Bio-ink manufacturing device

Abstract

The invention discloses a bio-ink manufacturing device. The bio-ink manufacturing apparatus according to the present invention comprises: a reaction container in which a decellularized heterogeneous organ tissue and an ink solution react; the bio-ink liquefying part is used for stirring and compacting the acellular xenogeneic organ tissues so as to liquefy the acellular xenogeneic organ tissues into bio-ink; and a bio-ink discharge unit for discharging the liquefied bio-ink to the outside of the reaction container.

Description

Technical Field

[0001] The present invention relates to a bioink manufacturing device. Background Art

[0002] With the global aging trend, the number of patients with chronic diseases has increased, and the technology of manufacturing artificial organs using 3D bioprinting has attracted much attention.

[0003] Bioink refers to an ink material used to output artificial organs through a 3D bioprinter, which is manufactured based on the extracellular matrix obtained by decellularizing xenogeneic organs.

[0004] Manufacturing artificial organs requires a large amount of bioink. However, since the technology for mass-producing bioink has not been developed, the supply-demand imbalance occurs, making it difficult to achieve large-scale expansion in research using bioink.

[0005] In addition, there is a lack of equipment capable of dissolving a large amount of decellularized xenogeneic organ (dECM) tissue during the solubilization process of bioink. Only a small amount (e.g., at the level of 8.4 ml) of ink is manufactured in a simple conical tube, resulting in non-uniform physical properties of bioink in different tubes, which becomes a problem in commercialization.

[0006] When manufacturing bioink according to consumer demand, the organ concentration of decellularized xenogeneic organs contained in the ink is high, and the viscosity of the bioink may be as high as hundreds of thousands of centipoise. However, no device has been proposed that can appropriately dispense the bioink after its manufacture. Summary of the Invention

[0007] Technical Problem

[0008] The present invention aims to provide a bioink manufacturing device that can liquefy a large amount of decellularized xenogeneic organ (dECM) tissue when manufacturing bioink of a general concentration (1% dECM) standard, and can also directly quantitatively discharge high-viscosity bioink from the same reaction vessel after liquefaction when manufacturing high-concentration bioink.

[0009] Technical Solution

[0010] The bioink manufacturing device according to an embodiment of the present invention may include: a reaction vessel for reacting a decellularized xenogeneic organ (dECM) tissue with an ink solution to prepare bioink; a bioink liquefaction unit for stirring and compressing the decellularized xenogeneic organ tissue in the reaction vessel to liquefy the decellularized xenogeneic organ tissue into bioink.

[0011] In addition, the bioink manufacturing device of the present invention may include: a bioink discharge unit arranged at a set distance from the bioink liquefaction unit and used for discharging the liquefied bioink in the reaction vessel to the outside of the reaction vessel.

[0012] The bioink manufacturing device may include a moving unit configured to move a reaction vessel that has completed liquefying the bioink from a bioink liquefying unit to a bioink discharging unit.

[0013] The reaction vessel may be formed in a cylindrical shape, with its upper part open and having a space inside capable of storing a decellularized xenogeneic organ (dECM) tissue.

[0014] The inner surface of the reaction vessel may be coated with a material that is chemically resistant to the decellularized xenogeneic organ tissue and the inkification solution.

[0015] The reaction vessel may have a double - jacketed form composed of an inner tube and an outer tube.

[0016] A cooling water inlet and a cooling water outlet may be respectively provided on the outer tube. The cooling water inlet is used to inject temperature - controlling cooling water into the space between the inner tube and the outer tube, and the cooling water outlet is used to discharge the injected cooling water to the outside of the outer tube.

[0017] The bioink liquefying unit may include: a first lid arranged above the reaction vessel and configured to cover the upper end of the reaction vessel; a rotating shaft rotatably coupled in the vertical direction to the upper end of the first lid and extending downward a set length below the first lid.

[0018] The bioink liquefying unit may include: an impeller coupled to the lower end of the rotating shaft and configured to stir and compact the decellularized xenogeneic organ tissue and the inkification solution injected into the reaction vessel.

[0019] The impeller may be made of or coated with a material that is chemically resistant to the decellularized xenogeneic organ tissue, the inkification solution, etc.

[0020] A drive motor may be installed above the first lid, and the drive motor is coupled to the upper end of the rotating shaft and configured to rotate the rotating shaft.

