CN114796628A - Melatonin nerve conduit and preparation method thereof - Google Patents
Melatonin nerve conduit and preparation method thereof Download PDFInfo
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- CN114796628A CN114796628A CN202210207175.4A CN202210207175A CN114796628A CN 114796628 A CN114796628 A CN 114796628A CN 202210207175 A CN202210207175 A CN 202210207175A CN 114796628 A CN114796628 A CN 114796628A
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Abstract
The invention relates to the field of biological materials, and particularly relates to a melatonin nerve conduit and a preparation method thereof. The invention provides a preparation method of a melatonin nerve conduit, which comprises the following steps: preparing a biodegradable material and a melatonin suspension or adding melatonin into a molten biodegradable material and mixing uniformly to obtain a mixture; and adding the suspension or the mixture into 3D printing or electrostatic spinning equipment, and printing or electrostatic spinning to obtain the melatonin nerve conduit. The melatonin nerve conduit prepared by the preparation method provided by the invention has ideal biomedical functional materials. Shown by rat sciatic nerve defect repair experiments, the melatonin nerve conduit provided by the invention promotes nerve regeneration, improves the maturity of regenerated nerves and the number of functional nerve fibers, promotes sciatic nerve function to recover, has an effect superior to that of autologous nerve transplantation repair, and has a good application prospect.
Description
The application is a divisional application of an invention patent with application date of 2018, 08 and 14 months, application number of 201810921130.7, and invention name of 'a melatonin nerve conduit composition, a nerve conduit, a preparation method and application thereof'.
Technical Field
The invention relates to the field of biological materials, and particularly relates to a melatonin nerve conduit and a preparation method thereof.
Background
Various biomedical catheters, including degradable catheters and non-degradable catheters, such as polyethylene tubes, are used for researching nerve regeneration of nerve catheters, and due to the fact that the catheters are not degraded, tissue fibrosis can be caused if the catheters are not treated after nerve regeneration is completed, toxic and side effects such as inflammation can be caused, and the clinical application effect is not ideal. Various biodegradable materials are developed to prepare various biomedical catheters, such as collagen, polylactic acid and the like, but the materials have the defects of strength, nerve regeneration speed, toxic and side effects and the like because of single use. Further research on these catheters has been recently developed, such as performing various regeneration on the surface or inside of the catheter to facilitate various lesions in the body, such as cell modification on the surface of the catheter, and loading various active substances for promoting the growth of the tract, such as nerve growth factors of nerve catheters, blood cells, etc.
According to the electrostatic spinning, a high-voltage direct-current power supply is applied to a capillary tube containing a polymer solution, under the action of an electric field, a liquid drop suspended at the tail end of the capillary tube deforms to form a Taylor cone, when the applied electric field exceeds a certain critical value, the electric field force overcomes the surface tension of the solution to form a thin jet flow with charged surface, the jet flow moves to a grounded collector under the action of the electric field, the jet flow is continuously stretched in the moving process, the jet flow can be split under certain conditions to form the thin jet flow, meanwhile, a solvent is continuously volatilized, and finally fibers with the diameter of several micrometers to dozens of nanometers or even several nanometers are obtained on the collector. The nerve conduit scaffold material prepared by electrostatic spinning can simulate the collagen fiber structure in extracellular matrix, has high porosity and specific surface area, and is favorable for cell adhesion, growth and proliferation.
