JP2022506369A - Magnesium wire / silk composite braided neural catheter and its manufacturing method - Google Patents

Abstract

The present invention discloses a neural catheter having a magnesium wire / silk composite braid structure and a method for manufacturing the same, and by adding a medical metal magnesium wire having strong mechanical properties to the silk braid structure as a shaft thread, the role of guidance in the vertical direction is provided. Not only can it improve the radial compression properties of the braided skeleton, and magnesium wire can slowly break down, promoting the growth and proliferation of Schwann cells, for the recovery of damaged nerves. Useful, the braided yarn is degammed silk, has good biocompatibility, ensures excellent mechanical properties and forms a biomicroenvironment to promote nerve regeneration.

Description

The present invention belongs to the technical field of biomedical materials, and specifically relates to a neural catheter having a magnesium wire / silk composite braid structure and a method for manufacturing the same.

Peripheral nerve injury is a common clinical disorder, and promoting the repair and regeneration of damaged nerves through biomaterials and tissue engineering techniques is a hotspot for research in the field of neuroscience. Ideal biomaterials, proper physical and mechanical guidance, and proper biological microenvironments are key factors that facilitate the recovery of biological functions such as the sensation and movement of damaged nerves. Currently, in research on neurocatheter, most of the techniques such as mold casting method, electrostatic nanospinning method, 3D bioprinting, and biodegradable materials such as silk fibroin, chitosan and collagen are used for physical guidance function. However, the neural catheters produced by these techniques are inferior in mechanical dynamics and flexibility. For example, in a nerve catheter using the directional guidance function of silk fibroin nanofibers, the silk fibroin solution is condensed and guided to form nanopores as physical guidance. The shape and size of the nanopores formed in the present invention. And direction control is difficult, the catheter's radial compression properties are inadequate, flexion resistance is not considered, and for example, films of various decomposition concentrations are first used, for example, with nano-aligned fibers. When the silk catheter is manufactured and then wound into a tubular structure nerve catheter, such a nerve catheter has excellent physical guidance to cells, but its own mechanical properties are inferior, and it is used for internal nerve regeneration. The space is small, and when, for example, 3D bioprinting is used, there are large restrictions on the material, and the current resolution is low, about 1 to 300 mPa / s.

As a result of research, magnesium is one of the important elements essential for the human body, is involved in the synthesis of proteins in the brain and central nervous system, activates various enzymes in the body, and regulates the activity of nerve muscles. In the microenvironment, metallic magnesium ions have various biological functions such as anti-inflammatory, anti-oxidation, anti-apoptosis and regulation of mitochondrial calcium buffer. According to the latest research, magnesium ions can promote the proliferation of Schwann cells such as secretory growth factor, extracellular matrix (ECM), and support and protect neurons when cultured in a suitable microenvironment. can. Silk moth silk is a natural animal protein synthesized and secreted by silk moth, and has various sources. Silk fibroin is the main component of silk, accounting for about 70% to 80% of the weight of silk, and the rest. The main components are sericin and carbohydrates. Silk fibroin contains a plurality of amino acids, of which the common alanine (Ala), glycine (Gly) and serine (Ser) make up about 85% of the total components. Silk fibroin itself has excellent physical and chemical properties, breathability, moisture permeability, and biocompatibility, and is decomposed into polypeptides and free amino acids in vivo and absorbed in vivo to promote the growth of nerve cells. be able to. Nerve catheters made of silk fibroin have less inflammatory response in vivo, are biodegradable, and can promote functional recovery of injured peripheral nerves. Chitosan, also called deacetylated chitin, is obtained by deacetylating chitin, which is widely present in nature. Its structure and properties are very similar to those of aminopolysaccharides in ECM, and it is adsorbed. It is highly sexual, its degradation rate is adjustable, and its degradation intermediate, chitosan oligosaccharides, can inhibit neuronal apoptosis, support cell adhesion, and promote the regeneration of damaged axons.

