去细胞化
细胞外基质
3D生物打印
材料科学
生物医学工程
肝细胞癌
间质细胞
组织工程
癌症研究
细胞生物学
医学
生物
作者
Xinwei Ma,Yu Chen,Pengrui Wang,Wei Xu,Xueyi Wan,Cheuk Sun Edwin Lai,Justin Liu,Anna Koroleva-Maharajh,Shaochen Chen
出处
期刊:Biomaterials
[Elsevier]
日期:2018-12-01
卷期号:185: 310-321
被引量:209
标识
DOI:10.1016/j.biomaterials.2018.09.026
摘要
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.
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