Bioreactor, apparatus and process for in vitro culture of reproductive tissues, and the like

An apparatus for the in vitro culture of reproductive tissues, comprising:

• at least one bioreactor for the in vitro culture of reproductive tissues including:
• a first component and a second component, mutually connected, which define between them at least one culture chamber,
• said first component including an inlet port for introducing a culture medium inside said culture chamber,
• said second component including an outlet port, to allow the outlet of the culture medium from said culture chamber,
• at least one porous support, provided inside said culture chamber, for supporting fragments of reproductive tissue, and nets, positioned above, and below, the fragments of reproductive tissue, with reference to the vertical, or substantially vertical, position of use of the bioreactor,
• wherein said bioreactor comprises a first net, able to be positioned under the fragments of reproductive tissue, and therefore above said porous support, and a second net, able to be placed over the fragments of reproductive tissue,
• said nets being shaped and configured so to maintain a plurality of fragments of reproductive tissue, inside the culture chamber, in respective predetermined spatial positions, and at appropriate mutual distances, and to exert a direct mechanical stress, by deformation, on the fragments,
• wherein the meshes of said nets have smaller dimensions than those of the fragments, comprising between 200 microns and 500 microns,
• and wherein the bioreactor comprises one or more actuators, provided inside said culture chamber, able to passively or actively stimulate the fragments of reproductive tissue, during culture, with controlled fluid and/or mechanical stress, in unison with the stress applied by said nets,
• said actuators being passive, and including ribs whose edges protrude from the inner wall of said first component of the bioreactor, or active, and including pressure surfaces actuated by stepper motors,
• the thickness of said nets being such that, when added to the dimensions, or displacements, of said actuators, they cause the tissue to be subjected to deformations less than 20%,
• said apparatus for the in vitro culture of reproductive tissues further comprising:
• a circuit for the circulation of a culture medium inside said bioreactor;
• a pump, mounted along said circuit, able to activate the circulation of the culture medium inside said bioreactor;
• a tank, which contains the culture medium, installed along said circuit;
• a gas exchanger, installed along the circuit, for allowing gas exchange with the culture medium.

A process for the in vitro culture of reproductive tissues, comprising the steps of:

• providing an apparatus for the in vitro culture of reproductive tissues including:
• at least one bioreactor for the in vitro culture of reproductive tissues including:
• a first component and a second component, mutually connected, which define between them at least one culture chamber,
• said first component including an inlet port for introducing a culture medium inside said culture chamber,
• said second component including an outlet port, to allow the outlet of the culture medium from said culture chamber,
• at least one porous support, provided inside said culture chamber, for supporting fragments of reproductive tissue, and nets, positioned above, and below, the fragments of reproductive tissue, with reference to the vertical, or substantially vertical, position of use of the bioreactor,
• wherein said bioreactor comprises a first net, able to be positioned under the fragments of reproductive tissue, and therefore above said porous support, and a second net, able to be placed over the fragments of reproductive tissue,
• said nets being shaped and configured so to maintain a plurality of fragments of reproductive tissue, inside the culture chamber, in respective predetermined spatial positions, and at appropriate mutual distances, and to exert a direct mechanical stress, by deformation, on the fragments,
• wherein the meshes of said nets have smaller dimensions than those of the fragments, comprising between 200 microns and 500 microns,
• and wherein the bioreactor comprises one or more actuators, provided inside said culture chamber, able to passively or actively stimulate the fragments of reproductive tissue, during culture, with controlled fluid and/or mechanical stress, in unison with the stress applied by said nets,
• said actuators being passive, and including ribs whose edges protrude from the inner wall of said first component of the bioreactor, or active, and including pressure surfaces actuated by stepper motors,
• the thickness of said nets being such that, when added to the dimensions, or displacements, of said actuators, they cause the tissue to be subjected to deformations less than 20%,
• said apparatus for the in vitro culture of reproductive tissues further comprising:
• at least one circuit for the circulation of a culture medium inside said bioreactor;
• at least one pump, mounted along said circuit, able to activate the circulation of the culture medium inside said bioreactor;
• at least one tank, which contains the culture medium, installed along said circuit;
• at least one gas exchanger, installed along the circuit, for allowing gas exchange with the culture medium;
• the process for the in vitro culture of reproductive tissues, further comprising the steps of:
• providing fragments of reproductive tissue, and inserting them inside the culture chamber of said bioreactor, positioning them on said porous support, interposed between said first net and said second net, at mutual predetermined distances;
• starting said apparatus, so as to feed said bioreactor with the culture medium;
• providing at least one actuator inside said culture chamber;
• and
• operating said actuator to passively or actively stress the fragments of reproductive tissue, during culture, by applying controlled fluid dynamic and/or mechanical stress.