Bio-ink manufacturing equipment

Abstract

The bio-ink manufacturing device according to the present invention includes a reaction vessel for reacting decellularized xenogeneic organ tissue with an ink-forming solution, a bio-ink liquefaction unit for agitating and chopping the decellularized xenogeneic organ tissue to liquefy it as bio-ink, and a bio-ink discharge unit for discharging the liquefied bio-ink out of the reaction vessel.

Description

[Technical Field]

[0001] The present invention relates to a bio-ink production apparatus. [Background technology]

[0002] Due to the global aging trend, the number of people with chronic diseases is increasing, and interest is growing in artificial organ manufacturing technology using 3D bioprinting.

[0003] Bioink is a term used to describe ink materials used to print artificial organs using 3D bioprinters, and is manufactured based on the extracellular matrix obtained after decellularizing xenogeneic organs.

[0004] A large amount of bioink is required to manufacture artificial organs, but the lack of technology to mass-produce bioink has made it difficult to meet the demand, and therefore research using bioink has not been able to be widely expanded.

[0005] In addition, when dissolving the bioink, there was no equipment capable of dissolving a large amount of decellularized xenogeneic organ (dECM) tissue, so only a small amount of ink (e.g., 8.4 ml) was produced in a simple conical tube. This resulted in inconsistent bioink properties for each tube, posing an issue for commercialization.

[0006] When bioink is manufactured to meet consumer needs, the viscosity of the ink can increase to hundreds of thousands of cP due to the high concentration of decellularized xenogeneic organs contained in the ink, and no device has been devised that can properly dispense the bioink after it has been manufactured. Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to provide a bioink manufacturing device that can liquefy large amounts of decellularized xenogeneic organ (dECM) tissue when manufacturing bioink based on a general concentration (1% dECM), and that can eject a fixed amount of highly viscous bioink from the same reaction vessel immediately after liquefying it, even when manufacturing high-concentration bioink. [Means for solving the problem]

[0008] A bioink manufacturing apparatus according to one embodiment of the present invention may include a reaction vessel for reacting decellularized xenogeneic organ (dECM) tissue with an ink-forming solution to produce bioink, and a bioink liquefaction unit for stirring and chopping the decellularized xenogeneic organ tissue in the reaction vessel and liquefying it into bioink.

[0009] The bio-ink manufacturing device may also include a bio-ink ejection unit that is positioned at a set distance from the bio-ink liquefaction unit and ejects the bio-ink that has been liquefied in the reaction vessel to the outside of the reaction vessel.

[0010] The bio-ink production device can include a transfer unit for transferring the reaction vessel in which the bio-ink has been completely liquefied from the bio-ink liquefaction unit to the bio-ink discharge unit.

[0011] The reaction vessel is formed in a cylindrical shape with an open top and a space inside where decellularized xenogeneic organ (dECM) tissue can be stored.

[0012] The inner surface of the reaction vessel is coated with a material that is chemically resistant to the decellularized xenogeneic organ tissue and the ink-forming solution.

[0013] The reaction vessel may have a double jacket configuration consisting of an inner tube and an outer tube.

[0014] The outer pipe is provided with a cooling water inlet for injecting cooling water for temperature control into the space between the inner pipe and the outer pipe, and a cooling water outlet for discharging the injected cooling water to the outside of the outer pipe.

[0015] The bioink liquefaction unit may include a first cover disposed on top of the reaction vessel for covering the upper end of the reaction vessel, and a rotation shaft vertically rotatably connected to the upper end of the first cover and protruding a set length from the bottom of the first cover.

[0016] The bio-ink liquefaction unit is connected to the lower end of the rotating shaft and can include an impeller for stirring and chopping the decellularized xenogeneic organ tissue and ink solution injected into the reaction vessel.

[0017] The impeller is made of or coated with a material that is chemically resistant to decellularized xenogeneic organ tissue and ink-forming solutions, etc.

[0018] A drive motor may be installed on the upper part of the first cover to be coupled with the upper end of the rotary shaft and rotate the rotary shaft.

[0019] The first cover may be provided with at least one solution inlet port for injecting ink-forming solution.