[0021] At least one solution injection port may be installed on the first lid for injecting the inkification solution.

[0022] A pH meter for measuring the hydrogen ion concentration index (pH) inside the reaction vessel may be installed on the first lid.

[0023] An internal observation camera for observing the inside of the reaction vessel may be installed on the first lid.

[0024] A first lifting unit for lifting and lowering the first lid in the vertical direction may be coupled to the first lid.

[0025] The first lifting part may include: a first coupling member that is liftably coupled to the first lid; and a first lifting operation part that is coupled to one end of the first coupling member and is used to lift the first coupling member.

[0026] The moving part may include: a support plate that is installed at the lower end of the reaction vessel and is used to support the reaction vessel; at least one sliding tube that is coupled to the lower end of the support plate; and a sliding guide rail that is installed between the base frame and the support plate along the length direction of the base frame, and the sliding tube is movably coupled to the sliding guide rail.

[0027] The sliding tube may be formed as a cylindrical tube with a hollow interior.

[0028] A fixing rod for stopping the movement of the sliding tube may be coupled to the sliding tube.

[0029] The sliding guide rail may be arranged parallel to the base frame.

[0030] A first support frame and a second support frame may be installed vertically at both ends of the base frame, and the sliding guide rail may be connected between the first support frame and the second support frame.

[0031] The bio-ink discharging part may include: a second lid that is arranged above the reaction vessel and is used to cover the upper end of the reaction vessel; a syringe piston that is arranged vertically at the lower end of the second lid and lifts and lowers vertically while sealing the interior of the reaction vessel.

[0032] In addition, the bio-ink discharging part may include: a bio-ink discharge pipe that is installed on one side of the reaction vessel and discharges the bio-ink that has been liquefied in the reaction vessel to the outside through the lowering of the syringe piston.

[0033] A servo motor for lifting and lowering the syringe piston may be coupled to the upper part of the second lid.

[0034] A second lifting part for lifting and lowering the servo motor in the vertical direction may be coupled to the servo motor.

[0035] The second lifting part may include: a second coupling member that is liftably coupled to the servo motor; and a second lifting operation part that is coupled to one end of the second coupling member and is used to lift the second coupling member.

[0036] A discharge pipe control valve for controlling the opening and closing of the bio-ink discharge pipe may be installed on the bio-ink discharge pipe.

[0037] The operation of the servo motor may be controlled through a controller connected to the servo motor to control the discharge amount of the bio-ink discharged from the discharge pipe control valve.

[0038] Advantages of the Invention

[0039] According to an implementation example of the present invention, when manufacturing a bioink with a general concentration (1% dECM) standard, a large amount of decellularized xenogeneic organ (dECM) tissue can be liquefied, and when manufacturing a high-concentration bioink, a highly viscous bioink can also be quantitatively discharged directly from the same reaction vessel after liquefaction.

[0040] That is, since the reaction vessel that has completed the liquefaction of the bioink is moved to the bioink discharge part by the moving part and the bioink is immediately discharged from the bioink discharge part, losses caused by the movement of the bioink can be prevented in advance.

[0041] A large amount of decellularized xenogeneic organ (dECM) tissue can be liquefied efficiently and discharged efficiently. In particular, uniformity during the physical property evaluation process between vials can be ensured when the bioink is liquefied, so it has a significant contribution effect on the commercialization and industrialization of the bioink. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 It is a schematic structural diagram of a bioink manufacturing device according to an embodiment of the present invention.

[0043] Figure 2 It is a schematic partial side view of the bioink discharge part of a bioink manufacturing device according to an embodiment of the present invention.

[0044] Figure 3 It is a photograph for explaining the process of putting sterilized porcine placenta decellularized xenogeneic organ powder and a liquefying solution into a reaction vessel using a bioink manufacturing device according to an embodiment of the present invention.

[0045] Figure 4 It is a photograph for monitoring the liquefaction process of sterilized porcine placenta decellularized xenogeneic organ and monitoring by liquefaction time using a bioink manufacturing device according to an embodiment of the present invention, where T represents time.

