Artificial tubular tissue perfusion culture device

By designing a perfusion culture device for artificial tubular tissue, the problem that artificial tubular tissue is difficult to achieve uniform mechanical stimulation and culture fluid distribution in the prior art is solved, and uniform cell perfusion culture of artificial tubular tissue under three-dimensional dynamic conditions is achieved, which improves the effects of cell proliferation and extracellular matrix synthesis.

CN119570620APending Publication Date: 2025-03-07稳健医疗(武汉)有限公司
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Patent Information

Application Number
CN202411724298.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-28
Publication Date
2025-03-07

AI Technical Summary

Technical Problem

The prior art lacks perfusion culture devices specifically for artificial tubular tissue, making it difficult for artificial tubular tissue to achieve uniform mechanical stimulation and culture medium distribution during cell proliferation and extracellular matrix synthesis.

Method used

An artificial tubular tissue perfusion culture device is designed, including a shell and tube, a liner and an end cap. The liner is a hollow structure, and a tubular interface is provided at both ends. The artificial tubular tissue is placed in the liner and the two ends are connected to the third interface. The device passes in and discharges the culture medium through the first and second interfaces, ensuring that the inner and outer walls of the artificial tubular tissue are uniformly immersed in the flowing culture medium.

Benefits of technology

The uniform cell perfusion culture of artificial tubular tissue under three-dimensional dynamic conditions was achieved, which promoted cell proliferation and the synthesis of extracellular matrix, and improved the mechanical strength of artificial tubular tissue and the applicability of allogeneic applications.

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Abstract

The invention discloses an artificial tubular tissue perfusion culture device which comprises a shell tube, a lining and two end covers, two first connectors are arranged on the outer wall of the shell tube, second connectors are arranged in the middles of the outer sides of the end covers, the lining is of a hollow structure, through tubular connectors are arranged at the two ends of the lining, and the ends, located outside the lining, of the tubular connectors are insertion openings. The tubular connector is located at one end of the inner portion of the lining and provided with third connectors, the artificial tubular tissue is arranged in the lining, one end of the artificial tubular tissue is inserted into the two third connectors, the lining is arranged in the shell tube, the two end covers are installed at the two ends of the shell tube, the two inserting connectors are inserted into the two second connectors respectively, and one of the first connector and the second connector is used for introducing a culture solution. And the other first interface and the other second interface are used for discharging the culture solution, so that the proliferation of cells on the inner wall and the outer wall of the artificial tubular tissue in a dynamic environment is facilitated.
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Description

Technical Field

[0001] The invention belongs to the technical field of artificial tubular tissue preparation, and in particular relates to an artificial tubular tissue perfusion culture device. Background Art

[0002] Artificial tubular tissues include artificial blood vessels, artificial nerve tubes and artificial larynx. Taking artificial blood vessels as an example, it is necessary to plant seed cells such as vascular smooth muscle cells, endothelial cells, stem cells, etc. in the prepared tissue engineering scaffolds, and culture them in vitro through a bioreactor (the purpose of culture is to allow the cells to secrete a large amount of extracellular matrix on the scaffold) to obtain tissue engineering blood vessels, which are then implanted into the body to replace the originally damaged or blocked natural blood vessels.

[0003] Currently, Laura E. Nicholson's (Humacyte Inc., an American regenerative medical technology company) research group is implanting vascular smooth muscle cells onto polyglycolic acid scaffold materials, and then placing them in a special bioreactor for flow culture for 8-10 weeks. During this period, simulated blood pressure is given for pulsation stimulation. The bioreactor gives the vascular scaffold mechanical stimulation that simulates natural blood vessels, prompting the vascular smooth muscle cells to proliferate in large quantities and synthesize extracellular matrix. As the culture time goes by, the polyglycolic acid scaffold gradually degrades, while the vascular smooth muscle cells and the extracellular matrix they secrete continue to accumulate and gain sufficient mechanical strength. After that, decellularization treatment can be performed to obtain artificial blood vessels that can be used in allogeneic applications. However, there is currently no device on the market specifically for perfusion culture of artificial tubular tissues. Summary of the invention

[0004] In order to solve the above technical problems, one of the objectives of the present invention is to provide an artificial tubular tissue perfusion culture device which has a simple structure and is easy to assemble and can realize cell perfusion culture of artificial tubular tissue under three-dimensional dynamic conditions.