[0020] A pH measuring device for measuring the hydrogen ion exponent (PH) in the reaction vessel can be installed on the first cover.

[0021] An internal observation camera for observing the inside of the reaction vessel can be installed on the first cover.

[0022] A first lifting unit for vertically lifting and lowering the first cover can be coupled to the first cover.

[0023] The first lifting unit may include a first connecting member connected to the first cover so as to be able to move up and down, and a first lifting operation unit connected to one end of the first connecting member for lifting and lowering the first connecting member.

[0024] The moving unit may include a support plate installed at a lower end of the reaction vessel to support the reaction vessel, at least one sliding tube coupled to the lower end of the support plate, and a sliding rail installed between the base frame and the support plate in the length direction of the base frame to which the sliding tube is movably coupled.

[0025] The sliding tube may consist of a cylindrical tube with an open interior.

[0026] A locking lever can be coupled to the sliding tube to stop the movement of the sliding tube.

[0027] The sliding rail may be arranged parallel to the base frame.

[0028] A first support frame and a second support frame are vertically installed at both ends of the base frame, and a sliding rail can be connected between the first support frame and the second support frame.

[0029] The bioink ejection unit can include a second cover that is placed on top of the reaction vessel to cover the upper end of the reaction vessel, and a syringe piston that is placed vertically at the lower end of the second cover to move vertically up and down while sealing the inside of the reaction vessel.

[0030] The bio-ink discharge unit may include a bio-ink discharge pipe that is installed on one side of the reaction vessel and that discharges the bio-ink that has been liquefied in the reaction vessel to the outside as the syringe piston descends.

[0031] A servo motor for raising and lowering the syringe piston can be coupled to the top of the second cover.

[0032] A second lifting unit can be coupled to the servo motor for vertically raising and lowering the servo motor.

[0033] The second lifting unit may include a second connecting member connected to the servo motor so as to be able to move up and down, and a second lifting operation unit connected to one end of the second connecting member for lifting and lowering the second connecting member.

[0034] The bio-ink discharge pipe may be provided with a discharge pipe control valve for controlling the opening and closing of the bio-ink discharge pipe.

[0035] The amount of bioink discharged from the discharge pipe control valve can be controlled by controlling the operation of the servo motor with a controller connected to the servo motor. [Effects of the Invention]

[0036] According to an embodiment of the present invention, when producing bioink based on a general concentration (1% dECM), it is possible to liquefy a large amount of decellularized xenogeneic organ (dECM) tissue, and even when producing bioink with a high concentration, it is possible to dispense a fixed amount of highly viscous bioink from the same reaction vessel immediately after liquefaction.

[0037] In other words, after the reaction vessel in which the bioink has been liquefied is moved to the bioink ejection section by the moving section, the bioink is immediately ejected from the bioink ejection section, thereby preventing loss of bioink due to movement.

[0038] It is possible to efficiently liquefy large amounts of decellularized xenogeneic organ (dECM) tissue and discharge it efficiently. In particular, when liquefying the bioink, it is possible to ensure homogeneity during evaluation of physical properties between vials, which can have an effect that can greatly contribute to the commercialization and business development of bioink. [Brief explanation of the drawings]

[0039] [Figure 1]1 is a schematic configuration diagram of a bio-ink production device according to an embodiment of the present invention. [Figure 2] 1 is a schematic partial side view of a bio-ink ejection unit of a bio-ink production device according to an embodiment of the present invention. [Figure 3] 10 is a photograph illustrating a process in which a sterilized porcine placenta decellularized xenogeneic organ powder and a liquefied solution are introduced into a reaction vessel using the bio-ink production apparatus according to one embodiment of the present invention. [Figure 4] 10A and 10B are photographs showing monitoring of the liquefaction process of a sterilized porcine placenta decellularized xenogeneic organ using a bio-ink manufacturing apparatus according to an embodiment of the present invention, where T represents time. [Figure 5] 5A and 5B are photographs of a sol-gel test for the dissolution process of a sterilized decellularized porcine placenta xenogeneic organ produced using the bioink production apparatus according to one embodiment of the present invention, in which (a) is a photograph of the dissolved state, (b) is a photograph of the gel state, and (c) is a graph showing the viscosity measurement results against shear rate. DETAILED DESCRIPTION OF THE INVENTION

[0040] Hereinafter, with reference to the accompanying drawings, embodiments of the present invention will be described so that those skilled in the art can easily implement the present invention. As will be easily understood by those skilled in the art, the following embodiments may be modified in various ways without departing from the concept and scope of the present invention. Wherever possible, the same or similar parts will be designated by the same reference numerals throughout the drawings.

