PACKED BED BIOREACTORS WITH CONTROLLED ZONAL POROSITY

A packed-bed cell culture matrix and bioreactor system for culturing cells is provided. The system includes a cell culture vessel having an inlet, an outlet, and an interior reservoir fluidly connected to and disposed between the inlet and the outlet. A cell culture matrix is disposed in the reservoir, the cell culture matrix having a structurally defined substrate with a substrate material defining a plurality of pores, and the substrate material is for adhering cells thereto. A permeability zone is located in a portion of the cell culture matrix, the at least one permeability zone having a higher permeability than a standard permeability of the cell culture matrix outside of the permeability zone. The permeability zone has an opening in the substrate, where the opening is larger than a diameter of any of the plurality of pores.