Pulse-medium perfusion bioreactor with improved mass transport for multiple-3-D cell constructs

A bioreactor system comprising:

• a. a bioreactor comprising an inlet halt having an opening at one end and an inlet aperture at its opposite end, and an outlet half having an opening at one end and an outlet aperture at its opposite end, wherein said halves are joined at their opening ends such that the hollow interior of said bioreactor forms a culture chamber, and comprising two identical nets for supporting at least one cell construct in said chamber, wherein the distance between said nets is equal to the thickness of said at least one cell construct, wherein each of said nets comprises an array of pyramidal elements protruding from the face of said net, wherein the vertex of each of said pyramidal elements comprises a circular opening
• b. a culture medium reservoir for storing a supply of a fluid culture medium, comprising a medium inlet and outlet, and further comprising a gas inlet and outlet;
• c. a gas supply for supplying gas to said medium contained in said reservoir,
• d. a heat exchanger for maintaining the temperature of said medium at a constant value, and
• e. a pump for pumping said medium from said reservoir into said bioreactor and back to said reservoir.

A method for the cultivation of 3-D cell constructs, comprising the following steps:

• a. providing a bioreactor system comprising
• i. a bioreactor, said bioreactor comprising an inlet half having an opening at one end and an inlet aperture at its opposite end, and an outlet half having an opening at one end and an outlet aperture at its opposite end, wherein said halves are joined at their opening ends such that the hollow interior of said bioreactor forms a culture chamber, and comprising two identical nets for supporting at least one cell construct in said chamber, wherein the distance between said nets is equal to the thickness of said at least one cell construct, wherein each of said nets comprises an array of pyramidal elements protruding from the face of said net, wherein the vertex of each of said pyramidal elements comprises a circular opening;
• ii. a culture medium reservoir for storing a supply of a fluid culture medium, comprising a medium inlet and outlet;
• iii. a gas supply for supplying gas to said medium contained in said reservoir;
• iv. a heat exchanger for maintaining the temperature of said medium at a constant value;
• and
• v. a pump for pumping said medium from said reservoir into said bioreactor and back to said reservoir;
• b. placing at least one cell construct within said culture chamber, between said nets;
• c. pumping said medium from said reservoir into said culture chamber, thereby causing medium perfusion into said cell construct for a suitable period of time;
• and
• d. harvesting the resulting construct.