[0041] The terminology used below is merely for the purpose of referring to particular embodiments and is not intended to limit the present invention. As used herein, the singular form includes the plural form unless the phrase clearly dictates otherwise. As used in the specification, the term "comprising" embodies certain properties, regions, integers, steps, operations, elements, and / or components, and does not exclude the presence or addition of other specific properties, regions, integers, steps, operations, elements, components, and / or groups.

[0042] All terms, including technical and scientific terms, used below have the same meaning as commonly understood by a person of ordinary skill in the art to which the present invention pertains. Terms defined in the dictionary are additionally interpreted to have a meaning consistent with the relevant technical literature and the presently disclosed content, and are not interpreted in an ideal or very formal sense unless otherwise defined.

[0043] FIG. 1 is a schematic configuration diagram of a bio-ink production apparatus according to one embodiment of the present invention, and FIG. 2 is a schematic partial side view of a bio-ink discharge unit of the bio-ink production apparatus according to one embodiment of the present invention.

[0044] 1 and 2, a bio-ink manufacturing apparatus according to an embodiment of the present invention may include a reaction vessel 100, a bio-ink liquefaction unit 200, a transfer unit 300, and a bio-ink discharge unit 400.

[0045] The reaction vessel 100 can react decellularized xenogeneic organ (dECM) tissue with an ink solution to produce bioink.

[0046] Furthermore, the bioink liquefaction unit 200 can agitate and chop the decellularized tissue of the xenogeneic organ stored in the reaction vessel 100 and liquefy it as bioink.

[0047] The bio-ink ejection unit 400 is positioned at a set distance from the bio-ink liquefaction unit, and can eject the bio-ink that has been liquefied in the reaction vessel 100 to the outside of the reaction vessel 100.

[0048] Furthermore, the moving unit 300 can move the reaction vessel 100 in which the bio-ink has been liquefied from the bio-ink liquefaction unit 200 to the bio-ink discharge unit 400 along the first direction (the X direction in FIG. 1).

[0049] The reaction vessel 100 is movably coupled to the moving part 300, and can be moved by the moving part 300 from the bio-ink liquefaction part 200 to the bio-ink discharge part 400 along a first direction (the X direction in FIG. 1).

[0050] The reaction vessel 100 is formed in a cylindrical shape or the like, with an open top so that decellularized xenogeneic organ (dECM) tissue can be introduced and a space inside in which the decellularized xenogeneic organ (dECM) tissue can be stored.

[0051] The inner surface of the reaction vessel 100 is coated with a material such as Teflon that is chemically resistant to the decellularized xenogeneic organ tissue and the ink solution.

[0052] In addition, the reaction vessel 100 may have a double jacket configuration consisting of an inner tube 101 and an outer tube 103 in order to control the temperature during the liquefaction process of the decellularized xenogeneic organ tissue.

[0053] The outer pipe 103 is provided with a cooling water inlet 105 for injecting cooling water for temperature control into the space between the inner pipe 101 and the outer pipe 103, and a cooling water outlet 106 for discharging the injected cooling water to the outside of the outer pipe 103.

[0054] The cooling water inlet 105 is connected to a cooling device 107 by a connecting pipe 108 .

[0055] A heat insulating material 110 is installed on the outside of the reaction vessel 100 to insulate the reaction vessel 100 while surrounding the reaction vessel 100 .

[0056] The bio-ink liquefaction unit 200 may include a first cover 210 , a rotating shaft 220 , and an impeller 230 .

[0057] The first cover 210 is disposed on the top of the reaction vessel 100 and can cover the upper end of the reaction vessel 100 .

