培养物袋装滚动加载的生物反应器研制及有限元仿真

发布时间：2018-06-02 10:43

本文选题：生物反应器 + 滚动加载　；参考：《天津理工大学》2012年硕士论文

【摘要】：目前,已经有很多物理因素如电磁场、超声波、离心力、微重力等用于组织或细胞的体外培养,其中直接的力学刺激更合适功能化软骨的构建。当前用各种力学刺激的生物反应器构建出的组织工程软骨在功能及理化性等方面上都不能满足临床需要。本课题根据软骨的实际运动和真实受载情况,研制了一种低污染的袋装滚压加载的生物反应器。该生物反应器能实现连续可调的压缩量和对载荷速度、频率的控制,并且将培养物放在培养袋中加载大大降低了污染的概率。参考人体膝关节软骨生理结构及人体正常行走时膝关节生理软骨的运动状态,使用有限元分析软件建立了关节软骨多层复合材料的滚压运动有限元模型,模拟袋装滚压加载(有膜)、直接加载(无膜)构建两种软骨模型,从有膜无膜、软骨压缩量、滚动速度三个角度对比分析了滚压载荷下软骨的位移、应力分布及差别。有限元仿真表明：一、在软骨组织工程构建中培养袋薄膜的膜弹性模量应有一个合适的值；二、当滚动载荷速度较大时,两种模型软骨所受的Mises应力值和位移大小基本相等,膜对软骨受力的影响可以忽略。当滚动载荷速度较小时,有膜模型条形软骨所受的Mises应力值和位移值较无膜模型稍小,我们根据这微小的差别,在加载时可以进行相应的推算,使得有膜模型条形软骨获得和无膜模型相同的位移压缩量,相对准确地控制生物实验部分对软骨施加的压缩量；三、在相同的滚压速度,不同压缩载荷下有膜无膜两种模型中各层软骨所受的Mises应力值相差很小,也就是在条形软骨上覆盖一层薄膜对于条形软骨所受的Mises应力影响可以忽略。四、有膜模型中滚压载荷经过软骨各层固定部位考察点时,此点所受的Mises应力、主应力、剪应力值出现一定的正负交替现象,即软骨发生交替的压缩和拉伸,该变形类型在一定程度上符合人体膝关节软骨日常走路时其所处的变形状态,这种力学刺激可能利于软骨组织功能化的构建。通过对关节软骨袋装滚动加载过程的有限元仿真,能为行离体软骨的体外培养实验中培养袋材料参数的选用提供一定理论依据。获取未成年大白兔膝关节的软骨作为研究对象,通过培养物袋装滚压加载生物反应器施加载荷初步研究该载荷对离体软骨的力学影响。切片显示：培养时间为14d的离体软骨生长增加量高于7d的；动态滚动加载组即实验组的生长情况好于静置培养组即对照组。这表明滚压载荷能够促进离体软骨的生长,这为构建功能化组织工程软骨可能提供了一种新方法。本论文阐述了研制的培养物袋装滚压加载生物反应器,通过有限元仿真获取实验条件及培养物力学状态,并进行离体软骨培养的生物学实验初步研究了滚压载荷对离体软骨的影响,探索了软骨组织工程的力学环境。
[Abstract]:At present, there are many physical factors such as electromagnetic field, ultrasonic wave, centrifugal force, microgravity and so on, which can be used for tissue or cell culture in vitro, and direct mechanical stimulation is more suitable for the construction of functional cartilage. At present, the tissue engineered cartilage constructed by biomechanical stimulation bioreactor can not meet the clinical needs in function and physicochemical properties. According to the actual movement and real loading of cartilage, a low pollution bioreactor with rolling loading was developed in this paper. The bioreactor can control the loading speed and frequency of the bioreactor, and the probability of contamination can be greatly reduced by loading the culture material in the culture bag. Referring to the physiological structure of articular cartilage and the movement state of physiological cartilage of knee joint during normal walking, a finite element model of rolling motion of articular cartilage multilayer composite material was established by using finite element analysis software. Two kinds of cartilage models were constructed by simulating bag rolling loading (membrane loading, direct loading (no film). The displacement, stress distribution and difference of cartilage under rolling load were compared and analyzed from three angles: membrane without membrane, cartilage compression amount and rolling speed. The finite element simulation shows that: first, the elastic modulus of the membrane should be an appropriate value in the construction of cartilage tissue engineering; second, when the rolling load speed is larger, the Mises stress and displacement of the two kinds of cartilage are basically equal. The effect of membrane on cartilage stress can be neglected. When the rolling load speed is small, the Mises stress and displacement of the strip cartilage of the membrane model are slightly smaller than that of the non-membrane model. According to this slight difference, we can make the corresponding calculation at the loading time. So that the membrane model strip cartilage to obtain the same displacement compression as the membrane model, relatively accurate control of the biological experiment part of the compression on the cartilage; third, at the same rolling speed, The Mises stress of each layer of cartilage under different compression loads is very small, that is to say, the influence of a layer of film on the Mises stress of strip cartilage can be neglected. Fourth, when the rolling load in the membrane model passes through the fixed point of the cartilage, the Mises stress, the principal stress and the shear stress of this point are alternately positive and negative, that is, the cartilage is alternately compressed and stretched. To a certain extent, this type of deformation accords with the deformation state of human articular cartilage during walking, and this kind of mechanical stimulation may be beneficial to the construction of cartilage tissue functionalization. The finite element simulation of the rolling loading process of articular cartilage bag can provide a theoretical basis for the selection of material parameters in vitro culture of articular cartilage. The cartilage of knee joint of immature white rabbit was taken as the research object. The mechanical effect of the load on the cartilage in vitro was studied by using the culture bag loaded bioreactor. The results showed that the growth of cartilage in vitro with 14 days of culture time was higher than that of 7 days, and the growth of the experimental group was better than that of the static culture group and the control group, and the dynamic rolling loading group was better than that of the static culture group. This suggests that rolling load can promote the growth of cartilage in vitro, which may provide a new method for the construction of functional tissue engineered cartilage. In this paper, the condition of experiment and the mechanical state of culture were obtained by finite element simulation. The effect of rolling load on the cartilage in vitro was studied and the mechanical environment of cartilage tissue engineering was explored.
【学位授予单位】：天津理工大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.01

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