Common techniques for manufacturing neural catheters include: (1) A casting-dipping method, which is easy to operate, but may leave a toxic solvent on the stent, making it difficult to control the size and distribution of the holes. (2) A conventional electrostatic spinning method that can form nanofibers with high porosity and specific surface area, and can create a microenvironment similar to the network structure of extracellular matrix, which is advantageous for nerve regrowth. However, the nerve catheter manufactured by the conventional electrostatic spinning method has insufficient mechanical strength, and it is difficult to provide a stable mechanical environment for the injured nerve. (3) A braiding technique, in which the surface area inside the catheter can be increased by knitting the yarn into a tubular weave using a spindle braiding machine, and the mechanical properties are improved. .. However, there are still drawbacks to directional cell migration and induction of tissue regeneration.

To solve the above problems, the present invention provides a neural catheter having a magnesium wire / silk composite braid structure and a method for manufacturing the same.

An object of the present invention is to provide a nerve catheter having a magnesium wire-silk composite braid structure capable of improving the regularity of nerve regeneration and the mechanical strength of the nerve catheter, and a method for manufacturing the same, in order to solve the above problems. ..

The technical proposal of the present invention is as follows.
A neural catheter with a magnesium wire / silk composite braid structure.
The outer layer of the neural catheter, the intermediate layer of the neural catheter, and the inner layer of the neural catheter are included, the intermediate layer of the neural catheter is coated on the outside of the inner layer of the neural catheter, and the outer layer of the neural catheter is the intermediate layer of the neural catheter. Covered on the outside, the outer layer of the neural catheter is a porous sponge structure formed by mixing a silk fibroin solution and a chitosan solution, and the outer layer of the neural catheter is 0.5 to 1.5 mm in thickness. The hole diameter is 20 to 150 μm, the void ratio is 75% to 90%, the intermediate layer of the neural catheter has a three-dimensional braided structure, and the intermediate layer of the neural catheter has a thickness of 0.3 to 1 The braiding angle of the three-dimensional braided structure is 45 to 60 °, the inner layer of the nerve catheter is a porous gel structure, and the inner layer of the nerve catheter has a diameter of 1.8 to 5 mm.

Further, the three-dimensional braided structure is either a diamond braided structure, a regular braided structure or a Hercules braided structure.

Further, the three-dimensional braided structure is a catheter skeleton having a three-dimensional structure in which a magnesium wire is used as a shaft thread and degumming silk is used as a braided thread to knit, and the magnesium wire has a diameter of 0.1 to 0.25 mm. , The number is 4 to 16, the distance between two adjacent magnesium wires is 200 to 2000 μm, and the thread density of the degummed silk is 20 to 120D.

Further, the porous gel structure is a composite gel layer composed of silk fibroin gel, Schwann cells and nerve growth factor, the silk fibroin gel freezes to form mesh fibers, and the Schwann cells and nerve growth factor are the mesh. Arranged within the fibers, the mesh fibers have a diameter of 10 to 1000 nm and a hole diameter of 10 to 500 μm.

Another technical proposal of the present invention is as follows.
A method for manufacturing a neural catheter with a magnesium wire / silk composite braid structure.
A step in manufacturing the intermediate layer of a neural catheter, in which the skeletal structure of a neural catheter is manufactured using a vertical spindle braiding machine with a core function, and magnesium wire is used as an axoneme and degumming silk is used as a braiding yarn. (1) and
Silk fibroin solution: chitosan solution = 1: 1 to 1: 5, the silk fibroin solution is gradually added to the chitosan solution, and the mixture is stirred for 6 to 12 hours to obtain a mixed solution 2 of the nerve catheter. The intermediate layer is fixed in a mold, then the mixed solution 2 is poured into the mold, placed in a refrigerator at −20 ° C. for 4 to 12 hours, then placed in a freeze dryer and freeze-dried for 12 to 36 hours. Then, the outer layer of the neural catheter having a porous hollow structure is obtained, and the manufacturing step (2) of the outer layer of the neural catheter is performed.
A solution of silk fibroin having a concentration of 0.01 to 0.5% in which Schwann cells were cultured was poured into the hollow structure of the outer layer of the neural catheter and left at a temperature of 37 ° C. for 12 hours to form a gelled catheter, and the gel was formed. The chemized catheter is inserted vertically into a liquid nitrogen tank and slowly frozen downward along the axial direction of the gelled catheter at a rate of 0.1-1 mm / s, then placed in a lyophilizer. It comprises the manufacturing step (3) of the inner layer of the neural catheter, which is freeze-dried for 24-48 hours to obtain a neural catheter having a magnesium wire-silk composite braid structure.