[0046] Figure 5 It is a sol-gel test photograph of the dissolution process of sterilized porcine placenta decellularized xenogeneic organ manufactured using a bioink manufacturing device according to an embodiment of the present invention, where (a) is a photograph of the dissolved state, (b) is a photograph of the gel state, and (c) is a chart showing the viscosity measurement results with respect to the shear rate. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0047] Hereinafter, embodiments of the present invention will be described with reference to the drawings so that those with ordinary knowledge in the technical field to which the present invention belongs can easily implement the present invention. As those with ordinary knowledge in the technical field to which the present invention belongs can understand, without departing from the concept and scope of the present invention, the following embodiments can be deformed into various forms. For the same or similar parts, the same reference numerals are used as much as possible in the drawings.

[0048] The technical terms used hereinafter are only used to refer to specific embodiments and are not intended to limit the present invention. Unless the contrary is clearly stated in the sentence, the singular form used herein also includes the plural form. The meaning of "including" used in the specification embodies specific features, regions, integers, steps, operations, elements, and / or components, but does not exclude the existence or addition of other specific features, regions, integers, steps, operations, elements, components, and / or groups.

[0049] All terms, including technical terms and scientific terms, used hereinafter have the same meaning as those commonly understood by a person of ordinary skill in the technical field to which the present invention pertains. Terms defined in a dictionary are further interpreted to have a meaning consistent with the relevant technical literature and the currently disclosed content, and should not be interpreted as ideal or overly formal meanings unless otherwise defined.

[0050] Figure 1 is a schematic structural diagram of a bioink manufacturing device according to an embodiment of the present invention, Figure 2 is a schematic partial side view of a bioink discharging unit of a bioink manufacturing device according to an embodiment of the present invention.

[0051] See Figure 1 and Figure 2 A bioink manufacturing device according to an embodiment of the present invention may include a reaction vessel 100, a bioink liquefaction unit 200, a moving unit 300, and a bioink discharging unit 400.

[0052] The reaction vessel 100 can be used for a decellularized xenogeneic organ (dECM) tissue to react with an inking solution to prepare a bioink.

[0053] In addition, the bioink liquefaction unit 200 can stir and compact the decellularized xenogeneic organ tissue stored in the reaction vessel 100, thereby liquefying the decellularized xenogeneic organ tissue into a bioink.

[0054] The bioink discharging unit 400 can be arranged at a set distance from the bioink liquefaction unit and can discharge the liquefied bioink in the reaction vessel 100 to the outside of the reaction vessel 100.

[0055] In addition, the moving unit 300 can move the reaction vessel 100 in which bioink liquefaction is completed along a first direction ( Figure 1 the X direction in

[0056] The reaction vessel 100 can be movably coupled to the moving unit 300 and can be moved along the first direction ( Figure 1in the X direction) moves from the bioink liquefaction unit 200 to the bioink ejection unit 400.

[0057] The reaction vessel 100 can be formed in a cylindrical shape or the like. The upper part of the reaction vessel 100 is open so that a decellularized xenogeneic organ (dECM) tissue can be introduced, and it has a space inside that can store the decellularized xenogeneic organ (dECM) tissue.

[0058] The inner surface of the reaction vessel 100 can be coated with a material such as polytetrafluoroethylene (Teflon) that has chemical resistance to the decellularized xenogeneic organ tissue and the ink solution.

[0059] In addition, the reaction vessel 100 can have a double jacket structure composed of an inner tube 101 and an outer tube 103 to control the temperature of the decellularized xenogeneic organ tissue liquefaction process.

[0060] A cooling water inlet 105 and a cooling water outlet 106 can be respectively provided on the outer tube 103. The cooling water inlet 105 is used to inject temperature-controlled cooling water into the space between the inner tube 101 and the outer tube 103, and the cooling water outlet 106 is used to discharge the injected cooling water to the outside of the outer tube 103.

[0061] The cooling water inlet 105 can be connected to the cooling device 107 through a connecting pipe 108.

[0062] A heat insulation material 110 can be installed outside the reaction vessel 100. The heat insulation material 110 surrounds the reaction vessel 100 and insulates the reaction vessel 100.

[0063] In addition, the bioink liquefaction unit 200 can include a first lid 210, a rotating shaft 220, and an impeller 230.

[0064] The first lid 210 can be arranged above the reaction vessel 100 and is used to cover the upper end of the reaction vessel 100.

