KR20100102454A - Artificial blood vessel with immunosuppressive properties and manufacturing thereof - Google Patents

Abstract

PURPOSE: An artificial blood vessel and a manufacturing method of the artificial blood vessel are provided, which block inflow of immunoglobulin and immunocyte and pass plasma efficiently. CONSTITUTION: A manufacturing method of the artificial blood vessel having immunodepression function comprises: a first step(S1) of preparing a tube member and a solid substrate; a second step(S2) of forming a first groove portion by oxidation-treating one side of the solid substrate; a third step(S3) of forming the second groove portion by processing the opposite side of the solid substrate; and a fourth step of combining a fine filter and the tube member.

Description

Artificial blood vessels having an immunosuppressive function and a method for producing the artificial blood vessels {ARTIFICIAL BLOOD VESSEL WITH IMMUNOSUPPRESSIVE PROPERTIES AND MANUFACTURING THEREOF}

The present invention relates to an artificial blood vessel having an immunosuppressive function and a method for producing the artificial blood vessel, and more particularly, to a micro filter located at the inlet and the outlet of an artificial blood vessel to physically block the inflow of immune cells and immunoglobulins. will be.

A common method of immunosuppression is to use immunosuppressive agents that reduce the function of immune cells. As cell therapy progressed, however, local immunosuppression was needed instead of systemic immunosuppressive agents. For example, if it is possible to block the influx of immune cells to cells transplanted at specific sites, such as organ transplantation, then they can minimize the attack of immune cells, prolong the survival of the transplanted cells, and prevent side effects from immunosuppressants. Can be.

For this purpose, a physical immune suppression method that blocks the access of immune cells and immunoglobulins using a micro filter has been studied. At this time, the microfilter should effectively pass the plasma while blocking the influx of immune cells and immunoglobulins, prevent the adhesion of the cells, and should be made of a robust structure that resists blood pressure.

The present invention provides an artificial blood vessel and a method for producing the artificial blood vessel having a fine filter made of a robust structure that passes the plasma efficiently while blocking the influx of immune cells and immunoglobulins, does not occur cell adhesion, and withstands blood pressure well. To provide.

Artificial blood vessel according to an embodiment of the present invention, i) a pipe member for providing a blood flow path, and ii) a solid substrate having a predetermined thickness, respectively located on the inlet side and the outlet side of the tube member Fine filters. A nanoscale first groove portion is formed on one surface of the solid substrate, and a microscale second groove portion communicating with the first groove portion is formed on the opposite side of the solid substrate. Artificial blood vessels block the influx of immune cells and immunoglobulins into the tube member by micro-filters and pass plasma.

The solid substrate has a diameter corresponding to the inner diameter of the tubular member and may be made of metal. The first groove may be formed on the entire surface of the solid substrate. The first groove portion may have a diameter in the range of 4 nm to 8 nm. The second groove portion may be formed in plural, and the plurality of second groove portions may be disposed to be symmetrical with respect to the center of the solid substrate.

Artificial blood vessels may be for bypass-mounting in living blood vessels. On the other hand, the artificial blood vessel may be for shunt mounting between the artery and the vein.

According to an embodiment of the present invention, a method of manufacturing artificial blood vessels includes: i) preparing a tubular member and a solid substrate, ii) anodizing one surface of the solid substrate to form a nanoscale first groove, and iv) solid Processing one side of the opposite side of the substrate to form a second micro-groove in communication with the first groove, and iii) fixing the micro filter having the first groove and the second groove to the inlet and outlet sides of the tubular member. Include them.

The solid substrate may comprise at least one of aluminum and titanium. The first groove portion may be formed to have a diameter in the range of 4 nm to 8 nm.

The second groove portion may be formed by any one of wet etching and dry etching. The second groove portion may be formed in plural, and the plurality of second groove portions may be formed to be symmetrical with respect to the center of the solid substrate.

The artificial blood vessel according to the present invention includes a fine filter in which a first groove portion on a nano scale and a second groove portion on a micro scale are formed. Therefore, it is possible to physically block the influx of immune cells and immunoglobulins and to permeate only the plasma, thereby having a local immune suppression function and minimizing side effects by taking immunosuppressants.

In addition, the artificial blood vessel according to the present invention forms a robust structure that withstands blood pressure well, and due to the dual scale concavo-convex structure in which the micro scale and the nano scale are mixed, the cells are not adhered well to the surface of the micro filter. Blockages can be minimized. Artificial blood vessels according to the present invention can be used for various cell transplants.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art may easily implement the present invention. As those skilled in the art would realize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the present invention.