Further, in step (2), in the method for producing the silk fibroin solution, raw silk yarn is weighed, degummed with a boiling Na ₂ CO ₃ aqueous solution for 30 minutes, stirred with a glass rod every 10 minutes, and removed. Rinse multiple times with ionized water, place in a draft chamber and air dry overnight to obtain dried silk fibroin fiber, dissolve the dried silk fibroin fiber in LiBr solution, dissolve in an oven at 60 ° C. for 4 hours, 1 Shake gently every hour to dissolve completely to obtain the mixed solution 1, centrifuge the mixed solution 1 after dialysis to obtain the silk fibroin solution, and put it in a refrigerator at 4 ° C. for use.

Further, in step (2), in the dialysis, the mixed solution 1 is poured into a dialysis bag having a molecular weight cut-off of 3500D, dialyzed against deionized water for 36 hours, and the water is replaced once every 4 hours.

Further, in step (2), in the centrifugation, the centrifuge is used for 20 minutes each time, and the centrifuge is performed twice at 9000 r / min.

Further, in step (2), in the method for producing a chitosan solution, chitosan having a deacetylation degree of 80 to 95% is weighed, dissolved in a 0.5 to 4% acetic acid solution, and stirred for 4 to 12 hours. Then, a chitosan solution having a mass fraction of 1 to 5% is produced.

The present invention provides a neural catheter having a magnesium wire / silk composite braid structure and a method for manufacturing the same, and its advantages are as follows.
(1) By improving the mechanical properties of the catheter such as radial compression characteristics and tension, and improving the flexibility and bending characteristics of the neural catheter, it is possible to adapt to the complex receiving environment in the living body. ..
(2) The catheter has excellent biocompatibility, surface activity and permeability, can promote the adhesion, growth and proliferation of nerve cells, and can increase the regeneration rate of damaged nerves.
(3) By adjusting the decomposition rate of the nerve catheter using various materials and degeneration processes, a growth space suitable for nerve regeneration is provided.
(4) Since the magnesium wire in the catheter has conductivity, it can stimulate and induce nerve growth, and magnesium ions generated during decomposition contribute to enhancing the activity of nerve cells.

In order to more clearly explain the technical proposal of the embodiment of the present invention, the drawings necessary for the description of the embodiment will be briefly described below, but clearly, the drawings described below are some of the drawings of the present invention. It is only an embodiment, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.
It is a structural schematic diagram of the nerve catheter in Example 1 of the said magnesium wire-silk composite braid structure of this invention. It is a structural schematic diagram in Example 2 of the neural catheter of the said magnesium wire-silk composite braid structure of this invention. It is a structural schematic diagram in Example 1 of the neural catheter of the said magnesium wire-silk composite braid structure of this invention. 1 is the braiding angle of a neural catheter having a magnesium wire / silk composite braided structure having inner diameters of 2 mm and 3 mm, respectively, manufactured with different parameters in Example 1 of the present invention. It is a load-tensile strain curve of a neural catheter of a magnesium wire / silk composite braid structure having inner diameters of 2 mm and 3 mm, respectively, manufactured with different parameters in Example 1 of the present invention.

In order to make it easier to understand the above object, feature and advantage of the present invention, the present invention will be described in more detail below with reference to specific embodiments and drawings.

