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Liver bioprinting within a novel support medium with functionalized spheroids, hepatic vein structures, and enhanced post-transplantation vascularization

Abstract:

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.biomaterials.2024.122681

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Oxford college:
Exeter College
Role:
Author
ORCID:
0000-0001-8223-5003
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author


Publisher:
Elsevier
Journal:
Biomaterials More from this journal
Volume:
311
Article number:
122681
Publication date:
2024-06-25
Acceptance date:
2024-06-23
DOI:
EISSN:
1878-5905
ISSN:
0142-9612
Pmid:
38944968


Language:
English
Keywords:
Pubs id:
2011348
Local pid:
pubs:2011348
Deposit date:
2024-08-02

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