KR20030087196A - Bio-resorbable nerve conduit and method for preparing the same - Google Patents

Abstract

PURPOSE: Provided are a bioabsorbing nerve conduit comprising, as an active material, toothapatite, polymer material or chitosan, which is a bioabsorbing ceramic, and a method for manufacturing the same. CONSTITUTION: The bioabsorbing nerve conduit consists of tube components or bioabsorbing polymer materials selected from the group consisting of collagen, alginate and ceramic, wherein coating layer is positioned inside the tube. The tube components further comprise polymer material. The ceramic is selected from the group consisting of toothapatite and bio-apatite. The polymer material is at least one selected from the group consisting of PHBV(poly-hydroxybutyrate-co-hydroxyvalerate), polyglycolic acid(PGA), polylactic acid(PLA), PLLA(poly(L-lactic acid)), polylactic-glycolic acid(PLGA), and chitosan.

Description

Bio-resorbable nerve conduit and method for preparing the same}

The present invention relates to a bioabsorbable neural conduit and a method of manufacturing the same, and more particularly, a conduit having a conduit formed from the group consisting of a bioabsorbable polymer, collagen, alginate, and a bioabsorbable ceramic, the tunnel-shaped, ball-ball Form, Dab horse, relates to a bioabsorbable neural conduit having a form and containing a chitosan coating layer formed therein or containing chitosan and a method for producing the same.

In the case of a nerve defect, the continuity of the neural tissue must be restored first to restore its function. The nerve reconstruction for this purpose has been remarkably developed with the development of the surgical microscope, and the nerve transplantation has been energized. Autologous nerve transplantation is widely used as a restorative substance of the missing nerve, but the recovery of its function is clinically very diverse, and it is still not complete. In addition, the autonomic nerve has a disadvantage of making another surgical site, and as such an autologous neuronal substitute, nerve reconstruction using artificial nerves has been attempted these days.

Nerve conduit serves as a pathway to connect the missing nerve tissue and regenerate nerve fibers. When using a nerve conduit, when both ends of the cut nerve are connected to this conduit, nerve fibers grow at both ends of the nerve in the catheter. This is the principle that will be reproduced. Until now, these neural conduits have been made of non-absorbent silicones, plastic tubes, etc. In this case, the neural regenerates and the inconvenience of having to remove them again. The material could not pass through the nerve regeneration is difficult and even if the regeneration had a disadvantage that is slow. In addition, there was a tissue rejection reaction and inflammation complications because it is not bioabsorbable.

On the other hand, since the Schwann cells serve as a kind of support for the growth of peripheral nerve fibers, the necessity to develop a good conduit to the Schwann cells is increasing. That is, in order to promote the regeneration of nerves and to improve the environment, a porosity is imparted to a conduit manufactured to be bioabsorbable, and the inside thereof is urgently required to develop a material and an environment in which nerve fibers can grow well.

Accordingly, the present inventors use a combination of biomaterials and tissue techniques in making such artificial neural conduits to replace autologous nerves to form a porous absorbent material in the form of peripheral nerve vessels, and regeneration of nerve fiber axons The present invention has been completed by providing a method for specially coating the inner surface of the conduit to facilitate the growth of nerve cells and the shape of the inner surface of the conduit advantageous for nerve regeneration.

It is an object of the present invention to provide a bioabsorbable neural conduit containing dental apatite, a polymeric material or chitosan as an active ingredient as a bioabsorbable ceramic, and a method for producing the same.

1 is a photograph showing the sciatic nerve appearance of the exfoliated rat,

Figure 2 is a photograph showing the nerve reconstruction using chitosan-coated collagen and alginate conduit (conduit 1),

FIG. 3 is a photograph showing nerve reconstruction using chitosan coated dental apatite and PHBV conduit (conduit 2) (12 weeks after surgery),

A of Fig. 4 is a photograph of the nerve conduit (conduit 3) with the tooth apatite, PHBV and chitosan composite,

Figure 4 B is a photograph showing the neuro-reconstruction surgery using dental apatite, PHBV and chitosan composites,

5 is S100 immunofluorescence staining showing cultured Schwann cells,

6 is a photograph showing the leg of a rat without automutilation,

7 is a photograph showing the leg of the rat showing a slight self-cutting state,

8 is a photograph showing the leg of the rat showing a normal self-cutting state,

9 is a photograph showing the leg of the rat showing a severe self-cutting state,

10 is a schematic diagram of a walking track designed to measure the sciatic nerve function index,

11 is a photograph showing gait analysis,

A; Normal, B; No self-cutting state,

C; Normal self-cutting state, D; Severe self-cutting condition

12 is a photograph showing conduit 1 after 12 weeks have elapsed;

Figure 13 is a photograph showing the tissue of the normal sciatic nerve,

P; Calf nerve, T; Shin nerve, S; Calf nerve

FIG. 14 is a low magnification histological picture showing fascicular discrimination located 5 mm from the closed mesial when conduit 1 is used, FIG .

