CN114832163A - Cerium oxide nano nerve conduit and preparation method thereof - Google Patents

Cerium oxide nano nerve conduit and preparation method thereof Download PDF

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CN114832163A
CN114832163A CN202210207173.5A CN202210207173A CN114832163A CN 114832163 A CN114832163 A CN 114832163A CN 202210207173 A CN202210207173 A CN 202210207173A CN 114832163 A CN114832163 A CN 114832163A
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cerium oxide
nerve
nerve conduit
oxide nano
biodegradable material
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欧阳元明
袁伟恩
范存义
钱运
赵笑天
程媛
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East Hospital Of Shanghai Sixth Peoples Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/025Other specific inorganic materials not covered by A61L27/04 - A61L27/12
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    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/32Materials or treatment for tissue regeneration for nerve reconstruction

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Abstract

The invention provides a cerium oxide nano nerve conduit and a preparation method thereof, belonging to the technical field of biological materials. The cerium oxide nano nerve conduit provided by the invention is a conduit bracket required by biology, and has the advantages of ideal biomedical functional materials, simple preparation, low cost, easily controlled quality, wide application and the like. The results of the examples show that the cerium oxide nano nerve conduit of the present invention can significantly promote nerve regeneration.

Description

Cerium oxide nano nerve conduit and preparation method thereof
The application is a divisional application with application date of 14/08/2018, application number of 201810921128.X and invention name of cerium oxide nano nerve conduit composition, nerve conduit and preparation method and application thereof.
Technical Field
The invention relates to the technical field of biological materials, in particular to a cerium oxide nano nerve conduit and a preparation method thereof.
Background
Various biomedical catheters, such as polyethylene catheters, are used as nerve catheters for researching nerve regeneration at present, and due to the undegraded catheters, if the catheters are not treated after the nerve regeneration is finished, tissue fibrosis can be caused, toxic and side effects such as inflammation can be caused, and the clinical application effect is not very 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. 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 degradable property is realized, the tissue in the body is waited for to be completely regenerated and completely degraded, and the tissue does not need to be taken out again after 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 unnecessary tissue regeneration, etc.
Disclosure of Invention
The invention provides a cerium oxide nano nerve conduit and a preparation method thereof.
The invention provides a cerium oxide nano nerve conduit, which is prepared by the following method: taking 99 wt% of biodegradable material polylactic acid and 1 wt% of cerium oxide nano, dissolving the biodegradable material by using 3-6 times of organic solvent dichloromethane, and then adding the cerium oxide nano to fully mix uniformly to prepare the biodegradable material composition for the nerve conduit; then injecting the mixture without the bubbles into an injection instrument to output at the speed of 10ml/h or 15ml/h, forming a tube by using an electrostatic spinning process, spraying the tube onto a rod-shaped mold with the rotation speed of 600rpm or 800rpm or 1000rpm and the diameter of 3mm or 5mm by using direct current voltage, wherein the voltage is 20KV, the receiving distance is 20cm, an electrostatic spinning spray head moves back and forth at the speed of 10cm/min or 15cm/min in the horizontal direction, the rod-shaped mold continues to rotate for 5-10 h after the solution is sprayed, volatilizing the solvent, taking off the nerve conduit from the mold, drying the completely volatilized solvent, and cutting the cerium oxide nanometer nerve conduit into different length specifications;
the outer surface of the conduit has an average pore size of 0.01 to 10 μm.
The invention also provides a preparation method of the cerium oxide nanometer nerve conduit, which comprises the following steps:
taking 99 wt% of biodegradable material polylactic acid and 1 wt% of cerium oxide nano, dissolving the biodegradable material by using 3-6 times of organic solvent dichloromethane, and then adding the cerium oxide nano to fully mix uniformly to prepare the biodegradable material composition for the nerve conduit;
and then injecting the mixture without the bubbles into an injection instrument to output at the flow rate of 10ml/h or 15ml/h, forming a pipe by using an electrostatic spinning process, spraying the pipe onto a rod-shaped mould with the rotation speed of 600rpm or 800rpm or 1000rpm and the diameter of 3mm or 5mm by using direct current voltage, wherein the voltage is 20KV, the receiving distance is 20cm, an electrostatic spinning spray head reciprocates at the speed of 10cm/min or 15cm/min in the horizontal direction, the rod-shaped mould continuously rotates for 5-10 h after the solution is sprayed, so that the solvent is volatilized, the nerve conduit is taken off from the mould, the solvent is completely volatilized by drying, and the cerium oxide nanometer nerve conduit with different length specifications is cut.
The invention has the advantages that:
1. provides a catheter stent with biological requirements and ideal biomedical functional materials.
2. The cerium oxide nano nerve conduit provided by the invention has sufficient strength, elasticity, hardness and degradability, can completely regenerate injured tissues in vivo and the like after being transplanted, can be completely degraded, and does not need to be taken out again through an operation;
3. animal experiments show that the nerve conduit has obvious nerve regeneration promoting effect and is superior to autogenous nerve and pure PCL conduit in effect.
4. Shown by rat sciatic nerve defect repair experiments, the cerium oxide nano nerve conduit can promote nerve regeneration, improve the maturity of regenerated nerves and the number of nerve fibers playing a role, improve the sciatic nerve function index of rats, promote the sciatic nerve function to recover to normal, has better effect than autologous nerve transplantation repair, and has good application prospect.
Drawings
FIG. 1 is a topographic map of a nerve conduit prepared according to an embodiment of the present invention.
FIG. 2 is a transmission electron microscope detection result diagram of the regeneration nerve of the pure PLA catheter.
FIG. 3 is a transmission electron microscope detection result chart of the regenerated nerve transplanted from the autonerve.
FIG. 4 is a diagram of the result of transmission electron microscopy analysis of regenerated nerves of a neurocatheter set prepared from the 1% cerium oxide nano-and PCL composition prepared in the example of the invention.
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
Taking 99% of polylactic acid by weight and 1% of cerium oxide nano (10-1000 nm) by weight, dissolving the polylactic acid by using dichloromethane with the weight being 3-6 times that of the polylactic acid, and then adding the cerium oxide nano to mix uniformly to prepare the biodegradable material composition for the nerve conduit.
