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Bioengineering
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Bioengineering Liver Transplantation
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Bioengineering Liver Transplantation

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 63586

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Luc J. W. van der Laan

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Guest Editor
Department of Surgery, Erasmus MC Transplant Institute, University Medical Center, 3015 CN Rotterdam, The Netherlands
Interests: regenerative medicine; liver transplantation; stem cells; tissue engineering; liver organoids
Special Issues, Collections and Topics in MDPI journals
Dr. Bart Spee

E-Mail Website
Guest Editor
Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Interests: bioprinting; liver iPSC; organoids; tissue engineering; regenerative medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Monique M. A. Verstegen

E-Mail Website
Guest Editor
Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Interests: liver extracellular matrix proteins; recellularization; biomechanical analysis; organoids; bile duct regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aim of this Special Issue is to review, understand, and evaluate new and exciting opportunities from the field on regenerative medicine, biomaterials, and stem cell research for the bioengineering of human liver grafts that can be applied for transplantation and personalized treatment of end-stage liver disease.

The development of culture conditions for long-term expansion of LGR5+ intestinal stem cells as crypt-villus structures demonstrated the feasibility of deriving complex, organ-like structures in vitro from primary adult tissues, including the liver. Moreover, human pluripotent stem cells (hPSCs) can be applied to generate functionally maturated liver and bile duct epithelial cells.

In this Special Issue, we welcome reviews and original papers focussing on hepatic cell sources, including adult hepatic stem cells, organoids, fetal and induced pluripotent stem cells, and primary cells (i.e., hepatocytes, cholangiocytes, and endothelial cells) and how these cells can be applied in tissue engineering strategies to generate implantable and personalized liver grafts. Potential topics include, but are not limited to, the following: liver tissue engineering, liver regeneration, graft repair, liver stem cells and organoids, bio-scaffolds, and 3D printing.

We invite you to contribute original research papers, as well as comprehensive reviews, aligned with these themes, to advance and improve the actual state-of-the-art in liver bioengineering and providing new opportunities for the imminent medical problem of organ and tissue shortage for transplantation.

Dr. Luc J.W. van der Laan
Dr. Bart Spee
Dr. Monique M. A. Verstegen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Tissue Engineering
  • Liver regeneration
  • Graft repair
  • Liver stem cells & organoids
  • Bio scaffolds
  • Bio printing

Published Papers (7 papers)

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Editorial

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3 pages, 174 KiB  
Editorial
Bioengineering Liver Transplantation
by Monique M.A. Verstegen, Bart Spee and Luc J.W. van der Laan
Bioengineering 2019, 6(4), 96; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering6040096 - 16 Oct 2019
Cited by 1 | Viewed by 5548
Abstract
Since the first in-man liver transplantation was performed by Starzl et al [...] Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)

Research

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14 pages, 1052 KiB  
Article
Oxygen Persufflation in Liver Transplantation Results of a Randomized Controlled Trial
by Anja Gallinat, Dieter Paul Hoyer, Georgios Sotiropoulos, Jürgen Treckmann, Tamas Benkoe, Jennifer Belker, Fuat Saner, Andreas Paul and Thomas Minor
Bioengineering 2019, 6(2), 35; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering6020035 - 27 Apr 2019
Cited by 7 | Viewed by 6732
Abstract
Oxygen persufflation has shown experimentally to favorably influence hepatic energy dependent pathways and to improve survival after transplantation. The present trial evaluated oxygen persufflation as adjunct in clinical liver preservation. A total of n = 116 adult patients (age: 54 (23–68) years, M/F: [...] Read more.
Oxygen persufflation has shown experimentally to favorably influence hepatic energy dependent pathways and to improve survival after transplantation. The present trial evaluated oxygen persufflation as adjunct in clinical liver preservation. A total of n = 116 adult patients (age: 54 (23–68) years, M/F: 70/46), were enrolled in this prospective randomized study. Grafts were randomized to either oxygen persufflation for ≥2 h (O2) or mere cold storage (control). Only liver grafts from donors ≥55 years and/or marginal grafts after multiple rejections by other centers were included. Primary endpoint was peak-aspartate aminotransferase (AST) level until post-operative day 3. Standard parameters including graft- and patient survival were analyzed by uni- and multivariate analysis. Both study groups were comparable except for a longer ICU stay (4 versus 3 days) of the donors and a higher recipient age (57 versus 52 years) in the O2-group. Serum levels of TNF alpha were significantly reduced after oxygen persufflation (p < 0.05). Median peak-AST values did not differ between the groups (O2: 580 U/l, control: 699 U/l). Five year graft- and patient survival was similar. Subgroup analysis demonstrated a positive effect of oxygen persufflation concerning the development of early allograft dysfunction (EAD), in donors with a history of cardiopulmonary resuscitation and elevated ALT values, and concerning older or macrosteatotic livers. This study favors pre-implantation O2-persufflation in concrete subcategories of less than optimal liver grafts, for which oxygen persufflation can be considered a safe, cheap and easy applicable reconditioning method. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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13 pages, 6078 KiB  
Article
3D Printing for Bio-Synthetic Biliary Stents
by Christen J. Boyer, Moheb Boktor, Hrishikesh Samant, Luke A. White, Yuping Wang, David H. Ballard, Robert C. Huebert, Jennifer E. Woerner, Ghali E. Ghali and Jonathan S. Alexander
Bioengineering 2019, 6(1), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering6010016 - 09 Feb 2019
Cited by 31 | Viewed by 9156
Abstract
Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. [...] Read more.
Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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Review

