WO2018230759A1 - Appareil servant à préparer un conduit nerveux - Google Patents

Appareil servant à préparer un conduit nerveux Download PDF

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Publication number
WO2018230759A1
WO2018230759A1 PCT/KR2017/006621 KR2017006621W WO2018230759A1 WO 2018230759 A1 WO2018230759 A1 WO 2018230759A1 KR 2017006621 W KR2017006621 W KR 2017006621W WO 2018230759 A1 WO2018230759 A1 WO 2018230759A1
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Prior art keywords
poly
neural conduit
glass fibers
porous
container
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PCT/KR2017/006621
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English (en)
Korean (ko)
Inventor
박기웅
정구찬
현정근
김종완
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주식회사리온
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Publication of WO2018230759A1 publication Critical patent/WO2018230759A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/10—Ceramics or glasses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction

Definitions

  • the present invention relates to a neural conduit manufacturing apparatus, and more specifically, to form a microchannel by utilizing the space between the glass fibers and evenly pressed to minimize the deviation of each neural conduit due to the defective rate and location during manufacturing.
  • the present invention relates to a porous neural conduit manufacturing apparatus using glass fibers.
  • the nerve conduit connects both ends of the missing nerve and acts as a pathway for nerve regeneration. It fixes both ends of the cut nerve in the nerve conduit and induces nerve connections into the conduit.
  • the use of neural conduits can prevent the penetration of scar tissue that interferes with nerve regeneration, induces the direction of nerve regeneration in the right direction, and maintains nerve regeneration promoters secreted from the nerve itself in the catheter and interferes with regeneration.
  • the materials to be used have the advantage that they can be blocked from the outside.
  • the neural conduit must be biocompatible without tissue rejection, biodegradable at the time of nerve regeneration, no neural catheter removal procedure after neural regeneration, and the degradation products of the neural catheter not toxic in the body, It should have mechanical properties to maintain internal space during nerve regeneration, and have proper elasticity and tensile strength so that the terminal part of nerve conduit can be stably maintained even after movement of procedure after insertion of nerve conduit. It should be easy to prevent damage to the normal tissue around the site and to perform the procedure.
  • Materials for such neural conduits are largely natural polymers (collagen, chitosan, etc.) and synthetic polymers (silicone, polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer) (polylactic acid-co-glycolic acid, PLGA), polycaprolactone, etc. are being studied.
  • the most widely used natural polymer material is collagen.
  • Collagen has been widely used as a material for neural conduits for nerve regeneration because of its excellent biocompatibility and weak antigenicity.
  • collagen has to be extracted from animals, making the manufacturing process difficult, difficult to store, and not suitable for mass production.
  • the manufacturing cost is expensive, there is a disadvantage in that it is limited in utilization in the clinical and very weak in tensile force in vivo.
  • synthetic polymer-based neural conduits such as polylactic acid and polylactic acid-glycolic acid copolymers, have been tested for biocompatibility and are made of a polymer tube without pores, so they have excellent structural stability and tensile strength, but are difficult to control physical properties. There is a disadvantage that is not easy to exchange.
  • the present inventor discloses neural conduit technology using glass fiber through Korean Patent Application No. 10-2014-0027854, but there is still a problem that it is not easy to exchange body fluids.
  • an object of the present invention is to provide a porous neural conduit manufacturing apparatus having a microporous structure together with a microchannel.
  • Another object of the present invention is to provide a porous neural conduit manufactured using the manufacturing apparatus of the present invention.
  • the present invention is (a) a container having an upper channel and a lower channel and a plurality of glass fibers are inserted; (b) polymer material injection means for injecting polymer material into the container; (c) a porous neural conduit manufacturing apparatus using glass fibers including a pressurizing means for applying a high pressure in the container, wherein the pressurizing means is (i) pressurized to be connected to the pressurizing tank to apply a high pressure to the pressurizing tank; Pump; (ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside; (iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And (iv) is connected to the pressure distribution control device, and provides a porous neural conduit manufacturing apparatus including a pressure chamber including the container and the injection means therein.
  • the distribution pressure control device may include 2 to 100 pressure control means including 1 to 100 air valves, regulators and 1 to 100 pressure release valves.
  • the lower channel has a smaller diameter than the upper channel and the vessel can be inclined at discrete angles.
  • the container may be made of a transparent material that can be visually confirmed the penetration of the polymer solution.
