Technology

In essence, the proprietary AMC-BAL consists of a bioreactor with a unique internal matrix on which more than ten billion liver cells are seeded (Figure 1). Hollow fibres are regularly distributed amidst the matrix layers for oxygen supply and CO2 removal. As a result, the cells organise as liver-like tissue in three dimensions. The blood flow of patients can be connected to the HepaRG-BAL and the blood plasma is perfused through the reactor and comes in direct contact with the cells. The rationale is that the BAL ‘cleans’ the patient’s blood from toxic elements, supports homeostasis and synthesizes vital proteins.
The AMC-BAL is currently based on the unique high-quality HepaRG cell line. The advantages of this system compared to competitive BAL systems are:

  • The matrix allows for 3D cell architecture to improve cell functionality
  • Hollow fibres integrated in the matrix provide optimal on site oxygenation
  • The design of the bioreactor allows direct cell-plasma contact for optimal mass transfer
  • The HepaRG cell line demonstrates long-term and superior coverage of the hepatic functionality spectrum when matured in the AMC-BAL
  • The AMC-BAL can easily contain the equivalent of 20% of normal human liver cell mass
  • The AMC-BAL has a simple construction, is cheap and can be sterilized.

 Figure 1. Schematic drawings of a transverse and longitudinal cross-section of the bioreactor (right), a scanning electron micrograph of a small section of the cell culture compartment (upper left), and a scanning electron micrograph of hepatocyte aggregates attached to a scaffold (lower left) are shown above. The system is composed of a dialysis housing (A) comprising a three-dimensional nonwoven fabric (B) for high density hepatocyte culture as small aggregates and hollow-fiber membranes (C) for oxygen supply and CO2 removal. The combination of the matrix and the oxygenation tubing creates a third compartment (D). These channels are used to perfuse the plasma of the recipient through the bioreactor which can get in direct contact with the hepatocytes in the fabric. Plasma is perfused through the bioreactor via the side ports (F). The integrated oxygenator of the bioreactor is connected to the gas supply via the endcaps (E). The homogenous distribution of the oxygenation fibers throughout the bioreactor compartment ensures that every hepatocyte has an oxygenation source within its direct surroundings.