[0065] In addition, the rotating shaft 220 can be rotatably coupled to the upper end of the first lid 210 along the vertical direction ( Figure 1 in the Y direction) and extends downward by a set length below the first lid 210.

[0066] The impeller 230 can be coupled to the lower end of the rotating shaft 220 and is used to stir and compact the decellularized xenogeneic organ tissue and the ink solution injected into the reaction vessel 100.

[0067] The impeller 230 can be made of a material that has chemical resistance to the decellularized xenogeneic organ tissue and the ink solution or is coated with a material such as polytetrafluoroethylene (Teflon).

[0068] The shape of the impeller 230 can be any shape as long as it can easily generate turbulence inside the reaction vessel 100 when rotating around the rotating shaft 220 and can rub against the inner wall of the reaction vessel 100 to achieve the compaction function.

[0069] In addition, a plurality of impellers 230 can be installed on a connection frame (not shown) at set intervals, and the connection frame is used to rotatably connect the impellers 230 to the rotating shaft 220.

[0070] Therefore, when the rotating shaft 220 rotates, the impeller 230 can generate a clearance due to centrifugal force, and thus move along the direction towards the inner surface of the reaction vessel 100 or towards the center of the reaction vessel 100. Therefore, the function of being able to rub against the inner surface of the reaction vessel 100 can be achieved, so as to efficiently achieve the compaction function of the xenogeneic organ tissue.

[0071] In addition, a drive motor 240 can be installed above the first lid 210. The drive motor 240 is coupled to the upper end of the rotating shaft 220 and is used to rotate the rotating shaft 220 at a set speed.

[0072] The drive motor 240 can control the rotation speed of the rotating shaft 220, for example, within the range of 0 to 500 rpm.

[0073] The drive motor 240 can be composed of a magnetically controlled motor or the like so that the rotating shaft 220 can be easily rotated.

[0074] At least one solution injection port 211 can be installed on the first lid 210 for injecting the ink solution required for the inkification of the decellularized xenogeneic organ tissue.

[0075] In addition, a pH meter 213 for measuring the hydrogen ion concentration index (pH) inside the reaction vessel 100 can be installed on the first lid 210.

[0076] An internal observation camera 215 can be installed on the first lid 210. The internal observation camera 215 is used to observe the inside of the reaction vessel 100 so as to confirm the liquefaction process of the decellularized xenogeneic organ tissue inside the reaction vessel 100, that is, whether the decellularized xenogeneic organ tissue is dissolved or not.

[0077] In addition, a first lifting part 250 can be coupled to the first lid 210. The first lifting part 250 is used to lift the first lid 210 in the vertical direction ( Figure 1 the Y direction in) so that the first lid 210 can be coupled to or separated from the reaction vessel 100.

[0078] The first lifting part 250 can include a first coupling member 251 and a first lifting operation part 253.

[0079] The first coupling member 251 can be coupled to the first lid 210 so as to be liftable integrally.

[0080] The first lifting operation unit 253 can be coupled to one end of the first coupling member 251 and is arranged to be spaced apart from the reaction vessel 100. The first lifting operation unit 253 can be used to lift the first coupling member 251.

[0081] The first lifting operation unit 253 can be controlled manually (as Figure 1 shown) or automatically (not shown).

[0082] When the first lifting operation unit 253 is a manual type controlled manually, a first operation handle 254 for manually operating it can be coupled to the upper end of the first lifting operation unit 253.

[0083] That is, the first lifting operation unit 253 can be lifted and lowered along the first support shaft 255 by rotating the first operation handle 254.

[0084] When the first lifting operation unit 253 is an automatic type controlled automatically, the first lifting operation unit 253 can be configured by a motor or a cylinder (not shown), etc.

[0085] In addition, the first support shaft 255 can be supported by a first vertical frame 257 and a first horizontal frame 258. Among them, the first vertical frame 257 is arranged on the base frame 10 along the vertical direction ( Figure 1 Y direction in it) and is spaced apart from the first support shaft 255 by a set interval. The first horizontal frame 258 is coupled to the upper end of the first vertical frame 257 along the direction perpendicular to the first vertical frame 257 ( Figure 1 X direction in it).

[0086] The base frame 10 can be installed on the installation surface or the ground along the length direction ( Figure 1 X direction in it).

[0087] In addition, the moving unit 300 can include a support plate 310, a sliding tube 320, and a sliding guide rail 330.

