KR101931545B1

KR101931545B1 - Manufacturing Device of Nerve Conduits

Info

Publication number: KR101931545B1
Application number: KR1020170073225A
Authority: KR
Inventors: 박기웅; 정구찬; 현정근; 김종완
Original assignee: 주식회사리온
Priority date: 2017-06-12
Filing date: 2017-06-12
Publication date: 2019-03-20
Also published as: KR20180135287A; WO2018230759A1

Abstract

More particularly, the present invention relates to a device for manufacturing a nerve conduit which forms a microchannel by utilizing a space between glass fibers and uniformly pressurizes the nerve conduit, The present invention relates to a device for manufacturing porous nerve conduits using glass fibers. The nerve conduit manufactured according to the present invention can be manufactured with various diameters and lengths according to the purpose and use of the nerve to be useful for in vitro and in vivo studies on the nerve.

Description

{Manufacturing Device of Nerve Conduits}

More particularly, the present invention relates to a device for manufacturing a nerve conduit which forms a microchannel by utilizing a space between glass fibers and uniformly pressurizes the nerve conduit, The present invention relates to a device for manufacturing porous nerve conduits using glass fibers.

If the peripheral nerve is injured by trauma, a method of direct segmentation of the severed nerve sections is performed. However, it is almost impossible to directly associate most of the nerves with each other. In cases where direct anastomosis is impossible, autologous nerve grafting is performed to restore the function. However, in the case of autologous nerve grafting, there is a disadvantage that it is difficult to match the size and shape of the nerve tissue to the damaged nerve tissue and the shape of the nerve tissue to be implanted, and there is a limitation in the harvestable nerve, have. Therefore, nerve conduit is used as a way to restore its function when a nerve defect site develops.

The nerve conduit connects both ends of the deficient nerve and acts as a pathway for nerve regeneration. It fixes both ends of the severed nerve in the nerve conduit and induces the connection of the nerve into the conduit. The use of nerve conduit can prevent penetration of scar tissue that interferes with nerve regeneration, can induce the direction of nerve regeneration in the right direction, keeps nerve regeneration substances secreted from the nerve itself in the conduit, Which can be shut off from the outside.

The nerve conduit should be biocompatible with no tissue rejection, biodegrade in accordance with the nerve regeneration period, do not require nerve conduit removal after nerve regeneration, should not have toxicity in the body, It should have mechanical properties to maintain the internal space during nerve regeneration and have proper stretchability and tensile strength so that the end portion of the nerve conduit can be stably maintained even after the insertion of the nerve conduit, And should be easy to prevent and treat normal tissue around the site. Materials for these nerve conduits are largely composed of natural polymers (collagen, chitosan, etc.) and synthetic polymers (silicone, polylactic acid, PLA, polyglycolic acid (PGA), polylactic acid- polylactic acid-co-glycolic acid (PLGA), polycaprolactone, and the like.

The most commonly used natural polymer material is collagen. Collagen has been widely used as a material for nerve conduction for nerve regeneration because of its excellent biocompatibility and weak antigenicity. However, since collagen must be extracted from animals, it is difficult to produce, difficult to store, and unsuitable for mass production. In addition, since the manufacturing cost is high, it is limited in clinical use and has a disadvantage in that the tensile force is very weak in vivo. In addition, the synthetic polymer-based nerve conduit which has been verified for biocompatibility such as polylactic acid, polylactic acid-glycolic acid copolymer, etc. is excellent in structural stability and tensile strength because it is formed in the form of a polymer tube without voids, It is not easy to exchange data.

In order to solve this problem, the present inventor has disclosed a nerve conduit technique using glass fiber through Korean Patent Application No. 10-2014-0027854, but still has a problem in that it is not easy to exchange body fluids.

SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a porous neural conduit manufacturing apparatus having a microporous structure together with a microchannel.

It is an object of the present invention to provide an apparatus for manufacturing porous nerve conduits using glass fibers, which forms a microchannel utilizing a space between glass fibers.

