Bioartificial liver devices: Perspectives on the state of the art

Abstract

Acute liver failure remains a significant cause of morbidity and mortality. Bioartificial liver (BAL) devices have been in development for more than 20 years. Such devices aim to temporarily take over the metabolic and excretory functions of the liver until the patients' own liver has recovered or a donor liver becomes available for transplant. The important issues include the choice of cell materials and the design of the bioreactor. Ideal BAL cell materials should be of good viability and functionality, easy to access, and exclude immunoreactive and tumorigenic cell materials. Unfortunately, the current cells in use in BAL do not meet these requirements. One of the challenges in BAL development is the improvement of current materials; another key point concerning cell materials is the coculture of different cells. The bioreactor is an important component of BAL, because it determines the viability and function of the hepatocytes within it. From the perspective of bioengineering, a successful and clinically effective bioreactor should mimic the structure of the liver and provide an in vivo-like microenvironment for the growth of hepatocytes, thereby maintaining the cells' viability and function to the maximum extent. One future trend in the development of the bioreactor is to improve the oxygen supply system. Another direction for future research on bioreactors is the application of biomedical materials. In conclusion, BAL is, in principle, an important therapeutic strategy for patients with acute liver failure, and may also be a bridge to liver transplantation. It requires further research and development, however, before it can enter clinical practice.

The use of bioreactors as in vitro models in pharmaceutical research

“…Unsurprisingly, an improvement in functionality of C3A cells in HFBs was noted when red blood cells were added in culture medium [49], highlighting that an adequate oxygen supply is a prerequisite for the maintenance of hepatocytes in vitro. Considering this, the Excorp medical bioartificial liver support system (BLSS) incorporates an oxygenator and heat exchanger along with a blood pump and HFB seeded with primary porcine hepatocytes in the ECS [50].…”

Effects of nitric oxide on ammonia decomposition by hepatocytes under shear stress

“…A bioartificial liver acts as a supportive device that either allows a patient's own liver time to regenerate or bridges the patient's liver functions until a liver transplant is possible [1]. Bioartificial livers must exhibit good viability and functionality but hepatocytes by themselves do not satisfy these requirements [1].…”

“…Bioartificial livers must exhibit good viability and functionality but hepatocytes by themselves do not satisfy these requirements [1]. In order to meet these requirements, important design considerations in liver bioreactor technology include fluidic shear stress (shear stress load), chemical cues, and the number of cell types and ratios (co-culture of hepatocytes with supporting cell types) [2].…”

Development of a bioreactor based on magnetically stabilized fluidized bed for bioartificial liver

“…Bioreactors are the key component, and their performance decides the efficacy in the BAL devices [2]. Generally, a bioartificial liver is required to involve at least 10 10 hepatocytes for an effective clinical therapy [3,4].…”

“…These bioreactors have shown exclusive advantages in providing physiologically related detoxification because they are convenient and adapted to high-pressure operation for blood perfusion [9]. However, if these hollow-fiber bioreactors get improvement on mass transfer, uniform cell distribution, and cell loading number, they will achieve more effective and efficient therapeutic effect [2,10]. Except for the referring hollow-fiber bioreactors, the bioreactors based on microcapsules should represent a potential alternative.…”