The present invention provides a neural catheter with a magnesium wire-silk composite braid structure. As shown in FIG. 1, the neural catheter is divided into three layers, and the outer layer 1 of the neural catheter is a porous sponge structure formed by mixing a silk fibroin solution and a chitosan solution, and has a thickness of 0.5. The hole diameter is 20 to 150 μm, the void ratio is 75% to 90%, the intermediate layer 2 of the neural catheter has a three-dimensional braided structure, and a diamond braided structure (1/1 mixed weave). , One of three braided structures, a regular braided structure (2/2 mixed weave) and a Hercules braided structure (3/3 mixed weave), with a thickness of 0.3 to 1 and a braid angle of 45. The temperature is about 60 °, the inner layer 3 of the nerve catheter has a porous gel structure, the diameter is 1.8 to 5 mm, and the decomposition time is 1 to 5 days. The intermediate layer 2 of the nerve catheter has a diameter of 0.1 to 0.25 mm, a number of 4 to 16, and a magnesium wire having an interval of 200 to 2000 μm as a shaft thread, and has a thread density of 4 to 16. It is a catheter skeleton having a three-dimensional structure in which degummed silk of 20 to 120D is combined and knitted as a braided thread 5, and the inner layer 3 of the nerve catheter is a composite gel composed of silk fibroin gel 6, Schwann cells 7, and nerve growth factor 8. It is a layer and has the effect of guiding the directional growth of nerve cells. Nerve growth factor 8 is a protein molecule necessary for the growth and survival of neurons, and the mesh fibers formed by freezing have a diameter of 10 to 1000 nm and a hole diameter of 10 to 500 μm. The catheter structure has excellent flexibility and bending characteristics, and can cope well with the complex receiving environment in the living body.

The method for manufacturing a neural catheter having a magnesium wire / silk composite braid structure described above includes the following steps.

(1) Manufacture of the intermediate layer 2 of the nerve catheter: The skeletal structure of the nerve catheter is manufactured using a vertical spindle braiding machine equipped with a core function, the magnesium wire is used as the shaft thread 4, and the degummed silk is used as the braided thread 5. , Combined and organized.

(2) Production of silk fibroin solution: Weigh 30 g of raw silk moth, degumming with 12 L of boiling Na ₂ CO ₃ aqueous solution (0.02 M) for 30 minutes, and stirring with a glass rod every 10 minutes. It was completely degummed, then rinsed several times with deionized water, and the washed silk fibroin fibers were placed in a draft chamber and air dried overnight. Weigh 25 g of dried silk fibroin fiber, dissolve in 100 mL of LiBr solution (9.3 M), dissolve in an oven at 60 ° C. for 4 hours, shake gently every hour, and dissolve completely to obtain mixed solution 1. rice field. The mixed solution 1 was poured into a dialysis bag (molecular weight cut off of 3500D), dialyzed against deionized water for 36 hours, and the water was replaced every 4 hours. The solution after dialysis is centrifuged twice at 9000 r / min for 20 minutes each time with a high-speed centrifuge to remove impurities, and finally, a silk fibroin solution is obtained and placed in a refrigerator at 4 ° C. for use. Served.

(3) Production of intermediate layer 1 of nerve catheter: Weigh 2 to 8 g of chitosan having a deacetylation degree of 80 to 95%, dissolve in 0.5 to 4% acetic acid solution, and stir for 4 to 12 hours. , A chitosan solution having a mass fraction of 1-5% was produced. Silk fibroin solution: Chitosan solution = 1: 1 to 1: 5 The silk fibroin solution was gradually added to the produced chitosan solution, and the mixture was stirred for 6 to 12 hours to obtain a mixed solution 2. The braided layer of degummed silk (intermediate layer 2 of the nerve catheter) is fixed in the mold, then the mixed solution 2 is poured into the mold, placed in a refrigerator at -20 ° C and frozen for 4 to 12 hours, and then in a freeze dryer. It was put in and freeze-dried for 12 to 36 hours, and then taken out to obtain a sponge outer layer material having a porous structure.

