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Viscoelastic hydrogels for 3D cell culture

机译：用于3D细胞培养的粘弹性水凝胶

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摘要

In tissues, many cells are surrounded by and interact with a three-dimensional soft extracellular matrix (ECM). Both the physical and biochemical properties of the ECM play a major role in regulating cell behaviours. To better understand the impact of ECM properties on cell behaviours, natural and synthetic hydrogels have been developed for use as synthetic ECMs for 3D cell culture. It has long been known that ECM and tissues are viscoelastic, or display a time-dependent response to deformation or mechanical loading, exhibiting stress relaxation and creep. However, only recently have there been efforts made to understand the role of the time-dependent aspects of the ECM mechanics on regulating cell behaviours using hydrogels for 3D culture. Here we review the characterization and molecular basis of hydrogel viscoelasticity and plasticity, and describe newly developed approaches to tuning viscoelasticity in hydrogels for 2D and 3D culture. Then we highlight several recent studies finding a potent impact of hydrogel stress relaxation or creep on cell behaviours such as cell spreading, proliferation, and differentiation of mesenchymal stem cells. The role of time-dependent mechanics on cell biology remains largely unclear, and ripe for further exploration. Further elucidation of this topic may substantially advance our understanding of cell-matrix interactions during development, homeostasis, wound healing, and disease, and guide the design of biomaterials for regenerative medicine.
机译：在组织中，许多细胞被三维软细胞外基质（ECM）包围并与三维软细胞外基质（ECM）相互作用。 ECM的物理和生化特性既在调节细胞行为方面发挥了重要作用。为了更好地了解ECM性能对细胞行为的影响，已经开发了天然和合成水凝胶作为3D细胞培养的合成ECM。众所周知，ECM和组织是粘弹性的，或者显示时间依赖于变形或机械负载的时间响应，表现出应力松弛和蠕变。然而，最近只有努力了解ECM力学的时间依赖性方面的作用，以利用水凝胶进行3D培养的调节细胞行为。在这里，我们审查了水凝胶粘弹性和可塑性的表征和分子基础，并描述了新开发的方法来调节水凝胶中的水凝块，用于2D和3D培养。然后，我们突出了几个最近的研究发现水凝胶应力松弛或蠕变对细胞行为（例如细胞扩散，增殖和间充质干细胞的分化）的有效影响。时间依赖力学对细胞生物学的作用仍然很大程度上不清楚，并成熟以进一步探索。进一步阐明本课题可能大大提高了我们在开发，稳态，伤口愈合和疾病期间对细胞基质相互作用的理解，并指导生物材料的设计进行再生药。

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