[0088] The support plate 310 can be installed at the lower end of the reaction vessel 100 and is used to support the reaction vessel 100.

[0089] In addition, at least one sliding tube 320 can be coupled to the lower end of the support plate 310.

[0090] The sliding guide rail 330 can be installed between the base frame 10 and the support plate 310 along the length direction of the base frame 10. The sliding tube 320 can be movably coupled to the sliding guide rail 330.

[0091] The sliding tube 320 can be constructed of a hollow cylindrical tube or the like so that it can easily move along the sliding guide 330.

[0092] At least one fixing rod 321 can be coupled to the sliding tube 320 to stop the movement of the sliding tube 320 along the sliding guide 330.

[0093] The sliding guide 330 can be arranged parallel to the base frame 10 so that the reaction vessel 100 can move easily.

[0094] On both end portions of the base frame 10, a first support frame 301 and a second support frame 302 can be installed in the vertical direction ( Figure 1 the Y direction in ), and the sliding guide 330 can be connected between the first support frame 301 and the second support frame 302.

[0095] In addition, the bioink ejection unit 400 can include a second cover 410, a syringe piston 420, a servo motor 430, and a bioink discharge tube 440.

[0096] The second cover 410 can be arranged above the reaction vessel 100 to cover the upper end portion of the reaction vessel 100.

[0097] In addition, the syringe piston 420 can be arranged at the lower end portion of the second cover 410 in the vertical direction ( Figure 1 the Y direction in ) and can move up and down in the vertical direction while sealing the inside of the reaction vessel 100.

[0098] The servo motor 430 can be coupled to the upper part of the second cover 410 to move the syringe piston 420 up and down.

[0099] In addition, the bioink discharge tube 440 can be installed on one side of the reaction vessel 100, and the bioink that has been liquefied in the reaction vessel 100 can be discharged into a vial (not shown) or the like by the lowering of the syringe piston 420.

[0100] A discharge tube control valve 441 for controlling the opening and closing of the bioink discharge tube 440 can be installed on the bioink discharge tube 440.

[0101] The discharge amount of the bioink discharged from the discharge tube control valve 441 can be achieved by the controller (not shown) controlling the operation of the servo motor 430, which is connected to the servo motor 430 and controls the operation of the servo motor 430.

[0102] The controller (not shown) can control the servo motor 430 to efficiently discharge the bioink even when the viscosity of the bioink reaches a level of hundreds of thousands of cP (centipoise).

[0103] In addition, the servo motor 430 may be combined with a second lifting unit 450, and the second lifting unit 450 is used to move the servo motor 430 along the vertical direction ( Figure 1 The syringe piston 420 is raised or lowered (in the Y direction) so that the syringe piston 420 can be inserted into or separated from the reaction container 100.

[0104] The second lifting portion 450 may include a second combining member 451 and a second lifting operation portion 453 .

[0105] The second combining member 451 may be combined with the servo motor 430 so as to be able to be lifted and lowered integrally.

[0106] In addition, the second elevating operation part 453 may be coupled to one end of the second coupling member 451 and arranged to be spaced apart from the reaction container 100 , and may elevate the second coupling member 451 .

[0107] The second lifting operation unit 453 can be manually operated (such as Figure 1 shown) or by automatic means (not shown).

[0108] When the second lifting operation part 453 is a manual type controlled manually, the upper end of the first lifting operation part 253 may be combined with a second operation handle 454 for manually operating the first lifting operation part 253 .

[0109] That is, the second lifting operation part 453 can be lifted and lowered along the second support shaft 455 by rotating the second operation handle 454 .

[0110] When the second lifting operation part 453 is an automatic type controlled in an automatic manner, the second lifting operation part 453 may be constructed by a motor or a cylinder (not shown) or the like.

[0111] In addition, the second support shaft 255 can be supported by a second vertical frame 457 and a second horizontal frame 458, wherein the second vertical frame 457 is arranged along the vertical direction ( Figure 1 The second horizontal frame 458 is arranged on the base frame 10 and is separated from the second support shaft 255 by a set interval. The second horizontal frame 458 is arranged along a direction perpendicular to the second vertical frame 457 ( Figure 1 In the X direction) it is connected to the upper end of the second vertical frame 457.

