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Screening of rat mesenchymal stem cell behaviour on polydimethylsiloxane stiffness gradients

机译:聚二甲基硅氧烷刚度梯度对大鼠间充质干细胞行为的筛选

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Substrate stiffness is emerging as an effective tool for the regulation of cell behaviours such as locomotion, proliferation and differentiation. In order to explore the potential application of this biophysical tool, material platforms displaying lateral and continuously graded stiffness are advantageous since they allow the systematic exploration of adherent cell response to substrate stiffness and the tuning of the material to elicit the desired cell behaviour. Here, we demonstrate a simple approach towards the fabrication of polydimethylsiloxane (PDMS) stiffness gradients (with an indentation modulus of 190 kPa-3.1 MPa across a 12 mm distance) by means of a temperature gradient during curing. We then apply these stiffness gradients to the screening of osteogenic differentiation in rat mesenchymal stem cells (rMSCs). Our proof-of-principle results show that mineralization of rMSCs is strongly dependent on the PDMS substrate stiffness, but is also influenced by the display of extracellular matrix proteins preadsorbed on the gradients. This screening capability holds tremendous potential for the design of improved implant materials and tissue engineering scaffolds.
机译:基质刚度正在成为调节细胞行为(如运动,增殖和分化)的有效工具。为了探索这种生物物理工具的潜在应用,显示侧向和连续分级刚度的材料平台是有利的,因为它们允许系统地探索贴壁细胞对基质刚度的响应以及对材料的调节以引发所需的细胞行为。在这里,我们展示了一种通过固化过程中的温度梯度来制造聚二甲基硅氧烷(PDMS)硬度梯度(压痕模量为190 kPa-3.1 MPa,跨12 mm距离)的简单方法。然后,我们将这些刚度梯度应用于大鼠间充质干细胞(rMSCs)的成骨分化筛选。我们的原理证明结果表明,rMSCs的矿化作用很大程度上取决于PDMS底物的刚度,但也受梯度上预吸附的细胞外基质蛋白显示的影响。这种筛选能力为设计改进的植入物材料和组织工程支架具有巨大的潜力。

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