Mechanobiology, translating mechanical signals into biological ones, greatly affects cellular behavior. Steering cellular behavior for cell-based regenerative medicine approaches requires a thorough understanding of the orchestrating molecular mechanisms, among which mechanotransducive ones are being more and more elucidated. Because of their wide use and highly mechanotransduction dependent differentiation, this review focuses on mesenchymal stromal cells (MSCs), while also briefly relating the discussed results to other cell types. While the mechanotransduction pathways are relatively well-studied in 2D, much remains unknown of the role and regulation of these pathways in 3D. Ultimately, cells need to be cultured in a 3D environment to create functional de novo tissue. In this review, we explore the literature on the roles of different material properties on cellular behavior and mechanobiology in 2D and 3D. For example, while stiffness plays a dominant role in 2D MSCs differentiation, it seems to be of subordinate importance in 3D MSCs differentiation, where matrix remodeling seems to be key. Also, the role and regulation of some of the main mechanotransduction players are discussed, focusing on MSCs. We have only just begun to fundamentally understand MSCs and other stem cells behavior in 3D and more fundamental research is required to advance biomaterials able to replicate the stem cell niche and control cell activity. This better understanding will contribute to smarter tissue engineering scaffold design and the advancement of regenerative medicine.

机械生物学将机械信号转换为生物信号，极大地影响细胞行为。指导基于细胞的再生医学方法的细胞行为需要对协调的分子机制有透彻的了解，其中越来越多地阐明了机械转导的机制。由于它们的广泛使用和高度机械转导依赖性分化，因此本综述着重于间充质基质细胞（MSC），同时还将所讨论的结果与其他细胞类型简要相关。尽管在2D中对机械传导途径进行了较为深入的研究，但仍不清楚这些途径在3D中的作用和调控情况。最终，需要在3D环境中培养细胞以重新创建功能组织。在这篇综述中，我们探索了有关2D和3D中不同材料特性对细胞行为和力学生物学作用的文献。例如，尽管刚度在2D MSC分化中起着主要作用，但它似乎在3D MSC分化中却从不重要，而矩阵重塑似乎是关键。此外，讨论了一些主要的机械转导参与者的作用和调节，重点是间充质基质细胞。我们才刚刚开始从根本上了解3D中的MSC和其他干细胞行为，并且需要进行3D方面的更基础研究来推进这一点。这种更好的理解将有助于更智能的组织工程支架设计和再生医学的发展。