Current development of bioreactors for extracorporeal bioartificial liver (Review)

Abstract

The research and development of extracorporeal bioartificial liver is gaining pace in recent years with the introduction of a myriad of optimally designed bioreactors with the ability to maintain long-term viability and liver-specific functions of hepatocytes. The design considerations for bioartificial liver are not trivial; it needs to consider factors such as the types of cell to be cultured in the bioreactor, the bioreactor configuration, the magnitude of fluid-induced shear stress, nutrients' supply, and wastes' removal, and other relevant issues before the bioreactor is ready for testing. This review discusses the exciting development of bioartificial liver devices, particularly the various types of cell used in current reactor designs, the state-of-the-art culturing and cryopreservation techniques, and the comparison among many today's bioreactor configurations. This review will also discuss in depth the importance of maintaining optimal mass transfer of nutrients and oxygen partial pressure in the bioreactor system. Finally, this review will discuss the commercially available bioreactors that are currently undergoing preclinical and clinical trials.

Cell and tissue engineering for liver disease

“…For example, the supplementation of plasma with amino acids has been shown to increase albumin and urea synthesis (73), and preconditioning with physiological levels of insulin (lower than standard culture medium), has been demonstrated to prevent abnormal lipid accumulation in hepatocytes (74). Overall, environmental conditions within a BAL device, such as oxygen tension and fluid shear forces can significantly affect hepatocyte functions (75). In addition, both the convective and diffusive properties of the systems must be optimized to provide vital nutrients to the cells while simultaneously allowing export of therapeutic cellular products.…”

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

“…Unfortunately, the scarcity of donor organs often limits liver transplantation in time. Among the different approaches that have been tested to maintain the patients until transplantation and/or to facilitate self-regeneration of the damaged liver is the bioartificial liver (BAL)[1]. In BAL devices, the plasma of the patient is treated by its circulation through a bioreactor that accommodates a biologically active component which performs the diminished or lacking hepatic metabolic functions.…”

Artificial and bioartificial liver support systems for acute and acute-on-chronic hepatic failure: A meta-analysis and meta-regression

“…Artificial LSSs transport a patient’s blood through a filter where it is mixed with albumin. The toxins and metabolic waste from the blood that are mixed with the albumin molecules are then carried out of the blood (6). Bioartificial LSSs, which are essentially bioreactors, utilize either human hepatocytes or porcine liver cells to process oxygenated blood plasma, which is subsequently separated from the other blood constituents (7).…”