[0058] In addition, the rotation shaft 220 is coupled to the upper end of the first cover 210 so as to be rotatable in a vertical direction (Y direction in FIG. 1), and may protrude below the first cover 210 by a set length.

[0059] The impeller 230 is connected to the lower end of the rotating shaft 220 and can agitate and chop the decellularized xenogeneic organ tissue and ink solution injected into the reaction vessel 100.

[0060] The impeller 230 is made of a material that is chemically resistant to decellularized xenogeneic organ tissue and ink-forming solutions, or is coated with a material such as Teflon (registered trademark).

[0061] The shape of the impeller 230 is not important as long as it can easily generate turbulence inside the reaction vessel 100 when rotated by the rotating shaft 220 and can perform the function of friction and cutting against the inner wall of the reaction vessel 100.

[0062] In addition, a plurality of impellers 230 may be installed at set intervals on a connecting frame (not shown) that rotatably connects the impellers 230 to the rotary shaft 220 .

[0063] Therefore, when the rotating shaft 220 rotates, centrifugal force generates play in the impeller 200, which can move in a direction toward the inner surface of the reaction vessel 100 or in a direction toward the center of the reaction vessel 100, thereby effectively realizing the function of cutting up heterologous organ tissue by rubbing against the inner surface of the reaction vessel 100.

[0064] In addition, a driving motor 240 may be installed on the upper part of the first cover 210 to be coupled to the upper end of the rotating shaft 220 and rotate the rotating shaft 220 at a set speed.

[0065] The drive motor 240 can control the rotation speed of the rotary shaft 220 to, for example, 0 to 500 rpm.

[0066] The drive motor 240 may be a magnetic type motor or the like so that the rotary shaft 220 can be easily rotated.

[0067] The first cover 210 may be provided with at least one solution inlet port 211 for injecting an ink-forming solution required for ink-forming the decellularized tissue of a xenogeneic organ.

[0068] In addition, a pH measuring device 213 for measuring the hydrogen ion exponent (PH) in the reaction vessel 100 can be installed on the first cover 210.

[0069] An internal observation camera 215 can be installed on the first cover 210 to observe the inside of the reaction vessel 100 so as to check the liquefaction process of the decellularized xenogeneic organ tissue in the reaction vessel 100, i.e., whether or not the decellularized xenogeneic organ tissue is dissolved.

[0070] The first cover 210 may be coupled to a first lifting unit 250 for raising and lowering the first cover 210 in the vertical direction (Y direction in FIG. 1) so that the first cover 210 can be attached to or detached from the reaction vessel 100.

[0071] The first lifting unit 250 may include a first connecting member 251 and a first lifting operation unit 253 .

[0072] The first connecting member 251 is connected to the first cover 210 so as to be able to move up and down integrally.

[0073] The first lifting operation part 253 is connected to one end of the first connecting member 251 and is arranged apart from the reaction vessel 100, and is capable of lifting and lowering the first connecting member 251.

[0074] The first lifting operation unit 253 can be controlled manually as shown in FIG. 1 or automatically (not shown).

[0075] When the first lifting operation unit 253 is of a manual type that is manually controlled, a first operation handle 254 for manually operating the first lifting operation unit 253 is coupled to the upper end of the first lifting operation unit 253.

[0076] That is, the first lifting operation part 253 can be raised and lowered along the first support shaft 255 by rotating the first operation handle 254 .

[0077] When the first lifting operation unit 253 is an automatic type that is automatically controlled, it may be made up of a motor or an air cylinder (not shown), etc.

[0078] In addition, the first support shaft 255 is supported by a first vertical frame 257 installed in the vertical direction (Y direction in FIG. 1) at a set interval on the base frame 10, and a first horizontal frame 258 connected to the upper end of the first vertical frame 257 in the vertical direction (X direction in FIG. 1).

[0079] The base frame 10 can be placed on the installation surface or bottom surface in the length direction (X direction in FIG. 1).

[0080] The moving part 300 may also include a support plate 310 , a sliding tube 320 , and a sliding rail 330 .

[0081] The support plate 310 is installed at the lower end of the reaction vessel 100 to support the reaction vessel 100 .

[0082] In addition, at least one sliding tube 320 is coupled to the lower end of the support plate 310 .