It is another object of the present invention to provide a porous neural conduit manufactured using the manufacturing apparatus of the present invention.

In order to solve the above-described problems, the present invention according to a first aspect provides a method of manufacturing a semiconductor device, comprising: (a) a container having an upper channel and a lower channel and into which a plurality of glass fibers are inserted; (b) a polymeric material injection means for injecting the polymeric material into the vessel; (c) a pressurizing means for applying a high pressure to the interior of the container, wherein the pressurizing means comprises: (i) a pressurizing means connected to the pressurizing tank for applying a high pressure to the inside of the pressurizing tank, Pump; (ii) a pressurizing tank having one side connected to the pressurizing pump and the inside maintained at a high pressure; (iii) a distribution pressure control device for connecting the other side of the pressure tank and the inside of the chamber to apply a high pressure to the inside of the container; And (iv) a pressure chamber connected to the dispensing pressure control device, the pressure chamber including the container and the injection means.

The distribution pressure control device may include 2 to 100 pressure control means including 1 to 100 air valves, a regulator, and 1 to 100 pressure relief valves.

The lower channel has a smaller diameter than the upper channel, and the container can be inclined at a discontinuous angle.

The container may be made of a transparent material through which the penetration of the polymer solution can be visually confirmed.

Further, the present invention according to a second aspect includes the steps of: (a) inserting a plurality of glass fibers into a container having upper and lower channels; (b) injecting the polymer material into the container into which the plurality of glass fibers are inserted; (c) applying a high pressure from the channel to permeate the polymeric material between the glass fibers; (d) separating the glass fibers from the vessel; And (e) immersing the separated glass fiber in water to dissolve the glass fiber, wherein (c) comprises: (i) forming a high pressure inside the pressurizing tank using a pressurizing pump; (ii) pressurizing the inside of the chamber by moving the air inside the pressurizing tank into the pressurizing chamber by using an air valve of the distribution pressurizing control device, and infiltrating the polymeric material through the glass fibers; And (iii) adjusting the interior of the chamber to atmospheric pressure using a pressure relief valve after the infiltration of the polymer material into the glass fibers is completed. The porous neural conduit manufacturing method .

The polymeric material may be a polymer such as collagen, gelatin, chitosan, alginate, hyaluronic acid, dextran, silk, cellulose, poly Polyhydroxybutyrate (PHB), polyhydroxyvalerate (PHV) and polyhydroxybutyrate-co-valerate (PHBV), polyorthoesters, Polyvinyl alcohol (PVA), polyethyleneglycol (PEG), polyurethane, polyacrylic acid, poly-N-isopropyl acrylamide, , Poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) copolymer (poly (ethyleneoxide) -poly (propyleneoxide) -poly (ethyleneoxide) copolymer), polydioxanone-b-caprolactone diox caprolactone (PCL), poly (lactic acid), PLA), poly-L-lactide (poly-L- lactide, PLLA), poly-D-lactide (PDLA), poly-D, L-lactide, PDLLA, poly (glycolic acid) , PGA) or poly (lactic acid-co-glycolic acid) (PLGA), and a mixture of at least one selected from the group consisting of methylene chloride, dichloromethane, DCM, 1,4-dioxane, chloroform, acetone, anisole, ethyl acetate, methyl acetate, N- N-methyl-2-pyrrolidone, hexafluoro isopropanol (HFIP), tetrahydrofuran (THF), dimethylsulfoxide (DMSO) 2-pyrollidone, Examples of the solvent include triethyl citrate, trifluoroacetic acid (TFA), dimethyl formamide (DMF), ethyl lactate, propylene carbonate, benzyl alcohol, One or more kinds selected from the group consisting of benzyl benzoate, Miglyol 810, isopropanol, ethanol, acetonitrile or tetraglycol (TG) And a mixed solvent.