T; Shin nerves; P; Calf nerve

FIG. 15 is a low magnification histological picture showing that nerve regeneration continues through the catheter, even when the catheter 1 is used, where the nerve is located at 10 mm from the sutured site.

FIG. 16 is a high magnification histological picture of a location 5 mm from the closed mesial part, using conduit 1, FIG .

FIG. 17 is a high magnification histological picture of 10 mm from the closed proximal when conduit 1 is used, showing continued neuronal regeneration.

In order to achieve the above object, the present invention provides a bioabsorbable nerve conduit.

The present invention also provides a method for producing the bioabsorbable neural conduit.

Hereinafter, the present invention will be described in detail.

The present invention provides bioabsorbable neural conduits.

The bioabsorbable neural conduit of the present invention is a conduit having a conduit formation or a bioabsorbable polymer material selected from the group consisting of collagen, alginate, and ceramic, and is characterized in that it comprises a chitosan coating layer inside the conduit.

In the above, the ceramic may be selected from the group consisting of dental apatite, bio-apatite, the polymer material is PHBV, polyglycolic acid (PGA), polylactic acid (PLA), PLLA, polylactic-glycolic acid (PLGA), chitosan Although it may be selected from one or more of the group consisting of (chitosan), the scope of the present invention is not limited to the ceramic and polymer materials listed above.

The neural conduit of the present invention can be a neural conduit characterized by being a collagen, alginate or collagen-alginate conduit coated with chitosan, and preferably a neural conduit characterized by chitosan-coated dental apatite and PHBV composite conduits. More preferably, the dental apatite, PHBV and chitosan composite conduits used in actual surgery. At this time, the internal shape of the conduit is characterized in that the inside is a hollow space in which one tunnel type or several small tunnels overlap each other, or a hollow space in which the end is rolled up with a bio glue. It may be in the form of a neural conduit, it is also possible to produce a neural conduit characterized in that it contains a small space around the fiber by filling the inner conduit with a plurality of absorbent polymer fibers, such as wires.

In the above, the ceramic may be selected from the group consisting of a toothite (toothapatite), an apatite strain, and preferably a tooth apatite. In addition, the polymer material may be selected from the group consisting of poly-hydroxybutyrate-co-hydroxyvalerate (PHBV), polyglycolic acid (PGA), polylactic acid (PLA), PLLA, polylactic-glycolic acid (PLGA), chitosan And, preferably, PHBV. However, the scope of the invention is not limited to the ceramic and polymeric materials listed above.

The tooth apatite is treated with hydrogen peroxide solution to completely remove blood stains, tissue residues and foreign matter from surrounding tissues, and heat-treated at a temperature of about 500 to 1,300 ° C. to remove organic matter and then pulverize it to a size of 400 μm or less. It can be used to have. The neural conduit of the present invention is preferably a ceramic-polymer composite material for tissue engineering, in which a bioabsorbable polymer, dental apatite and a solvent are mixed, and the polymer is 60 to the weight of the dental apatite-polymer composite material. To 90% by weight, the dental apatite is preferably mixed in 10 to 40% by weight. In the above, the solvent may be selected from the group consisting of methylene chloride, chloroform, dimethyl sulfoxide (DMSO) and weak acid (week acid), but is not necessarily limited thereto.

In the present invention, the ceramic-polymer composite material is characterized in that the pore-forming resin and sodium chloride (NaCl) sintered to 200 to 300 ㎛ as eluent is further mixed as 80 to 90% by weight with respect to the mixed solution, the polymer The mixture of the dental apatite and the solvent can be prepared by a solvent-casting / particulate-leaching method to which a thermopressing process is added.

