3D puzzle-inspired construction of large and complex organ structures for tissue engineering.

3D printing as a powerful technology enables the fabrication of organ structures with a programmed geometry, but it is usually difficult to produce large-size tissues due to the limited working space of the 3D printer and the instability of bath or ink materials during long printing sessions. Moreover, most printing only allows preparation with a single ink, while a real organ generally consists of multiple materials. Inspired by the 3D puzzle toy, we developed a "building block-based printing" strategy, through which the preparation of 3D tissues can be realized by assembling 3D-printed "small and simple" bio-blocks into "large and complex" bioproducts. The structures that are difficult to print by conventional 3D printing such as a picture puzzle consisting of different materials and colors, a collagen "soccer" with a hollow yet closed structure, and even a full-size human heart model are successfully prepared. The 3D puzzle-inspired preparation strategy also allows for a reasonable combination of various cells in a specified order, facilitating investigation into the interaction between different kinds of cells. This strategy opens an alternative path for preparing organ structures with multiple materials, large size and complex geometry for tissue engineering applications.