An in vitro analysis of the effect of geometry-induced flows on endothelial cell behavior in 3D printed small-diameter blood vessels.

Clinical recovery from vascular diseases has increasingly become reliant upon the successful fabrication of artificial blood vessels (BVs) or vascular prostheses due to the shortage of autologous vessels and the high incidence of vessel graft diseases. Even though many attempts at the clinical implementation of large artificial BVs have been reported to be successful, the development of small-diameter BVs remains one of the significant challenges due to the limitation of micro-manufacturing capacity in complexity and reproducibility, as well as the development of thrombosis. The present study aims to develop 3D printed small-diameter artificial BVs that recapitulate the longitudinal geometric elements in the native BVs using biocompatible polylactic acid (PLA). As their intrinsic physical properties are crystallinity dependent, we used two PLA filaments with different crystallinity to investigate the suitability of their physical properties in the micro-manufacturing of BVs. To explore the mechanism of venous thrombosis, our study provided a preliminarily comparative analysis of the effect of geometry-induced flows on the behavior of human endothelial cells (ECs). Our results showed that the adhered healthy ECs in the 3D printed BV exhibited regulated patterns, such as elongated and aligned parallel to the flow direction, as well as geometry-induced EC response mechanisms that are associated with hemodynamic shear stresses. Furthermore, the computational fluid dynamics simulation results provided insightful information to predict velocity profile and wall shear stress distribution in the geometries of BVs in accordance with their spatiotemporally-dependent cell behaviors. Our study demonstrated that 3D printed small-diameter BVs could serve as suitable candidates for fundamental BV studies and hold great potential for clinical applications.