Abstract:
Bioartificial liver system are being developed as extracorporeal availability liver support therapy for patients with acute liver failure. In the system, bioreactor takes part in an important role. Up to new, many types bioreactors have been designed and studied. They are flat plate, hollow fiber, perfused beds or scaffolds, and beds with encapsulated or suspended cells bioreactor. In the article, the action, function, and criteria of bioreactor are introduced and 4 main types bioreactor's study development is reviewed.Keywords:
Bioartificial liver device
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These studies were performed to determine the efficiency of liver slices to metabolize lidocaine and ammonia. Rabbit liver slices 1cm in diameter with an average weight of 50mg were cultured in a newly designed flat plate bioreactor. Fifty slices were placed on top of wire mesh stretched over each of four metal plates (5 ± 10cm). Plates were seated at a 45° angle in a sealed chamber at 37°C. Media pumped to the top of the plate perfused the tissue by gravity flow. Two hundred ml of Williams E media with 10%FCS was circulated through the chamber and a reservoir at 400ml/min. A mixture of 95% oxygen, 5% CO2 at +1 ATM was maintained in the chamber throughout the study. The gas mixture was exchanged every 12 minutes. Over a three day period, bolus doses of lidocaine and ammonia were injected. A 2mg bolus dose of Lidocaine was cleared at a rate of 3.6ug/g liver/min. The lidocaine metabolite DMX (dimethyl xylidine) was produced at a rate of 33ug/g Hver/Hr. In response to a 60mg dose of Lidocaine, DMX was produced at the rate of 196ug/g liver/Hr. Ammonium chloride was delivered in bolus doses ranging between 2 and 100mg. The rate of urea synthesis increased with the dose (Table 1).TableClearance and metabolism rates were consistent throughout the three day perfusion period. The results of this study demonstrate that liver slices in a oxygenated, flat-plate perfusion system have the potential to be used in a bioartificial liver device.
Bolus (digestion)
Ammonium chloride
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A new bioartificial liver support system has been developed for the treatment of liver failure. The basis of the system is that the complex functions of the liver are replaced by hepatocytes cultured in a special bioreactor. The system consists of two circuits: the patient circuit and the bioreactor circuit. Fluids in the circuits dialyse against each other through the semipermeable membranes of hollow-fibres in a dialysis cartridge. Toxic molecules from the patient pass across the membrane and are metabolised by hepatocytes cultivated in the bioreactor while hepatocyte-synthesised products pass across the membrane to the patient in the opposite direction.
Bioartificial liver device
Semipermeable membrane
Cartridge
Membrane bioreactor
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Bioartificial liver is close to normal liver in function.Bioreactor and hepatocytes cell culture are the main parts of the bioartificial liver,they decides the efficiency and effectiveness of bioartificial liver systerm.The artificial liver treatment cannot break away from artificial liver support devices.This article reviewed the bioreactor,liver cell culture,artificial liver support system principle,hardware and application.
Bioartificial liver device
Artificial liver
Liver cell
Human liver
Liver tissue
Liver function
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Matrix (chemical analysis)
Component (thermodynamics)
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P89 Aims: A radial-flow bioreactor (RFB) is a high-functional three-dimensional culture system, which can be used for high-density culture. The RFB was used for three-dimensional perfusion culture of hepatocellular carcinoma (HCC) cells and renal cells, in order to create a bioartificial liver and kidney. Methods: The cylindrical reactor is filled with porous hydroxy apatite beads, polyvinylalcohol, or cellulose microcarrier. RFB can be characterized as a system in which the medium flows from the periphery towards the center of the reactor. To obtain a high-density cell culture, it is essential to ensure that biased distribution of oxygen and nutrients at the inlet and outlet of the culture medium is minimized. If the medium flows from the periphery towards the center, the high perfusion rate at the center would allow adequate supply of oxygen and nutrients to the cells at the center even while oxygen and nutrients are consumed at the periphery, thereby allowing the cells to remain viable. Two to 5 ×107 cells were injected in the reservoir of the RFB system. Isolated cells were loaded in the RFB column using a circulation pump, and became trapped and adhered to the porous culture beads. For each data point, RNA was obtained from the cells cultured in the RFB or monolayer dish and we performed real-time quantitative PCR Furthermore, we estimated the concentration of some factors in the supernatant. Results: When HCC cells were incubated in the RFB system, they were cultured with high density and maintained viable for long periods of time. The ability of HCC cells to produce albumin was higher when cultured in the RFB system than in monolayer culture. Mesangial cells (HMC) and proximal tubular cells (LLC-PK1) were cultured in the RFB for more than 14 days as well as HCC cells. Then the mRNA expression of some enzymes involved in a urea cycle and cytochrome p450s in HCC cells, of the 1-alpha-hydroxylase (CYP27B1) in LLC-PK1 cells, or of CIP1 in HMC were higher than those in a monolayer culture. Furthermore, testosterone, which is one of substrates for CYP3A4, and Ammonium chloride were metabolized to a 6-beta hydroxy testosterone and Ammonia, respectively. Conclusions: These results suggested that the RFB system composed of HCC cells or renal cells were useful for bioartificial liver and kidney.
