Biomimetic hepatic lobules from three-dimensional imprinted cell sheets

Jinglin Wang ¹Danqing Huang ¹Hanxu Chen ²Yuanjin Zhao³

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作者信息

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
3. 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
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Abstract

Liver-tissue engineering has proven valuable in treating liver diseases,but the construction of liver tis-sues 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 informa-tion 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.

Key words

Biomimetic/Hepatic lobules/Cell sheets/3D imprinting/Tissue engineering/Artificial liver

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基金项目

国家自然科学基金(T2225003)

国家自然科学基金(82100664)

国家重点研发计划(2022YFA1105300)

Jiangsu Provincial Science and Technology Special Fund for Outstanding Young Scholars(BK20230051)

Nanjing Health Science and Technology Development Project for Distinguished Young Scholars(JQX22003)

Nanjing Medical Science and Technique Development Foundation(ZKX21019)

Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)

Clinical Trials from Nanjing Drum Tower Hospital(2021-LCYJ-PY-46)

Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)

出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

参考文献量33

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