The weight / volume% (w / v%) of the polymer and the solvent may be 10 to 40%.

The solvent is separated from the polymer by being phase-separated with the water in the step of immersing in the water, so that the polymer can be porous.

The polymeric material may be in a solution state at room temperature.

The method for manufacturing a porous neural tube using the glass fiber comprises the steps of: cooling the nerve conduit formed after the step of dissolving the glass fiber with liquid nitrogen; And cutting and shaping the cooled nerve conduit.

The pressurization may be repeated a plurality of times.

The present invention according to the third aspect also provides a porous nerve conduit produced by the above method.

The nerve conduit may form a microchannel in the axial direction of the nerve conduit as the glass fiber is inserted in the axial direction of the container.

The nerve conduit may have micropores formed in the nerve conduit as the solvent dissolves in water.

The effects according to the present invention are as follows.

1. A hydrophobic tetraglycol (TG) polymer is prepared by impregnating a hydrophobic polymer with a mixed solvent of a polylactic acid-glycolic acid copolymer (PLGA) and a hydrophobic solvent tetraglycol (TG) Is physically separated from the polymer constituting the nerve conduit, thereby making it possible to form micropores capable of body fluid exchange.

2. As the melting point of the polymer solution is lowered through the mixing of the polylactic acid-glycolic acid copolymer (PLGA) and tetraglycol (TG), after the PLGA is once dissolved in TG, the solution state is maintained at room temperature. Can be used without melting again.

3. It is possible to manufacture a nerve conduit of uniform density by repeatedly applying high pressure several times after infiltrating a polymer solution having a predetermined viscosity into a space between glass fibers.

1 is a photograph showing a method of manufacturing a porous nerve conduit; B is a silicone tube and a Luer lock syringe to which a 2-way valve is connected, and C is a Luer lock with a silicone tube to which a 2-way valve is connected, wherein A is a glass fiber, a capillary glass tube and a glass fiber- (Luer lock) syringe, and D is a syringe to apply pressure to the inside of the glass tube.
2 is a schematic view showing a method of manufacturing a porous nerve conduit.
FIGS. 3A and 3B are diagrams showing channel forming effects according to a discontinuous (a) or continuous (b) container inclination.
Figure 4 is a cross-sectional SEM image of a porous neural duct; Scale bar = (left) 100 μm, (right) 10 μm.
Figure 5 is a SEM image of a microstructure enlarged in a cross-section of a porous neural tube; Scale bar = (A, C) 10 μm, (B, D) 1 μm, ▶ = micropores inside the channel.
Figure 6 is a longitudinal section SEM image of a porous neural duct; Scale bar = (A) 100 μm, (B) 10 μm, (C) 10 μm, and (D) 1 μm.
Figure 7 is a photograph showing that the TG exiting the porous neural duct is sinking below the DW; Yellow arrow: TG.
Figure 8 is a photograph of a porous neural conduit of various diameters and lengths, depending on the application.
9 schematically shows a distribution pressure control apparatus according to an embodiment of the present invention.

(A) a container having an upper channel and a lower channel and into which a plurality of glass fibers are inserted; (b) a polymeric material injection means for injecting the polymeric material into the vessel; (c) a pressurizing means for applying a high pressure to the interior of the container, wherein the pressurizing means comprises: (i) a pressurizing means connected to the pressurizing tank for applying a high pressure to the inside of the pressurizing tank, Pump; (ii) a pressurizing tank having one side connected to the pressurizing pump and the inside maintained at a high pressure; (iii) a distribution pressure control device for connecting the other side of the pressure tank and the inside of the chamber to apply a high pressure to the inside of the container; And (iv) a pressurizing chamber connected to the dispensing pressure control device, the pressurizing chamber including the container and the injection means therein.

