Stem cells reside in complex three-dimensional (3D) environments within the body that change with time, promoting various cellular functions and processes such as migration and differentiation. These complex changes in the surrounding environment dictate cell fate yet, until recently, have been challenging to mimic within cell culture systems. Hydrogel-based biomaterials are well suited to mimic aspects of these in vivo environments, owing to their high water content, soft tissue-like elasticity, and often-tunable biochemical content. Further, hydrogels can be engineered to achieve changes in matrix properties over time to better mimic dynamic native microenvironments for probing and directing stem cell function and fate. This review will focus on techniques to form hydrogel-based biomaterials and modify their properties in time during cell culture using select addition reactions, cleavage reactions, or non-covalent interactions. Recent applications of these techniques for the culture of stem cells in four dimensions (i.e., in three dimensions with changes over time) also will be discussed for studying essential stem cell processes.

中文翻译：

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用于4D干细胞培养的生物材料。

干细胞位于体内复杂的三维（3D）环境中，该环境会随时间而变化，从而促进各种细胞功能和过程，例如迁移和分化。周围环境中的这些复杂变化决定了细胞的命运，直到最近，在细胞培养系统中进行模拟仍是一个挑战。基于水凝胶的生物材料因其高水含量，柔软的类组织弹性和经常可调节的生化含量而非常适合于模拟这些体内环境。此外，可以对水凝胶进行改造，以实现基质特性随时间的变化，从而更好地模拟动态天然微环境，以探测和指导干细胞的功能和命运。这项审查将侧重于形成基于水凝胶的生物材料并使用选择的加成反应，裂解反应或非共价相互作用在细胞培养过程中及时修改其特性的技术。这些技术在干细胞培养的四个方面（即随着时间变化的三个方面）的最新应用也将被讨论，以研究基本的干细胞过程。