基于压印细胞片组装的仿生肝小叶  

Biomimetic hepatic lobules from three-dimensional imprinted cell sheets

作　　者：王经琳 黄丹青 陈涵旭 赵远锦 Jinglin Wang;Danqing Huang;Hanxu Chen;Yuanjin Zhao(Department of Hepatobiliary Surgery,Hepatobiliary Institute,Nanjing Drum Tower Hospital,Medical School,Nanjing University,Nanjing 210008,China;State Key Laboratory of Bioelectronics,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China)

机构地区：[1]Department of Hepatobiliary Surgery,Hepatobiliary Institute,Nanjing Drum Tower Hospital,Medical School,Nanjing University,Nanjing 210008,China [2]State Key Laboratory of Bioelectronics,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China

出　　处：《Science Bulletin》2024年第10期1448-1457,共10页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(T2225003,and 82100664);the National Key Research and Development Program of China(2022YFA1105300);the Jiangsu Provincial Science and Technology Special Fund for Outstanding Young Scholars(BK20230051);the Nanjing Health Science and Technology Development Project for Distinguished Young Scholars(JQX22003);the Nanjing Medical Science and Technique Development Foundation(ZKX21019);the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01,and 2021-LCYJ-PY-46);the Guangdong Basic and Applied Basic Research Foundation(2021B1515120054).

摘　　要：Liver-tissue engineering has proven valuable in treating liver diseases,but the construction of liver tissues with high fidelity remains challenging.Here,we present a novel three-dimensional(3D)-imprinted cell-sheet strategy for the synchronous construction of biomimetic hepatic microtissues with high accuracy in terms of cell type,density,and distribution.To achieve this,the specific composition of hepatic cells in a normal human liver was determined using a spatial proteogenomics dataset.The data and biomimetic hepatic micro-tissues with hexagonal hollow cross-sections indicate that cell information was successfully generated using a homemade 3D-imprinted device for layer-by-layer imprinting and assembling the hepatic cell sheets.By infiltrating vascular endothelial cells into the hollow section of the assembly,biomimetic hepatic microtissues with vascularized channels for nutrient diffusion and drug perfusion can be obtained.We demonstrate that the resultant vascularized biomimetic hepatic micro-tissues can not only be integrated into a microfluidic drug-screening liver-on-a-chip but also assembled into an enlarged physiological structure to promote liver regeneration.We believe that our 3D-imprinted cell sheets strategy will open new avenues for biomimetic microtissue construction.

关 键 词：BIOMIMETIC Hepatic lobules Cell sheets 3D imprinting Tissue engineering Artificial liver 

分 类 号：R318[医药卫生—生物医学工程]