[0005] In order to achieve the above-mentioned purpose, the technical scheme of the present invention is as follows: An artificial tubular tissue perfusion culture device comprises a shell tube, an inner liner and two end caps, wherein two first interfaces are arranged on the outer wall of the shell tube, a second interface is arranged in the middle part of the outer side of the end cap, the inner liner is a hollow structure, and both ends thereof are provided with penetrating tubular interfaces, the end of the tubular interface located outside the inner liner is a plug interface, the end of the tubular interface located inside the inner liner is a third interface, the artificial tubular tissue is placed in the inner liner, and one end of the artificial tubular tissue is plugged into the two third interfaces, the inner liner is placed in the shell tube, the two end caps are installed at the two ends of the shell tube, and the two plug interfaces are respectively plugged into the two second interfaces, one of the first interface and the second interface is used to pass the culture solution, and the other of the first interface and the second interface is used to discharge the culture solution.

[0006] The beneficial effect of the above technical solution is that: after the artificial tubular tissue is placed inside the lining and its two ends are docked with the two third interfaces, the entire artificial tubular tissue perfusion culture device can be assembled, and the culture solution is introduced into any one of the first interfaces and any one of the second interfaces, while the culture solution is discharged from the remaining first interfaces and the remaining second interfaces, so that it can be ensured that the inner wall and the outer wall of the artificial tubular tissue are fully immersed in the culture solution, and the culture solution is in a flow state, which is conducive to a more uniform distribution of cells on the inner wall and the outer wall of the artificial tubular tissue during proliferation.

[0007] In the above technical solution, the two first interfaces are arranged at two ends of the outer wall of the shell tube.

[0008] The beneficial effect of the above technical solution is that the culture fluid in the outer space of the artificial tubular tissue can be distributed more evenly.

[0009] The end cover in the above technical solution is a groove-shaped cover with an internal thread on its inner groove wall. Both ends of the shell tube are provided with external threads, and the end cover is threadedly screwed on the corresponding ends of the shell tube.

[0010] The beneficial effect of the above technical solution is that the two end covers are threadedly mounted on the two ends of the shell tube, thereby making it easier to disassemble and assemble the end covers and the shell tube.

[0011] The lining described in the above technical solution includes two support plates and multiple support strips. The two support plates are parallel to each other and spaced apart. The multiple support strips are circumferentially spaced apart at the edge between the two support plates. The two ends of each support strip are respectively connected to the edges of the two support plates. The two tubular interfaces are respectively arranged in the middle of the two support plates.

[0012] The beneficial effect of the above technical solution is that its structure is simple, so that the artificial tubular tissue can be butt-jointed at two third interfaces between two adjacent support bars on the liner.

[0013] The support bar in the above technical solution is vertically connected to the two support plates.

[0014] The beneficial effects of the above technical solution are: its structure is simple and its appearance is good.

[0015] The support bars described in the above technical solution are provided with - roots.

[0016] The beneficial effect of the above technical solution is that the structural strength of the entire lining is increased.

[0017] In the above technical solution, a limit strip is convexly provided on the inner wall of the shell tube along the axial direction, and the two support plates are recessed with mutually aligned limit notches for the limit strip to be inserted, and the limit strip is inserted into the corresponding two limit notches to limit the rotation of the liner in the shell tube.

[0018] The beneficial effect of the above technical solution is that when the liner is installed in the shell tube, the liner can be prevented from rotating in the shell tube by inserting the limit strip into the limit notch.