[0112] Below, refer to Figure 1 and Figure 2 , the operation of the bio-ink manufacturing device according to one embodiment of the present invention is described.

[0113] When liquefying the bio-ink to produce the bio-ink, the reaction container 100 is first placed in the center of the slide rail 330 , and then the decellularized xenogeneic organ (dECM) tissue is introduced into the lower end of the reaction container 100 .

[0114] Then, the reaction vessel 100 is moved by the moving unit 300 to the left side of the central portion of the sliding guide rail 330 ( Figure 1 the left side in

[0115] i.e., the bioink liquefaction unit 200), and the fixing rod 321 is locked to stop the movement of the sliding tube 320.

[0116] In this state, the first coupling member 251 is lowered in the vertical direction by the first lifting operation unit 253 of the first lifting unit 250, so that the first lid 210 is lowered to cover the upper end portion of the reaction vessel 100 for sealing.

[0117] Then, through the solution injection port 211 provided on the first lid 210, an ink solution required for inkification of the decellularized xenogeneic organ tissue is injected into the interior of the reaction vessel 100.

[0118] At this time, after controlling the temperature inside the reaction vessel 100 to the set temperature, the drive motor 240 is started to rotate the rotary shaft 220 at a set speed.

[0119] As the rotary shaft 220 rotates, the impeller 230 inserted into the interior of the reaction vessel 100 rotates, thereby stirring and compacting the decellularized xenogeneic organ tissue and the ink solution injected into the reaction vessel 100.

[0120] Thus, through the reaction of the decellularized xenogeneic organ tissue and the ink solution, it can be liquefied into bioink.

[0121] In addition, whether the decellularized xenogeneic organ tissue inside the reaction vessel 100 is dissolved can be confirmed through the internal observation camera 215 located above the reaction vessel 100 to observe the bioink liquefaction process.

[0122] On the other hand, since the reaction vessel 100 has a form such as a double-layer sleeve composed of an inner tube 101 and an outer tube 103, the internal control of the reaction vessel 100 can be set to the temperature required for the liquefaction process of the decellularized xenogeneic organ tissue.

[0123] After the bioink liquefaction is completed in the reaction vessel 100, the drive of the drive motor 240 is stopped to stop the rotation of the rotary shaft 220 and the impeller 230. Subsequently, the first coupling member 251 is lifted in the vertical direction by the first lifting operation unit 253, so that the first lid 210 rises and separates upward from the upper part of the reaction vessel 100.

[0124] That is, after unlocking the locking engagement of the fixing rod 321 to release the stopped state of the sliding tube 320, the reaction vessel 100 is moved from the bioink liquefaction unit 200 to the right side of the sliding guide 330 (i.e., the bioink ejection unit 400) by the moving unit 300, and then the fixing rod 321 is locked to stop the movement of the sliding tube 320.

[0125] In this state, the second coupling member 451 is lowered in the vertical direction by the second lifting operation unit 453 of the second lifting unit 450, so that the second lid 410 is lowered, and thus the lower end of the servo motor 430 covers the upper end of the reaction vessel 100 for sealing.

[0126] Then, if the servo motor 430 is operated to lower the syringe piston 420, the liquefied bioink in the reaction vessel 100 is discharged from the inside of the reaction vessel 100 through the bioink discharge pipe 440 into a vial or the like located outside the reaction vessel 100 due to the descent of the syringe piston 420.

[0127] At this time, the discharge pipe control valve 441 is controlled to be in an open state, and the discharge amount of the bioink discharged from the discharge pipe control valve 441 can be achieved by the controller (not shown) controlling the operation of the servo motor 430, and the controller is connected to the servo motor 430 and controls the operation of the servo motor 430.

[0128] Therefore, a large amount of decellularized xenogeneic organ (dECM) tissue can be efficiently liquefied and efficiently ejected, and particularly, the uniformity during the physical property evaluation between vials can be ensured when the bioink is liquefied.

[0129] In addition, after the bioink in the reaction vessel 100 is ejected, the second coupling member 451 is lifted in the vertical direction by the second lifting operation unit 453 of the second lifting unit 450, so that the second lid 410 rises and is separated from the upper part of the reaction vessel 100 by a set distance.

