1 Department of Biomechanical Engineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, The Netherlands .
2 Orthopaedic Research Lab, Radboud Institute for Health Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
Tissue Eng Part B Rev. 2017 Oct;23(5):494-504. doi: 10.1089/ten.TEB.2016.0500. Epub 2017 May 3.
Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.
机械信号为控制细胞和组织发育提供了一种很有前途的方法。已经证实，细胞不断探测其机械微环境，并利用力反馈机制来改变自身，在可能的情况下，还改变其环境，以达到平衡状态。因此，正确的机械微环境（外部力以及细胞周围环境的力学特性和形状）对于细胞的正常功能是必要的。在体外或在体内非生物植入物的情况下，细胞处于人工环境中，因此添加适当的机械信号可以使细胞像在体内一样正常发挥功能。因此，已经开发了多种方法来向体外细胞施加机械刺激（例如基质拉伸、流动诱导的剪切应力、基质刚度、形貌和附着面积的调制）。这些方法不仅揭示了机械信号对细胞的影响，还为探测细胞分子和结构提供了方法，从而可以深入了解其作用的机制。然而，与体内条件相比，这些方法仍然较为简单，因为细胞的机械微环境是多种机械信号共同作用的结果。因此，体外细胞也施加了机械刺激的组合。这些研究的重点各不相同——开发了新的平台来施加复杂的机械刺激组合，观察刺激之间的合作/竞争，结合多种刺激的优势来实现一个应用，或揭示其作用的潜在机制。总的来说，这些研究提供了新的见解，这些见解是无法从以前的知识中预测到的。我们在这里回顾了一些这样的研究及其获得的见解，从而提出了继续和进一步发展这些研究的理由。