Nerve conduits although some research progress has been made, for example, chinese patent CN100479785C discloses a method for preparing nerve conduits, there is a certain distance from the autologous nerve repair. In addition, a plurality of patents disclose different preparation methods (such as Chinese invention patent CN101439205A, published Japanese 2009.5.27, CN101507842A, published Japanese 2009.8.19, CN106668938A, published Japanese 2017.05.17, CN106924820A and published Japanese 2017.07.07), but the catheters have the problems of strength, toxic and side effects, quality control or cost and the like. Chinese patent 2010800025691 discloses a method and apparatus for preparing a three-dimensional porous tubular scaffold, and specifically discloses that a 3D tubular scaffold can be made of non-biodegradable polymers, biodegradable polymers or a combination thereof, the biodegradable polymers including, for example, polylactic acid (PLA), polyglycolic acid (PGA), etc., the 3D tubular scaffold can be added with hormones such as melatonin, etc., and the 3D tubular scaffold can also be used as a peripheral nerve conduit to guide the regeneration of damaged nerves; although the patent discloses the use of melatonin and polylactic acid for the preparation of nerve conduits, it does not disclose the effect of melatonin in promoting nerve repair. The nerve conduits disclosed in the prior art do not have ideal biomedical conduits. An ideal catheter would have: has sufficient strength, elasticity, hardness and the like; the degradability is realized, the tissue in the body is waited for until the damaged tissue is completely regenerated and completely degraded, and the tissue does not need to be taken out again by operation; the materials have no toxic or side effect as much as possible; a suitable degradation period; can guide the tissue to grow in the proper direction; preventing unwanted tissue regeneration, etc.
Disclosure of Invention
The melatonin nerve conduit obtained by the invention has sufficient strength, elasticity, hardness and degradability, can promote nerve regeneration, and improves the maturity of regenerated nerves and the number of functional nerve fibers.
In order to achieve the above purpose, the invention provides the following technical scheme:
the invention provides a preparation method of a melatonin nerve conduit, which comprises the following steps: preparing a biodegradable material and a melatonin suspension or adding melatonin into a molten biodegradable material and mixing uniformly to obtain a mixture; and adding the suspension or the mixture into 3D printing or electrostatic spinning equipment, and printing or electrostatic spinning to obtain the melatonin nerve conduit.
Preferably, the weight percentage of the biodegradable material is 90-99.5%, and the weight percentage of the melatonin is 0.5-10%.
Preferably, the weight percentage of the biodegradable material is 95-99%, and the weight percentage of the melatonin is 1-5%.
Preferably, the biodegradable material is one or more of polylactic acid, polylactic acid-polyglycolic acid, polycaprolactone, fibroin, collagen, gelatin, hyaluronic acid and chitosan;
the melatonin is single-layer melatonin and/or multi-layer melatonin.
Preferably, the electrospinning comprises the steps of: dissolving a biodegradable material by using an organic solvent with the weight being 3-6 times that of the biodegradable material, adding melatonin, fully and uniformly mixing, injecting the mixture into an injection instrument, forming a tube by using an electrostatic spinning process, spraying the tube onto a rod-shaped mould which continuously rotates through direct current voltage, taking off a nerve conduit from the mould after forming the tube, drying the volatile solvent, and cutting the tube into melatonin nerve conduits with different length specifications;
the organic solvent is dichloromethane or ethyl acetate.
Preferably, when the diameter of the rod-shaped die is 3mm, the rotating speed of the rod-shaped die is 800 rpm;
when the diameter of the rod-shaped die is 5mm, the rotating speed of the rod-shaped die is 100 rpm;
the voltage in the electrostatic spinning process is 20kV, and the receiving distance is 20 cm; the moving speed of the spray head in the horizontal direction is 10cm/min or 15 cm/min.
Preferably, obtaining the melatonin nerve conduit further comprises: printing or electrostatic spinning a layer of biological adhesion substance in the melanin nerve conduit, and performing crosslinking and solidification; the biological adhesion substance is one or more of dopamine, biological adhesion peptide and extracellular matrix.
The invention also provides the melatonin nerve conduit prepared by the preparation method in the technical scheme.
Preferably, the melatonin nerve conduit also comprises a biological adhesion layer inside.
Preferably, the mean pore diameter of the outer surface of the melatonin nerve conduit is 0.01-10 μm; the average pore diameter of the biological adhesion layer is 10-1000 μm.
The invention has the advantages that:
1. provides a catheter stent with biological requirements and ideal biomedical functional materials.
