Hepatocellular carcinoma (HCC), as the fifth most common malignant cancer, develops and progresses mostly in a cirrhotic liver where stiff nodules are separated by fibrous bands. Scaffolds that can provide a 3D cirrhotic mechanical environment with complex native composition and biomimetic architecture are necessary for the development of better predictive tissue models. Here, we developed photocrosslinkable liver decellularized extracellular matrix (dECM) and a rapid light-based 3D bioprinting process to pattern liver dECM with tailorable mechanical properties to serve as a platform for HCC progression study. 3D bioprinted liver dECM scaffolds were able to stably recapitulate the clinically relevant mechanical properties of cirrhotic liver tissue. When encapsulated in dECM scaffolds with cirrhotic stiffness, HepG2 cells demonstrated reduced growth along with an upregulation of invasion markers compared to healthy controls. Moreover, an engineered cancer tissue platform possessing tissue-scale organization and distinct regional stiffness enabled the visualization of HepG2 stromal invasion from the nodule with cirrhotic stiffness. This work demonstrates a significant advancement in rapid 3D patterning of complex ECM biomaterials with biomimetic architecture and tunable mechanical properties for in vitro disease modeling.

肝细胞癌（HCC）是第五种最常见的恶性肿瘤，主要在肝硬化肝脏中发生和进展，其中坚硬的结节被纤维带分隔开。可以提供具有复杂天然成分和仿生结构的 3D 肝硬化机械环境的支架对于开发更好的预测组织模型是必要的。在这里，我们开发了可光交联的肝脏脱细胞细胞外基质 (dECM) 和基于光的快速 3D 生物打印工艺，以具有可定制机械性能的肝脏 dECM 图案，作为 HCC 进展研究的平台。3D 生物打印肝脏 dECM 支架能够稳定地重现肝硬化肝组织的临床相关机械特性。当封装在具有肝硬化硬度的 dECM 支架中时，与健康对照相比，HepG2 细胞的生长减少，同时侵袭标记物上调。此外，具有组织规模组织和独特区域刚度的工程化癌症组织平台能够可视化具有肝硬化刚度的结节的 HepG2 间质侵袭。这项工作展示了复杂 ECM 生物材料快速 3D 图案化方面的重大进步，该生物材料具有仿生结构和可调机械性能，可用于体外疾病建模。