  • the present invention also includes the steps of (a) inserting a plurality of glass fibers into a container having upper and lower channels; (b) injecting a polymer material into the container into which the plurality of glass fibers are inserted; (c) applying a high pressure from the channel to infiltrate the polymer material between the glass fibers; (d) separating the glass fibers from the container; And (e) immersing the separated glass fibers in water to dissolve the glass fibers, wherein step (c) comprises; (i) forming a high pressure inside the pressurized tank using a pressurized pump; (ii) pressurizing the inside of the chamber by moving air in the pressurizing tank into the pressurizing chamber by using an air valve of a distribution pressurizing control device, and penetrating the polymer material between the glass fibers; And (iii) controlling the inside of the chamber to a normal pressure by using a pressure release valve after the penetration of the polymer material between the glass fibers is completed.
  • step (c) comprises; (
  • the polymer material is a collagen (collagen), gelatin (gelatin), chitosan, alginate, hyaluronic acid, dextran, silk (silk), cellulose, poly Poly 3-hydroxybutyrate (PHB), polyhydroxyvalerate (PHV) and poly hydroxybutyrate-co-valerate (PHBV), polyorthoesters , Polyviniyalcohol (PVA), polyethylene glycol (poly (ethyleneglycol), PEG), polyurethane, polyacrylic acid, poly-N-isopropyl acrylamide (poly (N-isopropyl acrylamide) , Poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) copolymer (poly (ethyleneoxide) -poly (propyleneoxide) -poly (ethyleneoxide) copolymer, polydioxanone-b-caprolactone (poly ( diox anone-b-caprolactone)), poly-
  • the weight / volume (w / v%) of the polymer and the solvent may be 10 to 40%.
  • the solvent may be phase-separated from the water and separated from the polymer to form pores in the polymer.
  • the polymer material may be in a solution state at room temperature.
  • Porous neural conduit manufacturing method using the glass fiber cooling the neural conduit formed after the step of dissolving the glass fiber with liquid nitrogen; And cutting the cooled neural conduit to form.
  • the pressurization may be repeated a plurality of times.
  • the present invention according to the third aspect also provides a porous neural conduit manufactured by the above method.
  • the neural conduit may have a microchannel in the axial direction of the neural conduit as the glass fiber is inserted in the axial direction of the container.
  • the neural conduit may form micropores in the neural conduit as the solvent is dissolved in water.
  • TG Hydrophobic tetraglycol
  • PLGA polylactic acid-glycolic acid copolymer
  • TG tetraglycol
  • the melting point of the polymer solution is lowered by mixing the polylactic acid-glycolic acid copolymer (PLGA) and tetraglycol (TG), the polymer material is maintained at room temperature after the PLGA has been dissolved with TG once. Can be used without remelting.
  • PLGA polylactic acid-glycolic acid copolymer
  • TG tetraglycol
  • A is a glass fiber, capillary glass and capillary glass tube with glass fiber inserted
  • B is a silicone tube with 2-way valve and Luer lock syringe
  • C is a Luer lock with silicon tube with 2-way valve (Luer lock) Syringe
  • D pressurizes the inside of glass tube using syringe.
  • Figure 2 is a schematic diagram showing a method of manufacturing a porous neural conduit.
  • 3 and 4 are diagrams showing the effect of channel formation according to discontinuous (a) or continuous (b) vessel tilt.
  • Figure 9 is a photograph showing a porous neural conduit made of various diameters and lengths according to the application.
  • FIG. 10 is a view briefly showing a dispensing pressure control device according to an embodiment of the present invention.
  • the present invention (a) a container having an upper channel and a lower channel is inserted a plurality of glass fibers; (b) polymer material injection means for injecting polymer material into the container; (c) a porous neural conduit manufacturing apparatus using glass fibers including a pressurizing means for applying a high pressure in the container, wherein the pressurizing means is (i) pressurized to be connected to the pressurizing tank to apply a high pressure to the pressurizing tank; Pump; (ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside; (iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And (iv) connected to the pressure distribution control device, and relates to a porous neural conduit manufacturing apparatus including a pressure chamber including the container and the injection means therein.
  • the present invention also includes the steps of (a) inserting a plurality of glass fibers in a container having an upper and a lower channel; (b) injecting a polymer material into the container into which the plurality of glass fibers are inserted; (c) applying a high pressure from the channel to infiltrate the polymer material between the glass fibers; (d) separating the glass fibers from the container; And (e) immersing the separated glass fibers in water to dissolve the glass fibers, wherein step (c) comprises; (i) forming a high pressure inside the pressurized tank using a pressurized pump; (ii) pressurizing the inside of the chamber by moving air in the pressurizing tank into the pressurizing chamber by using an air valve of a distribution pressurizing control device, and penetrating the polymer material between the glass fibers; And (iii) controlling the inside of the chamber to a normal pressure by using a pressure release valve after the penetration of the polymer material between the glass fibers is completed.
  • step (c)
  • polymeric material is prepared by dissolving a hydrophobic polymer in a hydrophobic solvent, and in the present invention, a collagen, gelatin, chitosan, alginate, hyaluronic acid as a hydrophobic polymer.