2. The nerve conduit has enough strength, elasticity, hardness and degradability, can completely regenerate injured tissues in vivo after being transplanted, can completely degrade the nerve conduit, and does not need to be taken out again after operation;
3. the rat sciatic nerve defect repair experiment shows that the melatonin nerve conduit can promote nerve regeneration, improve the maturity of regenerated nerves and the number of functional nerve fibers, improve the sciatic nerve function index of rats, promote the sciatic nerve function to recover, has better effect than autologous nerve transplantation repair, and has good application prospect.
Drawings
FIG. 1 is a topographical view of a nerve conduit prepared in accordance with an embodiment of the present invention;
FIG. 2 is a transmission electron microscope detection result diagram of pure PLA catheter regenerated nerve;
FIG. 3 is a transmission electron microscope result chart of the regenerated nerve transplanted from the autologous nerve;
fig. 4 is a transmission electron microscope detection result diagram of 1% melatonin and PCL composition prepared nerve conduit group regeneration nerves.
Detailed Description
The invention will be further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, it should be understood that various changes and modifications can be made by those skilled in the art after reading the disclosure of the present invention, and equivalents fall within the scope of the appended claims.
Example 1 biodegradable Material composition for nerve conduits
And (2) taking 99% of polylactic acid and 1% of melatonin by weight, dissolving the polylactic acid by using dichloromethane with the weight of 3-6 times that of the polylactic acid, and then adding the melatonin to fully and uniformly mix to prepare the biodegradable material composition for the nerve conduit.
Example 2 biodegradable Material composition for nerve conduits
Taking 99.5 percent of polylactic acid-polyglycolic acid and 0.5 percent of melatonin by weight, dissolving the polylactic acid-polyglycolic acid with 3-6 times of ethyl acetate by weight, and then adding the melatonin to fully and uniformly mix to prepare the nerve conduit biodegradable material composition.
EXAMPLE 3 biodegradable Material composition for nerve conduits
And (2) dissolving polycaprolactone by using dichloromethane in an amount which is 3-6 times the weight of the polycaprolactone by taking the weight ratio of 98% of polycaprolactone and 2% of melatonin by weight, and then adding the melatonin to the mixture and fully mixing the mixture to prepare the nerve conduit biodegradable material composition.
Example 4 biodegradable Material composition for nerve conduits
And (2) taking 95 wt% of polylactic acid and 5 wt% of melatonin, and adding the melatonin into the molten polylactic acid to be fully and uniformly mixed to prepare the biodegradable material composition for the nerve conduit.
Example 5 biodegradable Material composition for nerve conduits
And (2) taking 90% by weight of polylactic acid-polyglycolic acid and 10% by weight of melatonin, adding the melatonin into the molten polylactic acid-polyglycolic acid, and fully and uniformly mixing to prepare the biodegradable material composition for the nerve conduit.
Example 6 preparation of nerve conduits
Preparing catheters from the biodegradable material composition of any one of embodiments 1-5 by conventional electrospinning techniques; or printing various catheters by adopting a 3D printing technology; or a duct mould is adopted to prepare various required ducts. For example, 3D printed and 1% melatonin PCL nerve conduits have good nerve regeneration properties such as better elastic modulus than pure PCL printing (48.32 and 31.77MPa, respectively).
Example 7 preparation of nerve conduits
On the basis of the nerve conduit of example 6, a layer of bioadhesive substance was internally printed or electrospun, and cross-linked and cured. The biological adhesion substance can be any one of dopamine, biological adhesion peptide or extracellular matrix, or the mixture of the dopamine, the biological adhesion peptide and the extracellular matrix in any proportion.
