Purpose

The cardiovascular endothelium experiences pulsatile and multidirectional fluid wall shear stress (WSS). While the effects of non-physiologic WSS magnitude and pulsatility on cardiovascular function have been studied extensively, the impact of directional abnormalities remains unknown due to the challenge to replicate this characteristic in vitro. To address this gap, this study aimed at designing a bioreactor capable of subjecting cardiovascular tissue to time-varying WSS magnitude and directionality.

Methods

The device consisted of a modified cone-and-plate bioreactor. The cone rotation generates a fluid flow subjecting tissue to desired WSS magnitude, while WSS directionality is achieved by altering the alignment of the tissue relative to the flow at each instant of time. Computational fluid dynamics was used to verify the device ability to replicate the native WSS of the proximal aorta. Cone and tissue mount velocities were determined using an iterative optimization procedure.

Results

Using conditions derived from cone-and-plate theory, the initial simulations yielded root-mean-square errors of 22.8 and 8.4% in WSS magnitude and angle, respectively, between the predicted and the target signals over one cycle, relative to the time-averaged target values. The conditions obtained after two optimization iterations reduced those errors to 3.5 and 0.5%, respectively, and generated 0.2% and 0.01% difference in time-averaged WSS magnitude and angle, respectively, relative to the target waveforms.

Conclusions

A bioreactor capable of generating simultaneously desired time-varying WSS magnitude and directionality was designed and validated computationally. The ability to subject tissue to in vivo-like WSS will provide new insights into cardiovascular mechanobiology and disease.

中文翻译：

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用于调节血管组织以适应时变多向流体剪切应力的新型生物反应器的设计和计算验证。

目的

心血管内皮经历脉动和多向流体壁剪切应力 (WSS)。虽然非生理性 WSS 幅度和脉动对心血管功能的影响已得到广泛研究，但由于在体外复制这一特征的挑战，方向异常的影响仍然未知。为了解决这一差距，本研究旨在设计一种生物反应器，该生物反应器能够使心血管组织受到时变 WSS 幅度和方向性的影响。

方法

该装置由改进的锥板生物反应器组成。圆锥体旋转产生流体流，使组织受到所需的 WSS 大小，而 WSS 方向性是通过在每个时刻改变组织相对于流的对齐来实现的。计算流体动力学用于验证设备复制近端主动脉的本机 WSS 的能力。使用迭代优化程序确定锥体和组织安装速度。

结果

使用源自锥板理论的条件，初始模拟在一个周期内的预测信号和目标信号之间的 WSS 幅度和角度的均方根误差分别为 22.8% 和 8.4%，相对于时间-平均目标值。两次优化迭代后获得的条件分别将这些误差降低到 3.5% 和 0.5%，并且相对于目标波形，时间平均 WSS 幅度和角度分别产生 0.2% 和 0.01% 的差异。

结论

设计并通过计算验证了能够同时生成所需的随时间变化的 WSS 幅度和方向性的生物反应器。使组织经受类似体内WSS的能力将为心血管力学生物学和疾病提供新的见解。