Page Mitchell I, Linde Peter E, Puttlitz Christian M
Orthopaedic Bioengineering Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering Colorado State University Ft Collins Colorado USA.
JOR Spine. 2021 May 25;4(3):e1152. doi: 10.1002/jsp2.1152. eCollection 2021 Sep.
In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue-level mechanical properties, it is intractable to experimentally measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modeling the CME in TE scaffolds using the finite element method.
A repeating unit of composite fiber scaffold for annulus fibrosus (AF) repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The distribution of CME in the scaffold was predicted and compared to proposed target mechanics based on anabolic responses of AF cells.
The multi-axial loading modality predicted the greatest percentage of cell volumes falling within the CME target envelope (%PTE) in the study (65 %PTE for 5.0% equibiaxial tensile strain with 50 kPa radial-direction compression; 7.6 %PTE without radial pressure). Additionally, the architectural scale had a moderate influence on the CME (maximum of 17 %PTE), with minimal change in the tissue-level properties of the scaffold. Scaffold materials and architectures had secondary influences on the predicted regeneration by modifying the tissue-level scaffold mechanics.
Scaffold loading modality was identified as the critical factor for TE the AF. Scaffold materials and architecture were also predicted to modulate the scaffold loading and, therefore, control the CME indirectly. This study facilitated an improved understanding of the relationship between tissue-level and cell-level mechanics to drive anabolic cell responses for tissue regeneration.
在组织工程（TE）策略中，细胞过程受机械刺激调节。尽管已经开发出TE支架来复制组织水平的力学性能，但要通过实验测量和规定这些构建体内产生的细胞微力学环境（CME）却很棘手。因此，本研究旨在通过使用有限元方法对TE支架中的CME进行建模来填补这一认知空白。
为用于纤维环（AF）修复的含纤维蛋白水凝胶基质的复合纤维支架的重复单元规定了一系列加载、材料和结构参数。预测了支架中CME的分布，并与基于AF细胞合成代谢反应提出的目标力学进行了比较。
在本研究中，多轴加载方式预测的落在CME目标范围内的细胞体积百分比最高（5.0%等双轴拉伸应变与50kPa径向压缩时为65%PTE；无径向压力时为7.6%PTE）。此外，结构尺度对CME有中等程度的影响（最大为17%PTE），而支架的组织水平性能变化最小。支架材料和结构通过改变支架的组织水平力学性能对预测的再生有次要影响。
支架加载方式被确定为AF组织工程的关键因素。还预测支架材料和结构会调节支架加载，从而间接控制CME。本研究有助于更好地理解组织水平和细胞水平力学之间的关系，以驱动促进组织再生的合成代谢细胞反应。
