A New Fluidized Bed Bioreactor Based on Diversion-Type Microcapsule Suspension for Bioartificial Liver Systems

Area of Science:

• Biomedical Engineering
• Hepatology
• Bioreactor Design

Background:

• Fluidized bed bioreactors (FBBs) show promise for bioartificial liver systems but conventional designs cause cell damage and large void volumes.
• High perfusion velocities in traditional FBBs compromise microcapsule integrity and overall performance for clinical applications.

Purpose of the Study:

• To develop and evaluate a novel diversion-type microcapsule-suspension fluidized bed bioreactor (DMFBB).
• To assess the DMFBB's performance in terms of void volume, microcapsule stability, and encapsulated cell function compared to conventional FBBs.

Main Methods:

• Investigated void volume and alginate/chitosan microcapsule stability under varying flow rates in the DMFBB.
• Assessed cell viability, synthesis functions (albumin, urea), and metabolizing enzyme expression (CYP1A2, CYP3A4) in encapsulated C3A cells.
• Quantified the transcription levels of CYP450-related and albumin-related genes.

Main Results:

• The DMFBB demonstrated significantly reduced void volume and improved microcapsule retention and stability.
• Encapsulated C3A cells in the DMFBB showed enhanced viability and CYP1A2/CYP3A4 activity.
• DMFBB culture led to dramatically increased transcription levels of CYP450 and albumin genes compared to FBB.

Conclusions:

• The diversion-type microcapsule-suspension fluidized bed bioreactor (DMFBB) is a promising advancement over conventional FBBs.
• The DMFBB offers improved mass transfer and scale-up potential for bioartificial liver systems utilizing encapsulated hepatocytes.
• This novel bioreactor design holds potential for treating acute hepatic failure and other severe liver diseases.