(A) inserting a plurality of glass fibers into a container having upper and lower channels; (b) injecting the polymer material into the container into which the plurality of glass fibers are inserted; (c) applying a high pressure from the channel to permeate the polymeric material between the glass fibers; (d) separating the glass fibers from the vessel; And (e) immersing the separated glass fiber in water to dissolve the glass fiber, wherein (c) comprises: (i) forming a high pressure inside the pressurizing tank using a pressurizing pump; (ii) pressurizing the inside of the chamber by moving the air inside the pressurizing tank into the pressurizing chamber by using an air valve of the distribution pressurizing control device, and infiltrating the polymeric material through the glass fibers; And (iii) adjusting the interior of the chamber to atmospheric pressure using a pressure relief valve after the infiltration of the polymer material into the glass fibers is completed. The porous neural conduit manufacturing method .

The term "polymeric material" refers to a hydrophobic polymer prepared by dissolving a hydrophobic polymer in a hydrophobic solvent. In the present invention, the hydrophobic polymer includes collagen, gelatin, chitosan, alginate, hyaluronic acid ), Dextran, silk, cellulose, poly 3-hydroxybutyrate (PHB), polyhydroxyvalerate (PHV) and polyhydroxybutyric acid-valeric acid Polyhydroxybutyrate-co-valerate (PHBV), polyorthoesters, polyvinyl alcohol (PVA), polyethyleneglycol (PEG), polyurethane, polyacrylic acid acid, poly (N-isopropyl acrylamide), poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) (ethylene oxide) copolymer, poly (dioxanone-b-caprolactone), poly-epsilon (caprolactone) , PCL), poly (lactic acid), PLA, poly-L-lactide (PLLA), poly-D-lactide (PDLA) D, L-lactide, PDLLA, poly (glycolic acid), PGA, or poly (lactic acid-co-glycolic acid) ), PLGA), a mixture of two or more selected from the group consisting of methylene chloride, dichloromethane (DCM), 1,4-dioxane, chloroform, It is also possible to use acetone, anisole, ethyl acetate, methyl acetate, N-methyl-2-pyrrolidone, hexafluoroisopropanol, fluoro isopropanol, HFIP), tetrahydrofuran (DMSO), 2-pyrollidone, triethyl citrate, trifluoroacetic acid (TFA), and dimethylformamide (dimethylformamide). formamide, DMF, ethyl lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, Miglyol 810, isopropanol, ethanol, , Acetonitrile or tetraglycol (TG). Preferably, the solvent is PLGA as a polymer and PLGA-polyacrylamide gel prepared by using TG as a solvent. TG solution.

The hydrophobic polymer may be polylactic acid-co-glycolic acid (PLGA), and the hydrophobic solvent may be tetraglycol (TG). According to the present invention, when PLGA is mixed with TG, PLGA is melted once with TG, and then the solution is maintained at room temperature. Therefore, the polymer material can be used without melting again.

The weight / volume% (w / v%) of the polymer and the solvent means the weight (g) of the polymer dissolved in 1 L of the solvent, and the weight / volume% (w / v%) is 10 to 40% 15% to 25%, and most optimally 20%. If it is less than the above range, there is a problem that the porosity increases greatly due to the use of an excessive amount of solvent, and in the opposite case, sufficient pore formation may be difficult.