[0130] Then, after unlocking the locking engagement of the fixing rod 321 to release the stopped state of the sliding tube 320, the reaction vessel 100 can be moved from the bioink ejection unit 400 to the central part of the sliding guide 330 by the moving unit 300, and the above-described bioink liquefaction process, reaction vessel movement process, and bioink ejection process are repeated.

[0131] (Example)

[0132] The liquefaction and ejection process of the sterilized porcine placenta decellularized xenogeneic organ (dECM) bioink will be described below.

[0133] 1) As Figure 3As shown, 5 g of sterilized porcine placental acellular xenogeneic organ (dECM) powder, 420 ml of 0.5 M acetic acid, and 0.5 g of pepsin powder are put into the lower end of the reaction vessel. This is the manufacturing process for producing 1% concentration of acellular xenogeneic organ (dECM) bioink.

[0134] 2) Then, move the lower end of the reaction vessel to the far left (i.e., the bioink liquefaction part side), and use the manipulator of the first lifting operation part to lower the first lid located at the upper end of the reaction vessel vertically along the vertical direction so that it covers the upper end of the reaction vessel for sealing (see Figure 1 ). At this time, confirm whether the O-ring at the lower end of the reaction vessel is in the correct position.

[0135] 3) The temperature of the double-layer sleeve reaction vessel can be regulated by setting the temperature of the refrigerated / heating circulator, which is set here to the activation temperature of pepsin, for example, 37°C. The rotation speed of the impeller inside the reaction vessel is adjusted to 350 rpm.

[0136] 4) As Figure 4 shown, for the bioink liquefaction process, the dissolution and liquefaction process of the acellular xenogeneic organ (dECM) tissue inside the reaction vessel can be monitored by using the internal observation camera installed at the upper end of the liquefaction reaction vessel. In this experiment, it was confirmed that the liquefaction was completed in about 8.5 hours.

[0137] 5) For the liquefied bioink, use the manipulator on the left side in Figure 1 to lift the first lid located at the upper end of the reaction vessel vertically along the vertical direction, and move the lower end of the reaction vessel to the far right (i.e., the bioink ejection part side) of the sliding rail of the moving part. Then, lock the moving part with the fixing rod. Figure 1 In

[0138] 6) Use the manipulator on the right side in Figure 1 to lower the servo motor vertically along the vertical direction, and seal the upper end of the reaction vessel while confirming the O-ring at the lower end of the reaction vessel.

[0139] 7) Then, for the bioink, the syringe piston can be lowered by using the servo motor controller to eject the bioink into the vial, or the bioink can be ejected in the same way by using the HMI system.

[0140] (Test results of performance, etc.)

[0141] The basis for the excellent performance of the digestion process of sterilized decellularized xenogeneic organs (dECM) can be supported by Figure 5 the Sol-Gel test and Viscosity measurement results shown below.

[0142] As Figure 5 shown in (a) of Figure 5 and (b) of

[0143] After gelation at 37°C for 30 minutes, it can be confirmed that the ink has successfully transformed into a gel state and there is no dripping phenomenon towards the lower end. Moreover, a large amount of bioink at the 500 ml level is generated, so that each vial exhibits excellent and uniform viscosity.

[0144] Description of reference numerals

[0145] 100: Reaction vessel

[0146] 200: Bioink liquefaction unit

[0147] 300: Bioink ejection unit

Claims

1. A bioink manufacturing device, comprising: A reaction vessel for reacting a decellularized xenogeneic organ dECM tissue with an inking solution to prepare a bioink; A bioink liquefaction unit for stirring and compressing the decellularized xenogeneic organ tissue in the reaction vessel, thereby liquefying the decellularized xenogeneic organ tissue into a bioink; And A bioink discharging unit arranged at a set distance from the bioink liquefaction unit and for discharging the bioink that has been liquefied in the reaction vessel to the outside of the reaction vessel.

2. The bioink manufacturing device according to claim 1, comprising: A moving unit for moving the reaction vessel in which bioink liquefaction is completed from the bioink liquefaction unit to the bioink discharging unit.

3. The bioink manufacturing device according to claim 2, wherein The reaction vessel is formed in a cylindrical shape, the upper part of the reaction vessel is open, and the inside has a space capable of storing the decellularized xenogeneic organ dECM tissue.

4. The bioink manufacturing 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 inking solution.

5. The bioink manufacturing device according to claim 3, wherein The reaction vessel has a double-layer jacket shape composed of an inner tube and an outer tube.

