Stem cells hold great promise for widespread biomedical applications, for which stem cell fate needs to be well tailored. Besides biochemical cues, accumulating evidence has demonstrated that spatiotemporal biophysical cues (especially mechanical cues) imposed by cell microenvironments also critically impact on the stem cell fate. As such, various biomaterials, especially hydrogels due to their tunable physicochemical properties and advanced fabrication approaches, are developed to spatiotemporally manipulate biophysical cues in vitro so as to recapitulate the 3D mechanical microenvironment where stem cells reside in vivo. Here, the main mechanical cues that stem cells experience in their native microenvironment are summarized. Then, recent advances in the design of hydrogel materials with spatiotemporally tunable mechanical properties for engineering 3D the spatiotemporal mechanical microenvironment of stem cells are highlighted. These in vitro engineered spatiotemporal mechanical microenvironments are crucial for guiding stem cell fate and their potential biomedical applications are subsequently discussed. Finally, the challenges and future perspectives are presented.

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3D时空机械微环境：指导干细胞命运的基于水凝胶的平台

干细胞在广泛的生物医学应用中具有广阔的前景，为此需要对干细胞的命运进行适当的调整。除了生化线索外，越来越多的证据表明，由细胞微环境施加的时空生物物理线索（特别是机械线索）也对干细胞的命运有重要影响。这样，各种生物材料，特别是由于其可调节的物理化学性质和先进的制造方法而形成的水凝胶，可以在时空上在体外操纵生物物理线索，从而概括干细胞在体内的3D机械微环境。在此，总结了干细胞在其天然微环境中经历的主要机械信号。然后，具有时空可调机械性能的水凝胶材料设计的最新进展，可用于工程3D干细胞的时空机械微环境。这些体外工程化的时空机械微环境对于指导干细胞的命运至关重要，随后将讨论它们的潜在生物医学应用。最后，提出了挑战和未来展望。