(4) Manufacture of inner layer 3 of nerve catheter:
1) The frozen catheter was sealed, and a solution of silk fibroin having a concentration of 0.01 to 0.5% in which Schwann cells were cultured was poured into the hollow structure of the neural catheter and left at 37 ° C. for 12 hours to induce gelation. .. 2) Insert the catheter vertically into a liquid nitrogen tank and slowly freeze it downward along the axial direction of the catheter at a rate of 0.1-1 mm / s, then place it in a lyophilizer and 24- It was lyophilized for 48 hours.

In order to make it easier to understand the above object, feature and advantage of the present invention, the technical proposal of the present invention will be described in more detail below with reference to the drawings and examples. However, the invention is not limited to the listed examples and should include any other known modifications within the claims of the invention.

First, the "one embodiment" or "example" referred to herein refers to a particular feature, structure or property that can be included in at least one embodiment of the invention. "In one example" at different locations herein does not refer to all the same examples, nor is it an example that is mutually exclusive with other examples, either separately or optionally. ..

Next, when the present invention is described in detail with a structural schematic diagram or the like and an embodiment of the present invention is described in detail, in order to facilitate the explanation, the schematic diagram does not follow a general scale but is a part. Moreover, the schematic diagram is merely an example, and does not limit the scope of protection of the present invention here. In addition, it is necessary to include a three-dimensional space of length, width, and depth during actual manufacturing.

Example 1
This example discloses a neural catheter structure having a magnesium wire / silk composite braid structure and a method for manufacturing the same. As shown in FIG. 1, the neural catheter has a total of three layers, of which the shaft thread 4 of the intermediate layer 2 of the neural catheter is magnesium wire, and the braided thread 5 of the intermediate layer 2 of the neural catheter is degummed silk. The outer layer 1 of the nerve catheter is a porous sponge structure formed by mixing a silk fibroin solution and a chitosan solution, the weight ratio of silk fibroin to chitosan is 10: 1, and the concentration of the chitosan solution is 3 to 3. It is 6 mg / mL, and the concentration of the silk fibroin aqueous solution is 5 to 10% (w / v). The inner layer 3 of the nerve catheter is a porous silk fibroin gel layer prepared with a silk fibroin aqueous solution having a concentration of 5 to 10% (w / v). The manufacturing process is as follows.
(1) The intermediate layer 2 of the nerve catheter is manufactured by the braiding method. That is, diamond braiding (1/1) using a vertical braiding machine with 8 to 32 spindles as a braiding process using 20 to 100 D degummed silk as raw materials and magnesium wire having a diameter of 0.05 to 0.2 mm. The braiding angle was set to 45 to 60 °, the gear ratio (large gear: small gear) was set to 80 to 120: 18 to 60, and the rotation speed was set to 5 to 100 rpm.
(2) The intermediate layer 2 of the braided nerve catheter was fixed in a tubular polytetrafluoroethylene mold, and the produced solution was poured into the mold to set the molding temperature to 60 ± 2 ° C. and the molding time to 15 to 30 min. Place in the refrigerator and freeze at -20 ° C for 4-12 hours, then place in a lyophilizer, lyophilize for 12-36 hours and then remove and remove the catheter 5-10 at a processing temperature of 50-70 ° C. Time steam treatment was performed to obtain a neural catheter with a porous sponge layer.
(3) The frozen catheter is sealed, a silk fibroin solution containing Schwann cells at a concentration of 0.01 to 0.5% is poured into the hollow structure of the catheter, and left at 37 ° C. for 12 hours to induce its gelation. The catheter is inserted vertically into a liquid nitrogen tank, slowly frozen downward along the axial direction of the catheter at a rate of 0.1-1 mm / s, and finally placed in a lyophilizer for 24-48 hours. Freeze-drying gave a silk fibroin gel layer containing Schwann cells.

