Rapid assembling organ prototypes with controllable cell-laden multi-scale sheets

A native organ has heterogeneous structures, strength, and cell components. It is a big challenge to fabricate organ prototypes with controllable shapes, strength, and cells. Herein, a hybrid method is developed to fabricate organ prototypes with controlled cell deposition by integrating extrusion-based 3D printing, electrospinning, and 3D bioprinting. Multi-scale sheets were first fabricated by 3D printing and electrospinning; then, all the sheets were assembled into organ prototypes by sol-gel reaction during bioprinting. With this method, macroscale structures fabricated by 3D printing ensure the customized structures and provide mechanical support, nanoscale structures fabricated by electrospinning offer a favorable environment for cell growth, and different types of cells with controllable densities are deposited in accurate locations by bioprinting. The results show that L929 mouse fibroblasts encapsulated in the structures exhibited over 90% survival within 10 days and maintained a high proliferation rate. Furthermore, the cells grew in spherical shapes first and then migrated to the nanoscale fibers showing stretched morphology. Additionally, a branched vascular structure was successfully fabricated using the presented method. Compared with other methods, this strategy offers an easy way to simultaneously realize the shape control, nanofibrous structures, and cell accurate deposition, which will have potential applications in tissue engineering.