Shen Shuxian, He Xuzhao, Chen Xiaoyi, Dong Lingqing, Cheng Kui, Weng Wenjian
School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Zhejiang University, Zhejiang, China.
The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang, China.
J Biomed Mater Res B Appl Biomater. 2021 Dec;109(12):2227-2236. doi: 10.1002/jbm.b.34884. Epub 2021 Jun 3.
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.
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直接电刺激过程中经常出现的多种不利干扰参数的影响,如表面电流、电化学反应产物和成分不均匀等。为了有效防止这些不利干扰,设计了一种新型的压电聚(偏二氟乙烯-三氟乙烯)(P(VDF-TrFE))层,将其涂覆在氧化铟锡(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,通过预极化过程可以轻松控制所设计的P(VDF-TrFE)涂层的表面电荷,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。令人惊讶的是,两个信号级联下游的串扰进一步增强了ERK通路的激活,促进了MSCs的成骨分化。因此,这种涂覆有P(VDF-TrFE)层的电刺激微电极提供了一种独特的策略,可操纵生物材料表面的多种元素来调节干细胞的命运决定。