The characteristics of the neural catheter having a magnesium wire / silk composite braid structure manufactured by the above method may be referred to FIGS. 4 to 5, and as can be seen from FIG. 4, the braiding angle of the neural catheter having a magnesium wire / silk composite braid structure can be seen. Is stable with a change between 40 and 55 °, and as can be seen from FIG. 5, the first peak represents the breakage peak of the braided yarn, at which time the tensile strain is 8% and the load is 35N. High, the second peak represents the break peak of the shaft thread, at which time the load reaches 65 N or more, indicating that the addition of the shaft thread significantly improves the tensile properties of the nerve catheter.

Example 2
This example discloses a neural catheter structure having a magnesium wire / silk composite braid structure and a method for manufacturing the same. As shown in FIG. 2, the neural catheter has a total of three layers, of which the axial thread 4 of the intermediate layer 2 of the neural catheter is a magnesium wire, and the braided thread 5 has four decomposable titanium-nickel alloys. The addition of the wire 9 improves the radial compression characteristics of the neural catheter, and the outer layer 1 of the neural catheter is a porous sponge layer prepared with a chitosan solution having a concentration of 3 to 6 mg / mL, and the outer layer 1 of the solution is a porous sponge layer. The concentration is 3 to 6 mg / mL, and the inner layer 3 of the neural catheter is a porous silk fibroin gel layer prepared with a silk fibroin aqueous solution having a concentration of 5 to 10% (w / v). The manufacturing process is as follows.
(1) The intermediate layer 2 of the nerve catheter is manufactured by the braiding method. That is, using 20-100D degummed silk as raw materials, magnesium wire with a diameter of 0.05-0.2 mm and titanium-nickel alloy, and using an 8-32 spindle vertical braiding machine as the braiding process, the rules. Braiding (2/2 mixed weaving) is performed, the braiding angle on the braiding machine is 45 to 60 °, the gear ratio (large gear: small gear) is 80 to 120: 18 to 60), and the rotation speed is 5 to 100 rpm. I set it.
(2) The intermediate layer of the nerve catheter was fixed in a tubular polytetrafluoroethylene mold, and the produced solution was poured into the mold to set the molding temperature to 60 ± 2 ° C. and the molding time to 15 to 30 min. Place in the refrigerator and freeze at -20 ° C for 4-12 hours, then place in a lyophilizer, lyophilize for 12-36 hours and then remove and remove the catheter 5-10 at a processing temperature of 50-70 ° C. Time steam treatment was performed to obtain a porous sponge layer of the nerve catheter.
(3) The frozen catheter is sealed, a silk fibroin solution containing Schwann cells at a concentration of 0.01 to 0.5% is poured into the hollow structure of the catheter, and left at 37 ° C. for 12 hours to induce its gelation. The catheter is inserted vertically into a liquid nitrogen tank, slowly frozen downward along the axial direction of the catheter at a rate of 0.1-1 mm / s, and finally placed in a lyophilizer for 24-48 hours. Freeze-drying gave a silk fibroin gel layer containing Schwann cells.

