O'Reilly Adam, Kelly Daniel J
Trinity Centre for Bioengineering, Trinity Biomedical Sciences, Trinity College Dublin, Dublin, Ireland.
Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
Ann Biomed Eng. 2016 Dec;44(12):3446-3459. doi: 10.1007/s10439-016-1664-9. Epub 2016 Jun 21.
We have previously developed a computational mechanobiological model to explore the role of substrate stiffness and oxygen availability in regulating stem cell fate during spontaneous osteochondral defect repair. This model successfully simulated many aspects of the regenerative process, however it was unable to predict the spatial patterns of endochondral bone and fibrocartilaginous tissue formation observed during the latter stages of the repair process. It is hypothesised that this was because the mechanobiological model did not consider the role of tissue strain in regulating specific aspects of chondrocyte differentiation. To test this, our mechanobiological model was updated to include rules whereby intermediate levels of octahedral shear strain inhibited chondrocyte hypertrophy, while excessively high octahedral shear strains resulted in the formation of fibrocartilage. This model was used to simulate spontaneous osteochondral defect repair, where it correctly predicted the experimentally observed patterns of bone formation. Overall the results suggest that oxygen availability regulates chondrogenesis and endochondral ossification during the early phases of osteochondral defect repair, while direct mechanical cues play a greater role in regulating chondrocyte differentiation during the latter stages of this process. In particular, these results suggest that an appropriate loading regime can assist in promoting the development of stable hyaline cartilage during osteochondral defect repair.
我们之前开发了一种计算力学生物学模型，以探讨在自发性骨软骨缺损修复过程中，底物硬度和氧气供应在调节干细胞命运方面的作用。该模型成功模拟了再生过程的许多方面，然而它无法预测在修复过程后期观察到的软骨内骨和纤维软骨组织形成的空间模式。据推测，这是因为力学生物学模型没有考虑组织应变在调节软骨细胞分化特定方面的作用。为了验证这一点，我们对力学生物学模型进行了更新，纳入了一些规则，即中等水平的八面体剪应变会抑制软骨细胞肥大，而过高的八面体剪应变则会导致纤维软骨形成。该模型被用于模拟自发性骨软骨缺损修复，它正确地预测了实验观察到的骨形成模式。总体而言，结果表明在骨软骨缺损修复的早期阶段，氧气供应调节软骨生成和软骨内成骨，而在该过程的后期阶段，直接的机械信号在调节软骨细胞分化中发挥更大作用。特别是，这些结果表明适当的加载方式有助于在骨软骨缺损修复过程中促进稳定透明软骨的发育。
