HERMETICALLY OR ASEPTICALLY SEALED BIOREACTOR SYSTEM AND RELATED METHOD THEREOF

Abstract

Disclosed herein are details of a hermetically or aseptically sealed bioreactor. The bioreactor comprises a bioreactor chamber, a membrane wall, a scaffold structure, a linear actuator, a linear transfer means, and a control system. Use of the bioreactor permits the inner scaffold structure to be moved and manipulated while still preserving a hermetic or aseptic seal inside the bioreactor chamber during operation.

Claims

1. A bioreactor comprising: a bioreactor chamber; a membrane wall disposed on said bioreactor chamber, wherein said bioreactor chamber and said membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor chamber is closed; a scaffold structure disposed inside said bioreactor chamber; a linear actuator disposed outside said bioreactor chamber; a linear transfer means for transferring linear motion between said linear actuator and said scaffold structure without breaching said membrane wall; and a control system in communication with said linear actuator configured to control the movement of said linear actuator.

2. The bioreactor of claim 1, wherein said bioreactor chamber and said membrane wall are configured to separate from said linear actuator, said linear transfer means, and said control system while maintaining the sterility or sanitation.

3. The bioreactor of claim 2, wherein said separated bioreactor chamber is configured for shipping, transporting, or transferring.

4. The bioreactor of claim 1, wherein said membrane wall has one or more surfaces which form an outer boundary of said bioreactor chamber.

5. The bioreactor of claim 1, wherein said membrane wall comprises at least one or more of the following materials: silicone, latex, or polymer.

6. The bioreactor of claim 1, wherein said scaffold structure is configured to be able to move along a one directional axis.

7. The bioreactor of claim 1, wherein said scaffold structure comprises one or more cell seeding scaffolds.

8. The bioreactor of claim 1, wherein said scaffold structure is double sided.

9. The bioreactor of claim 1, wherein said scaffold structure is configured to be removable from said bioreactor chamber when said bioreactor chamber is in an open position.

10. The bioreactor of claim 1, wherein said bioreactor chamber is configured to allow repeated insertion and removal of said scaffold structure when said bioreactor chamber is in an open position.

11. The bioreactor of claim 1, wherein said linear actuator is a stepper motor or servomotor.

12. The bioreactor of claim 1, wherein said linear actuator is a rack and pinion.

13. The bioreactor of claim 1, wherein said linear actuator is a piston.

14. The bioreactor of claim 13, wherein said piston is a pneumatic, magnetic or hydraulic type piston.

15. The bioreactor of claim 1, wherein said linear actuator is a crank and slider mechanism.

16. The bioreactor of claim 1, wherein said linear actuator is a solenoid.

17. The bioreactor of claim 1, wherein said linear actuator is a leadscrew mechanism.

18. The bioreactor of claim 1, wherein said linear actuator is configured to be activated cyclically or for specified time periods or durations.

19. The bioreactor of claim 1, wherein said linear actuator is configured to be detachable from said bioreactor chamber while maintaining the sterility or sanitation.

20. The bioreactor of claim 1, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure; wherein: either said linear actuator coupling or scaffold structure coupling is an adhesive material; or both said linear actuator coupling or scaffold structure coupling is an adhesive material.

21. The bioreactor of claim 1, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

22. The bioreactor of claim 21, wherein said coupling mechanism comprises: at least one magnet disposed on said linear actuator to define a linear actuator magnet; and at least one magnet disposed on said scaffold structure to define a scaffold structure magnet, wherein said at least one linear actuator magnet and said at least one scaffold structure magnet are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

23. The bioreactor of claim 22, wherein said at least one linear actuator magnet and said at least scaffold structure magnet are: permanent type magnets; electromagnet type magnets; or combination of both permanent magnet and electromagnet type magnets.

24. The bioreactor of claim 21, wherein said coupling mechanism comprises: at least one magnet disposed on said linear actuator to define a linear actuator magnet; and at least one ferromagnetic material device disposed on said scaffold structure to define a scaffold structure ferromagnetic material device, wherein said at least one linear actuator magnet and said at least one scaffold structure ferromagnetic material device are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

25. The bioreactor of claim 21, wherein said coupling mechanism comprises: at least one ferromagnetic material device disposed on said linear actuator to define a linear actuator magnet; and at least one magnet disposed on said scaffold structure to define a scaffold structure magnet, wherein said at least one linear actuator ferromagnetic material device and said at least one scaffold structure magnet are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

26. The bioreactor of claim 1, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure; wherein: either said linear actuator coupling or scaffold structure coupling is a suction cup; or both said linear actuator coupling or scaffold structure coupling is a suction cup.

27. The bioreactor of claim 21, wherein said coupling mechanism comprises: a buckle device, wherein said buckle device includes a first buckle and a second buckle, wherein said first buckle is disposed on the linear actuator and said second buckle is disposed on the scaffold structure, wherein said first buckle and said second buckle are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

28. The bioreactor of claim 1, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator and comprises an outer surface ball; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure and comprises an inner surface ball; wherein said membrane wall has an outer surface and an inner surface, wherein said outer surface comprises an outer socket configured to receive said outer surface ball and said inner surface comprises an inner socket configured to receive said inner surface ball.

29. The bioreactor of claim 1, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator and comprises an outer surface screw; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure and comprises an inner surface screw; wherein said membrane wall has an outer surface and an inner surface, wherein said outer surface comprises an outer threaded socket configured to receive said outer surface screw and said inner surface comprises an inner threaded socket configured to receive said inner surface screw.

30. The bioreactor of claim 1, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator and comprises an outer surface male connector; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure and comprises an inner surface male connector; wherein said membrane wall has an outer surface and an inner surface, wherein said outer surface comprises an outer female socket configured to receive said outer surface male connector and said inner surface comprises an inner female socket configured to receive said inner surface male connector.

31. The bioreactor of claim 21, wherein said coupling mechanism is permanently or temporarily attached to said membrane.

32. The bioreactor of claim 21, wherein said coupling mechanism is permanently or temporarily coupling said linear actuator to said scaffold structure.

33. The bioreactor of claim 1, wherein said bioreactor chamber is configured to be hermetically sealed.

34. The bioreactor of claim 1, wherein said bioreactor chamber is configured to be aseptically sealed.

35. The bioreactor of claim 1, wherein the inner portion of said bioreactor chamber does not contain exposed metal surfaces.

36. The bioreactor of claim 1, wherein the control system and linear actuator are disposed outside of the bioreactor chamber, and do not permeate the bioreactor chamber.

37. The bioreactor of claim 1, further comprising one or more ports disposed on said bioreactor chamber.

38. The bioreactor of claim 1, wherein said bioreactor chamber is configured to permit gas and/or nutrient exchange.

39. The bioreactor of claim 1, further comprising a removable lid assembly.

40. The bioreactor of claim 39, wherein said removable lid assembly has one or more ports for the flow of gases and/or nutrients.

41. The bioreactor of claim 39, wherein said removable lid assembly is configured to permit gas and/or nutrient exchange.

42. The bioreactor of claim 1, wherein said membrane wall has sufficient flexibility whereby said membrane wall can be displaced resultant to said linear motion in a linear direction for a distance of one the following: a range of about 1 mm to about 10 mm; a range of about 1 mm to about 5 mm; a range of about 1 mm to about 6 mm; a range of about 2 mm to about 4 mm; or about 3 mm.

43. The bioreactor of claim 1, wherein said membrane wall has sufficient flexibility whereby said membrane wall can be displaced resultant to said linear motion in a linear direction for a distance of one the following: a range of about 1 mm to about 10 cm; a range of about 10 cm to about 1 m; or a range of about 1 m to about 3 m.

