3D-Printed, Modular, and Parallelized Microfluidic System with Customizable Scaffold Integration to Investigate the Roles of Basement Membrane Topography on Endothelial Cells

Because dysfunctions of endothelial cells are involved in many pathologies, in vitro endothelial cell models for pathophysiological and pharmaceutical studies have been a valuable research tool. Although numerous microfluidic-based endothelial models have been reported, they had the cells cultured on a flat surface without considering the possible three-dimensional (3D) structure of the native extracellular matrix (ECM). Endothelial cells rest on the basement membrane in vivo, which contains an aligned microfibrous topography. To better understand and model the cells, it is necessary to know if and how the fibrous topography can affect endothelial functions. With conventional fully integrated microfluidic apparatus, it is difficult to include additional topographies in a microchannel. Therefore, we developed a modular microfluidic system by 3D-printing and electrospinning, which enabled easy integration and switching of desired ECM topographies. Also, with standardized designs, the system allowed for high flow rates up to 4000 mu L/min, which encompassed the full shear stress range for endothelial studies. We found that the aligned fibrous topography on the ECM altered arginine metabolism in endothelial cells and thus increased nitric oxide production. There has not been an endothelial model like this, and the new knowledge generated thereby lays a groundwork for future endothelial research and modeling.

Automated summary

The dysfunction of endothelial cells plays a role in various pathologies, making in vitro endothelial cell models essential for pathophysiological and pharmaceutical studies. A modular microfluidic system using 3D printing and electrospinning was developed, enabling easy integration and switching of desired ECM topographies. This study reveals that the aligned fibrous topography on the ECM can increase nitric oxide production in endothelial cells, providing new insights for future research and modeling in this field.