Packed-bed bioreactor systems and methods of using the same

A bioreactor system comprising:

• a cell culture vessel comprising a first end, a second end, and at least one reservoir between the first and second ends;
• and
• a cell culture matrix disposed in the at least one reservoir, the cell culture matrix comprising a plurality of woven substrates each comprising a plurality of interwoven fibers with surfaces configured for adhering cells thereto,
• wherein the bioreactor system is configured to flow material through the at least one reservoir in a flow direction from the first end to the second end,
• wherein the substrates of the plurality of woven substrates are stacked such that each woven substrate is substantially parallel to each of the other woven substrates and is substantially parallel to the flow direction, and
• wherein at least a portion of the plurality of substrates are not separated by a spacer material or barrier.

A bioreactor system comprising:

• a cell culture vessel comprising a first end, a second end, and at least one reservoir between the first and second ends;
• and
• a cell culture matrix disposed in the at least one reservoir, the cell culture matrix comprising a plurality of woven substrates each comprising a plurality of interwoven fibers with surfaces configured for adhering cells thereto,
• wherein the bioreactor system is configured to flow material through the at least one reservoir in a flow direction from the first end to the second end,
• wherein the substrates of the plurality of woven substrates are stacked such that each woven substrate is substantially parallel to each of the other woven substrates and is substantially parallel to the flow direction,
• wherein each of the substrates comprises a first side, a second side opposite the first side, a thickness separating the first and second sides, and a plurality of openings pass through the thickness of the substrate, and
• wherein a ratio of the opening diameter to the fiber diameter is from about 1.0 to about 3.5, from about 1.25 to about 3.25, from about 1.4 to about 3.0, from about 1.5 to about 2.9, from about 1.5 to about 2.4, or from about 2.4 to about 2.9.