(I) a pressurizing pump connected to the pressurizing tank and applying a high pressure to the inside of the pressurizing tank; (ii) a pressurizing tank having one side connected to the pressurizing pump and the inside maintained at a high pressure; (iii) a distribution pressure control device for connecting the other side of the pressure tank and the inside of the chamber to apply a high pressure to the inside of the container; And (iv) a pressurizing chamber connected to the dispensing pressure control device, the pressurizing chamber including the container and the injection means, wherein the step (c) comprises the steps of: (i) ; (ii) pressurizing the inside of the chamber by moving the air inside the pressurizing tank into the pressurizing chamber by using an air valve of the distribution pressurizing control device, and infiltrating the polymeric material through the glass fibers; And (iii) adjusting the interior of the chamber to atmospheric pressure using a pressure relief valve after the infiltration of the polymer material into the glass fibers is completed. When the chamber is pressurized using a conventional pressurizing pump, it is difficult to pressurize the chamber at a constant speed, and the pressure at the portion connected to the conduit becomes higher than the pressure at the portion far from the conduit. Therefore, the polymer material is uniformly injected into the porous neural conduit it's difficult. In particular, since the present invention permeates the polymer material through the glass fibers using pressure, the possibility of failure in the nerve conduit is greatly increased if a constant pressure is not formed. Therefore, it is preferable that the pressurizing tank 400 is used to pressurize the chamber at a constant speed, and the chamber pressure is controlled by using the distribution pressure control device 100 so that the entire chamber has a constant pressure. The distribution pressure control apparatus 100 includes 2 to 100 pressure control means 110 including 1 to 100 air valves 112, a regulator 111 and 1 to 100 pressure relief valves 113, So as to have a constant pressure regardless of the position inside the chamber. In order to automate the production of the nerve conduit, the pressure pump, the pressurizing tank, the chamber, and the distribution pressure control device are provided with pressure sensors and control means, respectively. The conduit connecting each device is provided with a valve, It is preferable to adjust the pressure to a constant pressure.

Further, it is preferable that the glass fiber is fixed by using a fixing means since the glass fiber can be moved by the pressure of pressure when the pressing is performed. The fixing means may be any means capable of fixing the glass fiber, but may be a wire, an elastic body or a band including a fiber, a polymer or a metal material. It is further preferable that the fixing means is fixed to the container so that the glass fiber does not deviate from the position during pressing. At this time, the fixing means can be fixed to the container by using hooks, protrusions or protrusions provided in the container. In addition, the fixing means may fix the glass fibers one by one, but it is also possible to hold and bundle 2 to 1000 glass fiber bundles, and 2 to 100 glass fiber bundles may be collected and fixed again.

The lower channel has a diameter smaller than that of the upper channel, so that the glass fiber injected into the container can be kept filled without flowing out in the container.

The container may be inclined at a discontinuous angle, and more specifically, the container may be formed by forming upper and lower channels inclined at discontinuous angles, but is not limited thereto.

Since the interval between the inserted glass fibers is constant due to the container inclined at the discontinuous angle and the upper and lower channels thereof, the interval of the microchannels formed in the space where the glass fibers are melted is also constant. That is, the porous nerve conduit manufactured according to the present invention can form microchannels at regular intervals, thereby inducing nerve regeneration in the same direction.

The container may be, but not limited to, forming an upper channel and a lower channel by heating a central portion of the glass tube to create a bottleneck point.

The polymer material may be in a solution state at room temperature.

The method of manufacturing a porous neural duct using the glass fiber comprises the steps of: cooling the nerve conduit formed by melting the glass fiber with liquid nitrogen; And cutting and shaping the cooled nerve conduit.

The container may be made of a transparent material through which the penetration of the polymer solution can be visually confirmed, and is preferably made of glass, but is not limited thereto.

The pressurization may be repeated a plurality of times so that a neural tube having a uniform density can be produced.

The present invention provides a porous neural conduit made according to the method of manufacture of the present invention.

The nerve conduit may be a microchannel formed in the axial direction of the nerve conduit as the glass fiber is inserted in the axial direction of the container. More specifically, after the glass fiber is axially inserted into the upper channel of the vessel (glass tube), the polymer material (PLGA-TG solution) is injected into the vessel, the pressure is applied to penetrate into the glass fiber, And immersed in water (DW) to melt all of the glass fibers, thereby forming microchannels of hydrophobic polymer (PLGA) in the space where the glass fibers were melted. That is, by inserting the glass fiber in the axial direction of the container, and melting the glass fiber, a nerve conduit in which microchannels are formed axially in the space where the glass fiber is melted is manufactured.

The term "microchannel" means an empty space having a size of 10 to 20 mu m formed in a space in which glass fibers are melted.