Example 2 biodegradable Material composition for nerve conduits
Taking 99.5 wt% of polylactic acid-polyglycolic acid and 0.5 wt% of cerium oxide nanoparticles, dissolving the polylactic acid-polyglycolic acid with 3-6 times of ethyl acetate, adding the cerium oxide nanoparticles, and fully mixing to prepare the biodegradable material composition for nerve conduits.
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 the weight ratio of the cerium oxide nanoparticles, and then adding the cerium oxide nanoparticles to the mixture and fully mixing the mixture to prepare the biodegradable material composition for the nerve conduit.
Example 4 biodegradable Material composition for nerve conduits
And (3) taking 95 wt% of polylactic acid and 5 wt% of cerium oxide nanometer, and adding the cerium oxide nanometer 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 conduit
Taking 90 wt% of polylactic acid-polyglycolic acid and 10 wt% of cerium oxide nanometer, adding the cerium oxide nanometer into the molten polylactic acid-polyglycolic acid, and fully mixing uniformly to prepare the biodegradable material composition for the nerve conduit.
Example 6 preparation of nerve conduits
Preparing catheters from the biodegradable material composition disclosed in any one of embodiments 1-5 by adopting a conventional electrostatic spinning technology; or printing various catheters by adopting a 3D printing technology; or a duct mould is adopted to prepare various required ducts. Such as 3D printed and 1% cerium oxide nano 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: the preparation method comprises the steps of taking the biodegradable material composition of the nerve conduit, removing bubbles, taking 100ml of the biodegradable material composition, injecting the composition into an injection instrument, outputting the composition at a flow rate of 15ml/h, forming a tube by using an electrostatic spinning process, and spraying the tube onto a rod-shaped die with the rotation speed of 600rpm and the diameter of 3mm through 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 10cm/min in the horizontal direction, and the length of a formed tube is 15-20 cm. And after the solution is sprayed, continuing rotating the rod-shaped mold 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 dichloromethane in an amount which is 3-6 times of the weight of the polylactic acid, and then adding the dopamine to the polylactic acid and fully mixing the mixture 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 spray head moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of a formed tube is 15-20 cm. And after the solution is sprayed, continuing to rotate the rod-shaped mould for 5-10 hours 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 spray head moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of a 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 of nerve conduit, injecting 100ml into an injection instrument, outputting at a flow rate of 10ml/h, forming into tube by electrostatic spinning process, and spraying onto a rod-shaped mold with a rotation speed of 900rpm and a diameter of 5mm by DC voltage, wherein the voltage is 20KV, and the receiving distance is 20 cm. The electrostatic spinning spray head moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of a formed tube is 15-20 cm. And after the solution is sprayed, the rod-shaped die continues to rotate, so that the solvent is volatilized. 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 99.5% of polylactic acid-polyglycolic acid and 0.5% of bioadhesive peptide by weight, dissolving the polylactic acid-polyglycolic acid with 3-6 times of ethyl acetate by weight, and then adding the bioadhesive 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 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 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 10cm/min in the horizontal direction, and the length of a 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 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 moves back and forth at the speed of 10cm/min in the horizontal direction, and the length of a 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 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 spray head moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of a 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 die, 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: taking 98% of polycaprolactone by weight and 2% of dopamine by weight, dissolving the polycaprolactone by using dichloromethane in an amount which is 3-6 times of the weight of the polycaprolactone, and then adding the dopamine to the dissolved polycaprolactone and fully mixing the dissolved polycaprolactone and the dopamine 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 spray head moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of a 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 spray head moves back and forth at the speed of 15cm/min in the horizontal direction, and the length of a 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 die, drying the nerve conduit to completely volatilize the solvent, and cutting the nerve conduit into different length specifications.
Example 14 animal experiments
The nerve conduit prepared in example 8 was implanted into sciatic nerve of rat (repair of 15MM injury), and a conduit of PCL material with 1% cerium oxide nanoparticles was selected as shown in fig. 1. As shown in fig. 2 to 4, myelin thickness is an important index reflecting maturation of regenerated nerves, and the results in the figure show that, at 12 weeks after operation, the myelin thickness of the nerve conduit prepared from 1% of the cerium oxide nano-and PCL composition is greater than that of the pure PLA conduit group and the autologous nerve transplantation group, 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 nerves 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; and B, performing bridging repair on the nerve conduit prepared in the embodiment 9, inserting the broken ends of two nerves into the conduit by 1mm respectively, keeping a gap of 10mm of nerve defect, suturing the conduit wall and the adventitia by 9-0 silk thread, and suturing 3-4 needles at each end. And (5) feeding in cages after operation. The sciatic nerve function index (SFI) values of rats in each group were measured at weeks 4, 6, 8, and 10, and SFI values near 0 indicated normal sciatic nerve function, and when SFI values were-100 indicated complete loss of sciatic nerve function. Calculated according to the SFI formula: SFI is 38.3 (EPL-NPL)/NPL +109.5 (ETS-NTS)/NTS +13.3 (EIT-NIT)/NIT-8.8 (E: Experimental Experimental foot; N: Normal 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 > 0.05), the SFI values in the two groups show significant difference from the 8 th week, and the SFI values in the B group are significantly improved compared with the SFI values in the A group, which indicates that the nerve conduit can significantly promote the recovery of the sciatic nerve function.
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 -86±2.75
4 weeks -74±2.65 -71±2.55
6 weeks -65±2.40 -58±2.45
8 weeks -51±2.35 -42±2.30
For 10 weeks -48±2.25 -33±2.15
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 245.1±15.8* 4.41±0.82* 1.42±0.12*
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 (2)

