Synchronous 3D Bioprinting of Large-Scale Cell-Laden Constructs with Nutrient Networks

Abstract

Maintaining an adequate supply of nutrients/oxygen is a major challenge in the biofabrication of large tissue constructs. However, building preformed nutrient networks may be an effective strategy for engineering thick tissues. Here, a novel way for bioprinting large-scale tissue constructs with intentional nutrient networks is presented. A special nozzle is developed which can print bioink and sacrificial ink half and half synchronously in a single filament. Nutrient networks of these bioprinted constructs are formed by subsequently dissolving away gelatin, which allows for effective oxygen, nutrient, and waste diffusion, facilitating the cell activity and the generation of functional tissues. Due to the cell-laden bioink and sacrificial ink working together and promoting each other's printability to support themselves, complex soft cell-laden constructs with nutrient networks can easily be printed. Furthermore, two different cell types (osteoblast, human umbilical vein endothelial cells) encapsulated in the bioprinted large-scale constructs (≥1 cm) with nutrient networks show enhanced cell viability and spreading within a period of culture. It is envisioned that the advanced bioprinting technology may have significant potentials in facilitating the engineering of complex structures for tissue-specific needs, and bioprinting large-scale tissue constructs with nutrient networks toward applications in organ transplantation and repair.

Keywords: gelatin methacryloyl (GelMA); large-scale; nutrient networks; synchronous 3D bioprinting; tissue engineering.