The nerve conduit may be micropores formed in the nerve conduit as the solvent dissolves in water. More specifically, in the process of immersing the glass fiber into which the polymer material (PLGA-TG solution) is impregnated with water DW, TG is reacted (dissolved) with the water DW and is discharged from the nerve conduit, . Dissolution in this context means that the TG is separated from the polymeric material.

The term "micropores" refers to fine voids formed in the microchannel as the solvent dissolves in the DW and exits from the nerve conduit. The nerve conduits manufactured according to the present invention are easily fluid-exchanged by microchannels when applied in vivo. The solvent exiting from the nerve conduit was more dense than DW (1.09 g / ml) and sinked to the underside of DW (Fig. 7).

Porous neural conduits manufactured according to embodiments of the present invention can be manufactured in various diameters and lengths and can be freely changed in diameter and length depending on the purpose and use of the neural tube in order to be useful for in vitro and in vivo studies on neurons have.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

Example 1 Preparation of Porous Neural Conduits Using Glass Fiber 1

(Density: 1.09 g / ml, Sigma-Aldrich, USA) containing polylactic acid-glycolic acid copolymer (PLGA) (lactic acid to glycolic acid mol%, 85:15) which is a hydrophobic polymer and hydrophobic solvent tetraglycol ) Was mixed to a weight-to-volume (w / v) ratio of 20% (w / v) and then dissolved at 60 ° C for 18 hours to prepare a 20% (w / v) PLGA-TG solution (polymeric material).

The central portion of the capillary glass tube having an inner diameter of 1.6 mm and a length of 13 cm was heated to form a bottleneck point to form upper and lower channels inclined at discontinuous angles. At this time, the lower channel was formed to have a smaller diameter than the upper channel. Thereafter, 7000 to 8500 strands of water-soluble glass fiber (50P ₂ O ₅ -20CaO-30Na ₂ O mol% (1100 ° C, 800rpm)) having a diameter of 10 to 20 μm were cut in units of 5 to 6 cm, (Figs. 1A and 2A).

A pressure device manufactured by connecting a Luer lock syringe with a 2-way valve to a silicone tube having an inner diameter of 0.8 mm and a length of 15 cm was prepared in the upper channel of the glass tube into which the glass fiber was inserted (Fig. 1B and Fig. 1C).

After the PLGA-TG solution was injected into the syringe, the glass tube was repeatedly pressurized with 20% (w / v) PLGA-TG solution at room temperature. ) PLGA-TG solution was completely penetrated into the gaps between the glass fibers (Fig. 1D and Fig. 2C).

In this embodiment, the width of the lower channel is narrowed at a discontinuous angle with respect to the upper channel as described above, and this is shown in FIG. When the angles are continuous (FIG. 3B), the interval between the glass fibers gradually becomes narrow, which makes it difficult to maintain a constant gap between the glass fibers. In the case where the intervals of the glass fibers are not constant, the nerve regeneration direction formed by the glass fibers changes depending on the channel, and therefore, there arises a problem that nerve regeneration in the same direction becomes difficult.

The glass fiber infiltrated with the PLGA-TG solution was completely immersed in distilled water (DW) at 10 to 20 ° C for more than 24 hours immediately after separating the infiltrated glass fiber from the glass tube using a wire having a diameter of 1.5 mm and a length of 15 cm ) And glass fibers were melted and the glass fibers were melted and the microchannels (microchannel diameter: 16.54 ± 3.6 μm) having a size of 10 to 20 μm composed of PLGA were formed in a space of about 7,000 to 8,500 (the number of microchannels: 7,777 ± 716.2) (Fig. 2E and Fig. 4). Glass fibers were dissolved in a DW of 10 to 20 占 폚, and PLGA was cured to form microchannels. In addition, during the immersion of the glass fiber infiltrated with the PLGA-TG solution into the DW, TG was reacted with DW (dissolved in DW), and the micropores were formed and micropores were formed in the microchannels (Figs. 4, 5, 6). TG exiting from the nerve conduit was more dense than DW, so that it fell to the underside of DW (Fig. 7).

