An innovative cell-printed microscale collagen model for mimicking intestinal villus epithelium

Cell-printing technology for obtaining a cell-laden structure has been extensively used in tissue engineering applications due to its advantages over the conventional scaffold, which is not simultaneously fabricated with cells. To date, a realistic villi model using cell-laden bioink with both the biocompatibility and mechanical strength to achieve villus structure has not been developed. Here, we developed a human intestinal villi model with an innovative cell-printing process. The cell-laden villus structure was fabricated using a cell-laden collagen bioink cross-linked with a natural polyphenol (tannic acid). The fabricating condition was optimized and a Caco-2-laden collagen villus structure was fabricated. Using the processing conditions, a 3D collagen villus structure with appropriate geometry and a high initial cell-viability (over 90%) was obtained. In vitro cellular activities of the cell-laden villus structure demonstrated satisfactory cell viability with a growth-rate meaningfully higher than that in the fabricated villi structure cultured with the cell-seeding method (control). Moreover, expression of MUC17, junction marker (E-Cadherin), and alkaline phosphatase, as differentiation indicators of the epithelial cells, was significantly higher and earlier in the cell-laden structure compared to that in the control. These results indicate that the modified cell-printing process using collagen-bioink would be a highly efficient model mimicking the human intestinal epithelium.