Hybrid 3D-printed tri-cultured intestine with tubular mesh structure

Abstract

In fetal patients with intestinal atresia, surgical resection often leads to short bowel syndrome, necessitating organ transplantation. Owing to a shortage of organ donors, alternatives such as 3D-bioprinted artificial intestines are receiving increased interest. However, the fabrication of transplantable artificial intestines integrating tri-cultures of viable functional cells remains challenging. This study introduces an innovative method for fabricating a tri-cultured tubular mesh intestine (TTMI) integrating myofibroblasts, endothelial, and epithelial cells. Low-concentration gelatin methacryloyl (GelMA) bioink is employed to improve cell viability, and a dual cooling module is incorporated to cool both the GelMA and the printing area for improve printability. To improve the mechanical properties of the TTMI for transplant and tubular stability, a multi-head four-axis bioprinter is used to apply bioinks and polycaprolactone (PCL). The final four-layered TTMI comprises three bioinks and PCL; the two middle layers are printed with a tubular mesh to enable cell-to-cell interactions. This technology can be used to fabricate intestines as well as other tubular organs consisting of different cells, ultimately enhancing the availability of functional tissues for transplantation therapy.