[0083] The sliding rail 330 is installed between the base frame 10 and the support plate 310 in the longitudinal direction of the base frame 10, and the sliding tube 320 is movably coupled thereto.

[0084] The sliding tube 320 may be a cylindrical tube or the like that is hollow inside to allow easy movement along the sliding rail 330 .

[0085] At least one sliding tube 320 is coupled with a fixing lever 321 for stopping the movement of the sliding tube 320 along the sliding rail 330 .

[0086] The sliding rails 330 can be arranged parallel to the base frame 10 for easy movement of the reaction vessel 100 .

[0087] A first support frame 301 and a second support frame 302 are installed at both ends of the base frame 10 in a vertical direction (Y direction in FIG. 1), and a sliding rail 330 is connected between the first support frame 301 and the second support frame 302.

[0088] The bio-ink discharge unit 400 may include a second cover 410 , a syringe piston 420 , a servo motor 430 , and a bio-ink discharge pipe 440 .

[0089] The second cover 410 is disposed on the top of the reaction vessel 100 and can cover the upper end of the reaction vessel 100 .

[0090] Furthermore, the syringe piston 420 is disposed in the vertical direction (Y direction in FIG. 1) at the lower end of the second cover 410, and can move up and down vertically while sealing the inside of the reaction vessel 100.

[0091] The servo motor 430 is coupled to the upper part of the second cover 410 and can move the syringe piston 420 up and down.

[0092] In addition, the bioink discharge pipe 440 is installed on one side of the reaction vessel 100, and can discharge the bioink that has completed liquefaction in the reaction vessel 100 into a vial (not shown) or the like by descending the syringe piston 420.

[0093] The bio-ink discharge pipe 440 is provided with a discharge pipe control valve 441 for controlling the opening and closing of the bio-ink discharge pipe 440 .

[0094] The amount of bioink discharged from the discharge pipe control valve 441 is controlled by controlling the operation of the servo motor 430 using a controller (not shown) that is connected to the servo motor 430 and controls the operation of the servo motor 430.

[0095] A controller (not shown) can control the servo motor 430 so that the servo motor 430 can effectively eject the bio-ink even if the viscosity of the bio-ink is at the level of hundreds of thousands of cP (centipoise).

[0096] A second lifting unit 450 is coupled to the servo motor 430 to lift the servo motor 430 in the vertical direction (Y direction in FIG. 1) so that the syringe piston 420 can be inserted into or separated from the reaction vessel 100.

[0097] The second lifting unit 450 may include a second connecting member 451 and a second lifting operation unit 453 .

[0098] The second connecting member 451 is connected to the servo motor 430 so as to be able to move up and down integrally.

[0099] The second lifting operation part 453 is coupled to one end of the second coupling member 451 and is disposed apart from the reaction vessel 100, and is capable of lifting and lowering the second coupling member 451.

[0100] The second lifting operation unit 453 can be controlled manually as shown in FIG. 1 or automatically (not shown).

[0101] When the second lifting operation unit 453 is of a manual type that is manually controlled, a second operation handle 454 is coupled to the upper end of the first lifting operation unit 253 for manually operating it.

[0102] That is, the second lifting operation unit 453 can be raised and lowered along the second support shaft 455 by rotating the second operation handle 454 .

[0103] When the second lifting operation unit 453 is an automatic type that is automatically controlled, it may be made up of a motor or an air cylinder (not shown), etc.

[0104] In addition, the second support shaft 255 is supported by a second vertical frame 457 installed vertically (Y direction in FIG. 1) at a set interval on the base frame 10, and a second horizontal frame 458 connected vertically (X direction in FIG. 1) to the upper end of the second vertical frame 457.

[0105] The operation of a bio-ink production apparatus according to one embodiment of the present invention will be described below with reference to FIGS.

[0106] When liquefying bioink to produce bioink, first, the reaction vessel 100 is positioned at the center of the sliding rail 330, and then decellularized xenogeneic organ (dECM) tissue is placed at the bottom of the reaction vessel 100.

[0107] Then, using the moving part 300, the reaction vessel 100 is positioned from the center of the sliding rail 330 to the left side (left side in Figure 1), i.e., in the bioink liquefaction part 200, and the fixed lever 321 is fixed to stop the movement of the sliding tube 320.

