Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium
Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation, mimicking physiological heterogeneous structures, and recreating the cellular microenvironment. However, the layer-by-layer printing method is significantly co...
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| Format: | Article |
| Language: | English |
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IOP Publishing
2025-01-01
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| Series: | International Journal of Extreme Manufacturing |
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| Online Access: | https://doi.org/10.1088/2631-7990/ada836 |
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| author | Weikang Lv Haoran Yu Abdellah Aazmi Tuya Naren Wanli Cheng Mengfei Yu Zhen Wang Xiaobin Xu Huayong Yang Liang Ma |
| author_facet | Weikang Lv Haoran Yu Abdellah Aazmi Tuya Naren Wanli Cheng Mengfei Yu Zhen Wang Xiaobin Xu Huayong Yang Liang Ma |
| author_sort | Weikang Lv |
| collection | DOAJ |
| description | Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation, mimicking physiological heterogeneous structures, and recreating the cellular microenvironment. However, the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink, making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials. To overcome this limitation, we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel. This medium possesses yield stress and self-healing properties, facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it. By adjusting the printing speed, we controlled the filament diameter, achieving a range from 250 μ m to 1000 μ m, and ensuring precise control over ink deposition locations and filament shapes. Using the in situ endothelialization method, we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells. In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue. We also investigated the impact of varying vascular densities on liver tissue function. Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways. In summary, this method is adaptable to various materials, allowing the rheological properties of the supporting bath and the tissue’s porosity to be modified using microgels, thus enabling precise regulation of the liver tissue microenvironment. Additionally, it facilitates the rapid construction of three-dimensional vascular structures within liver tissue. The resulting vascularized liver tissue model exhibits enhanced biological functionality, opening new opportunities for biomedical applications. |
| format | Article |
| id | doaj-art-7db40b02a36142bea5bf01de236959f9 |
| institution | Kabale University |
| issn | 2631-7990 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | IOP Publishing |
| record_format | Article |
| series | International Journal of Extreme Manufacturing |
| spelling | doaj-art-7db40b02a36142bea5bf01de236959f92025-01-28T13:48:33ZengIOP PublishingInternational Journal of Extreme Manufacturing2631-79902025-01-017303500210.1088/2631-7990/ada836Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding mediumWeikang Lv0https://orcid.org/0009-0005-4671-7968Haoran Yu1Abdellah Aazmi2Tuya Naren3Wanli Cheng4Mengfei Yu5https://orcid.org/0000-0002-7700-4697Zhen Wang6Xiaobin Xu7Huayong Yang8Liang Ma9https://orcid.org/0000-0002-6242-1850State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University , Hangzhou 310058, People’s Republic of China; School of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaState Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University , Hangzhou 310058, People’s Republic of China; School of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaState Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University , Hangzhou 310058, People’s Republic of China; School of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaState Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University , Hangzhou 310058, People’s Republic of China; School of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaSchool of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaThe Affiliated Stomatologic Hospital, School of Medicine, Zhejiang University , Hangzhou 310003, People’s Republic of ChinaCenter for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College , Hangzhou, Zhejiang 310014, People’s Republic of ChinaSchool of Materials Science and Engineering, Tongji University , Shanghai 201804, People’s Republic of ChinaState Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University , Hangzhou 310058, People’s Republic of China; School of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaState Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University , Hangzhou 310058, People’s Republic of China; School of Mechanical Engineering, Zhejiang University , Hangzhou 310058, People’s Republic of ChinaConstructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation, mimicking physiological heterogeneous structures, and recreating the cellular microenvironment. However, the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink, making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials. To overcome this limitation, we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel. This medium possesses yield stress and self-healing properties, facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it. By adjusting the printing speed, we controlled the filament diameter, achieving a range from 250 μ m to 1000 μ m, and ensuring precise control over ink deposition locations and filament shapes. Using the in situ endothelialization method, we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells. In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue. We also investigated the impact of varying vascular densities on liver tissue function. Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways. In summary, this method is adaptable to various materials, allowing the rheological properties of the supporting bath and the tissue’s porosity to be modified using microgels, thus enabling precise regulation of the liver tissue microenvironment. Additionally, it facilitates the rapid construction of three-dimensional vascular structures within liver tissue. The resulting vascularized liver tissue model exhibits enhanced biological functionality, opening new opportunities for biomedical applications.https://doi.org/10.1088/2631-7990/ada8363D bioprintingbiphasic cell-laden mediumsacrificial embedded printingvascularized liver tissue model |
| spellingShingle | Weikang Lv Haoran Yu Abdellah Aazmi Tuya Naren Wanli Cheng Mengfei Yu Zhen Wang Xiaobin Xu Huayong Yang Liang Ma Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium International Journal of Extreme Manufacturing 3D bioprinting biphasic cell-laden medium sacrificial embedded printing vascularized liver tissue model |
| title | Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium |
| title_full | Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium |
| title_fullStr | Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium |
| title_full_unstemmed | Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium |
| title_short | Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium |
| title_sort | construction of complex three dimensional vascularized liver tissue model in vitro based on a biphasic cell laden embedding medium |
| topic | 3D bioprinting biphasic cell-laden medium sacrificial embedded printing vascularized liver tissue model |
| url | https://doi.org/10.1088/2631-7990/ada836 |
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