44. The bioreactor of claim 21, wherein said membrane wall has sufficient flexibility in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to flex in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

45. The bioreactor of claim 1, wherein said membrane wall has sufficient elasticity in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to stretch in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

46. The bioreactor of claim 1, wherein said membrane wall has sufficient deformability in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to deform in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

47. The bioreactor of claim 21, wherein said membrane wall is configured to allow movement in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to move in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

48. The bioreactor of claim 1, further comprising a securement means for securing said scaffold structure in place.

49. The bioreactor of claim 48, wherein said securement means is a clamp or screw adjustably mounted to said chamber wherein said clamp or screw is configured to make contact with said membrane to impart a force on said membrane to be transferred to said scaffold structure for maintaining a desired position of said scaffold structure.

50. The bioreactor of claim 1, wherein said bioreactor chamber includes any one of the following structures: housing, enclosure, box, container, casing, tank, compartment, cavity, pipe, or trunk.

51. A bioreactor device, said device comprising: a bioreactor chamber and a membrane wall disposed on said bioreactor chamber, wherein said bioreactor chamber is configured to hold a scaffold structure or other component; and said membrane wall is configured to allow transfer of linear motion to said scaffold structure or other component without breaching said membrane wall.

52. The bioreactor device of claim 51, wherein said bioreactor chamber said membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor chamber is closed.

53. The device of claim 51, wherein said linear motion is a type of motion that can be generated by a linear actuator disposed outside said bioreactor chamber.

54. The device of claim 51, wherein said device is provided as part of a kit, wherein said kit includes a linear actuator, wherein said linear actuator is configured to provide said linear motion.

55. A system configured to receive said bioreactor device of claim 51, said system comprising: a linear actuator disposed outside said bioreactor chamber, wherein said linear actuator is configured to provide said linear motion; and a linear transfer means for transferring linear motion between said linear actuator and said scaffold structure or said other component without breaching said membrane wall.

56. The system of claim 54, further comprising: a control system in communication with said linear actuator configured to control the movement of said linear actuator.

57. The system of claim 56, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

58. The system of claim 55, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

59. A bioreactor comprising: a bioreactor chamber; a membrane wall disposed on said bioreactor chamber; a scaffold structure disposed inside said bioreactor chamber; a linear actuator disposed outside said bioreactor chamber; a linear transfer means for transferring linear motion between said linear actuator and said scaffold structure without breaching said membrane wall; and a control system in communication with said linear actuator configured to control the movement of said linear actuator.

60. The bioreactor of claim 59, wherein said bioreactor chamber and said membrane wall are configured to separate from said linear actuator, said linear transfer means, and said control system.

61. The bioreactor of claim 60, wherein said bioreactor chamber and membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor is closed.

62. The bioreactor of claim 59, wherein said bioreactor chamber and said membrane wall is configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor is closed.

63. The bioreactor of claim 59, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

64. A bioreactor comprising: a bioreactor chamber; a membrane wall disposed on said bioreactor chamber, wherein said bioreactor chamber and said membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor chamber is closed; a scaffold structure disposed inside said bioreactor chamber; an actuator disposed outside said bioreactor chamber; a transfer means for transferring motion between said actuator and said scaffold structure without breaching said membrane wall; and a control system in communication with said actuator configured to control the movement of said actuator.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0053] The foregoing and other objects, features and advantages of the present invention, as well as the invention itself, will be more fully understood from the following description of preferred embodiments, when read together with the accompanying drawings.

[0054] The accompanying drawings, which are incorporated into and form a part of the instant specification, illustrate several aspects and embodiments of the present invention and, together with the description herein, serve to explain the principles of the invention. The drawings are provided only for the purpose of illustrating select embodiments of the invention and are not to be construed as limiting the invention. Note that some structures or elements may be omitted from some of the drawings and not shown for the sake of clarity. Some elements or structures may be omitted as well when not necessary to show the operation of the embodiments.

[0055] FIG. 1(A) schematically illustrates an embodiment of a bioreactor, a bioreactor chamber, a linear transfer means that transfers motion through or across a membrane wall, a linear actuator, a scaffold structure, and a control system.

[0056] FIG. 1(B) schematically illustrates an embodiment of a bioreactor system of which is made up of a bioreactor chamber, a scaffold structure, control system, and a linear actuator, wherein in this embodiment the linear transfer means is a coupling mechanism, comprising an inner coupling mechanism and an outer coupling mechanism, which is used to transfer linear motion through or across the membrane wall.

[0057] FIG. 2(A) schematically illustrates an embodiment of a bioreactor comprising a bioreactor chamber, a membrane wall, outer and inner coupling mechanisms on either side of the membrane wall, a scaffold structure, a linear actuator, and a control system.

[0058] FIG. 2(B) schematically illustrates an embodiment of the bioreactor of FIG. 2(A) with the outer coupling mechanism (e.g., linear actuator coupling) advanced linearly inward (toward the right as rendered), toward the bioreactor chamber, such that it rests against the outer surface of the membrane wall.

[0059] FIG. 2(C) schematically illustrates an embodiment of the bioreactor of FIG. 2(A) with the outer coupling mechanism, further advanced compared to FIG. 2(B), engaged against the membrane wall deforming the membrane wall so as to be in contact with the inner coupling mechanism.

[0060] FIG. 2(D) schematically illustrates an embodiment of the bioreactor of FIG. 2(C) having the inner and outer coupling mechanisms advanced linearly outward (toward the left as rendered) displacing the membrane wall so as to be stretched to the outer bounds of movement (or a specified outward position).

[0061] FIG. 2(E) schematically illustrates an embodiment of the bioreactor of FIG. 2(D) having the inner and outer coupling mechanisms advanced linearly inward (toward the right as rendered) displacing with the membrane wall so as to be stretched to the inner bounds of movement (or a specified inward position).

[0062] FIG. 3 schematically illustrates an embodiment of a bioreactor chamber with a lid structure, clamp screws, and membrane mount structure.

[0063] FIG. 4 schematically illustrates an embodiment of a membrane mount structure.

[0064] FIG. 5 schematically illustrates an embodiment of a membrane wall, having two surfaces.

[0065] FIG. 6 schematically illustrates an embodiment of a scaffold structure with cell seeding scaffolds and associated inner coupling mechanisms.

[0066] FIG. 7 schematically illustrates an embodiment of a cell seeding structure.

[0067] FIG. 8 schematically illustrates an embodiment of a cell seeding structure with a cell seeding brace.

[0068] FIG. 9 schematically illustrates a top view of an embodiment of a lid structure with lid ports.

[0069] FIG. 10 schematically illustrates a side view of the drawing of FIG. 9.

[0070] FIG. 11 schematically illustrates a front view of the drawing of FIG. 9.

[0071] FIG. 12 schematically illustrates top view an embodiment of an outer coupling mechanism and a linear actuator having a lead screw and motor.

[0072] FIG. 13 schematically illustrates a side view of the bioreactor with the section view location for FIG. 14 specified.

[0073] FIG. 14 schematically illustrates a top section view of the bioreactor in the initial state after the scaffold structure is installed, and neither the screws or clamps nor the coupling mechanism are engaged.

[0074] FIG. 15 schematically illustrates a side view of the bioreactor with the section view location for FIG. 16 specified.

[0075] FIG. 16 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 14, where the clamps or screws are engaged in a way which prevents the scaffold structure from moving, and the coupling mechanism is not engaged.

[0076] FIG. 17 schematically illustrates a side view of the bioreactor with the section view location for FIG. 18 specified.

[0077] FIG. 18 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 16, where the clamps or screws remain engaged and the coupling mechanism is engaged.

[0078] FIG. 19 schematically illustrates a side view of the bioreactor with the section view location for FIG. 20 specified.

[0079] FIG. 20 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 18, where the clamps or screws are disengaged and the coupling mechanism remains engaged.

[0080] FIG. 21 schematically illustrates a side view of the bioreactor with the section view location for FIG. 22 specified.

[0081] FIG. 22 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 20, where the clamps or screws remain disengaged, the coupling mechanism remains engaged, and the linear actuator is retracted causing one side of the scaffold structure to move and causing elongation of the cell seeding scaffold.

