标题： 一种功能性的人体肝脏组织模型：3D生物打印共培养圆盘 显示英文标题

标题： A Functional Human Liver Tissue Model: 3D Bioprinted Co-culture Discoids

摘要： 为减少开发新药和有效药物相关的成本和延误，迫切需要改进的人类肝脏组织模型。 在这里，我们描述了一种用于3D生物打印功能性人类肝脏组织模型的方法，其中我们制造了厚度为200{\mu }m、直径为1-3 mm的圆盘状结构（圆盘），嵌入由紧密堆积的微凝胶制成的高渗透性支撑介质中。 我们证明该方法精确、准确且可扩展；每小时可制造多达100个组织，直径的变异性和误差约为4%。 印刷圆盘的组织学和免疫组织化学评估显示了自我组织、细胞粘附和关键肝脏标志物的表达。 在培养3-4周的过程中，这些组织稳定地以高水平合成白蛋白和尿素，优于球体组织模型。 我们发现这些组织表达超过100个与分子吸收、分布、代谢和排泄（ADME）相关的基因，其表达水平在人类肝脏范围内。 在暴露于多种测试化合物后，肝脏组织模型表现出酶促形成代谢物。 总之，这些结果展示了3D打印圆盘在药理学和毒理学应用中的前景。 显示英文摘要

摘要： To reduce costs and delays related to developing new and effective drugs, there is a critical need for improved human liver tissue models. Here we describe an approach for 3D bioprinting functional human liver tissue models, in which we fabricate disc-shaped structures (discoids) 200 {\mu}m in thickness and 1-3 mm in diameter, embedded in a highly permeable support medium made from packed microgels. We demonstrate that the method is precise, accurate, and scalable; up to 100 tissues per hour can be manufactured with a variability and error in diameter of about 4%. Histologic and immunohistochemical evaluation of printed discs reveal self-organization, cell cohesion, and key liver marker expression. During the course of 3-4 weeks in culture, the tissues stably synthesize albumin and urea at high levels, outperforming spheroid tissue models. We find the tissues express more than 100 genes associated with molecular absorption, distribution, metabolism, and excretion (ADME) at levels within the range of human liver. The liver tissue models exhibit enzymatic formation of metabolites after exposure to multiple test compounds. Together, these results demonstrate the promise of 3D printed discoids for pharmacological and toxicological applications.