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Monolithic microfluidic platform for exerting gradients of compression on cell-laden hydrogels, and application to a model of the articular cartilage
Sensors and Actuators B: Chemical ( IF 8.4 ) Pub Date : 2020-03-13 , DOI: 10.1016/j.snb.2020.127917
Carlo Alberto Paggi , Bastien Venzac , Marcel Karperien , Jeroen C.H. Leijten , Séverine Le Gac

Movement is essential to our quality of life, and regulates cell behavior via mechanical stimulation. Here, we report a monolithic microfluidic platform, in which engineered tissues composed of cells in a hydrogel are exposed to gradients of mechanical compression. Mechanical stimulation is applied through the deflection of a thin polydimethylsiloxane (PDMS) vertical membrane. The device design and all actuation parameters were optimized in this work to produce physiologically relevant compression on a cartilage model (strain of 5-12%), as well as gradients of compression ranging from healthy to hyper-physiological conditions in the same device, as evidenced by the measured gradients in cell deformation. While this work focuses on mechanical compression of engineered tissues, we also demonstrated that our platform allowed creating more sophisticated multi-modal stimulation patterns. As the membrane is actuated by three independently addressed yet connected pressurized chambers, a variety of programmable deflection patterns and various cell stimulation modalities can easily be created by tuning the pressure applied in the different chambers (positive vs. negative, and amplitude). Advantageously, the fabrication of this monolithic platform is straightforward, with a single-step process. Moreover, the vertical membrane configuration allows for real-time imaging of cells encapsulated in the hydrogel matrix. The herein reported platform is highly versatile and of great interest to model other types of tissues, which also experience complex mechanical actuation patterns in vivo.



中文翻译:

用于在载有细胞的水凝胶上施加压缩梯度的整体式微流控平台,并应用于关节软骨模型

运动对我们的生活质量至关重要,并通过机械刺激调节细胞行为。在这里,我们报告了一个整体的微流控平台,其中由水凝胶中的细胞组成的工程组织暴露于机械压缩的梯度。通过薄的聚二甲基硅氧烷(PDMS)垂直膜的偏转施加机械刺激。在这项工作中,对设备设计和所有驱动参数进行了优化,以在软骨模型上产生生理相关的压缩(5-12%的应变),以及同一设备中从健康状态到超生理状态的压缩梯度,所测得的细胞变形梯度证明了这一点。尽管这项工作的重点是工程组织的机械压缩,我们还证明了我们的平台允许创建更复杂的多模式刺激模式。由于膜是由三个独立寻址但已连接的加压腔室驱动的,因此可以通过调节施加在不同腔室中的压力(正值)轻松地创建各种可编程的偏转模式和各种细胞刺激模式。负数和幅度)。有利地,该单片平台的制造是简单的,并且具有单步工艺。此外,垂直膜配置允许对水凝胶基质中封装的细胞进行实时成像。本文报道的平台是高度通用的,并且对建模其他类型的组织也具有极大的兴趣,所述组织在体内也经历复杂的机械致动模式。

更新日期:2020-03-16
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