Pump-Less Platform Enables Long-Term Recirculating Perfusion of 3D Printed Tubular Tissues.

The direction and pattern of fluid flow affect vascular structure and function, in which vessel-lining endothelial cells exhibit variable cellular morphologies and vessel remodeling by mechanosensing. To recapitulate this microenvironment, some approaches have been reported to successfully apply unidirectional flow on endothelial cells in organ-on-a-chip systems. However, these platforms encounter drawbacks such as the dependency on pumps or confinement to closed microfluidic channels. These constraints impede their synergy with advanced biofabrication techniques like 3D bioprinting, thereby curtailing the potential to introduce greater complexity into engineered tissues. Herein, we demonstrate a pumpless recirculating platform with an open-well design (UniPlate) that enables unidirectional media recirculation through 3D printed tubular tissue constructs on a programmable rocker. To ensure that the platform is scalable for industrial manufacturing, the device was made of polystyrene via injection molding in combination with 3D printed gelatin that serves as a sacrificial template. We first engineered tubular blood vessels with unidirectional perfusion. Then we expanded the design to incorporate duo-recirculating flow for culturing vascularized renal proximal tubules with glucose reabsorption function. In addition to media recirculation, human monocyte recirculation in engineered blood vessels was also demonstrated for over 24 h, with minimal loss of cells, cell viability, and inflammatory activation. UniPlate can be a valuable tool to more precisely control the cellular microenvironment of organ-on-a-chip systems for drug discovery. This article is protected by copyright. All rights reserved.