Studying endothelial cell shedding and orientation using adaptive perfusion-culture in a microfluidic vascular chip.

Abstract

Most tissue-engineered blood vessels are endothelialized by static cultures in vitro. However, it has not been clear whether endothelial cell-shedding and local damage may occur in an endothelial layer formed by static cultures under the effect of blood flow shear postimplantation. In this study, we report a bionic and cost-effective vascular chip platform, and proved that a static culture of endothelialized tissue-engineered blood vessels had the problem of a large number of endothelial cells falling off under the condition imitating the human arterial blood flow, and we addressed this challenge by regulating the flow field in a vascular chip. Electrospun membranes made of highly oriented or randomly distributed poly(ε-caprolactone) fibers were used as the vascular scaffolds, on which endothelial cells proliferated well and eventually formed dense intima layers. We noted that the monolayers gradually adapted to the artery-like microenvironment through the regulation of chip flow field, which also revealed improved cellular orientations. In conclusion, we have proposed a vascular chip with adaptive flow patterns to gradually accommodate the statically cultured vascular endothelia to the shear environment of arterial flow field and enhanced the orientation of the endothelial cells. This strategy may find numerous potential applications such as screening of vascular engineering biomaterials and maturation parameters, studying of vascular biology and pathology, and construction of vessel-on-a-chip models for drug analysis, among others.