[0019] The above technical solution also includes a tubular adapter plugged into the third interface, and the two ends of the artificial tubular tissue are plugged into the two adapters.

[0020] The beneficial effect of the above technical solution is that adapters of different specifications can be plugged into the third interface to meet the docking requirements of artificial tubular tissues with different pore diameters, thereby making the entire artificial tubular tissue perfusion culture device more applicable.

[0021] In the above technical solution, both the end of the third interface and the end of the adapter for the artificial tubular tissue to be plugged in are provided with external threads.

[0022] The beneficial effect of the above technical solution is that: in this way, the friction resistance of the artificial tubular tissue is large when it is connected with the third interface or the adapter, so that it is not easy to get loose.

[0023] The outer wall of the plug interface in the above technical solution is a frosted surface.

[0024] The beneficial effect of the above technical solution is that: in this way, the insertion interface is inside the second interface, and the two fitting surfaces can have better sealing performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a schematic structural diagram of the artificial tubular tissue perfusion culture device according to an embodiment of the present invention;

[0026] Figure 2 for Figure 1 Sectional view at AA in the middle;

[0027] Figure 3 An exploded view of the artificial tubular tissue perfusion culture device according to an embodiment of the present invention;

[0028] Figure 4 is a vertical view of the end cover described in an embodiment of the present invention;

[0029] Figure 5 is a vertical view of the liner described in an embodiment of the present invention;

[0030] Figure 6 is a vertical view of the shell and tube described in an embodiment of the present invention;

[0031] Figure 7 It is a schematic diagram of the adapter and the third interface docking in an embodiment of the present invention.

[0032] In the figure: 1, shell tube; 11, first interface; 12, limit strip; 2, lining; 21, tubular interface; 211, plug interface; 212, third interface; 213, adapter; 22, support plate; 221, limit notch; 23, support strip; 3, end cover; 31, second interface. DETAILED DESCRIPTION

[0033] The principles and features of the present invention are described below in conjunction with the accompanying drawings. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention. The present invention is described in more detail by way of example with reference to the accompanying drawings in the following paragraphs. The advantages and features of the present invention will become clearer according to the following description and claims. It should be noted that the drawings are all in a very simplified form and are not in precise proportions, and are only used to conveniently and clearly assist in explaining the purpose of the embodiments of the present invention.

[0034] like Figure 1-Figure 3 As shown, this embodiment provides an artificial tubular tissue perfusion culture device, including a shell tube 1, a liner 2 and two end caps 3, the outer wall of the shell tube 1 is provided with two first interfaces 11, the middle part of the outer side of the end cap 3 is provided with a second interface 31, the liner 2 is a hollow structure, and both ends thereof are provided with a through tubular interface 21, the end of the tubular interface 21 located outside the liner 2 is a plug interface 211, and the end of the tubular interface 21 located inside the liner 2 is a third interface 212, the artificial tubular tissue 4 is placed in the liner 2, and one end of the artificial tubular tissue 4 is plugged into the two third interfaces 212, the liner 2 is placed in the shell tube 1, the two end caps 3 are installed at the two ends of the shell tube 1, and the two plug interfaces 211 are respectively inserted into the two second interfaces 31, wherein one of the first interface 11 and the second interface 31 is used to introduce culture solution, and the other of the first interface 11 and the second interface 31 is used to discharge culture solution, so that the artificial tubular tissue is placed inside the lining, and after its two ends are docked with the two third interfaces, the entire artificial tubular tissue perfusion culture device can be assembled, at this time, the culture solution is introduced into any one of the first interfaces and any one of the second interfaces, and the culture solution is discharged from the remaining first interfaces and the remaining second interfaces, so that it can be ensured that the inner wall and the outer wall of the artificial tubular tissue are fully immersed in the culture solution, and the culture solution is in a flow state, which is conducive to a more uniform distribution of cells on the inner wall and the outer wall of the artificial tubular tissue during proliferation.

