Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSCs). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSCs are interconnected via intracellular Ca2+ Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.

中文翻译：

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具有可编程生物指令性的聚合物薄板促动器。

干细胞能够感知和处理环境输入，将这些信息转换为通过信号级联输出特定细胞谱系。尽管机械，热和生化信号具有组合性质，但这些刺激通常已分离并独立应用，需要通过控制单元进行连续调节。我们采用可编程的聚合物执行器片来自动同步施加到间充质干细胞（MSC）的热和机械信号。使用其下侧的网格，可以可视化和量化聚合物片材的形状变化以及细胞形态，钙（Ca2 +）流入和粘着斑组装。本文提供了令人信服的证据，表明MSC的温度感测和机械传感通过细胞内Ca2 +相互关联。Ca2+的上调导致组蛋白H3K9乙酰化的显着改变和成骨相关基因的激活。物理，热和生化信号之间的相互作用被用来加速细胞向成骨谱系的分化。可编程生物指导性方法为功能性生物材料在分化程序中表现出多方面的刺激提供了基本原理。有望在骨膜组织工程中治疗骨缺损。并利用生化信号加速细胞向成骨细胞系的分化。可编程生物指导性方法为功能性生物材料在分化程序中表现出多方面的刺激提供了基本原理。有望在骨膜组织工程中治疗骨缺损。并利用生化信号加速细胞向成骨细胞系的分化。可编程生物指导性方法为功能性生物材料在分化程序中表现出多方面的刺激提供了基本原理。有望在骨膜组织工程中治疗骨缺损。