After the glass fiber and TG were removed by DW treatment, the porous microchannel made of PLGA, that is, the prepared nerve conduit was frozen in liquid nitrogen for about 30 seconds and then cut and formed into a size suitable for the purpose of use (Fig. 8).

Example 2 Preparation of Porous Neural Conduits Using Glass Fiber 2

In Example 1, a pressure was applied using a syringe, but a porous neural conduit was prepared using an automatic pressure regulating method using a pressurizing chamber instead of the syringe. The same channel as in Example 1 was prepared, and then the upper channel was connected to the pressure chamber. The valves 112 and 113 connected to the respective conduits were adjusted to be OFF, and then the pressurizing pump 200 was operated to pressurize the pressure tank 400 to prepare it. Thereafter, the inside of the chamber is pressurized to a predetermined pressure through three pressure control means 110 connected to the distribution pressure control device 100. After the pressurization is completed, the inside of the chamber is adjusted to normal pressure using each pressure release valve 113 . The subsequent procedure was carried out in the same manner as in Example 1.

Example 3: Confirmation of the internal microstructure of the porous nerve conduit

The microstructure formed in the microchannels inside the nerve conduit prepared in Example 1 by dissolving the glass fiber in water was confirmed by scanning electron microscopy (SEM) (FIGS. 4, 5 and 6).

Fig. 4 is a cross-sectional view of the nerve conduit, Fig. 5 is an enlarged microstructure of the nerve conduit in cross section, Fig. 6 is a longitudinal section of the nerve conduit showing that the microchannels inside the nerve conduit are continuous from the distal portion to the proximal portion, It was confirmed that fine pores were formed in the microstructure inside the microchannel.

However, it was confirmed that the size and distribution of microchannels in each nerve conduit were not constant when the nerve conduit was manufactured by repeating 10 times by the method of Example 1. On the other hand, It was confirmed that a neural catheter including microchannels having a uniform size and distribution can be produced when the catheter is manufactured. This is because it is judged that a certain pressure is not applied because the syringe is manipulated by the human senses when the pressure is applied by the method of Embodiment 1. In Embodiment 2 using the valve and the pressurizing chamber, And it was confirmed that it was distributed in the conduit.

The nerve conduit manufactured according to this embodiment can be manufactured with various diameters and lengths according to the purpose and use of the nerve to be useful for in vitro and in vivo studies on the nerve.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereto will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

100: Dispense pressure control device
110: pressure control means
111: Regulator
112: Valve
113: Pressure relief valve
200: Pressure pump
300: valve
400: pressure tank

Claims

(a) a container having an upper channel and a lower channel and into which a plurality of glass fibers are inserted;
(b) polymer material injection means for injecting the polymer material into the container;
(c) pressurizing means for applying a high pressure to the inside of the vessel;
The porous nerve conduit producing apparatus using the glass fiber,
Wherein the pressing means comprises:
(i) a pressurized pump connected to the pressurized tank and applying a high pressure to the interior of the pressurized tank;
(ii) a pressurizing tank having one side connected to the pressurizing pump and the inside maintained at a high pressure;
(iii) a distribution pressure control device for connecting the other side of the pressure tank and the inside of the chamber to apply a high pressure to the inside of the container; And
(iv) a pressurization chamber connected to the dispensing pressure control device and including the container and the injection means therein;
/ RTI >
Wherein the dispensing pressure control device comprises 2 to 100 pressure control means connected in parallel, including 1 to 100 air valves, a regulator and 1 to 100 pressure release valves. .

delete

The method according to claim 1,
Wherein the lower channel has a smaller diameter than the upper channel and the container is inclined at a discontinuous angle.

