Are slaughterhouse-obtained livers suitable for use in perfusion research?

Objectives: The success of the machine perfusion of pig livers used for preclinical research depends on organ quality and availability. In this study, we investigated whether livers obtained from slaughterhouses are suitable and equivalent to livers obtained from laboratory pigs.

Methods: Livers were obtained from slaughterhouse pigs stunned by electrocution or CO inhalation and from laboratory pigs.

Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling.

Metabolic and toxic liver disorders, such as fatty liver disease (steatosis) and drug-induced liver injury, are highly prevalent and potentially life-threatening. To allow for the study of these disorders from the early stages onward, without using experimental animals, we collected porcine livers in a slaughterhouse and perfused these livers normothermically. With our simplified protocol, the perfused slaughterhouse livers remained viable and functional over five hours of perfusion, as shown by hemodynamics, bile production, indocyanine green clearance, ammonia metabolism, gene expression and histology.

High level of polarized engraftment of porcine intrahepatic cholangiocyte organoids in decellularized liver scaffolds.

In Europe alone, each year 5500 people require a life-saving liver transplantation, but 18% die before receiving one due to the shortage of donor organs. Whole organ engineering, utilizing decellularized liver scaffolds repopulated with autologous cells, is an attractive alternative to increase the pool of available organs for transplantation. The development of this technology is hampered by a lack of a suitable large-animal model representative of the human physiology and a reliable and continuous cell source.

Biomimetic Cell-Laden MeHA Hydrogels for the Regeneration of Cartilage Tissue.

Methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (CS)-biofunctionalized MeHA (CS-MeHA), were crosslinked in the presence of a matrix metalloproteinase 7 (MMP7)-sensitive peptide. The synthesized hydrogels were embedded with either human mesenchymal stem cells (hMSCs) or chondrocytes, at low concentrations, and subsequently cultured in a stem cell medium (SCM) or chondrogenic induction medium (CiM). The pivotal role of the synthesized hydrogels in promoting the expression of cartilage-related genes and the formation of neocartilage tissue despite the low concentration of encapsulated cells was assessed.

An ex vivo human osteochondral culture model.

To reduce animal experimentation and to overcome translational issues in cartilage tissue engineering, there is a need to develop an ex vivo human tissue-based approach. This study aims to demonstrate that a human osteochondral explant at different stages of osteoarthritis (OA) can be kept in long-term culture while preserving its viability and composition. Osteochondral explants with either a smooth or fibrillated cartilage surface, representing different OA stages, were harvested from fresh human tibial plateaus.

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids.

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable.

Development of an ex vivo aneurysm model for vascular device testing.

An ex vivo aneurysm model that closely resembles the in vivo situation can provide an important tool for testing therapies. The model should mimic a variety of conditions, such as in vivo hemodynamics and native arterial structure and characteristics, avoiding animal experimentation.  Therefore, the aim of this study is to develop an ex vivo aneurysm model by vessel wall stiffening to be used to assess treatment strategies.

Biomedical Applications of Photo- and Sono-Activated Rose Bengal: A Review.

The aim of this review is to discuss and compare the extensive range of biomedical applications of photo- and sono-activated Rose Bengal (RB). RB is a xanthene dye that due to its interesting photo- and sono-sensitive properties is gaining attention in the scientific field. This study is a literature review using the database PubMed.

A novel hybrid silk-fibroin/polyurethane three-layered vascular graft: towards in situ tissue-engineered vascular accesses for haemodialysis.

Clinically available alternatives of vascular access for long-term haemodialysis-currently limited to native arteriovenous fistulae and synthetic grafts-suffer from several drawbacks and are associated to high failure rates. Bioprosthetic grafts and tissue-engineered blood vessels are costly alternatives without clearly demonstrated increased performance. In situ tissue engineering could be the ideal approach to provide a vascular access that profits from the advantages of vascular grafts in the short-term (e.

Cartilage Regeneration in Preannealed Silk Elastin-Like Co-Recombinamers Injectable Hydrogel Embedded with Mature Chondrocytes in an Ex Vivo Culture Platform.

Tissue engineering for cartilage repair requires biomaterials that show rapid gelation and adequate mechanical properties. Although the use of hydrogel is the most promising biomaterial, it often lacks in rigidity and anchorage of cells when they are surrounded by synovial fluid while they are subjected to heavy loads. We developed and produced the Silk Elastin-Like co-Recombinamer (SELR), which contains both the physical interaction from elastin motifs and from silk motifs.

Ex vivo culture platform for assessment of cartilage repair treatment strategies.

There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors specific to the different needs of bone and cartilage.

Flow-perfusion interferes with chondrogenic and hypertrophic matrix production by mesenchymal stem cells.

Flow-perfusion is being promoted as a way to grow tissue-engineered cartilage in vitro. Yet, there is a concern that flow-perfusion may induce unwanted mechanical effects on chondrogenesis and terminal differentiation. Therefore, the aim of this study is to evaluate the effect of fluid flow on chondrogenesis and chondrocyte hypertrophy of MSCs in a well-established pellet culture model.

Sliding indentation enhances collagen content and depth-dependent matrix distribution in tissue-engineered cartilage constructs.

Background: Current tissue-engineered cartilage constructs contain insufficient amounts of collagen, whose function is to resist tension. We postulate that dynamic tension is necessary to stimulate collagen formation. Another shortcoming is that tissue-engineered cartilage does not possess native zonal variations.

Low agarose concentration and TGF-β3 distribute extracellular matrix in tissue-engineered cartilage.

Background: The mechanical properties of articular cartilage are dominated by the interterritorial matrix, as the matrix in this region is stiffer, greater in volume, and more interconnected compared to that in the pericellular and territorial region. Hence, tissue-engineered constructs in which a newly synthesized matrix accumulates in the pericellular and territorial regions may be of a lower mechanical quality compared to constructs in which the interterritorial region contains abundant matrix.

Objective: In this study, we explored the extent to which matrix distribution may be modulated by altering the agarose concentration and the presence of the transforming growth factor-β (TGF-β) and how this affects the mechanical properties of cultured cartilage constructs.

Tissue engineering of functional articular cartilage: the current status.

Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply.

RGD-dependent integrins are mechanotransducers in dynamically compressed tissue-engineered cartilage constructs.

Recent studies have shown that integrins act as mechanoreceptors in articular cartilage. In this study, we examined the effect of blocking RGD-dependent integrins on both ECM gene expression and ECM protein synthesis. Chondrocytes were isolated from full-depth porcine articular cartilage and seeded in 3% agarose constructs.