Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks

Hepatic sinusoids are uniquely organized structures that help maintain a spectrum of hepatic functions. Although several in vitro liver models have been developed to replicate liver sinusoids, most of these platforms require complex, multi-step fabrication methods making it difficult to achieve trul...

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Main Authors: Somnath Maji, Minkyoung Lee, Jooyoung Lee, Jaehee Lee, Hyungseok Lee
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Materials Today Bio
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006423001837
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author Somnath Maji
Minkyoung Lee
Jooyoung Lee
Jaehee Lee
Hyungseok Lee
author_facet Somnath Maji
Minkyoung Lee
Jooyoung Lee
Jaehee Lee
Hyungseok Lee
author_sort Somnath Maji
collection DOAJ
description Hepatic sinusoids are uniquely organized structures that help maintain a spectrum of hepatic functions. Although several in vitro liver models have been developed to replicate liver sinusoids, most of these platforms require complex, multi-step fabrication methods making it difficult to achieve truly three-dimensional (3D) channel geometries. In this study, a single-step bioprinting technique was demonstrated to simultaneously print a chip platform and develop a perfusable vascularized liver sinusoid in vitro model. The integrated system uses a co-axial-based bioprinting approach to develop a liver sinusoid-like model that consists of a sacrificial core compartment containing a perfusable pre-vascular structure and an alginate-collagen-based shell compartment containing hepatocytes. The lumen-based perfusable 3D liver sinusoid-on-a-chip (LSOC-P) demonstrated significantly better hepatocyte viability, proliferation, and liver-specific gene and protein expression compared to a 3D hepatocyte-based core/shell model with static media and the standard hepatocyte-based 2D sandwich culture system. A drug toxicity evaluation of hepatotoxins highlighted the comparatively higher sensitivity of the LSOC system with a close estimation of the therapeutic range of safe drug concentrations for humans. In conclusion, the current findings indicate that the combinatorial single-step co-axial bioprinting technique is a promising fabrication approach for the development of a perfusable LSOC platform for drug screening applications.
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spelling doaj.art-33ed8bf642444549ab666c5621d3c0892023-07-28T04:26:45ZengElsevierMaterials Today Bio2590-00642023-08-0121100723Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinksSomnath Maji0Minkyoung Lee1Jooyoung Lee2Jaehee Lee3Hyungseok Lee4Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Animal Industry Convergence, Kangwon National University, Chuncheon, Republic of Korea; Department of Smart Health Science and Technology, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Smart Health Science and Technology, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Smart Health Science and Technology, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Republic of Korea; Department of Smart Health Science and Technology, Kangwon National University, Chuncheon, Republic of Korea; Corresponding author. Department of Mechanical and Biomedical Engineering, Kangwon National University (KNU), 1, Kangwondaehak-gil, Chuncheon-si, Gangwon-do, Republic of Korea.Hepatic sinusoids are uniquely organized structures that help maintain a spectrum of hepatic functions. Although several in vitro liver models have been developed to replicate liver sinusoids, most of these platforms require complex, multi-step fabrication methods making it difficult to achieve truly three-dimensional (3D) channel geometries. In this study, a single-step bioprinting technique was demonstrated to simultaneously print a chip platform and develop a perfusable vascularized liver sinusoid in vitro model. The integrated system uses a co-axial-based bioprinting approach to develop a liver sinusoid-like model that consists of a sacrificial core compartment containing a perfusable pre-vascular structure and an alginate-collagen-based shell compartment containing hepatocytes. The lumen-based perfusable 3D liver sinusoid-on-a-chip (LSOC-P) demonstrated significantly better hepatocyte viability, proliferation, and liver-specific gene and protein expression compared to a 3D hepatocyte-based core/shell model with static media and the standard hepatocyte-based 2D sandwich culture system. A drug toxicity evaluation of hepatotoxins highlighted the comparatively higher sensitivity of the LSOC system with a close estimation of the therapeutic range of safe drug concentrations for humans. In conclusion, the current findings indicate that the combinatorial single-step co-axial bioprinting technique is a promising fabrication approach for the development of a perfusable LSOC platform for drug screening applications.http://www.sciencedirect.com/science/article/pii/S2590006423001837Liver-on-a-chipBioprintingSingle-step fabricationLiver sinusoidDrug screening
spellingShingle Somnath Maji
Minkyoung Lee
Jooyoung Lee
Jaehee Lee
Hyungseok Lee
Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks
Materials Today Bio
Liver-on-a-chip
Bioprinting
Single-step fabrication
Liver sinusoid
Drug screening
title Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks
title_full Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks
title_fullStr Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks
title_full_unstemmed Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks
title_short Development of lumen-based perfusable 3D liver in vitro model using single-step bioprinting with composite bioinks
title_sort development of lumen based perfusable 3d liver in vitro model using single step bioprinting with composite bioinks
topic Liver-on-a-chip
Bioprinting
Single-step fabrication
Liver sinusoid
Drug screening
url http://www.sciencedirect.com/science/article/pii/S2590006423001837
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