Nokhbatolfoghahaei Hanieh, Bohlouli Mahboubeh, Adavi Kazem, Paknejad Zahrasadat, Rezai Rad Maryam, Khani Mohammad Mehdi, Salehi-Nik Nasim, Khojasteh Arash
Dental Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Proc Inst Mech Eng H. 2020 Dec;234(12):1397-1408. doi: 10.1177/0954411920944039. Epub 2020 Jul 21.
Bioreactor system has been used in bone tissue engineering in order to simulate dynamic nature of bone tissue environments. Perfusion bioreactors have been reported as the most efficient types of shear-loading bioreactor. Also, combination of forces, such as rotation plus perfusion, has been reported to enhance cell growth and osteogenic differentiation. Mathematical modeling using sophisticated infrastructure processes could be helpful and streamline the development of functional grafts by estimating and defining an effective range of bioreactor settings for better augmentation of tissue engineering. This study is aimed to conduct computational modeling for newly designed bioreactors in order to alleviate the time and material consuming for evaluating bioreactor parameters and effect of fluid flow hydrodynamics (various amounts of shear stress) on osteogenesis. Also, biological assessments were performed in order to validate similar parameters under implementing the perfusion or rotating and perfusion fluid motions in bioreactors' prototype. Finite element method was used to investigate the effect of hydrodynamic of fluid flow inside the bioreactors. The equations used in the simulation to calculate the velocity values and consequently the shear stress values include Navier-Stokes and Brinkman equations. It has been shown that rotational fluid motion in rotating and perfusion bioreactor produces more velocity and shear stress compared with perfusion bioreactor. Moreover, implementing the perfusion together with rotational force in rotating and perfusion bioreactors has been shown to have more cell proliferation and higher activity of alkaline phosphatase enzyme as well as formation of extra cellular matrix sheet, as an indicator of bone-like tissue formation.
生物反应器系统已被用于骨组织工程,以模拟骨组织环境的动态特性。灌注生物反应器据报道是最有效的剪切加载生物反应器类型。此外,据报道,诸如旋转加灌注等力的组合可增强细胞生长和成骨分化。使用复杂基础设施过程的数学建模可能会有所帮助,并通过估计和定义生物反应器设置的有效范围来简化功能性移植物的开发,以更好地促进组织工程。本研究旨在对新设计的生物反应器进行计算建模,以减少评估生物反应器参数以及流体流动流体动力学(各种剪切应力)对成骨作用影响所耗费的时间和材料。此外,进行了生物学评估,以验证在生物反应器原型中实施灌注或旋转及灌注流体运动时的类似参数。采用有限元方法研究生物反应器内部流体流动的流体动力学效应。模拟中用于计算速度值并进而计算剪切应力值的方程包括纳维 - 斯托克斯方程和布林克曼方程。结果表明,与灌注生物反应器相比,旋转和灌注生物反应器中的旋转流体运动产生更高的速度和剪切应力。此外,在旋转和灌注生物反应器中同时施加灌注和旋转力已显示出具有更多的细胞增殖、更高的碱性磷酸酶活性以及细胞外基质片的形成,作为骨样组织形成的指标。