[0108] In this state, the first coupling member 251 is vertically lowered using the first lifting operation part 253 of the first lifting part 250, and the first cover 210 is lowered to cover and seal the upper end of the reaction vessel 100.

[0109] Then, an ink-forming solution required for turning the decellularized tissue of the xenogeneic organ into ink is injected into the reaction vessel 100 through the solution inlet port 211 provided on the first cover 210 .

[0110] At this time, after the temperature inside the reaction vessel 100 is controlled to the set temperature, the drive motor 240 is driven to rotate the rotation shaft 220 at the set speed.

[0111] As the rotating shaft 220 rotates, the impeller 230 inserted inside the reaction vessel 100 rotates, stirring and chopping the decellularized xenogeneic organ tissue and ink solution injected into the reaction vessel 100.

[0112] This allows the decellularized tissue of the xenogeneic organ to react with the ink solution, liquefying it into a bioink.

[0113] In addition, the internal observation camera 215 located at the top of the reaction vessel 100 can be used to check whether the decellularized xenogeneic organ tissue inside the reaction vessel 100 is dissolved, thereby allowing the bioink liquefaction process to be observed.

[0114] Meanwhile, since the reaction vessel 100 has a form such as a double jacket consisting of an inner tube 101 and an outer tube 103, the inside of the reaction vessel 100 can be controlled to the set temperature required for the liquefaction process of the decellularized xenogeneic organ tissue.

[0115] In this way, when the liquefaction of the bioink is completed in the reaction vessel 100, the drive motor 240 is stopped to stop the rotation of the rotating shaft 220 and the impeller 230, and then the first connecting member 251 is vertically raised using the first lifting operation unit 253 to raise the first cover 210 and separate it from the top of the reaction vessel 100.

[0116] Then, the reaction vessel 100 in which the bio-ink liquefaction has been completed in the bio-ink liquefaction unit 200 is moved to the bio-ink discharge unit 400 by the moving unit 300 .

[0117] That is, after releasing the fixed connection of the fixed lever 321 to release the stopped state of the sliding tube 320, the reaction vessel 100 is positioned from the bioink liquefaction section 200 to the right side of the sliding rail 330, i.e., the bioink discharge section 400, using the moving section 300, and the fixed lever 321 is fixed to stop the movement of the sliding tube 320.

[0118] In this state, the second connecting member 451 is vertically lowered using the second lifting operation part 453 of the second lifting part 450, thereby lowering the second cover 410 so that the lower end of the servo motor 430 covers and seals the upper end of the reaction vessel 100.

[0119] Then, when the servo motor 430 is operated to lower the syringe piston 420, the bioink that has been liquefied in the reaction vessel 100 due to the descent of the syringe piston 420 is discharged from the inside of the reaction vessel 100 through the bioink discharge pipe 440 to a vial or the like located outside the reaction vessel 100.

[0120] At this time, the discharge pipe control valve 441 is controlled to an open state, and the amount of bioink discharged from the discharge pipe control valve 441 is controlled by controlling the operation of the servo motor 430 using a controller (not shown) connected to the servo motor 430 and controlling the operation of the servo motor 430.

[0121] Therefore, a large amount of decellularized xenogeneic organ (dECM) tissue can be efficiently liquefied and discharged, and in particular, homogeneity can be ensured during evaluation of physical properties between vials when liquefying the bioink.

[0122] Also, when the ejection of the bioink in the reaction vessel 100 is completed, the second lifting operation part 453 of the second lifting part 450 is used to vertically lift the second connecting member 451, thereby lifting the second cover 410 and separating it from the top of the reaction vessel 100 by a set distance.

[0123] Then, after releasing the fixed connection of the fixed lever 321 to release the stopped state of the sliding tube 320, the reaction vessel 100 is moved from the bio-ink ejection section 400 to the center of the sliding rail 330 using the moving section 300, and the bio-ink liquefaction process, reaction vessel moving process, and bio-ink ejection process can be repeated as described above. [Example]

[0124] (Example) Below, the sterile porcine placenta decellularized xenogeneic organ (dECM) bioink liquefaction and extrusion process is described.

