Bioreactor for a larger scale hepatocyte in vitro perfusion

Area of Science:

• Biomedical Engineering
• Hepatology
• Cellular Biology

Background:

• Liver support systems are crucial for patients with liver failure.
• Current bioreactors face challenges in maintaining optimal cell function and metabolite gradients.
• Hepatocytes and liver sinusoidal endothelial cells are key for liver function.

Purpose of the Study:

• To describe a novel bioreactor design for hepatocytes and liver sinusoidal endothelial cells.
• To evaluate the biochemical performance and scalability of the constructed bioreactor.
• To assess the potential of the bioreactor as an extracorporeal bridging device for liver transplantation.

Main Methods:

• Construction of a bioreactor utilizing capillary membranes for hepatocyte immobilization.
• Development of a three-dimensional framework with four discrete capillary membrane systems for decentralized cell perfusion.
• Evaluation of biochemical performance over 3 weeks with 2.5 x 10^9 hepatocytes.

Main Results:

• Demonstrated sustained hepatocyte function over 3 weeks.
• Achieved significant albumin synthesis (4.7 mg/day) and metabolism of lidocaine (813.7 µg/hr), galactose (210.1 mg/hr), and midazolam (37.1 µg/hr) on day 21.
• The bioreactor design facilitates decentralized oxygenation and CO2 removal, minimizing metabolite gradients.

Conclusions:

• The described bioreactor construction provides efficient cell perfusion and waste removal.
• The system's design supports scale-up for hybrid liver support systems.
• This technology holds potential as an extracorporeal bridging device for liver transplantation.