Electrical stimulation has been proved to be critical to regulate cell behavior. But, cell behavior is also susceptible to multiple parameters of the adverse interferences such as surface current, electrochemical reaction products, and non-uniform compositions, which often occur during direct electric stimulation. To effectively prevent the adverse interferences, a novel piezoelectric poly(vinylidene fluoride-trfluoroethylene)(P(VDF-TrFE)) layer was designed to coat onto the indium tin oxide (ITO) planar microelectrode. We found the electrical stimulation was able to regulate the osteogenic differentiation of mesenchymal stem cells (MSCs) through calcium-mediated PKC signaling pathway. Meanwhile, the surface charge of the designed P(VDF-TrFE) coating layer could be easily controlled by the pre-polarization process, which was demonstrated to trigger integrin-mediated FAK signaling pathway, finally up-regulating the osteogenic differentiation of MSCs. Strikingly, the crosstalk in the downstream of the two signaling cascades further strengthened the ERK pathway activation for osteogenic differentiation of MSCs. This P(VDF-TrFE) layer coated electrical stimulation microelectrodes therefore provide a distinct strategy to manipulate multiple-elements of biomaterial surface to regulate stem cell fate commitment.

中文翻译：

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在 P(VDF-TrFE) 层包被的微电极上增强间充质干细胞的成骨分化

电刺激已被证明对调节细胞行为至关重要。但是，细胞行为也容易受到多种不利干扰参数的影响，例如表面电流、电化学反应产物和不均匀的成分，这些不利干扰通常发生在直接电刺激过程中。为了有效防止不利干扰，设计了一种新型压电聚（偏二氟乙烯-三氟乙烯）（P（VDF-TrFE））层来涂覆在氧化铟锡（ITO）平面微电极上。我们发现电刺激能够通过钙介导的 PKC 信号通路调节间充质干细胞 (MSCs) 的成骨分化。同时，设计的P（VDF-TrFE）涂层的表面电荷可以通过预极化过程轻松控制，这被证明可以触发整合素介导的 FAK 信号通路，最终上调 MSCs 的成骨分化。引人注目的是，两个信号级联下游的串扰进一步加强了 ERK 通路对 MSCs 成骨分化的激活。因此，这种 P(VDF-TrFE) 层涂覆的电刺激微电极提供了一种独特的策略来操纵生物材料表面的多种元素以调节干细胞命运承诺。