Bioprinting promises enormous control over the spatial deposition of cells in three dimensions^{1,2,3,4,5,6,7}, but current approaches have had limited success at reproducing the intricate micro-architecture, cell-type diversity and function of native tissues formed through cellular self-organization. We introduce a three-dimensional bioprinting concept that uses organoid-forming stem cells as building blocks that can be deposited directly into extracellular matrices conducive to spontaneous self-organization. By controlling the geometry and cellular density, we generated centimetre-scale tissues that comprise self-organized features such as lumens, branched vasculature and tubular intestinal epithelia with in vivo-like crypts and villus domains. Supporting cells were deposited to modulate morphogenesis in space and time, and different epithelial cells were printed sequentially to mimic the organ boundaries present in the gastrointestinal tract. We thus show how biofabrication and organoid technology can be merged to control tissue self-organization from millimetre to centimetre scales, opening new avenues for drug discovery, diagnostics and regenerative medicine.

生物打印有望在^{1,2,3,4,5,6,7}三个维度上对细胞的空间沉积进行巨大控制，但是目前的方法在复制复杂的微体系结构，细胞类型多样性和通过细胞自组织形成的天然组织功能方面取得的成功有限。我们引入了三维生物打印概念，该概念使用形成类器官的干细胞作为构建基块，可以直接沉积到有助于自发自组织的细胞外基质中。通过控制几何形状和细胞密度，我们产生了厘米级规模的组织，这些组织包括具有体内类隐窝和绒毛域的自组织特征，例如内腔，分支脉管系统和管状肠上皮。沉积支持细胞以调节时空的形态发生，并依次印刷不同的上皮细胞以模拟胃肠道中存在的器官边界。