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基于数值方法的模拟,用于预测血脑屏障芯片器官中的脑血管剪切应力。

Numerical approach-based simulation to predict cerebrovascular shear stress in a blood-brain barrier organ-on-a-chip.

作者信息

Jeong Sehoon, Seo Jae-Hyeong, Garud Kunal Sandip, Park Sung Woo, Lee Moo-Yeon

机构信息

Department of Healthcare Information Technology, Inje University, Gimhae, 50834, Republic of Korea; Department of Information Communication System, Inje University, Gimhae, 50834, Republic of Korea; Paik Institute for Clinical Research, Inje University, Busan, 47392, Republic of Korea.

Department of Mechanical Engineering, Dong-A University, Busan, 49315, Republic of Korea.

出版信息

Biosens Bioelectron. 2021 Jul 1;183:113197. doi: 10.1016/j.bios.2021.113197. Epub 2021 Mar 26.

Abstract

Most of the compounds are impermeable to the blood-brain barrier (BBB), which poses a significant challenge in the development of therapeutics for the treatment of neurological diseases. Most of the existing in vitro BBB models are not capable of mimicking the in vivo conditions and functions. The numerical approach-based simulation model was proposed to accurately predict the in vivo level shear stress for the microfluidic BBB-on-a-chip. The in vivo level shear stress was predicted for various conditions of volume flow rates, porosities of the polycarbonate membrane of the BBB model, and dimensions of the microfluidic channel. The in vivo shear stress of the microfluidic BBB model increased with a decrease in the dimension of the microfluidic channel and a decrease in the porosity. The in vivo shear stress predicted by the optimized numerical approach-based simulation was validated within 2.17% error with the experimental in vivo level of shear stress at the porosity of 0.01% and all volume flow rates. The shear stress value, according to the volume flow rate of the microfluidic BBB chip with the optimal microfluidic channel size, was effective for the successful formation of tight junctions in primary endothelial cell culture. In this regard, the proposed method provided a standard for the development of various microfluidic organ-on-chip devices that replicate the in vivo conditions and shear stress.

摘要

大多数化合物无法透过血脑屏障(BBB),这给神经疾病治疗药物的研发带来了重大挑战。现有的大多数体外血脑屏障模型都无法模拟体内条件和功能。基于数值方法的模拟模型被提出来,用于准确预测微流控芯片上血脑屏障的体内水平剪切应力。针对不同的体积流速、血脑屏障模型聚碳酸酯膜的孔隙率以及微流控通道尺寸等条件,预测了体内水平剪切应力。微流控血脑屏障模型的体内剪切应力随着微流控通道尺寸的减小和孔隙率的降低而增加。在孔隙率为0.01%以及所有体积流速下,基于优化的数值方法模拟预测的体内剪切应力与实验测得的体内水平剪切应力的误差在2.17%以内。根据具有最佳微流控通道尺寸的微流控血脑屏障芯片的体积流速得出的剪切应力值,对于原代内皮细胞培养中紧密连接的成功形成是有效的。在这方面,所提出的方法为开发各种能够复制体内条件和剪切应力的微流控芯片上器官装置提供了一个标准。

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