Electrospun membranes are widely used in tissue engineering. Regretfully, there is limited research on how its morphological characteristics precisely regulate macrophage activation and immune response. Therefore, electrospun poly-l-lactic acid (PLLA) membranes with different alignments (align and random) and diameters (nanoscale and microscale) are prepared to investigate the effects of different surface morphologies on M2 macrophage polarization. Additionally, transcriptome, proteome, and phosphoproteome sequencings are combined to examine the underlying regulatory mechanisms. The results show that the electrospun PLLA membranes with different surface morphologies have good biocompatibility and can regulate the phenotype and function of macrophages by changing the micromorphology of the matrix surface. Especially, macrophages cultured on the electrospun membranes of the A600 group exhibit higher M2 macrophage polarization than the other three groups. Furthermore, the findings demonstrate that electrospun PLLA membranes enhance AMP-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) signaling activation by upregulating the expression of integrin phosphoenolpyruvate carboxykinase 2 (PCK2), which is critical for M2 macrophage polarization. Taken together, electrospun PLLA membranes promote M2 macrophage polarization by regulating the PCK2/AMPK/mTOR signaling pathway. This research can provide further theoretical bases for scaffold design, immunoregulatory mechanisms, and clinical application based on electrospinning technology in the future.

中文翻译：

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电纺聚 L-乳酸膜通过调节 PCK2/AMPK/mTOR 信号通路促进 M2 巨噬细胞极化

静电纺丝膜广泛应用于组织工程中。遗憾的是，关于其形态特征如何精确调节巨噬细胞激活和免疫反应的研究还很有限。因此，制备了具有不同排列（排列和随机）和直径（纳米级和微米级）的电纺聚L-乳酸（PLLA）膜，以研究不同表面形态对M2巨噬细胞极化的影响。此外，结合转录组、蛋白质组和磷酸蛋白质组测序来检查潜在的调控机制。结果表明，不同表面形貌的电纺PLLA膜具有良好的生物相容性，可以通过改变基质表面的微形貌来调节巨噬细胞的表型和功能。特别是，在 A600 组的电纺膜上培养的巨噬细胞表现出比其他三组更高的 M2 巨噬细胞极化。此外，研究结果表明，电纺 PLLA 膜通过上调整合素磷酸烯醇丙酮酸羧激酶 2 (PCK2) 的表达来增强 AMP 激活蛋白激酶 (AMPK)/哺乳动物雷帕霉素靶点 (mTOR) 信号激活，这对于 M2 巨噬细胞极化至关重要。总之，电纺 PLLA 膜通过调节 PCK2/AMPK/mTOR 信号通路促进 M2 巨噬细胞极化。该研究可为未来基于静电纺丝技术的支架设计、免疫调节机制及临床应用提供进一步的理论基础。