Shapiro J M, Oyen M L
Cambridge University Engineering Department, Trumpington Street, Cambridge, UK.
Horm Metab Res. 2016 Nov;48(11):726-736. doi: 10.1055/s-0042-100469. Epub 2016 Apr 14.
The microenvironment, which can be considered the sum of all the components and conditions surrounding a particular cell, is critical to moderating cellular behavior. In bone, interactions with the microenvironment can influence osteogenic differentiation, and subsequent extracellular matrix deposition, mineralization, and bone growth. Beyond regenerative medicine purposes, tissue engineering tools, namely cell-scaffold constructs, can be used as models of the bone microenvironment. Hydrogels, which are hydrophilic polymer networks, are popularly used for cell culture constructs due to their substantial water content and their ability to be tailored for specific applications. As synthetic microenvironments, a level of control can be exerted on the hydrogel structure and material properties, such that individual contributions from the scaffold on cellular behavior can be observed. Both biochemical and mechanical stimuli have been shown to modulate cellular behaviors. Hydrogels can be modified to present cell-interactive ligands, include osteoinductive moieties, vary mechanical properties, and be subject to external mechanical stimulation, all of which have been shown to affect osteogenic differentiation. Following "bottom-up" fabrication methods, levels of complexity can be introduced to hydrogel systems, such that the synergistic effects of multiple osteogenic cues can be observed. This review explores the utility of hydrogel scaffolds as synthetic bone microenvironments to observe both individual and synergistic effects from biochemical and mechanical signals on osteogenic differentiation. Ultimately, a better understanding of how material properties can influence cellular behavior will better inform design of tissue engineering scaffolds, not just for studying cell behavior, but also for regenerative medicine purposes.
微环境可被视为围绕特定细胞的所有成分和条件的总和，对调节细胞行为至关重要。在骨骼中，与微环境的相互作用可影响成骨分化以及随后的细胞外基质沉积、矿化和骨骼生长。除了用于再生医学目的外，组织工程工具，即细胞-支架构建体，可用作骨微环境的模型。水凝胶是亲水性聚合物网络，由于其高含水量以及能够针对特定应用进行定制，因而广泛用于细胞培养构建体。作为合成微环境，可以对水凝胶的结构和材料特性进行一定程度的控制，从而能够观察到支架对细胞行为的个体影响。生化刺激和机械刺激均已显示可调节细胞行为。水凝胶可以进行修饰以呈现细胞相互作用配体、包含骨诱导部分、改变机械性能并受到外部机械刺激，所有这些均已显示会影响成骨分化。遵循“自下而上”的制造方法，可以增加水凝胶系统的复杂性，从而能够观察到多种成骨信号的协同效应。本综述探讨了水凝胶支架作为合成骨微环境在观察生化和机械信号对成骨分化的个体和协同效应方面的效用。最终，更好地了解材料特性如何影响细胞行为将不仅有助于组织工程支架的设计，以便更好地研究细胞行为，还能用于再生医学目的。