  • the hydrophobic polymer may be a polylactic acid-co-glycolic acid (PLGA), and the hydrophobic solvent may be tetraglycol (tetraglycol, TG).
  • PLGA polylactic acid-co-glycolic acid
  • TG tetraglycol
  • the weight / volume% (w / v%) of the polymer and the solvent refers to the weight (g) of the polymer dissolved in 1L of solvent, the weight / volume% (w / v%) is 10 to 40%, more preferably 15-25%, most optimally 20%. If less than the above range, there is a problem that the porosity is greatly increased due to the use of excessive solvent, and vice versa, sufficient pore formation may be difficult.
  • the pressurizing means includes: (i) a pressurizing pump connected to the pressurizing tank to apply high pressure to the pressurizing tank; (ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside; (iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And (iv) a pressure chamber connected to the distribution pressure control device, the pressure chamber including the container and the injection means therein, wherein step (c) includes (i) a high pressure inside the pressure tank using a pressure pump.
  • the distribution pressure control device 100 includes 2 to 100 pressure control means 110 including 1 to 100 air valves 112, a regulator 111, and 1 to 100 pressure release valves 113. It is more preferable to have a constant pressure regardless of the position inside the chamber, including.
  • the pressure pump, the pressure tank, the chamber, and the distribution pressure control device are each provided with a pressure sensor and a control means, and a conduit connecting each device is provided with a valve to automatically inside the chamber. It is desirable to be adjusted to a constant pressure.
  • the glass fiber may be moved by the pressure of the pressure during the pressing, it is preferable to fix the glass fiber using a fixing means.
  • the fixing means may be any means as long as it can fix the glass fiber, but may be a wire, an elastic body or a band including a fiber, a polymer or a metal material.
  • the fixing means is more preferably fixed to the container so that the glass fiber does not leave the position when pressed.
  • the fixing means may be fixed to the container by using hooks, protrusions or protrusions installed on the container.
  • the fixing means may be fixed to the glass fibers one by one, but also can be fixed by wrapping the 2 to 1000 glass fiber bundles, it is also possible to collect and fix the 2 to 100 glass fiber bundles as described above.
  • the lower channel has a smaller diameter than the upper channel, so that the glass fibers injected into the container can remain filled without flowing in the container.
  • the container may be inclined at a discontinuous angle, and more specifically, the container may be formed of upper and lower channels inclined at a discontinuous angle, but is not limited thereto.
  • the spacing of the glass fibers to be inserted is constant, so the spacing of the microchannels formed in the space where the glass fibers are melted is also constant. That is, the porous neural conduit manufactured according to the present invention forms microchannels at regular intervals, thereby inducing neural regeneration in the same direction.
  • the container may be to form a bottleneck point by heating a central portion of the glass tube to form an upper channel and a lower channel, but is not limited thereto.
  • the polymer material may be in a solution state at room temperature.
  • Porous neural conduit manufacturing method using the glass fiber cooling the neural conduit formed after the step of melting the glass fiber with liquid nitrogen; And cutting the cooled neural conduit to form.
  • the container may be made of a transparent material in which the penetration of the polymer solution can be visually confirmed, but may be preferably made of glass, but is not limited thereto.
  • the pressing may be performed repeatedly a plurality of times, thereby producing a neural conduit of uniform density.
  • the present invention provides a porous neural conduit prepared according to the method of the present invention.
  • the neural 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, the glass fiber is axially inserted into the upper channel of the container (glass tube), and then the polymer material (PLGA-TG solution) is injected into the container and pressure is applied to infiltrate the glass fiber and separated from the container. The glass fibers were melted by immersion in water (DW) to form microchannels made of hydrophobic polymer (PLGA) in the space where the glass fibers were melted. That is, by inserting the glass fibers in the axial direction of the container to melt the glass fibers, a neural conduit was formed in which the microchannels were formed in the axial direction in the space where the glass fibers were melted.
  • DW immersion in water
  • microchannel refers to an empty space of 10 to 20 ⁇ m size formed in the space where the glass fibers are melted.
  • the neural conduit may be micropores formed in the neural conduit as the solvent is dissolved in water. More specifically, TG reacts (dissolves) with water (DW) in the process of immersing glass fiber infiltrated with polymer material (PLGA-TG solution) in water (DW) and exits from the neural conduit to form micropores inside the microchannel. Formed. Dissolution in this specification means that TG is separated from the polymeric material.
  • microporous pores refers to the fine pores that form in the microchannels as the solvent dissolves in the DW and exits the neural conduit.
  • the neural conduit prepared according to the present invention facilitates fluid exchange by microchannels when applied in vivo.
  • the solvent exiting the neural conduit was denser than the DW (1.09 g / ml) and settled in a haze at the bottom of the DW (FIG. 7).
