KR101864256B1 - Bioreactor for artificial trachea - Google Patents

Abstract

The present invention provides an incubator for culturing a cell support-based artificial cell, comprising: a chamber having a hemispherical cavity formed therein; A first horizontal connector connected to the chamber in a horizontal plane direction to allow the culture liquid to flow in and out of the cavity; And a hollow vertical connector through which a catheter-shaped cell support is inserted, which is penetrated below the chamber and is disposed perpendicular to the cavity inner side surface and in which the artificial cells are cultured, Thereby providing a suitable culture environment for the ductal type cells.

Description

[0001] BIOACTOR FOR ARTIFICIAL TRACHEA [0002]

The present invention relates to an incubator suitable for culturing duct-like cells having hollows such as blood vessels or trachea.

Recently, regenerative medicine has been attracting attention as a method of regenerating or replacing a biologic tissue that has become impaired. Biotissue for replacement of deficient tissue can be produced by artificially culturing cells in a bioreactor. In the conventional case, an incubator for cell culture has a general culture dish or bottle shape. However, such a conventional incubator structure is not suitable for culturing duct type cells having hollows such as blood vessels and bronchi.

The catheter-shaped cells should be formed to have flexibility such as lateral flexion and extension in the longitudinal direction. In this case, since the media circulation can only be performed by the culture apparatus of a general culture dish or a bottle, there is a limitation that the growth environment of the duct type cells can not be suitably provided, such as the villous stimulation of the hollow wall or the longitudinal stimulation of the cells.

On the other hand, Korean Patent Laid-Open Publication No. 1988-0001801 discloses a bioreactor for cell culture as a related art. The bioreactor tank or the gas exchanger disclosed in the above patent documents exemplifies the connection of a conduit through which a gas or a medium flows in and out in a horizontal direction. Conventionally, as in the above-mentioned patent documents, the culture medium is injected and discharged only in the horizontal direction of the incubator to provide a culture environment of the cells. As described above, in this case, since the medium can be circulated to the outside of the cell during cell culture, it can not stimulate or grow the inner wall of the blood vessel or trachea, Have a difficult limit.

Korean Patent Publication No. 1988-0001801

Accordingly, the present invention provides an incubator for providing an environment optimized for the regeneration of specific organs such as blood vessels or villi of ducts such as trachea, as well as horizontal circulation as well as vertical circulation during cell culture.

According to an aspect of the present invention, there is provided an incubator for culturing an artificial cell based on a cell support, comprising: a chamber having a hemispherical cavity; A first horizontal connector connected to the chamber in a horizontal plane direction to allow the culture liquid to flow in and out of the cavity; And a hollow vertical connector through which a catheter-shaped cell support is inserted, which is penetrated below the chamber and is disposed perpendicular to the cavity inner side surface and in which the artificial cells are cultured, Thereby providing a culture environment of the ductal type cells.

Preferably, the first horizontal connector includes a conduit through which the culture liquid flows and a conduit through which the culture liquid is discharged, and each conduit may be introduced from both sides of the chamber so that the end protrudes inside the cavity.

Preferably, the first horizontal connector may be connected in a horizontal plane direction of the chamber at a position higher than one end of the vertical connector disposed perpendicularly to the inner ground surface of the cavity.

Preferably, the first horizontal connector is configured such that a conduit through which the culture solution flows and a conduit through which a culture solution flows out are respectively inserted into both ends of the catheter-shaped cell support, thereby fixing the cell-shaped cell support on the horizontal plane of the chamber .

Preferably, the incubator according to the present invention may further comprise a second horizontal connector connected in an axial direction different from the first horizontal connector on the horizontal plane of the chamber to circulate the media in the chamber.

Preferably, the incubator according to the present invention may further include a hollow fixed conduit attached to the upper portion of the chamber so as to face the vertical connector in the cavity so as to fix the upper end of the cell support.

Preferably, the fixed conduit is inserted into an upper end of the cell support on an axis, such as one end of the vertical connector, disposed perpendicular to an inner ground surface of the cavity; And an arm extended in a lateral direction of the insertion portion and pressed and fixed to an inner surface of the cavity, wherein the insertion portion may be hollow.

Preferably, the vertical connector may be an 'L' shaped conduit that is penetrated at the front of the chamber and is bent in a direction perpendicular to the inner surface of the cavity.

According to the present invention, a chamber design of an incubator in which a vertical connector is provided is advantageous for cell growth and environmental stimulation by enabling vertical air or media circulation to the cell support. Particularly, according to the present invention, the cell support can be fixed horizontally through the first horizontal connector, or the cell support can be vertically fixed through the vertical connector. In addition, the cavity of the chamber may be provided hemispherically and the second horizontal connector may circulate the media within the chamber to suitably stimulate the outer surface of the cell support.

1 is a perspective view of an incubator according to an embodiment of the present invention.
Fig. 2 shows a coupling configuration of an incubator according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to or limited by the exemplary embodiments. Like reference numerals in the drawings denote members performing substantially the same function.