In a preferred embodiment of the invention, the neural conduit is a collagen or alginate conduit coated with chitosan, a collagen-alginate mixture conduit, a ceramic-polymer composite conduit coated with chitosan, a ceramic-polymer-chitosan composite conduit.

The nerve conduit of the present invention controls the inner and outer diameters according to the size of the missing nerve, and in the nerve reconstruction of the rat of the present experiment, it is preferable that the inner diameter is 1 to 1.5 mm and the outer diameter is 1.5 to 2.5 mm. Build the size.

The addition and coating of chitosan can reinforce strength and elasticity, which can solve the shortcoming of the nerve regeneration due to the wrinkling of the conduit and has the advantage of maintaining the nerve regeneration pathway during the regeneration period. In addition, the bioabsorbable neural conduit of the present invention is prepared using a mixture of bioabsorbable materials such as collagen, alginate, chitosan, dental apatite and PHBV, so it is excellent in safety and naturally decomposed in vivo without being removed after the procedure. There is an advantage that it is not necessary to remove the artificially implanted conduits later. When the conduit of the present invention is viewed under an electron microscope, it has a micropore size of about 8 to 300 μm, and the size of the micropore is controlled by adjusting the grain size of sodium chloride and mixed with the conduit material, and then dissolved in water. Size can be produced.

The present invention also provides a method for producing the bioabsorbable neural conduit.

The bioabsorbable nerve conduit of the present invention

1) preparing a conduit mold;

2) preparing the conduit by placing the conduit forming material in the conduit mold of step 1) or by buried the conduit forming material around the conduit mold; And

3) inserting the fiber into the conduit of step 2).

In the above, the conduit mold of step 1) may be selected from the group consisting of tunnel type, ball hole type, and dumb horse type, but are not necessarily limited thereto.

In a conduit manufacturing method, a tunnel-type conduit may be prepared by placing the conduit forming material in a conduit mold of a desired size or by removing the conduit mold after the conduit forming material is buried around the conduit mold.

In addition, the ball-hole-shaped conduit can be prepared by making a conduit mold embossed in the shape of a ball-hole coal by pouring the conduit-forming material and hardening it and then removing the mold.

A dumb conduit is made by making the conduit forming material uniformly and then rounding it and attaching both sides with a bioabsorbable glue, or by making the catheter forming material evenly and rolling it roundly. It is prepared by attaching a bioabsorbable adhesive.

In the case of the coating method, the tunnel-type conduit is made by attaching the material to be coated on the conduit made by the above method and removing the conduit mold. Dumb-shaped conduits are made by adding a coating material on the innermost side of the follicle. In the case of making the conduit forming material uniformly as a dull, then rolling it roundly and attaching it with a bioabsorbable adhesive, the desired material may be coated by adding a coating material to the innermost part of the dimple.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example 1 Preparation of Absorbent Artificial Neural Conduit

<1-1> conduit 1; Collagen-alginate conduit coated with chitosan

The inventors of the present invention utilize the collagen and alginate as an absorbent material so that the tissue fluid can be properly introduced into the tube without providing other cells, including fibrous cells, to give micropores that can nourish neurons or Schwann cells. Conduits with diameters and lengths suitable for the capillaries of peripheral nerves, such as nerves and facial nerve branches, were prepared. The collagen to alginate ratio is produced according to the conduit fabrication method at a ratio of about 50-50 to 80-20, depending on the size of the nerve thickness. In this case, the chitosan is coated on the outside of the conduit mold having a diameter of about 1.5 mm and then the mixture is buried. At this time, coating was performed using chitosan to enhance cell activity during neuronal regeneration, and nerve cells grew from distal and proximal ends by having multiple conduits of about 200 μm diameter to reproduce the nerve fascicle structure. It made a space to enter (see Figs . 1 and 2 ).

<1-2> conduit 2; Toothapatite and Poly hydroxybutyrate-co-hydroxyvalerate (PHBV) conduits coated with chitosan

The present inventors fabricated a tunnel-shaped conduit through which nerve cells can grow using dental apatite and PHBV as ceramic-polymer composites. The material produced by maintaining the advantages of ceramics and polymers is easy to manipulate the shape and excellent hydrophilicity than the conventional biopolymers such as PLLA is excellent in cell affinity.

According to the conduit manufacturing method, the chitosan is first coated on the outside of the conduit mold, and then the chitosan is attached onto the coated chitosan. At this time, to form a space for the nerve cells to grow from the distal and proximal end, and to maintain the porosity. In addition, coating was performed using chitosan to enhance cellular activity in the catheter ( FIG. 3 ).