[0035] In this embodiment, the shell tube 1, the liner 2 and the two end covers 3 can all be made of plastic materials, and of course, can also be made of stainless steel materials.

[0036] The culture medium of this embodiment may be mixed with suspended cells, and the cells enter the artificial tubular tissue perfusion culture device together with the culture medium and use the inner and outer walls of the artificial tubular tissue as carriers for adherent growth.

[0037] In the above technical solution, the two first interfaces 11 are arranged at the two ends of the outer wall of the shell tube 1, so that the culture fluid in the outer space of the artificial tubular tissue can be distributed more evenly.

[0038] like Figure 4 As shown, the end cover 3 in the above technical solution is a groove-shaped cover with an internal thread on its inner groove wall, and the two ends of the shell tube 1 are provided with external threads. The end cover 3 is threadedly screwed on the corresponding ends of the shell tube 1. By threading the two end covers at the two ends of the shell tube (a gasket can be added in the groove of the end cover to improve the sealing of the joint between the end cover and the shell tube, and the gasket can be a silicone gasket), the end cover and the shell tube are more convenient to disassemble and assemble.

[0039] like Figure 5 As shown, the lining 2 in the above technical solution includes two support plates 22 and a plurality of support bars 23, the two support plates 22 are parallel to each other and spaced apart, the plurality of support bars 23 are circumferentially spaced apart at the edge between the two support plates 22, the two ends of each support bar 23 are respectively connected to the edges of the two support plates 22, the two tubular interfaces 21 are respectively arranged in the middle of the two support plates 22, and the structure is simple, so that the artificial tubular tissue can be connected at the two third interfaces between the two adjacent support bars on the lining; preferably, the support bar 23 is vertically connected to the two support plates 22, and the structure is simple and the aesthetics is good.

[0040] like Figure 5 As shown, the support plate in this embodiment is a circular plate, and the tubular interface is coaxially distributed with the support plate; further preferably, the support bars 23 are provided with 2-4 (preferably two, and the two support bars are relatively distributed), so that the structural strength of the entire liner is higher; further preferably, as Figure 5 and Figure 6As shown, a limiting strip 12 is convexly provided on the inner wall of the shell tube 1 along the axial direction, and the two support plates 22 are concavely provided with mutually aligned limiting notches 221 for the insertion of the limiting strip 12. The limiting strip 12 is inserted into the corresponding two limiting notches 221 to limit the rotation of the liner 2 in the shell tube 1, so that when the liner is installed in the shell tube, the limiting strip is inserted into the limiting notch, and the rotation of the liner in the shell tube can be avoided at this time. In this embodiment, two limiting strips can be provided, and at this time, two limiting notches are also provided on each of the support plates. The two limiting notches aligned with each other on the two support plates correspond to one limiting strip. After the liner is assembled in the shell tube, it is necessary to ensure that the support strip is not at the position of the first interface, so as to avoid the support strip covering and blocking the first interface.

[0041] like Figure 7 As shown, the above technical solution also includes a tubular adapter 213 plugged into the third interface 212, and the two ends of the artificial tubular tissue 4 are plugged into the two adapters 213, so that adapters of different specifications can be plugged into the third interface to meet the docking of artificial tubular tissues with different pore diameters, thereby making the entire artificial tubular tissue perfusion culture device more applicable. Preferably, the end of the third interface 212 and the end of the adapter 213 for the artificial tubular tissue 4 to be plugged are both provided with external threads, so that the friction resistance of the artificial tubular tissue is large when docking with the third interface or the adapter, so that it is not easy to loosen. The other end of the adapter in this embodiment can be provided with an internal thread that matches the third interface, and the adapter can be threadedly installed at the corresponding third interface. In this embodiment, adapters of various specifications can be provided for selection, and the adapters are all paired with each other in two specifications. The outer diameters of the external thread ends of different pairs of adapters are different, but their internal thread ends must remain threaded with the third interface.

