Fabrication of cell culture devices with integrated microfluidic networks via vat multimaterial 3D printing

Abstract

Over the past century, in vitro models such as cell cultures have been fundamental tools in the development of medicine and biology. However, these models are usually cultured in a static configuration that does not consider the complex conditions that occur in vivo, such as continuous nutrient and oxygen supply, and waste discharge. This study presents a bimaterial well plate called the BioFlowWellplate, which is characterised by wells that are connected through a microfluidic system. The device was fabricated using digital light processing (DLP), an additive manufacturing technique that allowed the complex geometry of the CAD model to be realised. A multimaterial approach was adopted for fabrication, with two different printable resins selected: PEGDA 250, which promotes cell adhesion and is transparent when printed in thin layers; and TEGORad®2800, which has great cytocompatibility and low drug retention. This has resulted in a biomedical device that enables users to save time and perform a more controlled procedure, while also allowing cells to be cultured in dynamic conditions for greater in vivo relevance in translational research. The presence of a microfluidic system connected to a pumping system not only allowed the automation of cell culture but also enhanced the relevance of an endothelium model cultured in both static and dynamic conditions. Finally, the BioFlowWellplate was successfully used for the dynamic perfusion of a 3D GelMA scaffold, paving the way for the dynamic culture of vascularised 3D in vitro models.