6. The bioink manufacturing device according to claim 5, wherein A cooling water inlet and a cooling water outlet are respectively provided on the outer tube. The cooling water inlet is used to inject temperature control cooling water into the space between the inner tube and the outer tube, and the cooling water outlet is used to discharge the injected cooling water to the outside of the outer tube.

7. The bioink manufacturing device according to claim 3, wherein The bioink liquefaction unit includes: A first lid arranged above the reaction vessel and for covering the upper end of the reaction vessel; A rotating shaft rotatably coupled in the vertical direction to the upper end of the first lid and extending a set length downward from the first lid; and An impeller coupled to the lower end of the rotating shaft and for stirring and compressing the decellularized xenogeneic organ tissue and the inking solution injected into the reaction vessel.

8. The bioink manufacturing device according to claim 7, wherein The impeller is made of or coated with a material that is chemically resistant to the decellularized xenogeneic organ tissue, the inking solution, etc.

9. The bioink manufacturing device according to claim 7, wherein A driving motor is installed above the first lid, and the driving motor is coupled to the upper end of the rotating shaft and for rotating the rotating shaft.

10. The bioink manufacturing device according to claim 7, wherein At least one solution injection port for injecting the inking solution is installed on the first lid.

11. The bioink manufacturing device according to claim 7, wherein A pH meter for measuring the hydrogen ion concentration index pH in the reaction vessel is installed on the first lid.

12. The bioink manufacturing device according to claim 7, wherein An internal observation camera for observing the inside of the reaction vessel is installed on the first lid.

13. The bio-ink manufacturing device according to claim 7, wherein, A first lifting part for lifting the first lid in the vertical direction is coupled to the first lid.

14. The bio-ink manufacturing device according to claim 13, wherein, The first lifting part includes: A first coupling member that is coupled to the first lid so as to be able to move up and down; and A first lifting operation part that is coupled to one end of the first coupling member and is used to lift the first coupling member.

15. The bio-ink manufacturing device according to claim 2, wherein, The moving part includes: A support plate that is installed at the lower end of the reaction vessel and is used to support the reaction vessel; At least one sliding tube that is coupled to the lower end of the support plate; and A sliding guide rail that is installed between the base frame and the support plate along the length direction of the base frame, and the sliding tube is movably coupled to the sliding guide rail.

16. The bio-ink manufacturing device according to claim 15, wherein, The sliding tube is formed as a cylindrical tube with a hollow interior.

17. The bio-ink manufacturing device according to claim 16, wherein, A fixing rod for stopping the movement of the sliding tube is coupled to the sliding tube.

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

19. The bio-ink manufacturing device according to claim 18, wherein, A first support frame and a second support frame are installed vertically at both ends of the base frame, The sliding guide rail is connected between the first support frame and the second support frame.

20. The bio-ink manufacturing device according to any one of claims 1 to 19, wherein, The bio-ink discharging part includes: A second lid that is arranged above the reaction vessel and is used to cover the upper end of the reaction vessel; A syringe piston that is arranged vertically at the lower end of the second lid and moves up and down vertically while sealing the interior of the reaction vessel; and A bio-ink discharge pipe that is installed on one side of the reaction vessel, and discharges the liquefied bio-ink in the reaction vessel to the outside through the downward movement of the syringe piston.

21. The bio-ink manufacturing device according to claim 20, wherein, A servo motor for lifting the syringe piston is coupled to the upper part of the second lid.

22. The bio-ink manufacturing device according to claim 21, wherein, A second lifting part for lifting the servo motor in the vertical direction is coupled to the servo motor.

23. The bio-ink manufacturing device according to claim 22, wherein, The second lifting part includes: A second coupling member that is coupled to the servo motor so as to be able to move up and down; and A second lifting operation part that is coupled to one end of the second coupling member and is used to lift the second coupling member.

24. The bio-ink manufacturing device according to claim 20, wherein, A discharge pipe control valve for controlling the opening and closing of the bio-ink discharge pipe is installed on the bio-ink discharge pipe.

25. The bioink manufacturing device according to claim 24, wherein, the discharge amount of the bioink discharged from the discharge pipe control valve is controlled by controlling the operation of the servo motor through a controller connected to the servo motor.

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