[0125] 1) As shown in Figure 3, 5 g of sterilized porcine placenta decellularized xenogeneic organ (dECM) powder, 420 ml of 0.5 M acetic acid, and 0.5 g of pepsin powder were added to the bottom of a reaction vessel. This is the manufacturing process for 1% concentration decellularized xenogeneic organ (dECM) bioink.

[0126] 2) Then, move the bottom end of the reaction vessel to the left end, i.e., the bioink liquefaction section side, and use the manipulator of the first lifting operation section to vertically lower the first cover located at the top end of the reaction vessel to cover and seal the top end of the reaction vessel (see Figure 1), and at this time, check that the O-ring at the bottom end of the reaction vessel is in the correct position.

[0127] 3) The temperature of the double-jacketed reaction vessel is controlled by the temperature setting of the Refrigerated / Heating Circulator and is set to the activation temperature of pepsin, e.g., 37°C. The rotation speed of the impeller inside the reaction vessel is adjusted to 350 rpm.

[0128] 4) As shown in Figure 4, the bioink liquefaction process can be monitored using an internal observation camera installed at the top of the liquefaction reaction vessel to observe the process of the decellularized xenogeneic organ (dECM) tissue inside the reaction vessel being dissolved and liquefied. In this experiment, liquefaction was confirmed to be complete in approximately 8.5 hours.

[0129] 5) After the bioink has been liquefied, the first cover located at the top of the reaction vessel is vertically raised using the manipulator located on the left side of Figure 1, and the bottom of the reaction vessel is moved to the right end of the sliding rail of the moving part, i.e., to the bioink discharge part side of Figure 1. Then, the moving part is fixed using the fixing lever.

[0130] 6) Using the manipulator located on the right side of Figure 1, vertically lower the servo motor and seal the top of the reaction vessel while checking the O-ring at the bottom of the reaction vessel.

[0131] 7) The bioink can then be ejected into the vial by lowering the syringe piston using a servo motor controller, or the bioink can be ejected in a similar manner using an HMI system.

[0132] (Test results for performance, etc.) The evidence that the digestion process of the sterilized decellularized xenogeneic organ (dECM) was performed successfully is supported by the results of the sol-gel test and viscosity measurement, as shown in Figure 5.

[0133] As shown in Figures 5(a) and 5(b), after 30 minutes of gelation at 37°C, the ink changed to a gel state and did not drip to the bottom. When a large amount of bioink was produced (500 ml), each vial showed excellent uniform viscosity.

[0134] Although the present disclosure has been described through the preferred embodiments as described above, it will be readily understood by those skilled in the art that the present invention is not limited thereto and that various modifications and variations are possible without departing from the scope of the claims set forth below. [Explanation of symbols]

[0135] 100: Reaction vessel 200: Bioink liquefaction unit 300: Bio-ink ejection unit

Claims

1. a reaction vessel for reacting the decellularized xenogeneic organ (dECM) tissue with an ink solution to produce a bioink; a bioink liquefaction unit for stirring and chopping the decellularized xenogeneic organ tissue in the reaction vessel and liquefying it as bioink; a bio-ink discharge unit that is disposed at a set distance from the bio-ink liquefaction unit and that discharges the bio-ink that has been liquefied in the reaction vessel to the outside of the reaction vessel; A bioink manufacturing device comprising:

2. The bio-ink production device according to claim 1 , further comprising a moving unit for moving the reaction vessel in which the bio-ink has been completely liquefied from the bio-ink liquefaction unit to the bio-ink discharge unit.

3. The bioink manufacturing apparatus of claim 2, wherein the reaction vessel is formed in a cylindrical shape with an open top and a space inside capable of storing decellularized xenogeneic organ (dECM) tissue.

4. The bioink production device according to claim 3 , wherein the inner surface of the reaction vessel is coated with a material that is chemically resistant to the decellularized xenogeneic organ tissue and the ink solution.

5. The bio-ink production apparatus according to claim 3 , wherein the reaction vessel has a double jacket configuration consisting of an inner tube and an outer tube.

