振荡流动对组织工程用灌注式生物反应器中剪切力分布影响

目的 考察振荡流动以及三维支架孔径和孔隙率对生物反应器内流速和剪切力分布的影响，并根据理论计算结果为脱细胞骨三维支架和灌注式生物反应器制备提出优化方法。方法 针对实验室前期制备的骨组织工程用脱细胞骨三维支架和灌注式生物反应器，将脱细胞骨三维支架简化为各向同性的多孔介质，对生物反应器内的流速和剪切力分布进行理论建模。结果 振荡流作用时，多孔支架材料内速度和达西剪切力呈现一致的变化规律，不同半径处流速和达西剪切力差异减小，有利于在骨组织工程中对种子细胞进行均匀三维培养。提高入口灌流速度可提高平均达西剪切力；增加多孔支架孔径或孔隙率对支架内流速峰值影响不大，但会显著降低平均达西剪切力；提高入口振荡流动振荡频率可降低支架内流速最大峰值，显著减小不同半径处流速的差异。结论 适宜的振荡流易产生利于骨组织工程干细胞所需剪切力，研究结果有望为优化骨组织工程中种子细胞的三维培养方法提供理论指导。

Effects of oscillatory flow on shear stress distributions in perfusion bioreactor for bone tissue engineering

Objective To study the effects of oscillatory flow, as well as pore size and porosity of the 3D scaffold on distributions of flow rate and shear stress in perfusion bioreactor, and to propose optimization methods for preparing the 3D decellularized bone scaffold and perfusion bioreactor based on theoretical results. Methods Based on the previously established 3D decelluarized scaffold and perfusion bioreactor for bone tissue engineering in the laboratory, the decelluarized scaffold was simplified as an isotropic porous media. The velocity and shear stress distributions in the bioreactor were further simulated theoretically. Results Under the oscillatory flow, the Darcy shear stress and velocity in the 3D porous scaffold presented a consistently regular pattern. Compared with the unidirectional flow, the difference of velocity and Darcy shear stress decreased at different radius, which could contribute to the homogeneous 3D culture of seed cells in bone tissue engineering. Increasing the inlet perfusion velocity could improve the average Darcy shear stress. Increasing the pore diameter or porosity of the scaffold had no obvious effects on the peak value of velocity, but sharply reduced the average Darcy shear stress. Increasing inlet oscillation frequency could decrease the peak value of velocity and obviously decrease the difference of velocity at different radius. Conclusions Appropriate oscillatory flow was beneficial for generating required shear stress for stem cells in bone tissue engineering. The research findings in this study are expected to provide theoretical guidance to optimize the 3D culture method of seed cells for bone tissue engineering.