[0082] FIG. 23 schematically illustrates a side view of the bioreactor with the section view location for FIG. 24 specified.

[0083] FIG. 24 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 22, where the linear actuator is returned to the starting or previous position in a non-elongated state (such as previously shown in FIG. 20) and the clamps or screws remain in a disengaged state and the coupling mechanism remains in an engaged state.

[0084] FIG. 25 schematically illustrates a side view of the bioreactor with the section view location for FIG. 26 specified.

[0085] FIG. 26 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 24, where (after the linear actuator had already been returned to the starting position, for example) the clamps or screws are engaged in a way which prevents the scaffold structure from moving, and the coupling mechanism remains engaged.

[0086] FIG. 27 schematically illustrates a side view of the bioreactor with the section view location for FIG. 28 specified.

[0087] FIG. 28 schematically illustrates a top section view of the bioreactor in a state following that shown in FIG. 26, where the clamps or screws remain engaged, and the coupling mechanism is disengaged.

[0088] FIG. 29 schematically illustrates a side view of the bioreactor chamber disconnected from the linear actuator with the section view location for FIG. 30 specified.

[0089] FIG. 30 schematically illustrates a top section view of the bioreactor chamber disconnected from the linear actuator (not shown instant Figure), with the clamps or screws in the position where the scaffold structure is secured and prevented from moving.

[0090] FIG. 31 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise an adhesive material 161, whereby the adhesive material 161 attach the inner and outer coupling mechanisms together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110.

[0091] FIG. 32 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise one or more suction cups 163 or other type of negative pressure connector, whereby the one or both suction cups 163 attach the inner and outer coupling mechanisms together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110.

[0092] FIG. 33 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise a buckle 165 that may include a frame 166 and prong 167 or other mechanical connector with a male and female component which attaches the inner and outer coupling mechanisms together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110.

[0093] FIG. 34 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise having one or more ball and socket joints 181 that may include a ball 182 and socket 183 that couples the outer coupling mechanism 154 and inner coupling mechanism 152 and wherein either the ball or socket side of the connector is attached or molded into the membrane (and wherein the inner and outer coupling mechanisms are connected together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane).

[0094] FIG. 35 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise one or more threaded rod, screw, or bolt connectors 185 coupled by attachment to a threaded receiving portion 186 or threaded socket attached or molded into the membrane 110 (and wherein the inner and outer coupling mechanisms are connected together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane).

[0095] FIG. 36 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprises one or more male-female 187 connectors that may include a male connector 188 and female connector 189 where female side of the connector is attached or molded into the membrane 110, and the corresponding male side of the connector is located on the outer and/or inner coupling mechanism (and wherein the inner and outer coupling mechanisms are connected together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane). In an alternative embodiment, the male side of the connector may be attached or molded into the membrane 110, and the corresponding female side of the connector is located on the outer and/or inner coupling mechanism.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0096] The present invention is described with reference to various embodiments of the invention. Throughout the description of the invention, reference is made to FIGS. 1-34. When referring to the figures, like structures and elements shown throughout are indicated with reference numerals. Note that some structures or elements may be omitted from some of the drawings and not shown for the sake of clarity. Some elements or structures may be omitted as well when not necessary to show the operation of the embodiments.

[0097] FIG. 1(A) schematically illustrates an embodiment of a bioreactor 100 which is made up of a bioreactor chamber 101, a linear transfer means 150 that transfers motion through or across a membrane wall 110, a linear actuator 130, a scaffold structure 120, and a control system 170.

[0098] FIG. 1(B) schematically illustrates an embodiment of a bioreactor system of which is made up of a bioreactor chamber 101, a scaffold structure 120, control system 170, and a linear actuator 130, wherein in this embodiment the linear transfer means is a coupling mechanism 159, comprising an inner coupling mechanism 152 (e.g., scaffold structure coupling) and an outer coupling mechanism 154 (e.g., linear actuator coupling), which is used to transfer linear motion through or across the membrane wall 110. The coupling mechanisms 159 may take the form of a coupling mechanism 159 configured to couple the linear actuator 130 to the scaffold structure 120 while maintaining the integrity of the membrane wall 110. In an embodiment, the control system 170 may be integrally formed with the linear actuator 130. In an embodiment, the control system 170 may be separately formed from the linear actuator 130. In an embodiment, the control system 170 and the linear actuator 130 may have varying subcomponents that have a mix of integrally formed and separately formed elements or functions.

[0099] In an embodiment, the control system 170 may be a mechanical, electrical, or electromechanical controller or processor. In an embodiment, this control system may contain, but is not limited to, one or more of a supervisory control and data acquisition system (SCADA), distributed control system (DCS), programmable logic controller (PLC), relay, cam timer, or drum sequencer. In an embodiment, the linear actuator 130 may be any one or more of the following: stepper motor, servomotor, rack and pinion, piston (e.g., pneumatic, magnetic or hydraulic type), crank and slider mechanism, solenoid, or leadscrew mechanism.

[0100] It should be noted that the control system 170 and linear actuator 130 do not permeate into the bioreactor chamber 101. For instance, the control system 170 and linear actuator 130 do not breach, occupy, penetrate, intrude upon, encroach nor invade the bioreactor chamber 101. When the bioreactor chamber 101 is sealed, no object will be able to invade into the bioreactor chamber 101. In an embodiment, the bioreactor chamber 101 may not contain any materials that may corrode or break down throughout the process (e.g., metals, non-sanitary materials), in order to limit contamination of the cells.

[0101] FIG. 2(A) schematically illustrates an embodiment of a bioreactor 100 comprising a bioreactor chamber 101, a membrane wall 110, control system 170, and a linear actuator 130, wherein the linear transfer means in this embodiment comprises a coupling mechanism 159 that includes outer coupling mechanisms 153, 154 (e.g., linear actuator couplings) and inner coupling mechanisms 151,152 (e.g., scaffold structure couplings) on either side of the membrane wall 110. Also shown is a scaffold structure 120 disposed in the bioreactor chamber 101. The coupling mechanisms 159 may take the form of a coupling mechanism 159 configured to couple the linear actuator 130 to the scaffold structure 120 while maintaining the integrity of the membrane wall 110. For example, but not limited thereto, a magnet may serve as either or both of the inner coupling mechanism 151, 152 (e.g., scaffold structure magnet) and outer coupling mechanism 153, 154 (e.g., linear actuator magnet).

[0102] FIGS. 2(B)-2(E) schematically illustrate a step-by-step process of the bioreactor representation of FIG. 2(A) engaging the coupling mechanism 159 and moving the scaffold structure 120 linearly along a path of motion desired for proper cell growth. It should be noted that although FIGS. 2(A)-2(E) contain two outer coupling mechanisms and two inner coupling mechanisms, this is not limiting on the design. In an embodiment, there may be one outer coupling mechanism and one inner coupling mechanism. In an embodiment, there may be three or more (or any plurality) outer coupling mechanisms and three or more (or any plurality) inner coupling mechanisms. In an embodiment, there may be any combination of one or more outer coupling mechanisms with one or more inner coupling mechanisms. In an embodiment, there may be any combination of one or more coupling mechanisms on one side of the membrane but not a corresponding coupling mechanism on the opposing side of the membrane (or a fewer number of coupling mechanisms on the opposing side of the membrane). Moreover, any of the types or styles of individual coupling mechanisms provided in this disclosure may be intermixed or matched with other (dissimilar) types or styles of individual coupling mechanisms.

