The design of cell-instructive biomaterials for tissue engineering and regenerative medicine is at a crossroads. Although the conventional tissue engineering approach is top-down (cells seeded to macroporous scaffolds and mature to form tissues), bottom-up tissue engineering strategies are becoming appealing. With such developments, we can study cell signaling events, thus enabling functional tissue assembly in physiologic and diseased models. Among many important signaling pathways, the Notch signaling pathway is the most diverse in its influence during tissue morphogenesis and repair following injury. Although Notch signaling is extensively studied in developmental biology and cancer biology, our knowledge of designing biomaterial-based Notch signaling platforms and incorporating Notch signaling components into engineered tissue systems is limited. By incorporating Notch signaling to tissue engineering scaffolds, we can direct cell-specific responses and improve engineered tissue maturation. This review will discuss recent progress in the development of Notch signaling biomaterials as a promising target to control cellular fate decisions, including the influences of ligand identity, biophysical material cues, ligand presentation strategies, and mechanotransduction. Notch signaling is consequently of interest to direct, control, and reprogram cellular behavior on a biomaterial surface. We anticipate that discussions in this article will allow for enhanced knowledge and insight into designing Notch targeted biomaterials for various tissue engineering and cell fate determinations.

中文翻译：

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设计生物材料以调节组织工程和再生医学中的 Notch 信号

用于组织工程和再生医学的细胞指导性生物材料的设计正处于十字路口。尽管传统的组织工程方法是自上而下的（细胞接种到大孔支架并成熟形成组织），但自下而上的组织工程策略正变得越来越有吸引力。有了这样的发展，我们可以研究细胞信号事件，从而在生理和疾病模型中实现功能性组织组装。在许多重要的信号通路中，Notch 信号通路在组织形态发生和损伤后修复过程中的影响最为广泛。尽管 Notch 信号在发育生物学和癌症生物学中得到了广泛的研究，我们在设计基于生物材料的 Notch 信号平台和将 Notch 信号组件整合到工程组织系统方面的知识是有限的。通过将 Notch 信号传导到组织工程支架，我们可以指导细胞特异性反应并改善工程组织的成熟。本综述将讨论 Notch 信号生物材料作为控制细胞命运决定的有希望的目标的最新进展，包括配体身份、生物物理材料线索、配体呈递策略和机械转导的影响。因此，Notch 信号传导对于指导、控制和重新编程生物材料表面上的细胞行为很重要。