Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
Center for Remote Health Technologies & Systems, Texas A&M Engineering Experiment Station, College Station, Texas, USA.
Cells Tissues Organs. 2023;212(1):96-110. doi: 10.1159/000521752. Epub 2022 Jan 10.
Peristalsis is a nuanced mechanical stimulus comprised of multi-axial strain (radial and axial strain) and shear stress. Forces associated with peristalsis regulate diverse biological functions including digestion, reproductive function, and urine dynamics. Given the central role peristalsis plays in physiology and pathophysiology, we were motivated to design a bioreactor capable of holistically mimicking peristalsis. We engineered a novel rotating screw-drive based design combined with a peristaltic pump, in order to deliver multi-axial strain and concurrent shear stress to a biocompatible polydimethylsiloxane (PDMS) membrane "wall." Radial indentation and rotation of the screw drive against the wall demonstrated multi-axial strain evaluated via finite element modeling. Experimental measurements of strain using piezoelectric strain resistors were in close alignment with model-predicted values (15.9 ± 4.2% vs. 15.2% predicted). Modeling of shear stress on the "wall" indicated a uniform velocity profile and a moderate shear stress of 0.4 Pa. Human mesenchymal stem cells (hMSCs) seeded on the PDMS "wall" and stimulated with peristalsis demonstrated dramatic changes in actin filament alignment, proliferation, and nuclear morphology compared to static controls, perfusion, or strain, indicating that hMSCs sensed and responded to peristalsis uniquely. Lastly, significant differences were observed in gene expression patterns of calponin, caldesmon, smooth muscle actin, and transgelin, corroborating the propensity of hMSCs toward myogenic differentiation in response to peristalsis. Collectively, our data suggest that the peristalsis bioreactor is capable of generating concurrent multi-axial strain and shear stress on a "wall." hMSCs experience peristalsis differently than perfusion or strain, resulting in changes in proliferation, actin fiber organization, smooth muscle actin expression, and genetic markers of differentiation. The peristalsis bioreactor device has broad utility in the study of development and disease in several organ systems.
蠕动是一种复杂的机械刺激，由多轴向应变（径向和轴向应变）和剪切应力组成。与蠕动相关的力调节着多种生物学功能，包括消化、生殖功能和尿液动力学。鉴于蠕动在生理学和病理生理学中的核心作用，我们设计了一种能够整体模拟蠕动的生物反应器。我们设计了一种新颖的旋转螺杆驱动设计，结合蠕动泵，以向生物相容性的聚二甲基硅氧烷（PDMS）膜“壁”提供多轴向应变和同时的剪切应力。通过有限元建模评估了螺杆驱动器对壁的径向压痕和旋转产生的多轴向应变。使用压电阻应变计进行应变的实验测量与模型预测值非常吻合（15.9±4.2%与预测的 15.2%）。对“壁”上的剪切应力进行建模表明存在均匀的速度分布和适度的剪切应力 0.4Pa。与静态对照、灌注或应变相比，在 PDMS“壁”上接种的人骨髓间充质干细胞（hMSCs）并受到蠕动刺激后，肌动蛋白丝排列、增殖和核形态发生了显著变化，表明 hMSCs 独特地感知和响应蠕动。最后，在钙调蛋白、钙调蛋白、平滑肌肌动蛋白和转胶蛋白的基因表达模式中观察到显著差异，这证实了 hMSCs 在响应蠕动时向肌源性分化的倾向。总的来说，我们的数据表明，蠕动生物反应器能够在“壁”上产生同时的多轴向应变和剪切应力。hMSCs 经历蠕动的方式与灌注或应变不同，导致增殖、肌动蛋白纤维组织、平滑肌肌动蛋白表达和分化的遗传标记发生变化。蠕动生物反应器设备在几个器官系统的发育和疾病研究中有广泛的应用。
