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首页> 美国卫生研究院文献>Biomicrofluidics >A method to integrate patterned electrospun fibers with microfluidic systems to generate complex microenvironments for cell culture applications
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A method to integrate patterned electrospun fibers with microfluidic systems to generate complex microenvironments for cell culture applications

机译：一种将图案化的电纺纤维与微流控系统集成以生成复杂的微环境以用于细胞培养应用的方法

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The properties of a cell’s microenvironment are one of the main driving forces in cellular fate processes and phenotype expression invivo. The ability to create controlled cell microenvironments invitro becomes increasingly important for studying or controlling phenotype expression in tissue engineering and drug discovery applications. This includes the capability to modify material surface properties within well-defined liquid environments in cell culture systems. One successful approach to mimic extra cellular matrix is with porous electrospun polymer fiber scaffolds, while microfluidic networks have been shown to efficiently generate spatially and temporally defined liquid microenvironments. Here, a method to integrate electrospun fibers with microfluidic networks was developed in order to form complex cell microenvironments with the capability to vary relevant parameters. Spatially defined regions of electrospun fibers of both aligned and random orientation were patterned on glass substrates that were irreversibly bonded to microfluidic networks produced in poly-dimethyl-siloxane. Concentration gradients obtained in the fiber containing channels were characterized experimentally and compared with values obtained by computational fluid dynamic simulations. Velocity and shear stress profiles, as well as vortex formation, were calculated to evaluate the influence of fiber pads on fluidic properties. The suitability of the system to support cell attachment and growth was demonstrated with a fibroblast cell line. The potential of the platform was further verified by a functional investigation of neural stem cell alignment in response to orientation of electrospun fibers versus a microfluidic generated chemoattractant gradient of stromal cell-derived factor 1 alpha. The described method is a competitive strategy to create complex microenvironments invitro that allow detailed studies on the interplay of topography, substrate surface properties, and soluble microenvironment on cellular fate processes.
机译：细胞的微环境特性是细胞命运过程和表型表达体内的主要驱动力之一。体外创建受控细胞微环境的能力对于研究或控制组织工程和药物发现应用中的表型表达变得越来越重要。这包括在细胞培养系统中定义良好的液体环境中修改材料表面特性的能力。一种模拟细胞外基质的成功方法是使用多孔电纺聚合物纤维支架，而微流体网络已被证明可以有效地产生时空限定的液体微环境。在这里，开发了一种将电纺纤维与微流体网络整合的方法，以形成具有改变相关参数能力的复杂细胞微环境。在玻璃基板上将排列和随机取向的电纺纤维的空间限定区域图案化，该玻璃基板不可逆地结合到聚二甲基硅氧烷中产生的微流体网络上。实验中表征了包含纤维的通道中获得的浓度梯度，并将其与通过计算流体动力学模拟获得的值进行了比较。计算了速度和切应力曲线以及涡旋形成，以评估纤维垫对流体性能的影响。用成纤维细胞系证明了该系统支持细胞附着和生长的适用性。该平台的潜力已通过对神经干细胞排列的功能研究进一步证实，该排列是响应于电纺丝纤维的取向与基质细胞衍生的因子1α的微流体产生的化学引力梯度形成的。所描述的方法是一种竞争性策略，可以体外创建复杂的微环境，从而可以详细研究地形，底物表面特性和可溶性微环境在细胞命运过程中的相互作用。

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