<1-3> conduit 3; Dental Apatite, PHBV and Chitosan Composite Conduits

The inventors made a conduit in the form of a tunnel through which nerve cells can grow using dental phosphate, PHBV and chitosan as ceramic-polymer-chitosan composites. Specifically, the polymer was mixed with 60 to 90% by weight and the dental apatite was 10 to 40% by weight based on the weight of the dental apatite-polymer composite material, and a tunnel-type conduit was manufactured by a proper proportion of PHBV and chitosan. . At this time, a space was formed to allow nerve cells to grow from distal and proximal ends, and also to maintain resilience of the conduit while maintaining porosity ( FIG. 4 ).

The properties of conduits 1 to 3 prepared above are summarized in Table 1 below.

diameter elasticity Absorption degree (12 weeks, in vivo) Biotissue Response Conduit 1 OD 3mm ID 1.5 mm Suture difficulty, easy tearing Partially or fully absorbed lowness Conduit 2 OD 2.5mm, ID 1.5mm Increased contrast, lack of elasticity Partial absorption, reduced strength lowness Conduit 3 OD 2mm, ID 1.5mm Sufficient elasticity, easy to sew Partial absorption, reduced strength lowness

OD: Outer ID: Inner Diameter

As described above, the present inventors manufactured three types of absorbent artificial neural conduits having an inner diameter of 1 to 1.5 mm and an outer diameter of 2 mm using a mixture of collagen, alginate, chitosan, dental apatite, and PHBV.

Experimental Example 1 Schwann cell culture and adhesion test

<1-1> Schwann Cell Culture

In order to cultivate Schwann cells, the present inventors first collected a dorsal root ganglion (DRG) or rat sciatic nerve of E16-20 rats and cultured them in a conventional manner, and then 0.5 ml of approximately 10 DRG or sciatic nerves. Schwann cells were obtained. To the Schwann cells obtained above, 1 ml of 0.25% collagenase and 0.1 ml of 0.2% DNase were added and incubated at 37 ° C. for 90 minutes. The supernatant was discarded and 2 ml of 0.125% trypsin-EDTA or papain solution was added and incubated for 10 minutes. The supernatant was discarded again, pipetted 10 times with 5 ml of culture medium and 2-4 ml of horse serum (HS) and allowed to stand for 3 minutes, followed by filtration using a cell strainer. (filtration) was performed. In the above, as a medium for culturing nerve cells, a medium to which 93 ml of MEM, 5 ml of HS, 1 ml of 50% glucose and 1 ml of gentamicin at a concentration of 2 mg / ml was added was used. The remaining Schwann cells were collected by washing the mass suspended in the cell strainer using 10 ml of medium, and centrifuged at 1,000 rpm for 5 minutes at 4 rpm. After removing the supernatant, 15 ml of medium was added, and cells were dispensed at a concentration of 1 × 10 ⁴ cells / ml in a petri dish coated with poly-D-lysine (or matrigel, polyetilemine). After culturing the cells for 3 to 4 days, the medium was replaced with a medium containing 5 μM of FDU (flurodeoxyuridine) or cytosine arabinoside, a DNA synthesis inhibitor, to remove rapidly growing fibroblasts. It was. After 2-3 days, the growth of Schwann cells was promoted by the addition of 0.2 μg / ml of GLDF (Glial cell line-derived neurotrophic factor) and 1 μg / ml of cholera toxin (activator of adenyl cyclase).

As a result, Schwann cell cultures having a cell density of 1.0 × 10 ⁴ cells / ml were obtained ( FIG. 5 ).

<1-2> Schwann cell attachment on nerve conduit

The present inventors examined the adhesion of Schwann cells to conduits 2 and 3 prepared in Example 1, wherein nothing was used as a control.

First, the sterile neural conduit was cut to 5 mm in length and then attached onto a Petri dish using type I collagen. The Petri dish was suspended in Schwann cells at a concentration of 1.0 × 10 ⁴ cells / ml, and then cultured in a CO ₂ incubator for 24 to 48 hours. Since Schwann cells are cells that can survive only in the attached state, the present inventors performed an MTT assay by an indirect method to measure Schwann cells attached to neural conduits. Specifically, MTT was mixed in PBS to have a final concentration of 2 mg / ml. 200 μl of culture and 50 μl of MTT solution were added to a 96-well plate containing conduits and incubated for 2 hours. After the supernatant was discarded, 150 μl of DMSO was added and shaken for 20 minutes, and the absorbance at 570 nm was measured.