1 is a partial cutaway perspective view of an artificial blood vessel 10 according to an embodiment of the present invention.

Referring to FIG. 1, the artificial blood vessel 10 of the present embodiment includes a tubular member 12 that replaces a living vessel and provides a passage through which blood flows, and microscopically positioned at an inlet side and an outlet side of the tubular member 12, respectively. And a filter 14.

As the tubular member 12, all kinds of tubular members developed to artificial blood vessels to date can be used. For example, the tubular member 12 is made of dark or stretched polytetrafluoroethylene (ePTFE) and is made of albumin, collagen, gelatin, fibrin or alginic acid. It can be surface treated with (alginic acid) or the like. The material of the tubular member 12 is not limited to the above-mentioned example, and can be variously modified.

FIG. 2 is a cross-sectional view of the fine filter 14 of the artificial blood vessel 10 shown in FIG. 1.

1 and 2, the fine filter 14 may include a solid substrate 16 having a predetermined thickness, a first nano-scale groove 18 formed on one surface of the solid substrate 16, and a solid substrate. It is formed on the opposite side of the (16) and includes a micro-scale second groove portion 20 in communication with the first groove portion (18). Here, the nanoscale means a size belonging to the range of 1 nm or more and less than 1,000 nm, and the micro scale means a size belonging to the range of 1 μm or more and less than 1,000 μm.

The solid substrate 16 has a diameter corresponding to the inner diameter of the tubular member 12 and may be made of metal among various solid materials. In particular, since the first groove 18 is preferably formed by anodizing, the solid substrate 16 may be made of a metal capable of anodizing. For example, the solid substrate 116 may include at least one of aluminum and titanium. Since the second groove 20 of the micro scale is in communication with the first groove 18 of the nanoscale, the fine filter 14 may include the first grooves 18 and the second grooves along the thickness direction of the solid substrate 16. 20 to form a fine hole (22).

Immunoglobulins have a smaller size than immune cells and other cells and are approximately 8.5 nm in size. In view of this, the first groove 18 has a diameter in a range of 8 nm or less. Therefore, the fine filter 14 may pass only plasma while blocking the inflow of immune cells and immunoglobulins by the first grooves 18. On the other hand, since the size of the first groove portion 18 that can be formed through anodizing is approximately 4 nm, the first groove portion 18 may have a diameter in the range of 4 nm to 8 nm.

The second groove portion 20 may be provided in plurality, and disposed to be symmetrical with respect to the center of the solid substrate 16. That is, the plurality of second grooves 20 may be disposed to be symmetrical along the up-down direction and the left-right direction of the solid substrate 16. In this case, it is possible to prevent the fine filter 14 from bending or bending in any direction while minimizing the decrease in strength of the fine filter 14.

1 and 2, for example, one circular second groove 20 is disposed at the center of the solid substrate 16, and four circular second grooves 20 are equally spaced along the circumference of the solid substrate 16. The structure arranged as shown. The shape, number and arrangement of the second grooves 20 are not limited to the illustrated example, and may be variously modified.

As described above, since the fine filter 14 is formed by forming the nanoscale first groove 18 and the microscale second groove 20 in combination, the fine filter 14 effectively blocks the influx of immune cells and immunoglobulins, and has a constant mechanical strength. It can ensure a robust structure to withstand blood pressure. In addition, since the fine filter 14 has a dual scale concavo-convex structure in which a micro scale and a nano scale are mixed, it is effective to suppress adhesion of cells.

That is, the immune cells and the immunoglobulins cannot pass through the first groove 18 on the nanoscale, and only a portion of the immune cells and the immunoglobulins pass. Therefore, the artificial blood vessel 10 may implement effective local immune suppression function by protecting cells transplanted inside the tubular member 12 from attack of immune cells. On the other hand, the plasma flows through the inlet side micro filter 14 to the inside of the tube member 12 to supply nutrients to the transplanted cells, and passes through the outlet side micro filter 14 to the outside of the tube member 12. Is discharged.

The fine filter 14 may increase the mechanical strength by increasing the thickness of the solid substrate 16 than in the case where only nanoscale micro holes are formed in the solid substrate having a small thickness. In particular, in the manufacturing process of the artificial blood vessel 10 described below, the first groove 18 is formed by anodizing, and the oxide film formed at this time has very strong brittleness. Therefore, the processability of the fine filter 14 can be improved by providing the non-oxidized part (that is, the part in which the 2nd groove part 20 is formed) and preventing the fine filter 14 from being broken.