[0103] Various aspects of embodiment of the invention may contain one or more outer and inner coupling mechanisms and a variety of types. For example, but not limited thereto, as shown later at least in part in FIGS. 1(B), 2A)-2(E), 13-36, these coupling mechanisms 159 may take the form of a coupling mechanism 159 configured to couple the linear actuator 130 to the scaffold structure 120 while maintaining the integrity of the membrane wall 110, wherein the coupling mechanism 159 can be in the form of, but is not limited to, one or more of any combination of the following: [0104] a) an adhesive material 161 on either or both of the inner coupling mechanism 152 and outer coupling mechanism 154; [0105] b) a magnet serving as either or both of the inner coupling mechanism 151, 152 and outer coupling mechanism 153, 154; [0106] c) a magnet or ferromagnetic material serving as either or both of the inner coupling mechanisms 151, 152 and either or both of the outer coupling mechanisms 153, 154; [0107] d) a suction cup 163 as part of either or both the inner coupling mechanism 152 and outer coupling mechanism 154; [0108] e) a ball and socket 181 as part of either or both of the inner coupling mechanism 152 and outer coupling mechanism 154; [0109] f) a screw/bolt/threaded rod 185 and threaded socket 186 as part of either or both the inner coupling mechanism 152 and outer coupling mechanism 154; or [0110] g) a male and female connector 187, wherein the male connector 188 is opposite the female connector 189 and can be part of either the outer coupling mechanism 154 or inner coupling mechanism 152.

[0111] For the sake of simplifying some of the illustrations, FIGS. 13-30, are depicted without the lid 140 disposed thereon. During normal operations, in an embodiment the bioreactor chamber 101 may include a lid 140 that may switch from being in either open or closed positions. During normal operations, in an embodiment the bioreactor chamber 101 may include a lid 140 that may disposed on top of the perimeter walls of the bioreactor chamber 101 to close the bioreactor chamber 101 or the lid 140 may be removed therefrom so as to open the bioreactor chamber 101. In various embodiments, it may be designed such that the lid or the like may be oriented on the top the bioreactor chamber 101 or may be oriented so as to take the place of any of the side walls or the bottom of the bioreactor chamber 101. Moreover, an example of the bioreactor chamber being closed is when the lid 140 is in a closed position or disposed on top of the bioreactor chamber 101 thereby closing off the top of bioreactor chamber 101, and whereby the bioreactor is formed by at least one side wall and a membrane wall 110.

[0112] In an embodiment the membrane wall 110 may make up an entire side wall (or top or bottom) of the bioreactor chamber 101 or only a portion of a side wall (or top or bottom) of the bioreactor chamber 101. Said differently, the area of the membrane wall 110 may be substantially equal to the area of one of the side walls (or bottom or top) of the bioreactor chamber 101 or may be substantially less (or slightly less) than the area of one of the side walls (or bottom or top) of the bioreactor chamber 101. In an embodiment the area of the membrane wall 110 may be greater than the area of an entire side wall (or top or bottom) of the bioreactor chamber 101. In an embodiment the membrane wall 110 may be integrally formed with side wall (or top or bottom) of the bioreactor chamber 101 while still maintaining the seal and characteristics disclosed herein. In an embodiment the membrane wall 110 may be separately formed from side wall (or top or bottom) of the bioreactor chamber 101 while still maintaining the seal and characteristics disclosed herein.

[0113] In an embodiment the lid 140 may be only a flap, door, or window that can opened and closed. In an embodiment the lid (or flap, door, or window) may have an area less than the area of the top of the bioreactor chamber 101, a side wall of the bioreactor chamber, or bottom of the bioreactor chamber. Said differently, the lid (or flap, door, or window) may be only a portion of the area of the top of the bioreactor chamber 101, a side wall of the bioreactor chamber, or the bottom of the bioreactor chamber.

[0114] In an embodiment the lid 140 (or flap, door, or window) may have an area substantially equal to the area of the top of the bioreactor chamber 101, a side wall of the bioreactor chamber, or the bottom of the bioreactor chamber. In an embodiment the area of the lid 140 may be greater than the area of an entire side wall (or top or bottom) of the bioreactor chamber 101.

[0115] FIG. 2(A) schematically illustrates an embodiment of a bioreactor 100 comprising a bioreactor chamber 101, a membrane wall 110, a coupling mechanism 159 comprising outer coupling 153, 154 (e.g., linear actuator coupling) and inner couplings 151, 152 (scaffold structure coupling) on either side of the membrane wall 110, a scaffold structure 120, a linear actuator 130, and a control system 170.

[0116] FIG. 2(B) schematically illustrates an embodiment of the bioreactor 100 of FIG. 2(A) with the outer couplings 153, 154 (e.g., linear actuator coupling) advanced linearly inward (toward the right as rendered and generally reflected by the arrow), and toward the bioreactor chamber, such that it rests against the outer surface of the membrane wall 110.

[0117] FIG. 2(C) schematically illustrates an embodiment of the bioreactor 100 of FIG. 2(A) with the outer couplings 153, 154 (e.g., linear actuator coupling), further advanced compared to FIG. 2(B), engaged against the membrane wall deforming the membrane wall inward (toward the right as rendered and generally reflected by the arrow) so as to be in contact with the inner couplings 151, 152 (e.g., scaffold structure couplings).

[0118] FIG. 2(D) schematically illustrates an embodiment of the bioreactor 100 of FIG. 2(C) having the inner couplings 151, 152 (e.g., scaffold structure couplings) and outer couplings 153, 154 (e.g., linear actuator coupling) advanced linearly outward (toward the left as rendered and generally reflected by the arrow) displacing the membrane wall 110 so as to be stretched to the outer bounds of movement (or a specified outward position).

[0119] FIG. 2(E) schematically illustrates an embodiment of the bioreactor of FIG. 2(D) having the inner coupling 151, 152 (e.g., scaffold structure couplings) and outer couplings 153, 154 advanced linearly inward (toward the right as rendered and generally reflected by the arrow) displacing with the membrane wall 110 so as to be stretched to the inner bounds of movement (or a specified inward position). In an embodiment, the inner couplings 151, 152 (e.g., scaffold structure couplings) and outer couplings 153, 154 (e.g., linear actuator coupling) may be advanced linearly inward or outward to any most outer bound or inner bound position or any specified position subsumed there between for any specified number of times or repetitions at any specified speed or duration.

[0120] While an embodiment in FIGS. 2(A)-2(E) indicates the linear advancement inward (forward) or outward (backward) as being toward the right or left as rendered and generally reflected by the arrows (e.g., one-directional axis), respectively, it should be appreciated that alternative advancement patterns, paths or axes are considered part of the present invention, and may be employed within the context of the invention. For example, but not limited thereto, an advancement may be in any x, y, or z axis (or a combination thereof). For example, but not limited thereto, an advancement may be in an oval or elliptical pattern with any such oval or elliptical pattern lying in any possible plane in the x, y, or z axis (or a combination thereof). For example, but not limited thereto, an advancement may be along the entire continual geometric spectrum of manipulation of x, y and/or z axes to provide and meet structural demands and operational requirements of the bioreactor and related bioreactor process.

[0121] FIG. 3 schematically illustrates one embodiment of a bioreactor 100 comprising a bioreactor chamber 101, membrane wall 110 (portion of a perimeter of membrane wall) a lid structure 140, clamp screws 190, and a membrane mount structure 111.

[0122] FIG. 4 schematically illustrates one embodiment of a membrane mount structure 111, wherein the membrane mount structure 111 may be an outline of the membrane wall 110 (not shown) that is applied to the outside of the membrane wall 110 (not shown in instant illustration) and pinches the membrane wall 110 (not shown in instant illustration) between the membrane mount structure 111 and the bioreactor chamber 101 (not shown in instant illustration), creating a sealed environment for the interior of the bioreactor 100 (not shown in instant illustration).

[0123] FIG. 5 schematically illustrates an embodiment of a membrane wall 110, having two surfaces, one inner surface 113 (not visible in instant illustration) and one outer surface 112.

[0124] FIG. 6 schematically illustrates an embodiment of a scaffold structure 120 with cell seeding scaffolds 121 and associated inner coupling mechanisms 151, 152 (shown in dashed lines) (e.g., scaffold structure couplings). The scaffold structure 120 is able to stretch linearly to allow the cell seeding scaffolds 121 to stretch the cell material 123 and allow for optimal growth, while the cell seeding scaffolds 121 are configured so as to be able to be removed from the scaffold structure 120 to facilitate the seeding process and allow seeding on either side of the cell seeding scaffold 121.

