Comparison of Neutrophil Attachment across 2D and 3D In Vitro Model Platforms
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Date
2020-07-16
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Abstract
In vivo animal models provide the most realistic information on flow dynamics and drug delivery research. However, the high cost of animal models, the inherent complexity of biological systems, and ethical concerns can make research of specific variables challenging and can easily lead to data misrepresentation. Current in vitro models, such as parallel plate flow chambers and rectangular microfluidics channels, are commonly used to investigate vasculatures. However, these approaches may be inaccurate representation of in vivo conditions. Our group has developed a simple and low cost PDMS microchannel fabrication process to provide a realistic in vivo geometry testing platform. This platform will ultimately be used to study the effects of flow velocity and shear rate to the efficacy of vascular-targeted drug carriers. The main focus of this study is to compare neutrophil attachment on HUVECs by using both existing 2D endothelial model in the parallel plate chamber and 3D cylindrical microchannel in vitro models. For microchannels, as shear rate was increased from 100 to 400 s^-1, there was a decreasing trend in neutrophil attachment. This trend is likely because the red blood cell – free layer reduces in width to the point where the layer thickness is smaller than neutrophil diameter. However, with the parallel plate flow chamber, neutrophil attachment increases with shear rate. This may be due to the red blood cell-free layer approaching a critical width, where the margination condition for neutrophils attachment is optimal. The attachment trends are opposed due to different channel geometry effecting the packing or distribution of red blood cell differently. Overall, our findings suggest that circular microchannels may be a better platform for studying the functionality of vascular-targeted drug carriers due to the physiological relevant geometry.
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Microchannel, neutrophil, attachment, fluid, in vitro, model