High-Throughput intestinal model using continuous chaotic bioprinting

Abstract

The outstanding need for simpler but physiologically relevant organ models has led to the use of chaotic flows for the bioprinting of multilayered structures in terms of minutes. Herein, an intestinal model with finger villi-like structures was accomplished through the use of a printhead equipped with an SMX static mixer. Intestinal cancer cells were embedded in a gelatin-methacryloyl (GelMA)- alginate hydrogel. Cells exhibit high viability even after their extrusion at 2 mL/ min. The high throughput of this method enables the fabrication of meters of fibers per minute with a constant cross-sectional microstructure. Fibers were monitored through periods of 21 days and viability, morphology, and relevant intestinal markers were analyzed. Caco-2 cells have a natural tendency to agglomerate leading to the natural formation of regular intestinal spheroids of nearly 150 ± 25 μm of diameter by day 17. Functional expression of the villin gene (VIL1) was observed in these constructs since day 7. This novel cost-effective intestinal model could be applied in the future for easier co-culture platforms with high reproducibility and performance.