As a result, as can be seen in Table 2 , when the conduit 2 or conduit 3 of the present invention was used, it was confirmed that Schwann cells adhered and survived more than the control group.

OD (A ₅₇₀ ) 24 hr (n = 4) 48 hr (n = 4) Conduit 2 0.123 ± 0.023 0.135 ± 0.057 Conduit 3 0.089 ± 0.046 0.129 ± 0.079 Control 0.067 ± 0.120 0.071 ± 0.034

Experimental Example 2 Animal Experiment

Experimental group 1 (n = 12) using conduit 1, experiment 2 group (n = 6) using conduit 2, and experiment 3 group (n = 12) using conduit 3 in 36 rats of 300 g ) And the control group (n = 6), which is an autologous nerve transplant group. In the experimental group, the conduits 1 to 3 of the present invention were implanted into the left sciatic nerve, and experimental group 1 and group 2 evaluated exploratory nerve regeneration at 12 weeks, and experimental group 3 evaluated nerve regeneration at 6 and 12 weeks. It was. The control group was explored at week 12.

Specifically, the present inventors inject the ketamine hydrochloride (Ketara, Yuhan) into the abdominal cavity of experimental animals in 300 g of SD rats, and then induced deep anesthesia, shaving the surgical site and using an iodine sponge Disinfection was performed. After placing the animal in the prone state, a 4 cm incision was made in the spine parallel to the posterior femur. The left sciatic nerve was exposed from the sciatic notch to the popliteal region and then cut into 10 mm long nerves. The nerve cuttings on the mesial and distal sides were connected to conduits 1 to 3 of the present invention 12 mm long. Sutures were performed at 2 to 4 sites using 10-0 nylon (Ethylon) so that about 1 mm of nerves in each of the nerve cuttings enter the conduit.

<2-1> gross findings

Twelve weeks after implantation of the neural catheter, the condition of foot and toe and auto-mutilation were observed. Specifically, trophic anomaly such as edema, redness, reduction of toenail length, atrophy of the plantar skin and epidermal wounds were observed, and then classified into mild, moderate, and severe. Extensive wounds, such as bone exposure, or loss of part of the foot or toes, are classified as autoclavable (in the case of wound tissue, loss of toenails, loss of toes), mild, moderate and severe. divided into grades (see Figs. 6-9).

<2-2> Measurement of Sciatic Nerve Function Index

Motor function was assessed using a sciatic functional index (SFI) at 3 week intervals for 12 weeks (Bain et al., 1989). Specifically, as shown in FIG . 10 , a walking tract of 8 × 50 cm in length was made dark so that a conditional trial was possible, wherein a long white patch was placed on the bottom of the track and the hind legs Was placed on the track rubbed with ink and then walked. As in the case of the gross findings, the degree of gait analysis was divided into mild, moderate and severe grades (see FIG. 11 ).

In addition, to measure the degree of toe spread, the rats were held by the back neck, and the rats were able to stand upright on the hind feet. The maximum toe extension was marked on the white bullock, and the same experiment was performed twice. Based on this, the sciatic nerve function index was calculated by substituting the following formula.

SFI = -38.3 (EPL-NPL / NPL) + 109.5 (ETS-NTS / NTS) + 13.3 (EIT-NIT / NIT)-8.8

EPL; Experimental paw length

NPL; Unoperated normal paw length

ETS; Distance between the first and fifth toes of operated experimental foot

NTS; Distance between the first and fifth toes of unoperated experimental foot

EIT; Distance between the second and forth toes of operated experimental foot

NIT; Distance between the second and forth toes of unoperated experimental foot

As a result, the artificial neural conduits of the present invention showed complete or partial absorption in 12 weeks of animal experiments confirmed that it is an ideal neural conduit naturally absorbed with the completion of nerve regeneration ( FIG. 12 ). In Experiment 1, 10 of 12 animals survived. In Experiment 2, 2 of 6 animals survived, and in Experiment 3, all 12 of 12 animals survived. . Gross findings and sciatic nerve function index averaged -64.6. Each SFI value is represented by a normal case of 0 and a very bad case of -100. From the above results, it was confirmed that the conduit of the present invention is superior to those reported so far.