Example 3
This example discloses a neural catheter structure having a magnesium wire / silk composite braid structure and a method for manufacturing the same. As shown in FIG. 3, the nerve catheter has a total of three layers, of which the shaft thread 4 of the intermediate layer 2 of the nerve catheter is a mixed weave of a magnesium wire and a degummed silk, and the braided thread 5 is a degummed silk. The outer layer 1 of the nerve catheter is a porous sponge layer made of a silk fibroin solution having a concentration of 5 to 10% (w / v). The inner layer 3 of the nerve catheter is a porous silk fibroin gel layer prepared with a silk fibroin aqueous solution having a concentration of 5 to 10% (w / v). The manufacturing process is as follows.
(1) The intermediate layer 2 of the nerve catheter is manufactured by the braiding method. That is, a Hercules braid structure (3 / 3 cross weaving) was performed, the braiding angle on the braiding machine was set to 45 to 60 °, the gear ratio (large gear: small gear) was set to 80 to 120: 18 to 60, and the rotation speed was set to 5 to 100 rpm.
(2) The intermediate layer of the nerve catheter was fixed in a tubular polytetrafluoroethylene mold, and the produced solution was poured into the mold to set the molding temperature to 60 ± 2 ° C. and the molding time to 15 to 30 min. Place in the refrigerator and freeze at -20 ° C for 4-12 hours, then place in a lyophilizer, lyophilize for 12-36 hours and then remove and remove the catheter 5-10 at a processing temperature of 50-70 ° C. After time steam treatment, a nerve catheter in which the outer layer 1 was a porous sponge layer was obtained.
(3) The frozen catheter is sealed, a silk fibroin solution containing Schwann cells at a concentration of 0.01 to 0.5% is poured into the hollow structure of the catheter, and left at 37 ° C. for 12 hours to induce its gelation. The catheter is inserted vertically into a liquid nitrogen tank, slowly frozen downward along the axial direction of the catheter at a rate of 0.1-1 mm / s, and finally placed in a lyophilizer for 24-48 hours. Freeze-drying gave a silk fibroin gel layer containing Schwann cells.

Therefore, the present invention discloses a neural catheter structure having a magnesium wire / silk composite braided structure and a method for manufacturing the same.
By adding a medical metal magnesium wire having strong mechanical properties to the silk braided structure as an axoneme, not only can it serve as a guide in the vertical direction, but also the radial compression characteristics of the braided skeleton can be improved. In addition, magnesium wire can slowly decompose and promote the growth and proliferation of Schwann cells, helping to recover damaged nerves, the braided yarn is degumized silk, has good biocompatibility and is excellent. It secures mechanical properties and forms a biomicroenvironment to promote nerve regeneration.

It should be noted that the above examples are merely for explaining the technical proposal of the present invention, and are not intended to limit the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art may modify or make equivalent substitutions of the invention without departing from the gist and scope of the invention. All of them should be included in the claims of the present invention.

1 outer layer of nerve catheter, 2 middle layer of nerve catheter, 3 inner layer of nerve catheter, 4 axial thread, 5 braided thread, 6 silk fibroin gel, 7 Schwann cells, 8 nerve growth factor, 9 titanium-nickel alloy wire.

Claims (9)