[0042] The outer wall of the plug-in port 211 in the above technical solution is a frosted surface, so that the plug-in port is inside the second port and the two mating surfaces have better sealing performance.

[0043] The artificial tubular tissue in this embodiment is perfused with culture fluid both inside and outside, so that the cells on the inner and outer surfaces of the artificial tubular tissue have better proliferation effects and a large amount of extracellular matrix is ​​synthesized.

[0044] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any ordinary technician in the industry can smoothly implement the present invention as shown in the drawings and described above. However, any equivalent changes, modifications and evolutions made by technicians familiar with the profession without departing from the scope of the technical solution of the present invention using the technical content disclosed above are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications and evolutions made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. An artificial tubular tissue perfusion culture device, characterized in that: The invention comprises a shell tube (1), an inner liner (2) and two end covers (3), wherein two first interfaces (11) are arranged on the outer wall of the shell tube (1), a second interface (31) is arranged in the middle of the outer side of the end cover (3), the inner liner (2) is a hollow structure, and both ends thereof are provided with penetrating tubular interfaces (21), one end of the tubular interface (21) located outside the inner liner (2) is a plug interface (211), and one end of the tubular interface (21) located inside the inner liner (2) is a third interface (212), and an artificial The tubular tissue (4) is placed in the inner liner (2), and one end of the tubular tissue (4) is plugged into the two third interfaces (212). The inner liner (2) is placed in the shell tube (1). The two end covers (3) are installed at both ends of the shell tube (1), and the two plug interfaces (211) are respectively plugged into the two second interfaces (31). One of the first interfaces (11) and the second interface (31) is used to introduce culture fluid, and the other of the first interfaces (11) and the second interface (31) is used to discharge culture fluid.

2. The artificial tubular tissue perfusion culture device according to claim 1, characterized in that: The two first interfaces (11) are arranged at two ends of the outer wall of the shell tube (1).

3. The artificial tubular tissue perfusion culture device according to claim 1, characterized in that: The end cover (3) is a groove-shaped cover, and its inner groove wall has internal threads. Both ends of the shell tube (1) are provided with external threads, and the end cover (3) is threadedly screwed on the corresponding ends of the shell tube (1).

4. The artificial tubular tissue perfusion culture device according to claim 1, characterized in that: The lining (2) comprises two support plates (22) and a plurality of support strips (23); the two support plates (22) are parallel to each other and spaced apart; the plurality of support strips (23) are circumferentially spaced apart at the edge between the two support plates (22); the two ends of each support strip (23) are respectively connected to the edge of the two support plates (22); and the two tubular interfaces (21) are respectively arranged in the middle of the two support plates (22).

5. The artificial tubular tissue perfusion culture device according to claim 4, characterized in that: The support bar (23) is vertically connected to the two support plates (22).

6. The artificial tubular tissue perfusion culture device according to claim 4, characterized in that: The number of support bars (23) is 2 to 4.

7. The artificial tubular tissue perfusion culture device according to claim 4, characterized in that: A limiting strip (12) is convexly provided on the inner wall of the shell tube (1) along the axial direction, and the two support plates (22) are concavely provided with mutually aligned limiting notches (221) for the insertion of the limiting strip (12), and the limiting strip (12) is inserted into the two corresponding limiting notches (221) to limit the rotation of the liner (2) in the shell tube (1).

8. The artificial tubular tissue perfusion culture device according to any one of claims 1 to 7, characterized in that: It also comprises a tubular adapter (213) plugged into the third interface (212), and the two ends of the artificial tubular tissue (4) are plugged into the two adapters (213).

9. The artificial tubular tissue perfusion culture device according to claim 8, characterized in that: The end of the third interface (212) and the end of the adapter (213) for the artificial tubular tissue (4) to be plugged in are both provided with external threads.

10. The artificial tubular tissue perfusion culture device according to any one of claims 1 to 7, characterized in that: The outer wall of the plug port (211) is a frosted surface.