<2-3> histological evaluation

In order to perform histological evaluation, the present inventors peeled and collected a sciatic nerve including a 12 mm long graft, and fixed it with 2% glutaraldehyde, followed by 2% osmium tetroxide (osmium). post-fixation to tetroxide). After each nerve was embedded in 100% Epon, the median portion (5 mm point) of the implant was cut to make a 1 mm thick section, and each tissue piece was stained with toluidine blue. The slides were observed under an optical microscope, and computer image analysis was performed to determine the area of the entire nerve bundle (mm ² ) and the number and density of axons (axon / mm ² ).

As a result, in the case of using the catheter 1 to the conduit 3 of the present invention is made to this won deep defect nerve regeneration was restored the continuity of the nerve, the nerve defect mesial portion showed a nerve in structure (13 to 17).

As described above, the artificial neural conduit of the present invention can be produced by freely adjusting the inner and outer diameters, and serves as a pathway for connecting the defective nerve tissue and regenerating nerve fibers, and in the future, the facial nerve branch or It can be usefully used to recover nerve defects such as the lower alveolar nerve and the optic nerve.

Claims (17)

A conduit having a conduit formation or a bioabsorbable polymeric material selected from the group consisting of collagen, alginate, and ceramic as the material, the bioabsorbable neural conduit comprising a chitosan coating layer inside the conduit. The nerve conduit of claim 1, wherein the conduit formation further comprises a polymeric material. 2. The nerve conduit of claim 1, wherein said ceramic is selected from the group consisting of dental apatite and bioapatite. The method of claim 1, wherein the polymeric material is selected from one or more consisting of PHBV, polyglycolic acid (PGA), polylactic acid (PLA), PLLA, polylactic-glycolic acid (PLGA), chitosan Characterized by a nerve conduit. The nerve conduit of claim 1, wherein the conduit is selected from the group consisting of collagen, alginate and collagen-alginate conduits coated with chitosan. The nerve conduit according to claim 1 or 2, wherein the conduit is a dental apatite and PHBV composite conduit coated with chitosan. The nerve conduit of claim 1 or 2, wherein the conduit is a dental apatite, PHBV and chitosan composite conduit. The neural conduit according to claim 1 or 2, wherein the conduit is an empty space in the form of a hollow ball in which one tunnel type or several small tunnels overlap. The neural conduit according to claim 1 or 2, wherein the conduit is an empty space in the shape of a dog rolled up and glued to its end by a bioadhesive. 10. The nerve conduit according to any one of claims 1 to 9, wherein the conduit is shaped to contain a small space around the fiber by filling the inner conduit with a plurality of absorbent polymer fibers, such as wires. The method of claim 1, wherein the tooth apatite is treated with a hydrogen peroxide solution to completely remove blood stains, tissue residues and foreign matter of the surrounding tissue and heat treated at a temperature of about 500 to 1,300 ℃ to remove the organic matter and then pulverized Neural conduit characterized in that it has a size of 400 ㎛ or less. 8. The conduit of claim 1, 2, 6, or 7, wherein the conduit is a composite conduit of a ceramic-polymer composite material for tissue engineering mixed with a bioabsorbable polymer, dental apatite and a solvent. Neural conduit. The nerve conduit according to claim 6 or 7, wherein the polymer is mixed with 60 to 90% by weight and the dental apatite is 10 to 40% by weight based on the weight of the dental apatite-polymer composite material. 13. The neural conduit of claim 12, wherein the solvent is selected from the group consisting of methylene chloride, chloroform, dimethylsulfoxide and a weak acid. The nerve conduit according to claim 1 or 2, wherein the pore-forming resin and sodium chloride sintered at 200 to 300 µm as the eluent are further mixed as 80 to 90 wt% with respect to the mixed solution. The method according to claim 6 or 7, wherein the ceramic-polymer composite material for tissue engineering is prepared by a solvent-injection / particle-leaching method in which a mixture of a polymer, dental apatite and a solvent is added by a heat press process. Neural conduit. 1) preparing a conduit mold; 2) preparing the conduit by placing the conduit forming material in the conduit mold of step 1) or by buried the conduit forming material around the conduit mold; And 3) A method for producing the biocompatible neural conduit of claim 1, comprising inserting a fiber into the conduit of step 2).