  • Porous neural conduit prepared according to an embodiment of the present invention can be produced in a variety of diameters and lengths, and can be freely changed in diameter and length according to the purpose and purpose of use to be useful in in vitro and in vivo studies of the nerves have.
  • Hydrophobic polymer polylactic acid-glycolic acid copolymer (mol% of lactic acid to glycolic acid, 85:15) and hydrophobic solvent tetraglycol (TG) (density: 1.09 g / ml, Sigma-Aldrich, USA ) was mixed so that the weight-to-volume (w / v) ratio was 20% (w / v) and then dissolved at 60 ° C. for 18 hours to prepare a 20% (w / v) PLGA-TG solution (polymeric material).
  • PLGA Hydrophobic polymer polylactic acid-glycolic acid copolymer
  • TG hydrophobic solvent tetraglycol
  • the central portion of the capillary tube 1.6 mm in inner diameter and 13 cm in length was heated to form a bottleneck, forming upper and lower channels that were inclined at discrete angles. At this time, the lower channel was manufactured to form a smaller diameter than the upper channel. Thereafter, water soluble glass fibers (50P 2 O 5 -20CaO-30Na 2 O in mol% (1100 ° C, 800rpm)) having a diameter of 10 to 20 ⁇ m were cut in 5 to 6 cm units to form a shaft in the upper channel of the glass tube. In the right direction (FIGS. 1A and 2A).
  • a pressure device prepared by connecting a Luer lock syringe with a 2-way valve attached to a silicon tube having an inner diameter of 0.8 mm and a length of 15 cm was inserted into an upper channel of a glass tube into which glass fibers were inserted (FIG. 1B and 1C).
  • the width of the lower channel is narrowed compared to the upper channel at a discontinuous angle, which is shown in FIG. 3. If the angle is continuous (Fig. 4), the gap between the glass fibers is gradually narrowed, there is a problem that it is difficult to maintain a constant gap between the glass fibers.
  • the spacing of the glass fibers is not constant, the nerve regeneration direction formed by the glass fibers varies depending on the channel, and thus a problem occurs that nerve regeneration in the same direction becomes difficult.
  • the glass fiber infiltrated with PLGA-TG solution was separated from the glass tube using a wire of 1.5 mm in diameter and 15 cm in diameter, and immediately immersed in 10-20 ° C. of distilled water (DW) for at least 24 hours (FIG. 2D). ), Approximately 7,000 to 8,500 (number of microchannels: 7,777 ⁇ ) of 10 to 20 ⁇ m microchannels (16.54 ⁇ 3.6 ⁇ m in diameter) consisting of PLGA in the space where all the glass fibers are dissolved and the glass fibers are melted. 716.2 pieces) (FIGS. 2E and 5). At the same time as the glass fibers were dissolved in the DW of 10 ⁇ 20 °C, PLGA was cured to form a microchannel.
  • DW distilled water
  • TG reacts with the DW (dissolves in DW) to escape from the microchannel, thereby forming micropores inside the microchannel (FIGS. 5, 6 and 7).
  • TG released from the neural conduit was denser than the DW and sunk in the lower part of the DW (Fig. 8).
  • the glass fiber and TG were removed through the DW treatment, and the porous microchannel made of PLGA, that is, the prepared neural conduit was frozen in liquid nitrogen for about 30 seconds, and cut and shaped to a size suitable for use (FIG. 9).
  • Example 1 a pressure was applied using a syringe, but a porous neural conduit was manufactured using an automatic pressure control method using a pressure chamber instead of the syringe.
  • the upper channel was connected to the pressurization chamber.
  • the valves 112 and 113 connected to each conduit were adjusted to be OFF, and then the pressure pump 200 was operated to pressurize the pressure tank 400 to prepare.
  • the chamber was pressurized to a predetermined pressure through the three pressure control means 110 connected to the distribution pressure control device 100, and after the pressurization was completed, the inside of the chamber was adjusted to the normal pressure by using each pressure release valve 113. . Thereafter, the procedure was performed in the same manner as in Example 1.
  • microstructures formed in the microchannels inside the neural catheter prepared in Example 1 by dissolving the glass fibers in water were confirmed by scanning electron microscopy (SEM) (FIGS. 5, 6 and 7).
  • FIG. 5 is a cross-sectional view of the neural conduit
  • FIG. 6 is a photograph showing an enlarged microstructure in the cross-sectional view of the neural conduit
  • FIG. 7 is a longitudinal cross-sectional view of the neural conduit, in which the microchannels inside the neural conduit are continuous from the distal to the proximal end. It was confirmed that micropores were formed in the microstructure inside the microchannel.
  • the neural conduits were manufactured by repeating the method 10 times, the size and distribution of the microchannels inside the neural conduits were not constant. On the contrary, the neural conduits were repeated 10 times by the method of Example 2.
  • the conduit was manufactured, it was confirmed that neural conduits including microchannels having a constant size and distribution can be produced. This is because it is determined that a constant pressure is not applied because the syringe is operated using a human sense when pressurized by the method of Example 1, and in Example 2 using a valve and a pressurized chamber, the microchannel having a constant size and distribution is neural. It was confirmed that it is distributed in the conduit.
  • the neural conduit prepared according to the present embodiment may be manufactured in various diameters and lengths according to the purpose and purpose of use so as to be useful for in vitro and in vivo studies of the nerve.

