A novel multi‐coaxial hollow fiber bioreactor for adherent cell types. Part 1: Hydrodynamic studies

Abstract

A novel multi-coaxial bioreactor for three-dimensional cultures of adherent cell types, such as liver, is described. It is composed of four tubes of increasing diameter placed one inside the other, creating four spatially isolated compartments. Liver acinar structure and physiological parameters are mimicked by sandwiching cells in the space between the two innermost semi-permeable tubes, or hollows fibers, and creating a radial flow of media from an outer compartment (ECC), through the cell mass compartment, and to an inner compartment (ICC). The outermost compartment is created by gas-permeable tubing, and the housing is used to oxygenate the perfusion media to periportal levels in the ECC. Experiments were performed using distilled water to correlate the radial flow rate (Q(r)) with (1) the pressure drop (DeltaP) between the media compartments that sandwich the cell compartment and (2) the pressure in the cell compartment (P(c)). These results were compared with the theoretical profile calculated based on the hydraulic permeability of the two innermost fibers. Phase-contrast velocity-encoded magnetic resonance imaging was used to visualize directly the axial velocities inside the bioreactor and confirm the assumptions of laminar flow and zero axial velocity at the boundaries of each compartment in the bioreactor. Axial flow rates were calculated from the magnetic resonance imaging results and were similar to the measured axial flow rates for the previously described experiments.

Effects of Enhanced O2 Transport on Hepatocytes Packed within a Bioartificial Liver Device

“…The HF culture system is an HF BAL prototype donated by J. MacDonald and L. Reid (University of North Carolina, Chapel Hill, NC). The details of the design have been described previously, 13,16 and it is schematically illustrated in Fig. 1.…”

Optimizing normoxic conditions in liver devices using enhanced gel matrices

“…This is particularly evident in the case of packed bed bioreactors. Sufficient oxygenation of the hepatocytes housed within the device must be assured (Hay et al, 2000;Wolfe et al, 2002). It is thus not surprising that a number of investigations have focused on understanding the impact of O 2 on hepatic systems (Gerlach et al, 1990;Suleiman and Stevens, 1987;Yanagi and Ohshima, 2000).…”

The Effectiveness of a Novel Cartridge-Based Bioreactor Design in Supporting Liver Cells

“…1 Of these, the capillary hollow-fiber-based systems have been most rapidly developed for clinical trials. 2,3 Unfortunately, this configuration has the inherent physical limitations of constrained total mass diffusion distances, limited cellular mass capacity, and nonuniform cell distributions. While the designs of encapsulation and suspension chambers can provide uniform microenvironments and ease of scaleup, [4][5][6] they can also offer poor cell stability (true for suspensions) and nutrient transport barriers (i.e., encapsulation systems).…”