The method according to claim 1,
Wherein the container is made of a transparent material through which the penetration of the polymer material can be visually confirmed.

(a) inserting a plurality of glass fibers into a container having upper and lower channels;
(b) injecting the polymer material into the container into which the plurality of glass fibers are inserted;
(c) applying a high pressure from the channel to permeate the polymeric material between the glass fibers;
(d) separating the glass fibers from the vessel; And
(e) immersing the separated glass fibers in water to dissolve the glass fibers;
/ RTI >
The step (c) comprises:
(i) forming a high pressure inside the pressurizing tank using a pressurizing pump;
(ii) pressurizing the inside of the chamber by moving the air inside the pressurizing tank into the pressurizing chamber by using an air valve of the distribution pressurizing control device, and infiltrating the polymeric material through the glass fibers; And
(iii) adjusting the interior of the chamber to atmospheric pressure using a pressure relief valve after the infiltration of the polymer material into the glass fibers is completed;
A method for manufacturing a porous neural conduit using the apparatus for manufacturing a nerve conduit according to any one of claims 1, 3, and 4,

6. The method of claim 5,
The polymeric material
Examples of the polymer include collagen, gelatin, chitosan, alginate, hyaluronic acid, dextran, silk, cellulose, polyhydroxybutyric acid ( polyhydroxybutyrate, polyhydroxybutyrate (PHBV), polyorthoesters, polyvinyl alcohol (PHB), polyhydroxybutyrate (PHB), polyhydroxybutyrate polyvinyl alcohol (PVA), poly (ethyleneglycol), PEG, polyurethane, polyacrylic acid, poly-N-isopropyl acrylamide, Poly (ethylene oxide) -poly (ethylene oxide) -poly (ethylene oxide) -poly (ethyleneoxide) copolymer, poly (dioxanone-b- caprolactone)), Paul poly-L-lactide (PLLA), poly-D-lactide (PLA), poly (? - caprolactone) (PDLA), poly-D, L-lactide, PDLLA, poly (glycolic acid), PGA) or poly (lactic acid-co (Lactic acid-co-glycolic acid), PLGA), and a mixture of one or more selected from the group consisting of
Examples of the solvent include methylene chloride, dichloromethane, DCM, 1,4-dioxane, chloroform, acetone, anisole, ethyl acetate, methyl Examples of the solvent include methyl acetate, N-methyl-2-pyrrolidone, hexafluoro isopropanol (HFIP), tetrahydrofuran (THF), dimethylsulfoxide dimethylformamide (DMSO), 2-pyrollidone, triethyl citrate, trifluoroacetic acid (TFA), dimethyl formamide (DMF), ethyl lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, Miglyol 810, isopropanol, ethanol, acetonitrile or tetraglycol (tetraglycol, TG) Alone or a mixed solvent of two or more kinds selected from;
0.0 > of: < / RTI >

The method according to claim 6,
Wherein the weight / volume% (w / v%) of the polymer and the solvent is 10 to 40%.

The method according to claim 6,
Wherein the solvent is separated from the polymer by being phase-separated with the water in the step of immersing in the water, thereby forming a porous membrane on the polymer.

6. The method of claim 5,
Wherein the polymeric material is in a solution state at room temperature.

6. The method of claim 5,
The porous neural conduit manufacturing method includes:
Cooling the nerve conduit formed after the step of dissolving the glass fiber with liquid nitrogen; And
Further comprising cutting and shaping the cooled neural conduit. &Lt; RTI ID = 0.0 > 21. < / RTI >

6. The method of claim 5,
Wherein the pressurization is repeated a plurality of times.

A porous neural conduit made by the method of claim 5.

13. The method of claim 12,
Wherein the nerve conduit is formed with microchannels in the axial direction of the nerve conduit as the glass fibers are inserted in the axial direction of the container.

13. The method of claim 12,
Wherein the nerve conduit has micropores formed in the nerve conduit as the solvent contained in the polymer material dissolves in water.