In contrast to homogeneous materials, the mechanical properties of fibrous substrates depend on the probing lengthscale. This suggests that cells feel very different mechanical cues than expected from the macroscale characterisation of the substrate materials. By means of multiscale computational analyses we study here the mechanical environment of cells adhering to typical electrospun networks used in biomedical applications, with comparable macroscopic stiffness but different fibre diameters. The stiffness evaluated at the level of focal adhesions varies significantly, and the overall magnitude is strongly affected by the fibre diameter. The microscopic stiffness evaluated at cell scale depends substantially on the network topology and is about one order of magnitude lower than the macroscopic stiffness of the substrate, and two to three orders of magnitude below the fibres' elastic modulus. Moreover, the translation of stiffness over the scales is modulated by global deformations of the scaffold. In particular, uniaxial or biaxial stretching of the substrate induces nonlinear microscopic stiffening. Finally, although electrospun networks allow long-range transmission of cell-induced deformations, the comparison between the range of forces measured in cell traction force microscopy and those required to markedly deform typical electrospun networks reveals an order of magnitude difference, suggesting that these scaffolds provide a rather rigid environment for cells. All these results underline that the achievement of mechanical biocompatibility at all relevant lengthscales, and over the whole range of physiological loading states is extremely challenging. At the same time, the study shows that the diameter, length and curvature of fibre segments might be tunable towards achieving this goal. STATEMENT OF SIGNIFICANCE: Electrospun fabrics have growing use as substrates and scaffolds in tissue engineering and other biomedical applications. Based on multiscale computational analyses, this study shows that substrates of comparable macroscopic stiffness can provide tremendously different mechanical micro-environments, and that cells adhering to fibrous substrates may thus experience by orders of magnitude different mechanical cues than it would be expected from macroscale material characterisation. The simulations further reveal that the transfer of stiffness over the length scales changes with macroscopic deformation, and identify some key parameters that govern the transfer ratio. We believe that such refined understanding of the multiscale aspects of mechanical biocompatibility is key to the development of successful scaffold materials.

中文翻译：

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电纺基材的多尺度刚度及其机械生物相容性方面。

与均质材料相比，纤维质基材的机械性能取决于探测长度范围。这表明细胞感觉到的机械暗示与衬底材料的宏观表征所预期的完全不同。通过多尺度计算分析，我们在这里研究了粘附在生物医学应用中典型电纺网络上的细胞的机械环境，具有相当的宏观刚度，但纤维直径不同。在粘着力水平评估的刚度变化很大，并且总体大小受纤维直径的强烈影响。在细胞尺度上评估的微观刚度基本上取决于网络拓扑，并且比基板的宏观刚度低大约一个数量级，比纤维的弹性模量低两到三个数量级。此外，刚度在标尺上的转换是通过脚手架的整体变形来调节的。特别地，基板的单轴或双轴拉伸引起非线性的微观硬化。最后，尽管静电纺丝网络允许细胞诱导的变形的远距离传递，但是在细胞牵引力显微镜下测得的力范围与使典型静电纺丝网络显着变形所需的力范围之间的比较显示出数量级的差异，表明这些支架提供了一个相当僵化的细胞环境。所有这些结果表明，在所有相关的长度范围内以及在整个生理负荷状态范围内实现机械生物相容性都极具挑战性。同时，研究表明，纤维段的直径，长度和曲率对于实现该目标可能是可调的。意义声明：电纺织物在组织工程和其他生物医学应用中越来越多地用作基材和支架。基于多尺度计算分析，这项研究表明，具有相当的宏观刚度的基底可以提供截然不同的机械微环境，因此粘附到纤维基底上的细胞所经历的机械线索可能会比宏观材料表征所预期的要高出几个数量级。 。该模拟进一步揭示，刚度在长度尺度上的传递随宏观变形而变化，并确定了控制传递比的一些关键参数。