VARIABLE FENESTRATION OF A 3D NANOPRINTED LIVER SINUSOID ON A CHIP

Abstract

Here we report a novel strategy for engineering liver sinusoids with designed fenestrae that yield near uniform microfuidic flow conditions along the length of the microstructure - capabilities enabled by the use two-photon direct laser writing (DLW). To better model organ systems, researchers have increasingly investigated the use of DLW as a promising means for mimicking both architectures and length scales of physiological components. DLW-based approaches could enable liver sinusoids to be recreated in vitro; however, recent efforts to construct permeated tubules exhibit dramatic decreases in fluid flow through the pores downstream. To overcome such issues, here we applied microfluidic circuit theory and in-situ DLW (isDLW) to manufacture liver sinusoids that included fenestrae with distinct sizes to better maintain a consistent fenestra-specifi c flow profi le. Specifically, fenestrae radii were increased from 0.75 μm to 2.01 μm over the length of a 510-μm sinusoid. Theoretical results revealed that the flow rate through the fenestrae could be more maintained along the length of the optimized sinusoid versus the unoptimized sinusoid with uniform fenestrae which results in inconsistent fluid flow. Preliminary results revealed successful isDLW fabrication of the optimized sinusoid, with proof-of-concept microfluidic flow demonstrations that suggest that the presented strategy could benefit numerous biomedical applications. These results suggest the potential of this design strategy for liver on-a-chip modeling, and given the numerous anatomical structures similar to the presented fenestrated sinusoid, this approach could be extended to model additional organ systems of the body for disease modeling and drug screening.