Devices, systems and apparatuses for generating self-sustaining hypoxic conditions and gaseous and non-gaseous chemical gradients for in vitro cell culture

An apparatus to produce hypoxic conditions for in vitro and/or ex vivo cell culture, the apparatus comprising:

• a luminal container comprising a bottom wall, at least one sidewall extending upwardly from the bottom wall, and an open top defined by the at least one sidewall;
• a cell support structure on the bottom wall,, wherein the cell support structure comprises a layer of an extracellular matrix protein or a scaffold comprising an extracellular matrix;
• a cover that is configured to engage the luminal container and sealably close the open top in an installed position, wherein a luminal reservoir is defined between a bottom surface of the cover and the cell support structure with the cover in the installed position, and wherein the apparatus is configured to generate a hypoxic condition in the luminal reservoir with the cover in the installed position, and with one or more cells and/or tissues on the cell support structure, whereby the one or more cells and/or tissues consume available oxygen to generate the hypoxic condition in the luminal reservoir;
• and
• a basal container comprising a bottom wall and at least one sidewall extending upwardly from the bottom wall, wherein the bottom wall and the at least one sidewall define a well, and wherein:
• the luminal container is held within the well of the basal container;
• the bottom wall of the basal container is spaced apart from the bottom wall of the luminal container;
• and
• a basal reservoir is defined between the bottom wall of the basal container and the bottom wall of the luminal container and/or between the at least one sidewall of the basal container and the at least one sidewall of the luminal container,
• wherein the apparatus is configured to produce a hypoxic condition for an in vitro and/or ex vivo cell culture on the support structure in the luminal container with the cover in the installed position, wherein a hypoxic condition is defined as an oxygen concentration in the luminal reservoir of less than about 21%.