EXAMPLE 8 preparation of nerve conduits
The biodegradable material composition of example 1 was used to prepare catheters in the following specific steps: taking the biodegradable material composition of the nerve conduit, removing bubbles, injecting 100ml into an injection instrument, outputting at the speed of 10ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto a rod-shaped mould with the rotating speed of 800rpm and the diameter of 3mm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of the formed tube is 15-20 cm. And after the solution is sprayed, continuing to rotate the rod-shaped die for 5-10 hours to volatilize the solvent. And (3) taking off the nerve conduit from the mould, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
Example 9 preparation of nerve conduits
The biodegradable material composition of example 1 was used to prepare catheters in the following specific steps: taking 99% of polylactic acid and 1% of dopamine by weight, dissolving the polylactic acid with 3-6 times of dichloromethane by weight, and then adding the dopamine to the dissolved polylactic acid and fully mixing the dissolved polylactic acid and the dopamine to obtain a mixture. Removing bubbles from the mixture, injecting 10ml into an injection instrument, outputting at a flow rate of 10ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto a rod-shaped mold with a rotation speed of 800rpm and a diameter of 3mm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of the formed tube is 15-20 cm. And after the solution is sprayed, continuing rotating the rod-shaped mould for 5-10h to volatilize the solvent. Taking the nerve conduit biodegradable material composition, removing bubbles, injecting 100ml into an injection instrument, outputting at the speed of 10ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto the surface of a rod-shaped mould tube body with the rotating speed of 800rpm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of the formed tube is 15-20 cm. And (3) taking off the nerve conduit from the mould, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
EXAMPLE 10 preparation of nerve conduit
The biodegradable material composition of example 2 was used to prepare catheters with the following specific steps: removing bubbles from the biodegradable material composition, injecting 100ml into an injection instrument, outputting at a flow rate of 5ml/h, forming into tube by electrostatic spinning, and spraying onto a rod-shaped mold with a diameter of 5mm and a rotation speed of 1000rpm by direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle reciprocates at the speed of 10cm/min in the horizontal direction, and the tube forming length is 15-20 cm. And after the solution is sprayed, the rod-shaped mold continues to rotate to volatilize the solvent. And (3) taking off the nerve conduit from the mould, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
EXAMPLE 11 preparation of nerve conduits
The biodegradable material composition of example 2 was used to prepare catheters with the following specific steps: taking the polylactic acid-polyglycolic acid with the weight ratio of 99.5 percent and the biological adhesive peptide with the weight ratio of 0.5 percent, dissolving the polylactic acid-polyglycolic acid with ethyl acetate with the weight of 3-6 times of that of the biological adhesive peptide, and then adding the biological adhesive peptide to be fully and uniformly mixed to obtain a mixture. Removing bubbles from the mixture, injecting 10ml into an injection instrument, outputting at a flow rate of 5ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto a rod-shaped mold with a rotation speed of 1000rpm and a diameter of 5mm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle reciprocates at the speed of 10cm/min in the horizontal direction, and the tube forming length is 15-20 cm. And after the solution is sprayed, the rod-shaped mold continues to rotate to volatilize the solvent. Taking the biodegradable material composition of the nerve conduit, removing bubbles, injecting 100ml into an injection instrument, outputting at the speed of 5ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto the surface of a rod-shaped mould tube body with the rotating speed of 1000rpm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle reciprocates at the speed of 10cm/min in the horizontal direction, and the tube forming length is 15-20 cm. And after the solution is sprayed, the rod-shaped mold continues to rotate to volatilize the solvent. And (3) taking off the nerve conduit from the mould, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
EXAMPLE 12 preparation of nerve conduits
The biodegradable material composition of example 3 was used to prepare catheters in the following specific steps: taking the biodegradable material composition of the nerve conduit, removing bubbles, injecting 100ml into an injection instrument, outputting at the speed of 15ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto a rod-shaped mould with the rotation speed of 1000rpm and the diameter of 5mm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of the formed tube is 15-20 cm. And after the solution is sprayed, the rod-shaped mold continues to rotate to volatilize the solvent. And (3) taking off the nerve conduit from the mould, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
EXAMPLE 13 preparation of nerve conduits
