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Computational Modeling of 3D Printed Hepatic Spheroids Inside a Bioreactor

机译:生物反应器内部3D打印肝球的计算建模

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Finding optimized conditions in analyzing in vitro drug hepatotoxicity especially during preliminary stages of drug development is highly appreciated. Recently, liver-on-chip platforms have been widely used in drug toxicity researches. Although perfusion in the bioreactor will enhance oxygen and nutrition delivery to the hepatocytes and decrease hypoxic zone in the bioreactor, high perfusion rate impose high shear stress on liver cells which may be detrimental or effect on their liver specific functions. Here, a three-dimensional bioreactor containing hepatic spheroids is developed numerically and velocity distribution, shear stress sensed by cells was calculated. Based on the rate of oxygen delivery and oxygen metabolic activities of the hepatocytes, the level of oxygen for each spheroid was analyzed. Also, albumin production of the hepatic cells was modeled as an example of modeling metabolic function capabilities. The computed albumin production was verified with the experimental results over 7 days of culture period which showed a good compatibility between the experimental results and numerical predictions. The results are of a great importance in finding an optimal design and working conditions of the bioreactors.
机译:在分析体外药物肝毒性时,尤其是在药物开发的初期阶段,找到最佳条件进行分析是高度赞赏的。近来,肝片平台已被广泛用于药物毒性研究。尽管在生物反应器中的灌注将增强向肝细胞的氧气和营养输送,并减少生物反应器中的缺氧区,但是高灌注率对肝细胞施加了高剪切应力,这可能有害或影响其肝特异性功能。在这里,三维开发了一个包含肝球体的三维生物反应器,并计算了速度分布,细胞感测到的剪切应力。基于肝细胞的氧气输送速率和氧气代谢活性,分析了每个球体的氧气水平。同样,肝细胞白蛋白的产生被建模为模拟代谢功能能力的一个例子。培养7天的实验结果验证了计算出的白蛋白产量,显示出实验结果与数值预测之间的良好兼容性。结果对于寻找生物反应器的最佳设计和工作条件非常重要。

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