Development of in vitro cardiovascular tissue models within capillary circuit microfluidic devices fabricated with 3D stereolithography printing

Abstract

This study presents the development and morphology analysis of bioinspired 3D cardiovascular tissue models cultured within a dynamic capillary circuit microfluidic device. This study is significant because our in vitro 3D cardiovascular tissue models retained within a capillary circuit microfluidic device provide a less expensive, more controlled, and reproducible platform for more physiologically-relevant evaluation of cellular response to microenvironmental stimuli. The overall aim of our study is to demonstrate our cardiovascular tissue model (CTM) and vascular tissue model (VTM) actively changed their cellular morphology and exhibited structural reorganization in response to biophysical stimuli provided by microposts within the device tissue culture chambers during a 5-day period. The microfluidic device in this study was designed with the Young–Laplace and Navier–Stokes principles of capillary driven fluid flow and fabricated with 3D stereolithography (SLA) printing. The cardiac tissue model and vascular tissue model presented in this study were developed by encapsulating AC16 cardiomyocytes (CTM) and Human umbilical vein endothelial cells (VTM) in a fibrin hydrogel which were subsequently loaded into a capillary circuit microfluidic device. The cardiovascular tissue models were analyzed with fluorescent microscopy for morphological differences, average tube length, and cell orientation. We determined the VTM displayed capillary-like tube formation and the cells within both cardiovascular tissue models continued to elongate around microposts by day-5 which indicates the microfluidic system provided biophysical cues to guide cell structure and direction-specific organization.