Development of a multi-component disjointed tissue culture system using three-dimensionally printed polymeric scaffolds and microfluidic pumping

Abstract

In-vitro cellular culture plays a crucial role in preclinical research. While cost-effective, the pre- vailing 2D culture approach falls short in simulating realistic cellular interactions when these cells are grown in different but interacting spaces. Organs-on-a-Chip (OoC) devices have been developed to address this limitation, creating controlled micro-environments that mimic in-vivo tissue interaction conditions. This research addressed designing and assessing a microfluidic chip device based on ad- ditive manufacturing to analyze fibroblast and monocyte cell interaction grown in a separate culture apparatus. The OoC devices were created using Computer-Aided Design (CAD), and additive manu- facturing strategies using translucent resin as constructive material. The developed chip consisted of 200 mm2 cell culture area, a glass window for monitoring, and two inlets and outlets for fluid transfer and sampling. An instrumented peristaltic micro-pumping system induces fluid motion through the tubing that connects the manufactured microchips. Here, we show the ability of the developed 3D printed system to culture different cell lines, allow treatment addition without disturbing the system, and connect with a continuous flow between the devices without generating detectable cellular stress by enzymatic quantification. Finally, the interconnected system communicates between fibroblast and monocyte cultures by connecting two chips with micropumps through microscopic and cellular stress markers in selected cell lines. This results in a prototype for a multi-organ-on-a-chip-like device.