A neural catheter with a magnesium wire / silk composite braid structure.
The outer layer of the neural catheter, the intermediate layer of the neural catheter, and the inner layer of the neural catheter are included, the intermediate layer of the neural catheter is coated on the outside of the inner layer of the neural catheter, and the outer layer of the neural catheter is the intermediate layer of the neural catheter. The outer layer of the neural catheter is coated on the outside and has a porous sponge structure formed by mixing a silk fibroin solution and a chitosan solution, and the outer layer of the neural catheter has a thickness of 0.5 to 1.5 mm. The hole diameter is 20 to 150 μm, the void ratio is 75% to 90%, the intermediate layer of the neural catheter has a three-dimensional braided structure, and the intermediate layer of the neural catheter has a thickness of 0.3 to 1. The braiding angle of the three-dimensional braided structure is 45 to 60 °, the inner layer of the nerve catheter is a porous gel structure, and the inner layer of the nerve catheter has a diameter of 1.8 to 5 mm. Nerve catheter with magnesium wire / silk composite braid structure. The magnesium wire-silk composite braided neural catheter according to claim 1, wherein the three-dimensional braided structure is one of a diamond braided structure, a regular braided structure, and a HERCULES braided structure. The three-dimensional braided structure is a catheter skeleton having a three-dimensional structure in which a magnesium wire is used as a shaft thread and degumming silk is used as a braided thread to knit. The magnesium wire has a diameter of 0.1 to 0.25 mm and is a number. The magnesium wire according to claim 1, wherein the number of magnesium wires is 4 to 16, the distance between two adjacent magnesium wires is 200 to 2000 μm, and the yarn density of the degummed silk is 20 to 120D. -Silk composite braided neural catheter. The porous gel structure is a composite gel layer composed of silk fibroin gel, Schwann cells and nerve growth factor, the silk fibroin gel freezes to form mesh fibers, and the Schwann cells and nerve growth factor are contained in the mesh fibers. The nerve catheter having a magnesium wire / silk composite braid structure according to claim 1, wherein the mesh fibers have a diameter of 10 to 1000 nm and a hole diameter of 10 to 500 μm. A method for manufacturing a neural catheter with a magnesium wire / silk composite braid structure.
A step in manufacturing the intermediate layer of a neural catheter, in which the skeletal structure of a neural catheter is manufactured using a vertical spindle braiding machine with a core function, and magnesium wire is used as an axoneme and degumming silk is used as a braiding yarn. (1) and
Silk fibroin solution: chitosan solution = 1: 1 to 1: 5, the silk fibroin solution is gradually added to the chitosan solution, and the mixture is stirred for 6 to 12 hours to obtain a mixed solution 2 of the nerve catheter. The intermediate layer is fixed in a mold, then the mixed solution 2 is poured into the mold, placed in a refrigerator at −20 ° C. for 4 to 12 hours, then placed in a freeze dryer and freeze-dried for 12 to 36 hours. Then, the outer layer of the neural catheter having a porous hollow structure is obtained, and the manufacturing step (2) of the outer layer of the neural catheter is performed.
A solution of silk fibroin having a concentration of 0.01 to 0.5% in which Schwann cells were cultured was poured into the hollow structure of the outer layer of the neural catheter and left at a temperature of 37 ° C. for 12 hours to form a gelled catheter, and the gel was formed. The chemized catheter is inserted vertically into a liquid nitrogen tank and slowly frozen downward along the axial direction of the gelled catheter at a rate of 0.1-1 mm / s, then placed in a lyophilizer. A manufacturing method comprising the step (3) of manufacturing an inner layer of a neural catheter, which is freeze-dried for 24 to 48 hours to obtain a neural catheter having a magnesium wire / silk composite braid structure. In step (2), in the method for producing the silk fibroin solution, raw silk yarn is weighed, degummed with a boiling Na ₂ CO ₃ aqueous solution for 30 minutes, stirred with a glass rod every 10 minutes, and deionized water. Rinse multiple times with, place in a draft chamber and air dry overnight to obtain dried silk fibroin fiber, dissolve the dried silk fibroin fiber in LiBr solution, dissolve in an oven at 60 ° C. for 4 hours, and every hour. It is characterized in that the mixed solution 1 is obtained by shaking lightly to obtain a mixed solution 1, the mixed solution 1 after dialysis is centrifuged to obtain a silk fibroin solution, and the mixture is placed in a refrigerator at 4 ° C. for use. The method for manufacturing a nerve catheter having a magnesium wire / silk composite braided structure according to claim 5. The step (2) is characterized in that, in the dialysis, the mixed solution 1 is poured into a dialysis bag having a molecular weight cut-off of 3500D, dialyzed with deionized water for 36 hours, and the water is changed once every 4 hours. The method for manufacturing a neural catheter having a magnesium wire / silk composite braid structure according to claim 6. The magnesium wire / silk composite braided structure according to claim 6, wherein in step (2), the centrifuge is centrifuged twice at 9000 r / min for 20 minutes each time in the centrifuge. How to make a neural catheter. In step (2), in the method for producing a chitosan solution, chitosan having a deacetylation degree of 80 to 95% is weighed, dissolved in a 0.5 to 4% acetic acid solution, and stirred for 4 to 12 hours. The method for producing a neural catheter having a magnesium wire / silk composite braid structure according to claim 5, wherein a chitosan solution having a mass fraction of 1 to 5% is produced.

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