Liu Haijiao, Usprech Jenna F, Parameshwar Prabu Karthick, Sun Yu, Simmons Craig A
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Sci Adv. 2021 May 7;7(19). doi: 10.1126/sciadv.abe7204. Print 2021 May.
Mechanobiological-based control of mesenchymal stromal cells (MSCs) to facilitate engineering and regeneration of load-bearing tissues requires systematic investigations of specific dynamic mechanical stimulation protocols. Using deformable membrane microdevice arrays paired with combinatorial experimental design and modeling, we probed the individual and integrative effects of mechanical stimulation parameters (strain magnitude, rate at which strain is changed, and duty period) on myofibrogenesis and matrix production of MSCs in three-dimensional hydrogels. These functions were found to be dominantly influenced by a previously unidentified, higher-order interactive effect between strain magnitude and duty period. Empirical models based on our combinatorial cue-response data predicted an optimal loading regime in which strain magnitude and duty period were increased synchronously over time, which was validated to most effectively promote MSC matrix production. These findings inform the design of loading regimes for MSC-based engineered tissues and validate a broadly applicable approach to probe multifactorial regulating effects of mechanobiological cues.
基于力学生物学对间充质基质细胞（MSC）进行调控，以促进承重组织的工程构建和再生，需要对特定的动态机械刺激方案进行系统研究。我们使用与组合实验设计和建模相结合的可变形膜微器件阵列，探究了机械刺激参数（应变幅度、应变变化速率和占空比）对三维水凝胶中MSC的肌成纤维细胞生成和基质产生的个体及综合影响。发现这些功能主要受应变幅度和占空比之间先前未被识别的高阶交互作用影响。基于我们的组合线索-反应数据的经验模型预测了一种最佳加载方案，即应变幅度和占空比随时间同步增加，这已被验证能最有效地促进MSC基质产生。这些发现为基于MSC的工程组织的加载方案设计提供了依据，并验证了一种广泛适用的方法来探究力学生物学线索的多因素调节作用。