In addition, the fine filter 14 may ensure structural stability by forming the first groove portion 18 and the second groove portion 20 on opposite sides thereof, and the first groove portion 18 and the micro scale of the nano scale may be secured. By forming the second groove portion 20 in a complex, cells in the blood can be prevented from easily adhered to the fine filter 14. Therefore, the artificial blood vessel 10 can effectively prevent the cells from adhering to the fine filter 14, thereby effectively preventing the clogging of the fine filter 14. In this case, the nano-scale first groove 18 may be formed on the entire surface of the solid substrate 16 to form a nano-scale uneven structure even at a portion that is not in communication with the second groove 20.

3 is a schematic diagram showing an application example in which the artificial blood vessel 10 of the present embodiment is bypassed to a living blood vessel.

Referring to FIG. 3, as the artificial blood vessel 10 is mounted in a bypass type, the blood flows into the living blood vessel and the artificial blood vessel 10, and then merges again into the living blood vessel. At this time, the islets of secreting insulin are implanted in the artificial blood vessel 10, and the fine filter 14 is positioned at the inlet and outlet of the artificial blood vessel 10.

In the above case, macrophage and immune cells such as T-cells and B-cells do not pass through the microfilter 14 and only plasma is introduced into the artificial blood vessel 10. Therefore, the pancreatic islets in the artificial blood vessel 10 may avoid the attack of immune cells, and at the same time, may perform a function of recognizing blood sugar by contacting plasma and secreting insulin suitable for blood sugar. As a result, the insulin concentration increases after the plasma passes through the artificial blood vessel 10.

4 is a schematic diagram showing an application example in which the artificial blood vessel 10 of the present embodiment is mounted in a shunt type between an artery and a vein.

Referring to FIG. 4, arteries and veins may be connected to an artificial blood vessel 10 in which islets secreting insulin are implanted. In this case, since the pressure difference between the arterial pressure and the vein pressure is large while performing the same function as the bypass artificial blood vessel 10 described above, the inflow of plasma through the fine filter 14 can be more easily performed.

Next, the manufacturing method of the artificial blood vessel 10 mentioned above is demonstrated.

5 is a process flowchart showing a method of manufacturing an artificial blood vessel according to an embodiment of the present invention.

Referring to FIG. 5, in the method of manufacturing an artificial blood vessel according to the present exemplary embodiment, a first step (S1) of preparing a tubular member and a solid substrate and anodizing one surface of the solid substrate may be performed on the first groove part of the nanoscale. The second step (S2) to form, the third step (S3) to form a second groove portion of the micro-scale by processing the opposite side of the solid substrate, and the fine filter completed through the tubular member and the second and third steps A fourth step of combining.

The solid substrate is made of a metal capable of anodizing, for example, it may be made of a metal including at least one of aluminum and titanium. The solid substrate is formed to correspond to the cross-sectional shape of the tubular member, and has a diameter corresponding to the inner diameter of the tubular member.

6 is a schematic cross-sectional view of the anodic oxidation apparatus.

Referring to FIG. 6, the anodic oxidation device 30 includes a circulating water tank 32 in which cooling water is circulated, and a magnetic stirrer 34 for stirring the electrolyte solution in the water tank 32 at a constant speed. The solid base material 16 and the counter electrode 36 are immersed in the electrolyte solution in the water tank 32, and an anode power supply and a cathode power supply are applied to the solid base material 16 and the counter electrode 36, respectively, and anodization process is performed. The electrolyte may include at least one of sulfuric acid, phosphoric acid, and oxalic acid, and the counter electrode 36 may be platinum (Pt).

FIG. 7 is a partial cross-sectional view of the solid substrate through the second step of FIG. 5.

Referring to FIG. 7, as the anodic oxidation process is performed, an oxide film 24 is formed on one surface of the solid substrate 16, and a nanoscale first groove 18 is formed on the oxide film 24. The diameter and depth of the first groove 18 can be easily controlled by adjusting the concentration of the electrolyte, the intensity of the applied voltage or the etching time. The first groove 18 is formed to have a diameter in the range of 4nm to 8nm.

The anodic oxidation process is low in manufacturing cost, can easily process a large amount of solid substrate 16, and can change the process conditions to control geometric characteristics such as diameter and depth of the first groove 18 relatively accurately. There is an advantage. As such, the solid substrate 16 that has undergone the second step forms the oxide film 24 and the first groove 18 on one surface thereof, and the remaining portion of the solid substrate 16 on which the oxide film 24 is not formed is not oxidized. Maintain the initial state.

8 and 9 are cross-sectional views of the solid substrate showing the state during and after the third step of FIG. 5, respectively.

