Elsaadany Mostafa, Yan Karen Chang, Yildirim-Ayan Eda
Department of Bioengineering, University of Toledo, Toledo, OH, USA.
Department of Mechanical Engineering, The College of New Jersey, Ewing, NJ, USA.
Biomech Model Mechanobiol. 2017 Jun;16(3):1049-1063. doi: 10.1007/s10237-017-0872-z. Epub 2017 Jan 16.
Successful tissue engineering and regenerative therapy necessitate having extensive knowledge about mechanical milieu in engineered tissues and the resident cells. In this study, we have merged two powerful analysis tools, namely finite element analysis and stochastic analysis, to understand the mechanical strain within the tissue scaffold and residing cells and to predict the cell viability upon applying mechanical strains. A continuum-based multi-length scale finite element model (FEM) was created to simulate the physiologically relevant equiaxial strain exposure on cell-embedded tissue scaffold and to calculate strain transferred to the tissue scaffold (macro-scale) and residing cells (micro-scale) upon various equiaxial strains. The data from FEM were used to predict cell viability under various equiaxial strain magnitudes using stochastic damage criterion analysis. The model validation was conducted through mechanically straining the cardiomyocyte-encapsulated collagen constructs using a custom-built mechanical loading platform (EQUicycler). FEM quantified the strain gradients over the radial and longitudinal direction of the scaffolds and the cells residing in different areas of interest. With the use of the experimental viability data, stochastic damage criterion, and the average cellular strains obtained from multi-length scale models, cellular viability was predicted and successfully validated. This methodology can provide a great tool to characterize the mechanical stimulation of bioreactors used in tissue engineering applications in providing quantification of mechanical strain and predicting cellular viability variations due to applied mechanical strain.
成功的组织工程和再生治疗需要对工程组织和驻留细胞中的力学环境有广泛的了解。在本研究中，我们融合了两种强大的分析工具，即有限元分析和随机分析，以了解组织支架内和驻留细胞中的机械应变，并预测施加机械应变时的细胞活力。创建了一个基于连续体的多长度尺度有限元模型（FEM），以模拟细胞嵌入组织支架上生理相关的等轴应变暴露，并计算在各种等轴应变下传递到组织支架（宏观尺度）和驻留细胞（微观尺度）的应变。有限元分析的数据用于通过随机损伤准则分析预测各种等轴应变幅度下的细胞活力。通过使用定制的机械加载平台（EQUicycler）对心肌细胞封装的胶原蛋白构建体进行机械拉伸来进行模型验证。有限元分析量化了支架径向和纵向以及位于不同感兴趣区域的细胞上的应变梯度。利用实验活力数据、随机损伤准则以及从多长度尺度模型获得的平均细胞应变，预测并成功验证了细胞活力。这种方法可以提供一个很好的工具，用于表征组织工程应用中使用的生物反应器的机械刺激，以量化机械应变并预测由于施加的机械应变导致的细胞活力变化。