6. The bioink production apparatus according to claim 5, wherein the external pipe is provided with a cooling water inlet for injecting cooling water for temperature control into the space between the internal pipe and the external pipe, and a cooling water outlet for discharging the injected cooling water to the outside of the external pipe.

7. The bio-ink liquefaction unit a first cover disposed on top of the reaction vessel for covering an upper end of the reaction vessel; a rotation shaft that is vertically rotatably coupled to an upper end of the first cover and that protrudes a predetermined length below the first cover; an impeller connected to a lower end of the rotating shaft for stirring and chopping the decellularized xenogeneic organ tissue and ink solution injected into the reaction vessel; The bio-ink production apparatus according to claim 3 , comprising:

8. The bioink production device according to claim 7 , wherein the impeller is made of or coated with a material that is chemically resistant to decellularized xenogeneic organ tissue, ink-forming solutions, and the like.

9. The bio-ink producing apparatus according to claim 7 , wherein a driving motor is installed on an upper portion of the first cover, the driving motor being coupled to an upper end of the rotating shaft and causing the rotating shaft to rotate.

10. The bio-ink production apparatus according to claim 7 , wherein the first cover is provided with at least one solution inlet port for injecting an ink-forming solution.

11. The bio-ink production apparatus according to claim 7 , wherein a pH meter for measuring a hydrogen ion exponent (PH) in the reaction vessel is installed in the first cover.

12. The bioink production apparatus according to claim 7 , wherein an interior observation camera for observing the interior of the reaction vessel is installed in the first cover.

13. The bio-ink production apparatus according to claim 7 , wherein a first lifting unit for vertically lifting and lowering the first cover is coupled to the first cover.

14. The first lifting unit is a first connecting member connected to the first cover so as to be movable up and down; a first lifting operation unit connected to one end of the first connecting member for lifting and lowering the first connecting member; The bio-ink production apparatus according to claim 13 , comprising:

15. The moving unit is a support plate installed at a lower end of the reaction vessel to support the reaction vessel; At least one sliding tube is connected to a lower end of the support plate; a sliding rail installed between the base frame and the support plate in the length direction of the base frame, to which the sliding tube is movably coupled; The bio-ink production apparatus according to claim 2 , comprising:

16. The bio-ink production apparatus according to claim 15 , wherein the sliding tube is a cylindrical tube with an open interior.

17. The bio-ink production apparatus according to claim 16 , wherein a fixing lever is coupled to the sliding tube for stopping the movement of the sliding tube.

18. The bio-ink production apparatus according to claim 17 , wherein the sliding rail is arranged parallel to the base frame.

19. A first support frame and a second support frame are vertically installed on both ends of the base frame, The bio-ink production apparatus of claim 18 , wherein the sliding rail is connected between the first support frame and the second support frame.

20. The bio-ink ejection unit a second cover disposed on the top of the reaction vessel for covering the upper end of the reaction vessel; a syringe piston disposed vertically at a lower end of the second cover and adapted to move vertically up and down while sealing the inside of the reaction vessel; a bio-ink discharge pipe installed on one side of the reaction vessel for discharging the bio-ink that has been liquefied in the reaction vessel to the outside by the downward movement of the syringe piston; The bioink production device according to any one of claims 1 to 19, comprising:

21. The bio-ink manufacturing apparatus according to claim 20 , wherein a servo motor for moving the syringe piston up and down is coupled to an upper portion of the second cover.

22. The bio-ink production apparatus according to claim 21 , wherein a second lifting unit is coupled to the servo motor for vertically lifting the servo motor.

23. The second lifting unit is a second connecting member connected to the servo motor so as to be able to move up and down; a second lifting operation unit coupled to one end of the second connecting member for lifting and lowering the second connecting member; The bio-ink production apparatus according to claim 22, comprising:

24. The bio-ink production apparatus according to claim 20 , wherein the bio-ink discharge pipe is provided with a discharge pipe control valve for controlling opening and closing of the bio-ink discharge pipe.

25. The bio-ink production apparatus according to claim 24 , wherein the amount of bio-ink discharged from the discharge pipe control valve is controlled by controlling the operation of the servo motor by a controller connected to the servo motor.

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