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 s...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.展开更多
基金supported by the National Natural Science Foundation of China(T2225003,and 82100664)the National Key Research and Development Program of China(2022YFA1105300)+4 种基金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).
文摘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.
