Rapid automated production of tubular 3D intestine-on-a-chip with diverse cell types using coaxial bioprinting†

Abstract

Despite considerable animal sacrifices and investments, drug development often falters in clinical trials due to species differences. To address this issue, specific in vitro models, such as organ-on-a-chip technology using human cells in microfluidic devices, are recognized as promising alternatives. Among the various organs, the human small intestine plays a pivotal role in drug development, particularly in the assessment of digestion and nutrient absorption. However, current intestine-on-a-chip devices struggle to accurately replicate the complex 3D tubular structures of the human small intestine, particularly when it comes to integrating a variety of cell types effectively. This limitation is primarily due to conventional fabrication methods, such as soft lithography and replica molding. In this research, we introduce a novel coaxial bioprinting method to construct 3D tubular structures that closely emulate the organization and functionality of the small intestine with multiple cell types. To ensure stable production of these small intestine-like tubular structures, we analyzed the rheological properties of bioinks to select the most suitable materials for coaxial bioprinting technology. Additionally, we conducted biological assessments to validate the gene expression patterns and functional attributes of the 3D intestine-on-a-chip. Our 3D intestine-on-a-chip, which faithfully replicates intestinal functions and organization, demonstrates clear superiority in both structure and biological function compared to the conventional 2D model. This innovative approach holds significant promise for a wide range of future applications.