The objects and effects of the present invention can be understood or clarified naturally by the following description, and the purpose and effect of the present invention are not limited by the following description. In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail.

Fig. 1 shows a perspective view of an incubator 1 according to an embodiment of the present invention. 1A shows an embodiment of an incubator 1 in which a catheter-shaped cell support is fixed in the vertical direction, and Fig. 1B shows an embodiment of an incubator 1 'in which a catheter-shaped cell support is fixed in the horizontal direction. 2A is a perspective view of an assembled view of the incubator 1 of FIG. 1A seen from the rear, FIG. 2B is a perspective view of the incubator 1 of FIG. 1A, Sectional view of the coupling structure as viewed from the rear.

1 and 2, the incubator 1 may include a chamber 10, a first horizontal connector 30, a second horizontal connector 50, a vertical connector 70, and a fixed conduit 90 have. The incubator 1 according to the present embodiment has a structure specialized for culturing the duct-like organs such as blood vessels and organs. As used herein, the term "anatomical term" refers to a tube connected between the larynx and the lungs, which means that Trachea exists in almost all animals breathing through the lungs, allowing air to flow through the breath. Human organs are about 25 mm (1 inch) in inside diameter and 10 to 16 cm (4 to 6 inch) in length. These organs can be cultured in a catheter-shaped cell support (4).

It is preferable that the cell support 4 has a structure which is robust against longitudinal torsion, forward and backward bending, and twisting characteristics due to rotation so as to be suitable for culturing a catheter-shaped organ.

In this embodiment, the cell support 4 may be provided in a net or mesh structure, and more particularly in the form of a conduit of a pattern of columns and glands. In Fig. 1, the support 4 can then be deposited by electrospinning, taking into account the engraftment of endothelial cells and the engraftment of fibroblasts. As an example, the cell support 4 may be excellent in forward and backward bending and twisting characteristics by a pattern of a column and an ejection body constituting the body. At this time, the column may be a pattern of the first diameter formed in the horizontal plane direction of the support body 4 and repeatedly arranged at regular intervals. The jet bodies may be formed with a slope in the longitudinal direction of the support body 4 and may be a pattern of a second diameter connecting the columns and the repeatedly arranged columns. In this case, it is preferable that the jet bodies are formed in different directions with different slopes between the columns and the columns.

The conduit type organs cultured in the cell support (4) should be capable of media circulation or air circulation externally and medially. The organs of the conduit type should be able to form some elasticity in the longitudinal direction, and the cell stimulation such as the villus is necessary inside the conduit. Hereinafter, each configuration of the incubator (1) of this embodiment, which is suitable for culturing a conduit type organs, will be described.

The chamber 10 may be in the form of a crucible having a hemispherical cavity 101 formed therein. The chamber 10 may be coupled with the upper cap 103 to seal the inner cavity 101, as shown in FIG. Unlike conventional cell culture, the chamber 10 according to the present embodiment is provided in a crucible form. This is to effectively stimulate the outer surface of the duct type cells to be cultured by effectively circulating the culture liquid in the cavity 101, and to remove foreign substances and the like.

The chamber 10 may be formed with a penetration hole through which the first horizontal connector 30, the second horizontal connector 50, and the vertical connector 70 are respectively inserted into the front, side, and lower sides. 1 and 2, the first horizontal connector 30 and the second horizontal connector 50 are provided as a pair of conduits into which the culture liquid or air is introduced or discharged. Thus, the chamber 10 is provided with a total of 5 Can be formed.

The first horizontal connector 30 is connected in the horizontal plane direction of the chamber 10 to allow the culture liquid to flow in and out of the cavity 101. The first horizontal connector 30 includes a conduit 301 into which the culture liquid flows and a conduit 303 through which the culture liquid flows out and each of the conduits is provided on both sides of the chamber 10 so as to protrude toward the inside of the cavity 101 Can be intrusive. Although not shown in the figure, the first horizontal connector 30 may be connected to an injection pump for supplying media and the like necessary for cell culture. The peripherals and the culture environment of the incubator (1) for supplying the cell culture environment are well known and will not be described in detail.

1B, the first horizontal connector 30 is configured such that the conduit 301 into which the culture liquid flows and the end of the conduit 303 through which the culture liquid flows out are inserted into both ends of the catheter-shaped cell support 4, Type cell support 4 can be fixed on the horizontal plane of the chamber 10. [ That is, the incubator 1 according to the present embodiment may be arranged such that the cell support 4 is vertically disposed in the chamber 10 as shown in FIG. 1A, or horizontally as shown in FIG. 1B.

The first horizontal connector 30 may be connected in the horizontal plane direction of the chamber 10 at a position higher than one end of the vertical connector 70 disposed perpendicularly to the inner ground surface of the cavity 101. [ Referring to FIG. 1B, the first horizontal connector 30 is penetrated into the chamber 10 at a higher position than the end of the vertical connector 70. Thus, the cell support 4 can be connected to the first horizontal connector 30 without interfering with the vertical connector 70, and can be fixed vertically or horizontally depending on the type of cultured cells.