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Abstract

La présente invention concerne un appareil servant à préparer un conduit nerveux et, plus particulièrement, un appareil servant à préparer un conduit nerveux poreux à l'aide d'une fibre de verre, qui forme un microcanal à l'aide d'un espace entre des fibres de verre et qui est uniformément mis sous pression, de façon à réduire au minimum la proportion défectueuse pendant la préparation et une différence entre les conduits nerveux en fonction de leurs positions. Un conduit nerveux fabriqué selon la présente invention peut être formé de façon à présenter divers diamètres et longueurs, en fonction du but et de l'utilisation, de sorte que le conduit nerveux préparé peut être utilisé efficacement pour des recherches in vitro et in vivo sur un nerf.
PCT/KR2017/006621 2017-06-12 2017-06-23 Appareil servant à préparer un conduit nerveux WO2018230759A1 (fr)

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KR10-2017-0073225 2017-06-12
KR1020170073225A KR101931545B1 (ko) 2017-06-12 2017-06-12 신경도관 제조장치

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100673498B1 (ko) * 2005-10-25 2007-01-24 한국과학기술연구원 조직공학용 생분해성 이중기공 고분자 지지체의 제조 방법
US7172096B2 (en) * 2004-11-15 2007-02-06 Advanced Technology Materials, Inc. Liquid dispensing system
US20110281358A1 (en) * 2010-05-17 2011-11-17 Pall Corporation System For Seeding Cells Onto Three Dimensional Scaffolds
KR20120127372A (ko) * 2012-10-08 2012-11-21 단국대학교 산학협력단 상분리법을 이용한 나노섬유 구조 생체고분자의 제조방법
US8691973B2 (en) * 2006-03-28 2014-04-08 Korea Institute Of Radiological & Medical Sciences Method of producing chitosan scaffold having high tensile strength and chitosan scaffold produced using the method
KR20150105826A (ko) * 2014-03-10 2015-09-18 단국대학교 천안캠퍼스 산학협력단 내부에 미세구조의 채널을 가지는 생분해성 신경도관 및 이의 제조방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7172096B2 (en) * 2004-11-15 2007-02-06 Advanced Technology Materials, Inc. Liquid dispensing system
KR100673498B1 (ko) * 2005-10-25 2007-01-24 한국과학기술연구원 조직공학용 생분해성 이중기공 고분자 지지체의 제조 방법
US8691973B2 (en) * 2006-03-28 2014-04-08 Korea Institute Of Radiological & Medical Sciences Method of producing chitosan scaffold having high tensile strength and chitosan scaffold produced using the method
US20110281358A1 (en) * 2010-05-17 2011-11-17 Pall Corporation System For Seeding Cells Onto Three Dimensional Scaffolds
KR20120127372A (ko) * 2012-10-08 2012-11-21 단국대학교 산학협력단 상분리법을 이용한 나노섬유 구조 생체고분자의 제조방법
KR20150105826A (ko) * 2014-03-10 2015-09-18 단국대학교 천안캠퍼스 산학협력단 내부에 미세구조의 채널을 가지는 생분해성 신경도관 및 이의 제조방법

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