Peripheral nerve injuries require a complex set of signals from cells, macrophages, and the extracellular matrix (ECM) to induce regeneration across injury sites and achieve functional recovery. Schwann cells (SCs), the major glial cell in the peripheral nervous system (PNS), are critical to nerve regeneration due to their inherent capacity for altering phenotype postinjury to facilitate wound healing. The ECM plays a vital role in wound healing as well as regulating cell phenotype during tissue repair. To examine the underlying mechanisms between the ECM and SCs, this work sought to determine how specific ECM cues regulate the phenotype of SCs. To address this, SCs were cultured on polydimethylsiloxane substrates of a variable Young's modulus coated with ECM proteins. Cells were analyzed for spreading area, proliferation, cell and nuclear shape, and c-Jun expression. It was found that substrates with a stiffness of 8.67 kPa coated with laminin promoted the highest expression of c-Jun, a marker signifying a "regenerative" SC. Microcontact printed, cell adhesive areas were then utilized to precisely control the geometry and spreading of SCs and by controlling spreading area and cellular elongation; expression of c-Jun was either promoted or downregulated. These results begin to address the significant interplay between ECM cues and phenotype of SCs, while offering a potential means to enhance PNS regeneration through cellular therapies.

中文翻译：

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细胞外基质提示调节雪旺细胞的形态，增殖和蛋白质表达。

周围神经损伤需要来自细胞，巨噬细胞和细胞外基质（ECM）的复杂信号集，以诱导跨损伤部位的再生并实现功能恢复。雪旺细胞（SCs）是周围神经系统（PNS）中的主要神经胶质细胞，由于其固有的改变表型损伤后促进伤口愈合的能力，对神经再生至关重要。ECM在伤口修复以及组织修复过程中调节细胞表型方面起着至关重要的作用。为了检查ECM和SC之间的潜在机制，这项工作试图确定特定的ECM提示如何调节SC的表型。为了解决这个问题，将SC培养在涂有ECM蛋白的可变杨氏模量的聚二甲基硅氧烷底物上。分析细胞的扩散面积，增殖，细胞和核的形状，以及c-Jun的表达。发现用层粘连蛋白涂覆的刚度为8.67 kPa的底物促进了c-Jun的最高表达，c-Jun是表示“再生” SC的标记。然后利用微接触印刷的细胞粘合区域来精确控制SC的几何形状和扩散，并通过控制扩散面积和细胞伸长率来控制SC的几何形状和扩散。c-Jun的表达被促进或被下调。这些结果开始解决ECM提示和SCs表型之间的重要相互作用，同时提供了通过细胞疗法增强PNS再生的潜在手段。然后利用细胞粘附区域来精确控制SC的几何形状和扩散，并通过控制扩散区域和细胞伸长率来控制SC的几何形状和扩散。c-Jun的表达被促进或被下调。这些结果开始解决ECM提示和SCs表型之间的重要相互作用，同时提供了通过细胞疗法增强PNS再生的潜在手段。然后利用细胞粘附区域来精确控制SC的几何形状和扩散，并通过控制扩散区域和细胞伸长率来控制SC的几何形状和扩散。c-Jun的表达被促进或被下调。这些结果开始解决ECM提示和SCs表型之间的重要相互作用，同时提供了通过细胞疗法增强PNS再生的潜在手段。