[0125] FIG. 7 shows a more detailed view of the cell seeding scaffold 121, having an open area (configured to hold or contain cell material 123) to allow for cell seeding and being made up of a top bracket 124 and bottom bracket 125 that are configured so as to be able to move away from one another linearly to facilitate the cell growth movement.

[0126] FIG. 8 schematically illustrates an embodiment of a cell seeding scaffold 121, to hold or contain the cell material 123, with a cell seeding brace 122. The cell seeding brace 122 is used to hold the cell seeding scaffold 121 stable while being transported or installed.

[0127] FIGS. 9-11 schematically illustrate an embodiment of a lid structure 140 which contains lid ports 141 in a top view, side view, and front view, respectively. These ports 141 allow for screw-on filters or the like to be attached, which allow for purified air to enter the bioreactor chamber 101 (not shown in instant Figure) without risking contamination of the cells of the cell material 123 (not shown in instant Figure). These lid ports 141 could also be used to allow for a nutrient fluid to flow into the bioreactor chamber 101 (not shown in instant Figure), so as to function such as a valve or the like, to aid in the cell growth process. These lid ports 141 could also be used to allow for nutrient exchange or the flow of oxygen, filtered oxygen, or other gases (or materials). Alternatively, or in combination thereof, the ports or other valves may be displaced or disposed on other locations of bioreactor chamber (not shown in instant Figure). In an embodiment the ports or valves may be located on any wall of the bioreactor chamber other than the lid. In an embodiment the ports or valves may be located on membrane wall.

[0128] FIG. 12 schematically illustrates a top view of an embodiment of the linear transfer means comprising outer coupling mechanisms 153, 154 (e.g., linear actuator couplings). Also shown is the linear actuator 130 comprising a lead screw 156 and a motor 155. This Figure illustrates how the linear actuator 130 may be configured so as to be able to linearly advance the outer coupling mechanisms 153, 154. For example, the lead screw 156 in communication with the outer coupling mechanisms 153, 154 moves (any one or plurality of times) the outer coupling mechanisms 153, 154 forward and backward (e.g., inward and outward) in response to the motion of the lead screw 156 while keeping the coupling mechanism 159 at specified or designated positions to preserve the integrity of the membrane wall 110 (not shown in instant Figure).

[0129] FIGS. 13-28 schematically illustrate the steps of operation of an embodiment of a bioreactor 100. FIGS. 13, 15, 17, 19, 21, 23, 25, and 27 schematically illustrate a side view of the bioreactor 100 with the section view locations for FIGS. 14, 16, 18,20, 22, 24, 26, and 28, respectively, specified. Collectively, FIGS. 13-28 schematically illustrate the bioreactor 100 comprising, at least in part, the bioreactor 100, bioreactor chamber 101, membrane wall 110 (e.g., as illustrated depicting an edge perimeter of the membrane wall), membrane mount structure 111, scaffold structure 120, cell seeding scaffold 121, linear actuator 130, inner coupling mechanism 151, 152, outer coupling mechanism 153, 154, motor 155, lead screw 156, and clamps or screws 190.

[0130] FIG. 14 schematically illustrates a top section view (as specified in cross-section of FIG. 13) of the bioreactor 100 in the initial state after the scaffold structure 120 is installed, and neither the screws or clamps 190 nor the coupling mechanism is engaged (meaning the outer coupling mechanisms 153, 154 (e.g., linear actuator couplings) are not engaged with the inner coupling mechanisms 151, 152 (e.g., scaffold structure couplings)).

[0131] FIG. 16 schematically illustrates a top section view (as specified in cross-section of FIG. 15) of the bioreactor 100 in a state following that shown in FIG. 14, where the clamps or screws 190 are engaged in a way which prevents the scaffold structure 120 from moving, and the coupling mechanism is not engaged (meaning the outer coupling mechanisms 153, 154 (e.g., linear actuator couplings) are not engaged with the inner coupling mechanisms 151, 152 (e.g., scaffold structure couplings) on either side of the membrane wall 110).

[0132] FIG. 18 schematically illustrates a top section view (as specified in cross-section of FIG. 17) of the bioreactor 100 in a state following that shown in FIG. 16, where the clamps or screws 190 remain engaged and the coupling mechanism is engaged (meaning the outer coupling mechanisms 153, 154 are engaged with the inner coupling mechanisms 151, 152 on either side of the membrane wall 110).

[0133] FIG. 20 schematically illustrates a top section view (as specified in cross-section of FIG. 19) of the bioreactor 100 in a state following that shown in FIG. 18, where the clamps or screws 190 are disengaged and the coupling mechanism remains engaged (meaning the outer coupling mechanisms 153, 154 are engaged with the inner coupling mechanisms 151, 152 on either side of the membrane wall 110).

[0134] FIG. 22 schematically illustrates a top section view (as specified in cross-section of FIG. 21) of the bioreactor 100 in a state following that shown in FIG. 20, where the clamps or screws 190 remain disengaged, the coupling mechanism remains engaged (meaning the outer coupling mechanisms 153, 154 are engaged with the inner coupling mechanisms 151, 152 on either side of the membrane wall 110), and the linear actuator 130 (e.g., a lead screw 156) is retracted (in the leftward direction as oriented by the illustration) causing one side of the scaffold structure 120 to move (in the leftward direction as oriented by the illustration) and causing elongation of the cell seeding scaffold 121.

[0135] FIG. 24 schematically illustrates a top section view (as specified in cross-section of FIG. 23) of the bioreactor 100 in a state following that shown in FIG. 22, where the linear actuator 130 is returned to the starting or previous position in a non-elongated state (such as previously shown in FIG. 20) and while the clamps or screws 190 remain in a disengaged state and the coupling mechanism remains in an engaged state (meaning the outer coupling mechanisms 153, 154 remain engaged with the inner coupling mechanisms 151, 152 on either side of the membrane wall 110).

[0136] FIG. 26 schematically illustrates a top section view (as specified in cross-section of FIG. 25) of the bioreactor 100 in a state following that shown in FIG. 24, where the clamps or screws 190 are engaged in a way which prevents the scaffold structure 120 from moving, and the coupling mechanism remains engaged (meaning the outer coupling mechanisms 153, 154 remain engaged with the inner coupling mechanisms 151, 152 on either side of the membrane wall 110).

[0137] FIG. 28 schematically illustrates a top section view (as illustrated in cross-section of FIG. 27) of the bioreactor 100 in a state following that shown in FIG. 26, where the clamps or screws 190 remain engaged, and the coupling mechanism is disengaged (meaning the outer coupling mechanisms 153, 154 are disengaged from the inner coupling mechanisms 151, 152 on either side of the membrane wall 110).

[0138] FIGS. 29 and 30 schematically illustrate an embodiment of a bioreactor chamber 101, side view and top view, respectively, wherein the bioreactor chamber 101 can be detached from the remainder of the bioreactor (not shown in instant Figure). This would allow the sealed bioreactor chamber 101 to be shipped, transported, or transferred separately from the remainder of the bioreactor while still maintaining a hermetic or aseptic seal. Alternatively, this would allow the sealed bioreactor chamber 101 to be viewed or accessed separately from the remainder of the bioreactor while still maintaining a hermetic or aseptic seal. FIG. 30 schematically illustrates the clamps or screws 190 in the position where the scaffold structure 120 is secured and prevented from moving.

[0139] FIGS. 31-36 schematically illustrate whereby the linear transfer means may be configured as a variety of, non-limiting, embodiments of the coupling mechanism 159.

[0140] FIG. 31 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise an adhesive material 161 (whereby the inner coupling mechanism 152 and the outer coupling mechanism 154 are coupled together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110).