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29 pages, 9888 KiB  
Review
Bioprinting for Liver Transplantation
by Christina Kryou, Valentina Leva, Marianneza Chatzipetrou and Ioanna Zergioti
Bioengineering 2019, 6(4), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering6040095 - 10 Oct 2019
Cited by 47 | Viewed by 11610
Abstract
Bioprinting techniques can be used for the in vitro fabrication of functional complex bio-structures. Thus, extensive research is being carried on the use of various techniques for the development of 3D cellular structures. This article focuses on direct writing techniques commonly used for [...] Read more.
Bioprinting techniques can be used for the in vitro fabrication of functional complex bio-structures. Thus, extensive research is being carried on the use of various techniques for the development of 3D cellular structures. This article focuses on direct writing techniques commonly used for the fabrication of cell structures. Three different types of bioprinting techniques are depicted: Laser-based bioprinting, ink-jet bioprinting and extrusion bioprinting. Further on, a special reference is made to the use of the bioprinting techniques for the fabrication of 2D and 3D liver model structures and liver on chip platforms. The field of liver tissue engineering has been rapidly developed, and a wide range of materials can be used for building novel functional liver structures. The focus on liver is due to its importance as one of the most critical organs on which to test new pharmaceuticals, as it is involved in many metabolic and detoxification processes, and the toxicity of the liver is often the cause of drug rejection. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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11 pages, 599 KiB  
Review
Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis
by Hedwig S. Kruitwagen, Hille Fieten and Louis C. Penning
Bioengineering 2019, 6(4), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering6040088 - 25 Sep 2019
Cited by 4 | Viewed by 7045
Abstract
Wilson Disease is a rare autosomal recessive liver disorder in humans. Although its clinical presentation and age of onset are highly variable, hallmarks include signs of liver disease, neurological features and so-called Kayser-Fleischer rings in the eyes of the patient. Hepatic copper accumulation [...] Read more.
Wilson Disease is a rare autosomal recessive liver disorder in humans. Although its clinical presentation and age of onset are highly variable, hallmarks include signs of liver disease, neurological features and so-called Kayser-Fleischer rings in the eyes of the patient. Hepatic copper accumulation leads to liver disease and eventually to liver cirrhosis. Treatment options include life-long copper chelation therapy and/or decrease in copper intake. Eventually liver transplantations are indicated. Although clinical outcome of liver transplantations is favorable, the lack of suitable donor livers hampers large numbers of transplantations. As an alternative, cell therapies with hepatocytes or liver stem cells are currently under investigation. Stem cell biology in relation to pets is in its infancy. Due to the specific population structure of dogs, canine copper toxicosis is frequently encountered in various dog breeds. Since the histology and clinical presentation resemble Wilson Disease, we combined genetics, gene-editing, and matrices-based stem cell cultures to develop a translational preclinical transplantation model for inherited copper toxicosis in dogs. Here we describe the roadmap followed, starting from the discovery of a causative copper toxicosis mutation in a specific dog breed and culminating in transplantation of genetically-engineered autologous liver stem cells. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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19 pages, 1594 KiB  
Review
New Perspectives in Liver Transplantation: From Regeneration to Bioengineering
by Debora Bizzaro, Francesco Paolo Russo and Patrizia Burra
Bioengineering 2019, 6(3), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering6030081 - 11 Sep 2019
Cited by 18 | Viewed by 8155
Abstract
Advanced liver diseases have very high morbidity and mortality due to associated complications, and liver transplantation represents the only current therapeutic option. However, due to worldwide donor shortages, new alternative approaches are mandatory for such patients. Regenerative medicine could be the more appropriate [...] Read more.
Advanced liver diseases have very high morbidity and mortality due to associated complications, and liver transplantation represents the only current therapeutic option. However, due to worldwide donor shortages, new alternative approaches are mandatory for such patients. Regenerative medicine could be the more appropriate answer to this need. Advances in knowledge of physiology of liver regeneration, stem cells, and 3D scaffolds for tissue engineering have accelerated the race towards efficient therapies for liver failure. In this review, we propose an update on liver regeneration, cell-based regenerative medicine and bioengineering alternatives to liver transplantation. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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30 pages, 1134 KiB  
Review
Hydrogels for Liver Tissue Engineering
by Shicheng Ye, Jochem W.B. Boeter, Louis C. Penning, Bart Spee and Kerstin Schneeberger
Bioengineering 2019, 6(3), 59; https://doi.org/10.3390/bioengineering6030059 - 05 Jul 2019
Cited by 61 | Viewed by 14503
Abstract
Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are [...] Read more.
Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are physiologically relevant. To make bioengineered livers, the two most important ingredients are hepatic cells and supportive materials such as hydrogels. In the past decades, dozens of hydrogels have been developed to act as supportive materials, and some have been used for in vitro models and formed functional liver constructs. However, currently none of the used hydrogels are suitable for in vivo transplantation. Here, the histology of the human liver and its relationship with LTE is introduced. After that, significant characteristics of hydrogels are described focusing on LTE. Then, both natural and synthetic materials utilized in hydrogels for LTE are reviewed individually. Finally, a conclusion is drawn on a comparison of the different hydrogels and their characteristics and ideal hydrogels are proposed to promote LTE. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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