Referring to FIGS. 8 and 9, the surface of the solid substrate 16 on which the mask pattern 26 is to be formed on one side of the solid substrate 16 on which the oxide film 24 is not formed to form the second groove 20. Expose some. Then, one surface of the solid substrate 16 on which the mask pattern 26 is formed is etched to form the second groove 20 of the micro scale.

The etching may be dry etching or wet etching, and the etching is performed until the second groove 20 reaches the first groove 18. Then, the second groove 20 is in communication with the first groove 18, the fine hole 22 consisting of the first groove 18 and the second groove 20 is formed. As illustrated in FIG. 1, the second groove portion 20 may be formed to be symmetrical along the up-down direction and the left-right direction of the solid substrate 16. Thereafter, the mask pattern 26 is removed to complete the fine filter 14.

The oxide film 24 forming the first grooves 18 of the fine filter 14 has high brittleness, but the remaining portion of the solid substrate 16 forming the second grooves 20 remains in its initial state. The crack of the filter 14 is prevented, and workability can be improved. The fine filter 14 completed by the above-described process is installed at the inlet side and the outlet side of the tubular member, respectively, to complete the artificial blood vessel.

The artificial blood vessel described above can be used for various cell transplantation. Unlike the chemical immune suppression method using drugs, the artificial blood vessels are effective for local immune suppression because they physically block immune cells, and minimize side effects of taking immunosuppressants. .

Although the preferred embodiments of the present invention have been described above, the present invention is not limited thereto, and various modifications and changes can be made within the scope of the claims and the detailed description of the invention and the accompanying drawings. Naturally, it belongs to the range of.

1 is a partial cutaway perspective view of an artificial blood vessel according to an embodiment of the present invention.

FIG. 2 is a cross-sectional view of the fine filter of the artificial blood vessel shown in FIG. 1.

3 is a schematic diagram showing an application example in which the artificial blood vessel of the present embodiment is bypassed to a living blood vessel.

Fig. 4 is a schematic diagram showing an application example in which the artificial blood vessel of this embodiment is mounted in a shunt type between an artery and a vein.

5 is a process flowchart showing a method of manufacturing an artificial blood vessel according to an embodiment of the present invention.

6 is a schematic cross-sectional view of the anodic oxidation apparatus.

FIG. 7 is a cross-sectional view illustrating the solid substrate that has passed through the second step of FIG. 5.

8 is a cross-sectional view illustrating a solid substrate in a third step of FIG. 5.

FIG. 9 is a cross-sectional view illustrating the solid substrate that has passed through the third step of FIG. 5.

Claims (12)

A tubular member providing a passage through which blood flows; And A micro filter having a solid substrate having a predetermined thickness, each positioned at an inlet side and an outlet side of the tubular member; Including, One surface of the solid substrate is formed with a nano-scale first groove portion, one surface of the opposite side of the solid substrate is formed with a micro-scale second groove portion communicating with the first groove portion, An artificial blood vessel that blocks the influx of immune cells and immunoglobulins into the tube member by the microfilter and passes plasma. The method of claim 1, Wherein said solid substrate has a diameter corresponding to the inner diameter of said tubular member and is made of metal. The method of claim 1, The first groove part is formed on the entire surface of the solid substrate. The method of claim 3, The first groove has an artificial blood vessel having a diameter in the range of 4nm to 8nm. The method of claim 1, The second groove portion is formed in a plurality, the plurality of second groove portion is artificial blood vessel disposed so as to be symmetrical with respect to the center of the solid substrate. 6. The method according to any one of claims 1 to 5, The artificial blood vessels are artificial blood vessels (bypass) to be mounted on the living blood vessels (artificial blood vessels). 6. The method according to any one of claims 1 to 5, The artificial blood vessel is to be mounted in a shunt (shunt) type between the artery and the vein. Preparing a tubular member and a solid substrate; Anodizing one surface of the solid substrate to form nanoscale first grooves; Processing an opposite side of the solid substrate to form a second micro-groove in communication with the first groove; Fixing the fine filter having the first groove portion and the second groove portion to the inlet side and the outlet side of the tubular member; Method of producing an artificial blood vessel comprising a. The method of claim 8, The solid substrate is a method of producing artificial blood vessels comprising at least one of aluminum and titanium. The method of claim 8, The first groove portion is a method of manufacturing an artificial blood vessel is formed to have a diameter in the range of 4nm to 8nm. The method of claim 8, The second groove portion is a method of manufacturing an artificial blood vessel is formed by any one of wet etching and dry etching. The method of claim 11, The second groove portion is formed in a plurality, the plurality of second groove portion is a manufacturing method of the artificial blood vessel is formed to be symmetrical with respect to the center of the solid substrate.

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