[0141] FIG. 32 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprises one or more suction cups 163 or other type of negative pressure connector (whereby the inner coupling mechanism 152 and the outer coupling mechanism 154 are coupled together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110).

[0142] FIG. 33 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprises a buckle 165 that may include a frame 166 and prong 167 or other mechanical connector with a male and female component which attaches the inner and outer coupling mechanisms 152, 154 together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110.

[0143] FIG. 34 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprises having one or more ball and socket joints 181 that may include a ball 182 and socket 183 that couples the outer coupling mechanism 154 and inner coupling mechanism 152 together across the membrane 110 (spanning the membrane, with the membrane there between), without causing a breach in the membrane 110, and wherein either the ball or socket side of the connector is attached or molded into the membrane.

[0144] FIG. 35 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise one or more threaded rod, screw, or bolt connectors 185 coupled by attachment to a threaded receiving portion or threaded socket 186 attached or molded into the membrane 110 (whereby the inner coupling mechanism 152 and the outer coupling mechanism 154 are coupled together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110).

[0145] FIG. 36 schematically illustrates an embodiment of a coupling mechanism 159 having the outer coupling mechanism 154 and inner coupling mechanism 152 wherein said outer coupling mechanism 154 and inner coupling mechanism 152 comprise one or more male-female 187 connectors that may include a male connector 188 and female connector 189 where the female side of the connector is attached or molded into the membrane 110, and the corresponding male side of the connector is located on the outer and/or inner coupling mechanism (whereby the inner coupling mechanism 152 and the outer coupling mechanism 154 are coupled together across the membrane 110 (spanning the membrane, with the membrane there between) without causing a breach in the membrane 110). In an alternative embodiment, the male side of the connector may be attached or molded into the membrane 110, and the corresponding female side of the connector is located on the outer and/or inner coupling mechanism.

EXAMPLES

[0146] Practice of an aspect of an embodiment (or embodiments) of the invention will be still more fully understood from the following examples, which are presented herein for illustration only and should not be construed as limiting the invention in any way.

[0147] Example 1. A bioreactor comprising: a bioreactor chamber; a membrane wall disposed on said bioreactor chamber, wherein said bioreactor chamber and said membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor chamber is closed; a scaffold structure disposed inside said bioreactor chamber; a linear actuator disposed outside said bioreactor chamber; a linear transfer means for transferring linear motion between said linear actuator and said scaffold structure without breaching said membrane wall; and a control system in communication with said linear actuator configured to control the movement of said linear actuator.

[0148] Example 2. The bioreactor of example 1, wherein said bioreactor chamber and said membrane wall are configured to separate from said linear actuator, said linear transfer means, and said control system while maintaining the sterility or sanitation.

[0149] Example 3. The bioreactor of example 2, wherein said separated bioreactor chamber is configured for shipping, transporting, or transferring.

[0150] Example 4. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-3, in whole or in part), wherein said membrane wall has one or more surfaces which form an outer boundary of said bioreactor chamber.

[0151] Example 5. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-4, in whole or in part), wherein said membrane wall comprises at least one or more of the following materials: silicone, latex, or polymer.

[0152] Example 6. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-6, in whole or in part), wherein said scaffold structure is configured to be able to move along a one directional axis.

[0153] Example 7. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-6, in whole or in part), wherein said scaffold structure comprises one or more cell seeding scaffolds.

[0154] Example 8. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-7, in whole or in part), wherein said scaffold structure is double sided.

[0155] Example 9. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-8, in whole or in part), wherein said scaffold structure is configured to be removable from said bioreactor chamber when said bioreactor chamber is in an open position.

[0156] Example 10. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-9, in whole or in part), wherein said bioreactor chamber is configured to allow repeated insertion and removal of said scaffold structure when said bioreactor chamber is in an open position.

[0157] Example 11. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-10, in whole or in part), wherein said linear actuator is a stepper motor or servomotor.

[0158] Example 12. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-11, in whole or in part), wherein said linear actuator is a rack and pinion.

[0159] Example 13. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-12, in whole or in part), wherein said linear actuator is a piston.

[0160] Example 14. The bioreactor of example 13, wherein said piston is a pneumatic, magnetic or hydraulic type piston.

[0161] Example 15. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-14, in whole or in part), wherein said linear actuator is a crank and slider mechanism.

[0162] Example 16. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-15, in whole or in part), wherein said linear actuator is a solenoid.

[0163] Example 17. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-16, in whole or in part), wherein said linear actuator is a leadscrew mechanism.

[0164] Example 18. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-17, in whole or in part), wherein said linear actuator is configured to be activated cyclically or for specified time periods or durations.

[0165] Example 19. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-18, in whole or in part), wherein said linear actuator is configured to be detachable from said bioreactor chamber while maintaining the sterility or sanitation.

[0166] Example 20. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-19, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall. The coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure; wherein: either said linear actuator coupling or scaffold structure coupling is an adhesive material; or both said linear actuator coupling or scaffold structure coupling is an adhesive material.

[0167] Example 21. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-20, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

[0168] Example 22. The bioreactor of example 21, wherein said coupling mechanism comprises: at least one magnet disposed on said linear actuator to define a linear actuator magnet; and at least one magnet disposed on said scaffold structure to define a scaffold structure magnet, wherein said at least one linear actuator magnet and said at least one scaffold structure magnet are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

[0169] Example 23. The bioreactor of example 22, wherein said at least one linear actuator magnet and said at least scaffold structure magnet are: permanent type magnets; electromagnet type magnets; or combination of both permanent magnet and electromagnet type magnets.

[0170] Example 24. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-23, in whole or in part), wherein said coupling mechanism comprises: at least one magnet disposed on said linear actuator to define a linear actuator magnet; and at least one ferromagnetic material device disposed on said scaffold structure to define a scaffold structure ferromagnetic material device, wherein said at least one linear actuator magnet and said at least one scaffold structure ferromagnetic material device are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

[0171] Example 25. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-24, in whole or in part), wherein said coupling mechanism comprises: at least one ferromagnetic material device disposed on said linear actuator to define a linear actuator magnet; and at least one magnet disposed on said scaffold structure to define a scaffold structure magnet, wherein said at least one linear actuator ferromagnetic material device and said at least one scaffold structure magnet are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

[0172] Example 26. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-25, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator. The coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure; wherein: either said linear actuator coupling or scaffold structure coupling is a suction cup; or both said linear actuator coupling or scaffold structure coupling is a suction cup.

[0173] Example 27. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-26, in whole or in part), wherein said coupling mechanism comprises: a buckle device, wherein said buckle device includes a first buckle and a second buckle, wherein said first buckle is disposed on the linear actuator and said second buckle is disposed on the scaffold structure, wherein said first buckle and said second buckle are configured to join with one another, in response to said linear motion, so as to accomplish said coupling on opposing sides of said membrane wall without breaching said membrane wall.

[0174] Example 28. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-27, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator and comprises an outer surface ball; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure and comprises an inner surface ball; wherein said membrane wall has an outer surface and an inner surface, wherein said outer surface comprises an outer socket configured to receive said outer surface ball and said inner surface comprises an inner socket configured to receive said inner surface ball.

[0175] Example 29. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-28, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator and comprises an outer surface screw; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure and comprises an inner surface screw; wherein said membrane wall has an outer surface and an inner surface, wherein said outer surface comprises an outer threaded socket configured to receive said outer surface screw and said inner surface comprises an inner threaded socket configured to receive said inner surface screw.

[0176] Example 30. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-29, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall; wherein said coupling mechanism comprises a linear actuator coupling that is disposed on said linear actuator and comprises an outer surface male connector; and wherein said coupling mechanism comprises a scaffold structure coupling that is disposed on said scaffold structure and comprises an inner surface male connector; wherein said membrane wall has an outer surface and an inner surface, wherein said outer surface comprises an outer female socket configured to receive said outer surface male connector and said inner surface comprises an inner female socket configured to receive said inner surface male connector.