The second horizontal connector 50 can be axially connected on the horizontal surface of the chamber 10 in a different axial direction than the first horizontal connector 30 to circulate the medium in the chamber 10. [ 1, the first horizontal connector 30 is penetrated in the lateral direction of the chamber 10, and the second horizontal connector 50 is penetrated in the chamber 10, which is a shaft different from the first horizontal connector 30, (10). The second horizontal connector 50 is composed of two conduits through which the culture liquid flows, and circulates the culture liquid in the cavity 101 to take charge of external circulation of the cell support 4.

The vertical connector 70 can be immersed below the chamber 10 to fix the catheter-shaped cell support 4, which is positioned perpendicular to the inner surface of the cavity 101 and into which the artificial cells are cultured. The vertical connector 70 can provide a culture environment for the duct type cells by allowing air to flow in and out of the support 4.

The vertical connector 70 may be provided as a conduit that is intruded from the front of the chamber 10 and is bent in a direction perpendicular to the inner surface of the cavity 101. The vertical connector 70 may be formed such that its outer diameter corresponds to the inner diameter of the cell support 4. [ Accordingly, the vertical connector can be inserted into the lower end of the cell support 4 to insert and fix the cell support 4.

The fixed conduit 90 is fixed to the upper portion of the chamber 10 so as to face the vertical connector 70 in the vertical direction in the cavity 101 to fix the upper end of the cell support 4. The fixed conduit 90 may include an insert 901 and an arm 903. The insertion portion 901 is inserted into the upper end of the cell support 4 on the same axis as one end of the vertical connector 70 disposed perpendicular to the inner ground surface of the cavity 101. [ In this case, the insertion portion 901 is provided in a hollow shape so that the air introduced from the vertical connector 70 can be flown out through the cell support 4.

The arm 903 is extended in the lateral direction of the insertion portion 901 and is pressed and fixed to the inner surface of the cavity 101. [ The arm 903 may be composed of a rod extending from the insertion portion 901 and a fixing surface having a wide contact surface formed at the end of the rod so as to press the inside of the cavity 101. [

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. will be. Therefore, the scope of the present invention should not be limited to the above-described embodiments, but should be determined by all changes or modifications derived from the scope of the appended claims and equivalents of the claims.

This research was supported by the Korea Research Foundation Foundation Research Project (No. 2014R1A1A2A16054777) and the Ministry of Health and Welfare funded by the Korea Health Industry Development Institute (KHIDI) research and development project (assignment number: HI14C3228) Thank you very much for your support of this project (FRD2014-02-02).

1, 1 'incubator
4: cell support
10: chamber
101: cavity
103: Cap
30: first horizontal connector
301: conduit into which the culture liquid flows
303: conduit through which the culture liquid is discharged
50: second horizontal connector
70: Vertical connector
90: Fixed conduit
901:
903: arm

Claims (8)

In an incubator for culturing an artificial cell based on a cell support,
A chamber in which a hemispherical cavity is formed to prevent turbulent flow of culture fluid;
A first horizontal connector connected in a horizontal plane direction of the chamber to allow the culture liquid to flow in and out;
A hollow vertical connector penetrating from below the chamber and disposed perpendicularly to the cavity inner side surface and the first horizontal connector, And
A catheter-shaped cell scaffold in which the artificial cells are cultured; / RTI >
The cell support may comprise,
Wherein the first horizontal connector is horizontally disposed between the first horizontal connectors or vertically connected to one side of the vertical connector,
Further comprising: a second horizontal connector connected in an axial direction different from the first horizontal connector on a horizontal plane of the chamber to circulate the media in the chamber.
The method according to claim 1,
The first horizontal connector includes:
A conduit through which the culture fluid flows,
Wherein the first horizontal connector includes a conduit through which the culture liquid is discharged,
Wherein each conduit is penetrated from both sides of the chamber so that the end protrudes inside the cavity.
3. The method of claim 2,
The first horizontal connector includes:
Wherein the vertical connector is connected in the horizontal plane direction of the chamber at a position higher than one end of the vertical connector disposed perpendicular to the inner ground surface of the cavity.
The method of claim 3,
The first horizontal connector includes:
Wherein a conduit through which the culture solution flows and a conduit through which the culture solution flows out are respectively inserted into both ends of a catheter-shaped cell support to fix a catheter-shaped cell support on a horizontal plane of the chamber.
delete The method according to claim 1,
Further comprising a hollow fixed conduit attached to an upper portion of the chamber so as to be opposed to the vertical connector in the cavity in the up and down direction to fix an upper end of the cell support.
The method according to claim 6,
The fixed conduit,
An insertion portion to be inserted into an upper end of the cell support on an axis such as one end of the vertical connector disposed perpendicular to an inner ground surface of the cavity; And
And an arm extending in a lateral direction of the insertion portion and being press-fitted to the inner surface of the cavity,
Wherein the insert is hollow.
The method according to claim 1,
The vertical connector includes:
L 'shaped conduit which is intruded from the front surface of the chamber and is bent in a direction perpendicular to the inner surface of the cavity.

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