The biodegradable material composition of example 3 was used to prepare catheters in the following specific steps: dissolving polycaprolactone with dichloromethane in an amount which is 3-6 times the weight of the polycaprolactone and 2% of dopamine by weight, and adding dopamine to the dissolved polycaprolactone and uniformly mixing to obtain a mixture. Removing bubbles from the mixture, injecting 10ml into an injection instrument, outputting at a flow rate of 15ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto a rod-shaped mold with a rotation speed of 1000rpm and a diameter of 5mm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of the formed tube is 15-20 cm. And after the solution is sprayed, the rod-shaped mold continues to rotate to volatilize the solvent. Taking the biodegradable material composition of the nerve conduit, removing bubbles, injecting 100ml into an injection instrument, outputting at the speed of 15ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto the surface of a rod-shaped mould tube body with the rotating speed of 1000rpm by using direct current voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning nozzle moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of the formed tube is 15-20 cm. And after the solution is sprayed, the rod-shaped mold continues to rotate to volatilize the solvent. And (3) taking off the nerve conduit from the mould, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
Example 14 animal experiments
The nerve catheters prepared in example 8 above were implanted into sciatic nerve of rats (repair of 15MM injury) and catheters of PCL material with 1% melatonin were selected as shown in fig. 1. As shown in fig. 2-4, myelin thickness is an important index reflecting the maturation of the regenerated nerve, and the results in the figure show that the myelin thickness of the nerve conduit prepared by 1% of the melatonin and PCL composition is larger than that of the pure PLA conduit group and the autologous nerve transplantation group at the 12 th week after the operation, which indicates that the nerve conduit of the present invention has a significant nerve regeneration promoting effect and an effect superior to that of the autologous nerve and the pure PCL conduit.
Example 15 animal experiments
Healthy adult male SD rats 30 were divided into A, B groups of 15 rats according to the random number table method. All rats were on the right side of the experiment and on the left side of the normal control. Under the anesthesia of the intraperitoneal injection of ketamine, the rat carries out a longitudinal incision on the posterior and lateral sides of the right thigh, and enters from the muscular space to expose sciatic nerve. Cutting 10mm sciatic nerve trunk from middle thigh, and transplanting A group with autologous nerve in situ; group B was repaired by bridging the nerve catheters prepared in example 9, the two nerve endings were inserted into the catheters 1mm apart, leaving a 10mm gap in the nerve defect, and the wall of the catheter and the adventitia were sutured with 9-0 silk, 3-4 needles at each end. And (5) feeding in cages after operation. The rats in each group were tested for sciatic nerve function index (SFI) values at weeks 4, 6, 8, and 10, with SFI values near 0 indicating normal sciatic nerve function and SFI values at-100 indicating complete loss of sciatic nerve function. Calculated according to the SFI formula: SFI ═ 38.3(EPL-NPL)/NPL +109.5 (ETS-NTS)/NTS +13.3(EIT-NIT)/NIT-8.8 (E: Experimental Experimental side foot; N: Normal side foot). The results are shown in the following table. In the second week after operation, the SFI values in the two groups are not significantly different (P is more than 0.05), the SFI values in the two groups show significant difference from the 8 th week, and the SFI value in the B group is significantly improved compared with the SFI value in the A group, which indicates that the nerve conduit can significantly promote the sciatic nerve function to be recovered to normal.
TABLE 1 post-operative comparison of functional indices SFI of two sciatic nerves
| Time after operation | Group A | Group B |
| 2 weeks | -87±2.90 | -85±2.90 |
| 4 weeks | -74±2.65 | -70±2.45 |
| 6 weeks | -65±2.40 | -59±2.30 |
| 8 weeks | -51±2.35 | -43±2.25 |
| For 10 weeks | -48±2.25 | -35±2.10 |
And (3) cutting a regenerated nerve at 2mm of a distal anastomosis stoma of the sciatic nerve at week 12, fixing the regenerated nerve by 4% glutaraldehyde and 1% osmic acid, embedding, slicing, staining, observing five unit visual fields of the left upper part, the left lower part, the middle center, the right upper part and the right lower part of the section under a transmission electron microscope, counting the number of the medullary nerve fibers, and measuring the axonal diameter and the myelin thickness. The results are shown in the following table. Axon diameter and myelin thickness are the major morphological hallmarks of nerve maturation, with more mature myelinated fibers in regenerating nerves effectively regenerating. As can be seen from the results in the table, group B is significantly higher than group a in the number of regenerated nerve fibers, axon diameter and myelin thickness, indicating that the nerve conduit of the present invention can promote nerve regeneration, increase the maturity of regenerated nerves and the number of functional nerve fibers.
