Bioengineered transplantable porcine livers with re-endothelialized vasculature
Abstract
Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure.
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Using allograft-derived scaffolds is more clinically relevant, but only a limited number of human organs can be obtained; organs from other species have also been utilized.
“Using allograft-derived scaffolds would be more clinically relevant, but only a very limited number of human organs can be obtained; hence, organs from other species have also been utilized6,7.”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [6]
Pretreating decellularized porcine liver scaffold with CD31 antibody followed by NHS/EDC immobilization and infusing murine ECs resulted in well-aligned, uniformly distributed ECs over vascular lumens, with significant reduction in platelet adhesion upon in vitro blood perfusion.
“This approach resulted in well-aligned, and uniformly distributed ECs over the lumens of the vascular structures, with a significant reduction in platelet adhesion upon blood perfusion in vitro (Fig. 4).”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [11]
Reendothelialized livers sustained physiological host blood flow for up to 24 h after heterotopic transplantation into pigs.
“Reendothelialized livers sustained physiological host blood flow for up to 24 h after heterotopic transplantation into pigs.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [11]
Cites
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RETRACTED: Engineered whole organs and complex tissues
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RetractedThe use of whole organ decellularization for the generation of a vascularized liver organoid
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“Over the last two decades, livers from mice, rats, ferrets, rabbits, sheep, pigs, and humans have been used for decellularization [8 – 11 , 13 – 27].”
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- Authors
- Ko, I. K., Peng, L., Peloso, A., Smith, C. J., Dhal, A., Deegan, D. B., Zimmerman, C., Clouse, C., Zhao, W., Shupe, T. D., Soker, S., Yoo, J. J., & Atala, A.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of Pavia (IT)
- Corresponding author
- Yoo, James J.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 40
- Pages
- 72-79
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2042510811
- Cited by
- 148
- References
- 2
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 7 · 2021: 17 · 2020: 11 · 2019: 21 · 2018: 22 · 2017: 15 · 2016: 13 · 2015: 7
- FWCI
- 10.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver transplantation, decellularized liver scaffold, re-endothelialization, anti-endothelial cell antibodies, endothelial cell adhesion, vascularization, porcine liver, platelet adhesion, end-stage liver failure, xenotransplantation
- MeSH terms
- Animals, Endothelium, Vascular, Female, Liver, Vascular Patency, Liver Transplantation, Prosthesis Implantation, Sus scrofa, Tissue Scaffolds, Bioengineering
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