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

Khati, Vamakshi and Turkki, Johannes Artturi and Ramachandraiah, Harisha and Pati, Falguni and et al, . (2022) Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel. Bioengineering, 9 (603). pp. 1-18. ISSN 2306-5354

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Abstract

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 HepG2 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 HepG2 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. © 2022 by the authors.

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IITH Creators:

IITH Creators	ORCiD
Pati, Falguni	http://orcid.org/0000-0002-3588-1800

Item Type:

Article

Additional Information:

This research was funded by Swedish Research Council, grant number 2015-05378, and by European Commission through the FP7 project CanDo, grant number 610472. G.G. acknowledges funding from the Swedish Research Council, grant number 2019-05170.

Uncontrolled Keywords:

co-culture; decellularized liver extracellular matrix; indirect 3D bioprinting; liver lobule; robust structure; sacrificial scaffold

Subjects:

Biomedical Engineering

Divisions:

Department of Biomedical Engineering

Depositing User:

. LibTrainee 2021

Date Deposited:

23 Nov 2022 11:39

Last Modified:

23 Nov 2022 11:39