[0177] Example 31. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-30, in whole or in part), wherein said coupling mechanism is permanently or temporarily attached to said membrane.

[0178] Example 32. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-31, in whole or in part), wherein said coupling mechanism is permanently or temporarily coupling said linear actuator to said scaffold structure.

[0179] Example 33. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-32, in whole or in part), wherein said bioreactor chamber is configured to be hermetically sealed.

[0180] Example 34. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-33, in whole or in part), wherein said bioreactor chamber is configured to be aseptically sealed.

[0181] Example 35. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-34, in whole or in part), wherein the inner portion of said bioreactor chamber does not contain exposed metal surfaces.

[0182] Example 36. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-35, in whole or in part), wherein the control system and linear actuator are disposed outside of the bioreactor chamber, and do not permeate the bioreactor chamber.

[0183] Example 37. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-36, in whole or in part), further comprising one or more ports disposed on said bioreactor chamber.

[0184] Example 38. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-37, in whole or in part), wherein said bioreactor chamber is configured to permit gas and/or nutrient exchange.

[0185] Example 39. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-38, in whole or in part), further comprising a removable lid assembly.

[0186] Example 40. The bioreactor of example 39, wherein said removable lid assembly has one or more ports for the flow of gases and/or nutrients.

[0187] Example 41. The bioreactor of example 39 (as well as subject matter in whole or in part of example 40), wherein said removable lid assembly is configured to permit gas and/or nutrient exchange.

[0188] Example 42. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-41, in whole or in part), wherein said membrane wall has sufficient flexibility whereby said membrane wall can be displaced resultant to said linear motion in a linear direction for a distance of one the following: [0189] a range of about 1 mm to about 10 mm; [0190] a range of about 1 mm to about 5 mm; [0191] a range of about 1 mm to about 6 mm; [0192] a range of about 2 mm to about 4 mm; or [0193] about 3 mm.

[0194] Example 43. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-42, in whole or in part), wherein said membrane wall has sufficient flexibility whereby said membrane wall can be displaced resultant to said linear motion in a linear direction for a distance of one the following: [0195] a range of about 1 mm to about 10 cm; [0196] a range of about 10 cm to about 1 m; or [0197] a range of about 1 m to about 3 m.

[0198] Example 44. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-43, in whole or in part), wherein said membrane wall has sufficient flexibility in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to flex in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

[0199] Example 45. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-44, in whole or in part), wherein said membrane wall has sufficient elasticity in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to stretch in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

[0200] Example 46. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-45, in whole or in part), wherein said membrane wall has sufficient deformability in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to deform in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

[0201] Example 47. The bioreactor of example 21 (as well as subject matter of one or more of any combination of examples 2-46, in whole or in part), wherein said membrane wall is configured to allow movement in the linear direction so as to permit said linear actuator and said scaffold structure to travel with respect to one another, in response to said linear motion, causing said membrane wall to move in an ample manner so as to allow said linear actuator and said scaffold structure to couple with one another.

[0202] Example 48. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-47, in whole or in part), further comprising a securement means for securing said scaffold structure in place.

[0203] Example 49. The bioreactor of example 48, wherein said securement means is a clamp or screw adjustably mounted to said chamber wherein said clamp or screw is configured to make contact with said membrane to impart a force on said membrane to be transferred to said scaffold structure for maintaining a desired position of said scaffold structure.

[0204] Example 50. The bioreactor of example 1 (as well as subject matter of one or more of any combination of examples 2-49, in whole or in part), wherein said bioreactor chamber includes any one of the following structures: housing, enclosure, box, container, casing, tank, compartment, cavity, pipe, or trunk.

[0205] Example 51. A bioreactor device, said device comprising: a bioreactor chamber and a membrane wall disposed on said bioreactor chamber, wherein said bioreactor chamber is configured to hold a scaffold structure or other component; and said membrane wall is configured to allow transfer of linear motion to said scaffold structure or other component without breaching said membrane wall.

[0206] Example 52. The bioreactor device of example 51, wherein said bioreactor chamber said membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor chamber is closed.

[0207] Example 53. The device of example 51 (as well as subject matter in whole or in part of example 52), wherein said linear motion is a type of motion that can be generated by a linear actuator disposed outside said bioreactor chamber.

[0208] Example 54. The device of example 51 (as well as subject matter of one or more of any combination of examples 52-53, in whole or in part), wherein said device is provided as part of a kit, wherein said kit includes a linear actuator, wherein said linear actuator is configured to provide said linear motion.

[0209] Example 55. A system configured to receive said bioreactor device of example 51 (as well as subject matter of one or more of any combination of examples 52-54, in whole or in part), said system comprising: a linear actuator disposed outside said bioreactor chamber, wherein said linear actuator is configured to provide said linear motion; and a linear transfer means for transferring linear motion between said linear actuator and said scaffold structure or said other component without breaching said membrane wall.

[0210] Example 56. The system of example 54 (as well as subject matter of one or more of any combination of examples 52-55, in whole or in part), further comprising: a control system in communication with said linear actuator configured to control the movement of said linear actuator.

[0211] Example 57. The system of example 56, wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

[0212] Example 58. The system of example 55 (as well as subject matter of one or more of any combination of examples 52-57, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

[0213] Example 59. A bioreactor comprising: a bioreactor chamber; a membrane wall disposed on said bioreactor chamber; a scaffold structure disposed inside said bioreactor chamber; [0214] a linear actuator disposed outside said bioreactor chamber; a linear transfer means for transferring linear motion between said linear actuator and said scaffold structure without breaching said membrane wall; and a control system in communication with said linear actuator configured to control the movement of said linear actuator.

[0215] Example 60. The bioreactor of example 59, wherein said bioreactor chamber and said membrane wall are configured to separate from said linear actuator, said linear transfer means, and said control system.

[0216] Example 61. The bioreactor of example 60, wherein said bioreactor chamber and membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor is closed.

[0217] Example 62. The bioreactor of example 59 (as well as subject matter of one or more of any combination of examples 60-61, in whole or in part), wherein said bioreactor chamber and said membrane wall is configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor is closed.

[0218] Example 63. The bioreactor of example 59 (as well as subject matter of one or more of any combination of examples 60-62, in whole or in part), wherein said linear transfer means is comprised of a coupling mechanism, wherein said coupling mechanism is configured to couple said linear actuator to said scaffold structure, in response to said linear motion, on opposing sides of said membrane wall without breaching said membrane wall.

[0219] Example 64. A bioreactor comprising: a bioreactor chamber; a membrane wall disposed on said bioreactor chamber, wherein said bioreactor chamber and said membrane wall are configured to maintain sterility or sanitation within said bioreactor chamber while said bioreactor chamber is closed; a scaffold structure disposed inside said bioreactor chamber; an actuator disposed outside said bioreactor chamber; a transfer means for transferring motion between said actuator and said scaffold structure without breaching said membrane wall; and a control system in communication with said actuator configured to control the movement of said actuator.

[0220] Example 65. The bioreactor of example 64 further comprising any of the elements, components, systems, devices, materials, or their sub-components, provided in any one or more of examples 1-50 or 59, in whole or in part.

[0221] Example 66. A method of manufacturing any of the elements, components, systems, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

[0222] Example 67. A method of using any of the bioreactors, systems, elements, components, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

[0223] Example 68. A method of transporting or transferring any of the bioreactors, systems, elements, components, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

[0224] Example 69. A method of manufacturing cells and tissues using any of the bioreactors, systems, elements, components, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

[0225] Example 70. A method of stimulating cell growth and/or maturation using any of the bioreactors, systems, elements, components, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

[0226] Example 71. Cells and/or tissues manufactured using the methods provided in any one or more of examples 69-70, in whole or in part.

[0227] Example 72. Cells and/or tissues manufactured using any of the bioreactors, systems, elements, components, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

[0228] Example 73. A system configured to perform the method of any one or more of examples 69-70.

