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Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel

The liver exhibits complex geometrical morphologies of hepatic cells arranged in a hexagonal lobule with an extracellular matrix (ECM) organized in a specific pattern on a multi-scale level. Previous studies have utilized 3D bioprinting and microfluidic perfusion systems with various biomaterials to...

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Autores principales: Khati, Vamakshi, Turkki, Johannes Artturi, Ramachandraiah, Harisha, Pati, Falguni, Gaudenzi, Giulia, Russom, Aman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687301/
https://www.ncbi.nlm.nih.gov/pubmed/36354514
http://dx.doi.org/10.3390/bioengineering9110603
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author Khati, Vamakshi
Turkki, Johannes Artturi
Ramachandraiah, Harisha
Pati, Falguni
Gaudenzi, Giulia
Russom, Aman
author_facet Khati, Vamakshi
Turkki, Johannes Artturi
Ramachandraiah, Harisha
Pati, Falguni
Gaudenzi, Giulia
Russom, Aman
author_sort Khati, Vamakshi
collection PubMed
description The liver exhibits complex geometrical morphologies of hepatic cells arranged in a hexagonal lobule with an extracellular matrix (ECM) organized in a specific pattern on a multi-scale level. Previous studies have utilized 3D bioprinting and microfluidic perfusion systems with various biomaterials to develop lobule-like constructs. However, they all lack anatomical relevance with weak control over the size and shape of the fabricated structures. Moreover, most biomaterials lack liver-specific ECM components partially or entirely, which might limit their biomimetic mechanical properties and biological functions. Here, we report 3D bioprinting of a sacrificial PVA framework to impart its trilobular hepatic structure to the decellularized liver extracellular matrix (dLM) hydrogel with polyethylene glycol-based crosslinker and tyrosinase to fabricate a robust multi-scale 3D liver construct. The 3D trilobular construct exhibits higher crosslinking, viscosity (182.7 ± 1.6 Pa·s), and storage modulus (2554 ± 82.1 Pa) than non-crosslinked dLM. The co-culture of HepG(2) liver cells and NIH 3T3 fibroblast cells exhibited the influence of fibroblasts on liver-specific activity over time (7 days) to show higher viability (90–91.5%), albumin secretion, and increasing activity of four liver-specific genes as compared to the HepG(2) monoculture. This technique offers high lumen patency for the perfusion of media to fabricate a densely populated scaled-up liver model, which can also be extended to other tissue types with different biomaterials and multiple cells to support the creation of a large functional complex tissue.
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spelling pubmed-96873012022-11-25 Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel Khati, Vamakshi Turkki, Johannes Artturi Ramachandraiah, Harisha Pati, Falguni Gaudenzi, Giulia Russom, Aman Bioengineering (Basel) Article The liver exhibits complex geometrical morphologies of hepatic cells arranged in a hexagonal lobule with an extracellular matrix (ECM) organized in a specific pattern on a multi-scale level. Previous studies have utilized 3D bioprinting and microfluidic perfusion systems with various biomaterials to develop lobule-like constructs. However, they all lack anatomical relevance with weak control over the size and shape of the fabricated structures. Moreover, most biomaterials lack liver-specific ECM components partially or entirely, which might limit their biomimetic mechanical properties and biological functions. Here, we report 3D bioprinting of a sacrificial PVA framework to impart its trilobular hepatic structure to the decellularized liver extracellular matrix (dLM) hydrogel with polyethylene glycol-based crosslinker and tyrosinase to fabricate a robust multi-scale 3D liver construct. The 3D trilobular construct exhibits higher crosslinking, viscosity (182.7 ± 1.6 Pa·s), and storage modulus (2554 ± 82.1 Pa) than non-crosslinked dLM. The co-culture of HepG(2) liver cells and NIH 3T3 fibroblast cells exhibited the influence of fibroblasts on liver-specific activity over time (7 days) to show higher viability (90–91.5%), albumin secretion, and increasing activity of four liver-specific genes as compared to the HepG(2) monoculture. This technique offers high lumen patency for the perfusion of media to fabricate a densely populated scaled-up liver model, which can also be extended to other tissue types with different biomaterials and multiple cells to support the creation of a large functional complex tissue. MDPI 2022-10-22 /pmc/articles/PMC9687301/ /pubmed/36354514 http://dx.doi.org/10.3390/bioengineering9110603 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Khati, Vamakshi
Turkki, Johannes Artturi
Ramachandraiah, Harisha
Pati, Falguni
Gaudenzi, Giulia
Russom, Aman
Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel
title Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel
title_full Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel
title_fullStr Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel
title_full_unstemmed Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel
title_short Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel
title_sort indirect 3d bioprinting of a robust trilobular hepatic construct with decellularized liver matrix hydrogel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687301/
https://www.ncbi.nlm.nih.gov/pubmed/36354514
http://dx.doi.org/10.3390/bioengineering9110603
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