Microcarrier
Bioartificial liver device
Peristaltic pump
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Bioartificial liver device
Microcarrier
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Recent developments in tissue engineering permit to use isolated hepatocytes in a bioreactor for the creation of a bioartificial liver which supports patients suffering from acute liver failure. In this study, the authors discuss the development of a flat membrane bioreactor using pig hepatocytes for the replacement of liver functions. The flat membrane bioreactor permits a high-density hepatocyte culture under sufficient oxygenation conditions, comparable to an in vivo microenvironment. In this bioreactor, built according to the in vivo organisation of the liver, pig hepatocytes are cultured with non-parenchymal cells within an extracellular matrix between oxygen-permeable flat-sheet membranes as individual plates. The performance of the "scale-up bioreactor" was tested in vitro for 18 days in static and flux conditions. Pig hepatocytes in the bioreactor were maintained in three-dimensional co-culture with non-parenchymal cells and are reorganised in a way similar to the liver cell plates in vivo: cells remained polarised in vitro clearly demonstrating biliary zones surrounding individual hepatocytes. The biochemical performance of the bioreactor was assessed by estimating its ability to remove two of the major toxins associated with hepatic encephalopathy: benzodiazepines and ammonia. The rates of ammonia elimination and drug biotransformation were maintained at constant high levels for almost two weeks. This "scaled-up bioreactor" provides conditions favourable for the formation of contiguous cell sheets, which allow to maintain constant liver specific functions.
Bioartificial liver device
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Bioartificial liver device
Sodium alginate
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We recently demonstrated that HepaRG cells encapsulated into 1.5% alginate beads are capable of self-assembling into spheroids. They adequately differentiate into hepatocyte-like cells, with hepatic features observed at Day 14 post-encapsulation required for external bioartificial liver applications. Preliminary investigations performed within a bioreactor under shear stress conditions and using a culture medium mimicking acute liver failure (ALF) highlighted the need to reinforce beads with a polymer coating. We demonstrated in a first step that a poly-l-lysine coating improved the mechanical stability, without altering the metabolic activities necessary for bioartificial liver applications (such as ammonia and lactate elimination). In a second step, we tested the optimized biomass in a newly designed perfused dynamic bioreactor, in the presence of the medium model for pathological plasma for 6 h. Performances of the biomass were enhanced as compared to the steady configuration, demonstrating its efficacy in decreasing the typical toxins of ALF. This type of bioreactor is easy to scale up as it relies on the number of micro-encapsulated cells, and could provide an adequate hepatic biomass for liver supply. Its design allows it to be integrated into a hybrid artificial/bioartificial liver setup for further clinical studies regarding its impact on ALF animal models.
Bioartificial liver device
Extracorporeal
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A special bioreactor SBR,including its principle and structure character,is introduced in this article,which is applied in biodialysis system LDBS.According to the result of the testing on animals,it is proved to be available that using this special bioreactor liver cells can be cultured in large quantities and chronically,and their activity and performance can be hold for a long period.Metabolism is also observed and the immunoreaction between blood and liver cells is validated.
Bioartificial liver device
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