[0229] Example 74. The bioreactor device of example 51 further comprising any of the elements, components, systems, devices, materials, or their sub-components, provided in any one or more of examples 2-48, in whole or in part.

[0230] Example 75. The bioreactor device of example 55 further comprising any of the elements, components, systems, devices, materials, or their sub-components, provided in any one or more of examples 2-48, in whole or in part.

[0231] Example 76. An article of manufacture that is manufactured using the methods provided in any one or more of examples 69-70, in whole or in part.

[0232] Example 77. An article of manufacture that is manufactured using any of the bioreactors, systems, elements, components, devices, materials, or their sub-components, provided in any one or more of examples 1-63, in whole or in part.

REFERENCES

[0233] The devices, systems, apparatuses, modules, compositions, articles of manufacture, materials, computer program products, non-transitory computer readable medium, and methods of various embodiments of the invention disclosed herein may utilize aspects (such as devices, apparatuses, modules, systems, compositions, articles of manufacture, materials, computer program products, non-transitory computer readable medium, and methods) disclosed in the following references, applications, publications and patents and which are hereby incorporated by reference herein in their entirety (and which are not admitted to be prior art with respect to the present invention by inclusion in this section). [0234] 1. U.S. Utility patent application Ser. No. 17/282,117 entitled “MODULAR BIOFABRICATION PLATFORM FOR DIVERSE TISSUE ENGINEERING APPLICATIONS AND RELATED METHOD THEREOF”, filed Apr. 1, 2021. [0235] 2. International Patent Application Serial No. PCT/US2019/054744 entitled “MODULAR BIOFABRICATION PLATFORM FOR DIVERSE TISSUE ENGINEERING APPLICATIONS AND RELATED METHOD THEREOF”, filed Oct. 4, 2019; Publication No. WO 2020/072933, Apr. 9, 2020. [0236] 3. U.S. Utility patent application Ser. No. 17/049,237 entitled “USE OF A HYALURONIC ACID-BASED HYDROGEL FOR TREATMENT OF VOLUMETRIC MUSCLE LOSS INJURY”, filed Oct. 20, 2020. [0237] 4. International Patent Application Serial No. PCT/US2019/028558 entitled “USE OF A HYALURONIC ACID-BASED HYDROGEL FOR TREATMENT OF VOLUMETRIC MUSCLE LOSS INJURY”, filed Apr. 22, 2019; Publication No. WO 2019/204818, Oct. 24, 2019. [0238] 5. U.S. Utility patent application Ser. No. 16/322,691 entitled “BIOREACTOR CONTROLLER DEVICE AND RELATED METHOD THEREOF”, filed Feb. 1, 2019. [0239] 6. International Patent Application Serial No. PCT/US2017/045299 entitled “BIOREACTOR CONTROLLER DEVICE AND RELATED METHOD THEREOF”, filed Aug. 3, 2017; Publication No. WO 2018/027033, Feb. 8, 2018. [0240] 7. U.S. Utility patent application Ser. No. 15/760,009 entitled “BIOREACTOR AND RESEEDING CHAMBER SYSTEM AND RELATED METHODS THEREOF”, filed Mar. 14, 2018; Publication No. US-2018-0265831-A1, Sep. 20, 2018. [0241] 8. International Patent Application Serial No. PCT/US2016/051948 entitled “BIOREACTOR AND RESEEDING CHAMBER SYSTEM AND RELATED METHODS THEREOF”, filed Sep. 15, 2016; Publication No. WO 2017/048961, Mar. 23, 2017. [0242] 9. U.S. Utility patent application Ser. No. 15/770,413, entitled “DEVICES, SYSTEMS AND METHODS FOR SAMPLE DETECTION”, filed Apr. 23, 2018; Publication No. US-2019-0054468-A1, Feb. 21, 2019. [0243] 10. International Patent Application Serial No. PCT/US2016/058263, entitled “DEVICES, SYSTEMS AND METHODS FOR SAMPLE DETECTION”, filed Oct. 21, 2016; Publication No. WO 2017/070571, Apr. 27, 2017. [0244] 11. U.S. Pat. No. 7,399,168 B1, Eberwein, “Air Driven Diaphragm Pump”, Jul. 15, 2008. Tapflo catalogue, “Air Operated Diaphragm Pumps”, 2013 (Rev. 1). https://www.tapflo.co.jp/images/Diaphragm_pumps_40_pages_catalogue_english.en.pdf [0245] 12. U.S. Pat. No. 7,695,967 B1, Russell, et al., “Method of Growing Stem Cells on a Membrane Containing Projections and Grooves”, Apr. 13, 2010. [0246] 13. U.S. Pat. No. 6,472,202 B1, Banes, “Loading Station Assembly and Method for Tissue Engineering”, Oct. 29, 2002. [0247] 14. U.S. Patent Application Publication No. US 2012/0100602 A1, Lu, et al., “Bioreactor System for Mechanical Stimulation of Biological Samples”, Apr. 26, 2012. [0248] 15. U.S. Patent Application Publication No. US 2011/0172683 A1, Yoo, et al., “Tissue Expander”, Jul. 14, 2011. [0249] 16. U.S. Patent Application Publication No. US 2018/0093015 A1, Murphy, et al., “Devices, Systems, and Methods for the Fabrication of Tissue”, Apr. 5, 2018. [0250] 17. U.S. Patent Application Publication No. US 2018/0265831 A1, Cao, et al., “Bioreactor and Reseeding Chamber System and Related Methods Thereof”, Sep. 20, 2018. [0251] 18. Korean Patent No. KR 10-1585328 B1, Kim, et al., “Hybrid Bio Print Apparatus for Manufacturing Scaffold Supporter and Method for Manufacturing Using the Same”, Jan. 14, 2016.

[0252] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting of the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced herein.

[0253] In summary, while the present invention has been described with respect to specific embodiments, many modifications, variations, alterations, substitutions, and equivalents will be apparent to those skilled in the art. The present invention is not to be limited in scope by the specific embodiment described herein. Indeed, various modifications of the present invention, in addition to those described herein, will be apparent to those of skill in the art from the foregoing description and accompanying drawings. Accordingly, the invention is to be considered as limited only by the spirit and scope of the following claims including all modifications and equivalents.

[0254] Still other embodiments will become readily apparent to those skilled in this art from reading the above-recited detailed description and drawings of certain exemplary embodiments. It should be understood that numerous variations, modifications, and additional embodiments are possible, and accordingly, all such variations, modifications, and embodiments are to be regarded as being within the spirit and scope of this application. For example, regardless of the content of any portion (e.g., title, field, background, summary, abstract, drawing figure, etc.) of this application, unless clearly specified to the contrary, there is no requirement for the inclusion in any claim herein or of any application claiming priority hereto of any particular described or illustrated activity or element, any particular sequence of such activities, or any particular interrelationship of such elements. Moreover, any activity can be repeated, any activity can be performed by multiple entities, and/or any element can be duplicated. Further, any activity or element can be excluded, the sequence of activities can vary, and/or the interrelationship of elements can vary. Unless clearly specified to the contrary, there is no requirement for any particular described or illustrated activity or element, any particular sequence or such activities, any particular size, speed, material, dimension or frequency, or any particular interrelationship of such elements. Accordingly, the descriptions and drawings are to be regarded as illustrative in nature, and not as restrictive. Moreover, when any number or range is described herein, unless clearly stated otherwise, that number or range is approximate. When any range is described herein, unless clearly stated otherwise, that range includes all values therein and all sub-ranges therein. Any information in any material (e.g., a United States/foreign patent, United States/foreign patent application, book, article, etc.) that has been incorporated by reference herein, is only incorporated by reference to the extent that no conflict exists between such information and the other statements and drawings set forth herein. In the event of such conflict, including a conflict that would render invalid any claim herein or seeking priority hereto, then any such conflicting information in such incorporated by reference material is specifically not incorporated by reference herein.