3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression.
3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression.
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DOI：
10.1016/j.actbio.2017.12.042
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发表时间：
2018-03-15
影响因子：
9.7
通讯作者：
Shah RN
中科院分区：
文献类型：
--
作者：
Lewis PL;Green RM;Shah RN
三维(3D)打印非常适合于组织工程器官的制造，这些器官具有重复的微结构，如肝脏。均匀的和几何上重复的组织支架的创建还可以控制细胞聚集和营养扩散。然而，在控制孔径大小的同时，不同几何形状的影响还有待于在肝细胞功能方面进行研究。在这项研究中，我们展示了精确控制3D打印明胶支架孔几何形状的能力。未分化肝细胞系(HuH7)种植在两种不同几何形状的3D打印支架上后，显示出高活性和高增殖能力。然而，与较少相互连接的几何图形和2D对照相比，在3D打印明胶培养中，肝细胞特异性功能(白蛋白分泌、细胞色素P450活性和胆汁转运)增加。此外，我们还说明了在简单的2D培养模式下基因表达和蛋白质功能之间的差异，以及重建生理模拟的3D环境对于诱导培养的肝细胞的表达和功能是必要的。
Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect of differing geometries, while controlling for pore size, has yet to be investigated in the context of hepatocyte function. In this study, we show the ability to precisely control pore geometry of 3D-printed gelatin scaffolds. An undifferentiated hepatocyte cell line (HUH7) demonstrated high viability and proliferation when seeded on 3D-printed scaffolds of two different geometries. However, hepatocyte specific functions (albumin secretion, CYP activity, and bile transport) increases in more interconnected 3D-printed gelatin cultures compared to a less interconnected geometry and to 2D controls. Additionally, we also illustrate the disparity between gene expression and protein function in simple 2D culture modes, and that recreation of a physiologically mimetic 3D environment is necessary to induce both expression and function of cultured hepatocytes.
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