Structure-induced cell growth by 3D printing of heterogeneous scaffolds with ultrafine fibers

Cell-scaffold interactions have drawn significant attention in tissue engineering. In this study, we define a heterogeneous scaffold, which can be customized with respect to gradient strength, variable fiber diameter, and pore sizes. Heterogeneous scaffolds with ultrafine fibers (3–22 μm in diameter) can be printed via high-resolution melt electrowriting (MEW) using only one nozzle by adjusting the printing parameters. With precise control of the diameter of deposited fibers, complex patterns, such as a star, Tai Chi, and an eagle can be fabricated. Owing to the ultrafine fiber and heterogeneous design, cell-scaffold interaction and other occurrences were observed. The size of the diameter of the printed fiber is close to that of cells (tens of microns), smaller than those of conventional 3D printed scaffolds (100 μm or more), and cell adhesion is highly sensitive to variations in fiber diameter. By specifically arranging thick and thin fibers, cells can be induced to elongate in anticipated direction in a grid. In this study, cell alignment exhibited 4 different orientations in a single scaffold with 4 regions, separately. The scaffolds can also be heterogeneous in pore size. In this study, the proliferation speed of the cells in small pores is 3 times that of the cells in large pores. Moreover, various pore sizes and fibers can be integrated in one scaffold, allowing the control of cell growth to different statuses by adjusting the scaffold structures. This study generally presents a strategy for structure-induced cell growth for better simulating in vivo environment.