TABLE 2 comparison of regenerated nerve fiber count, axon diameter and myelin thickness in two groups at 12 weeks post-surgery
| Number of nerve fibers | Axon diameter (μm) | Myelin thickness (μm) | |
| Group A | 225.1±13.5 | 3.61±0.64 | 1.21±0.08 |
| Group B | 242.7±15.2* | 4.28±0.76* | 1.36±0.06* |
Note: p < 0.05 compared to group a.
The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and additions can be made without departing from the method of the present invention, and these modifications and additions should also be regarded as the protection scope of the present invention.
Claims (10)
1. A preparation method of a melatonin nerve conduit is characterized by comprising the following steps: preparing a biodegradable material and a melatonin suspension or adding melatonin into a molten biodegradable material and mixing uniformly to obtain a mixture; and adding the suspension or the mixture into 3D printing or electrostatic spinning equipment, and printing or electrostatic spinning to obtain the melatonin nerve conduit.
2. The method according to claim 1, wherein the content of the biodegradable material is 90 to 99.5 wt% and the content of the melatonin is 0.5 to 10 wt%.
3. The method according to claim 2, wherein the content of the biodegradable material is 95 to 99% by weight and the content of the melatonin is 1 to 5% by weight.
4. The preparation method according to claim 3, wherein the biodegradable material is one or more of polylactic acid, polylactic-polyglycolic acid, polycaprolactone, silk fibroin, collagen, gelatin, hyaluronic acid and chitosan;
the melatonin is single-layer melatonin and/or multi-layer melatonin.
5. The method for preparing according to claim 1, wherein said electrospinning comprises the steps of: dissolving a biodegradable material by using an organic solvent with the weight 3-6 times that of the biodegradable material, then adding melatonin, fully mixing the melatonin uniformly, injecting the mixture into an injection instrument, forming a tube by using an electrostatic spinning process, spraying the tube onto a rod-shaped mould which continuously rotates through direct current voltage, taking off a nerve conduit from the mould after forming the tube, drying the volatile solvent, and cutting the tube into melatonin nerve conduits with different length specifications;
the organic solvent is dichloromethane or ethyl acetate.
6. The production method according to claim 5, wherein the rotation speed of the rod-shaped die is 800rpm when the diameter of the rod-shaped die is 3 mm;
when the diameter of the rod-shaped die is 5mm, the rotating speed of the rod-shaped die is 100 rpm;
the voltage in the electrostatic spinning process is 20kV, and the receiving distance is 20 cm; the moving speed of the spray head in the horizontal direction is 10cm/min or 15 cm/min.
7. The method for preparing the melatonin nerve conduit according to claim 1, wherein obtaining the melatonin nerve conduit further comprises: printing or electrostatic spinning a layer of biological adhesion substance in the melanin nerve conduit, and performing crosslinking and solidification; the biological adhesion substance is one or more of dopamine, biological adhesion peptide and extracellular matrix.
8. The melatonin nerve conduit prepared by the preparation method of any one of claims 1-6.
9. The melatonin nerve conduit of claim 8, further comprising a bioadhesive layer inside the melatonin nerve conduit.
10. The melatonin nerve conduit according to claim 8, wherein an average pore size of an outer surface of the melatonin nerve conduit is 0.01-10 μ ι η; the average pore diameter of the bioadhesive layer is 10-1000 μm.
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