血酶浓度在不存在或存在成纤维细胞的情况下对三维纤维蛋白基质结构模量或刚度的影响。我们已经制备了不同纤维蛋白原和凝血酶配方的无成纤维细胞和嵌入成纤维细胞的3D纤维蛋白基质，并使用标准的机械测试方法测试了这些结构的刚度。结果表明，随着凝血酶和纤维蛋白原浓度的增加，硬度相应增加；纤维蛋白原组的增加更为显著，凝血酶组的增加程度较小。我们还研究了成纤维细胞对纤维蛋白结构刚度的影响。我们观察到成纤维细胞合并纤维蛋白结构的刚度随着它们的增殖和表现出扩散的形态而小幅增加。据我们所知，这是第一份详细阐述纤维蛋白原和凝血酶浓度、细胞增殖和三维纤维蛋白基质硬度之间关系的综合报告。获得的数据可能导致优化设计合适的生物支架，我们可以控制细胞增殖和结构完整性，用于各种组织工程应用。
Fibrin is a substance formed through catalytic conversion of coagulation constituents: fibrinogen and thrombin. The kinetics of the two constituents determines the structural properties of the fibrin architecture. We have shown previously that changing the fibrinogen and thrombin concentrations in the final three-dimensional (3D) fibrin matrix influenced cell proliferation and differentiation. In this study, we further examined the effect of changing fibrinogen and thrombin concentrations in the absence or presence of fibroblasts on the structural modulus or stiffness of 3D fibrin matrices. We have prepared fibroblast-free and fibroblast-embedded 3D fibrin matrices of different fibrinogen and thrombin formulations, and tested the stiffness of these constructs using standard mechanical testing assays. Results showed that there was a corresponding increase in stiffness with increasing thrombin and fibrinogen concentrations; the increase was more notable with fibrinogen and to a lesser degree with thrombin. The effect of fibroblasts on the stiffness of the fibrin construct was also examined. We have observed a small increase in the stiffness of the fibroblast-incorporated fibrin construct as they proliferated and exhibited spreading morphology. To our knowledge, this is the first comprehensive report detailing the relationship between fibrinogen and thrombin concentrations, cell proliferation, and stiffness in 3D fibrin matrices. The data obtained may lead to optimally design suitable bioscaffolds where we can control both cell proliferation and structural integrity for a variety of tissue engineering applications.
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