Recently, four-dimensional (4D) printing is emerging as the next-generation biofabrication technology. However, current 4D bioprinting lacks biocompatibility or multi-component printability. In addition, suitable implantable targets capable of applying 4D bioprinted products have not yet been established, except theoretical and in vitro study. Herein, we describe a cell-friendly and biocompatible 4D bioprinting system including more than two cell types based on digital light processing (DLP) and photocurable silk fibroin (Sil-MA) hydrogel. The shape changes of 3D printed bilayered Sil-MA hydrogels were controlled by modulating their interior or exterior properties in physiological conditions. We used finite element analysis (FEA) simulations to explore the possible changes in the complex structure. Finally, we made trachea mimetic tissue with two cell types using this 4D bioprinting system and implanted it into a damaged trachea of rabbit for 8 weeks. The implants were integrated with the host trachea naturally, and both epithelium and cartilage were formed at the predicted sites. These findings demonstrate that 4D bioprinting system could make tissue mimetic scaffold biologically and suggest the potential value of the 4D bioprinting system for tissue engineering and the clinical application.

最近，四维（4D）打印正在成为下一代生物制造技术。但是，当前的4D生物打印缺乏生物相容性或多组件可打印性。此外，除理论和体外研究外，尚未确定能够应用4D生物打印产品的合适可植入靶标。在这里，我们描述了一种基于数字光处理（DLP）和光固化丝素蛋白（Sil-MA）水凝胶的细胞友好型生物相容4D生物打印系统，包括两种以上的细胞类型。通过在生理条件下调节其内部或外部特性，可以控制3D打印的双层Sil-MA水凝胶的形状变化。我们使用有限元分析（FEA）模拟来探索复杂结构中的可能变化。最后，我们使用此4D生物打印系统制作了具有两种细胞类型的气管模拟组织，并将其植入兔子受损的气管中8周。植入物自然地与宿主气管整合在一起，并且在预测部位形成了上皮和软骨。这些发现证明4D生物打印系统可以生物学地制造组织模拟支架，并暗示了4D生物打印系统对于组织工程和临床应用的潜在价值。