1. The cerium oxide nano nerve conduit is characterized by being prepared by the following method: taking 99 wt% of biodegradable material polylactic acid and 1 wt% of cerium oxide nano, dissolving the biodegradable material by using 3-6 times of organic solvent dichloromethane, and then adding the cerium oxide nano to fully mix uniformly to prepare the biodegradable material composition for the nerve conduit; then injecting the mixture without the bubbles into an injection instrument to output at the speed of 10ml/h or 15ml/h, forming a tube by using an electrostatic spinning process, spraying the tube onto a rod-shaped mold with the rotation speed of 600rpm or 900rpm or 1000rpm and the diameter of 3mm or 5mm by using direct current voltage, wherein the voltage is 20KV, the receiving distance is 20cm, an electrostatic spinning spray head moves back and forth at the speed of 10cm/min or 15cm/min in the horizontal direction, the rod-shaped mold continues to rotate for 5-10 h after the solution is sprayed, volatilizing the solvent, taking off the nerve conduit from the mold, drying the completely volatilized solvent, and cutting the cerium oxide nanometer nerve conduit into different length specifications;
the average pore diameter of the outer surface of the cerium oxide nano nerve conduit is 0.01 to 10 mu m.
2. The method for preparing the cerium oxide nano nerve conduit according to claim 1, which comprises the steps of:
taking 99 wt% of biodegradable material polylactic acid and 1 wt% of cerium oxide nano, dissolving the biodegradable material by using 3-6 times of organic solvent dichloromethane, and then adding the cerium oxide nano to fully mix uniformly to prepare the biodegradable material composition for the nerve conduit;
and then injecting the mixture after removing the bubbles into an injection instrument to output at the speed of 10ml/h or 15ml/h, forming a tube by using an electrostatic spinning process, spraying the tube onto a rod-shaped mold with the rotation speed of 600rpm or 800rpm or 1000rpm and the diameter of 3mm or 5mm by using direct current voltage, wherein the voltage is 20KV, the receiving distance is 20cm, an electrostatic spinning spray head moves back and forth at the speed of 10cm/min or 15cm/min in the horizontal direction, the rod-shaped mold continues to rotate for 5-10 h after the solution is sprayed, volatilizing the solvent, taking off the nerve conduit from the mold, drying the nerve conduit to completely volatilize the solvent, and cutting the cerium oxide nanometer nerve conduit into different length specifications.
CN202210207173.5A 2018-08-14 2018-08-14 Cerium oxide nano nerve conduit and preparation method thereof Pending CN114832163A (en)

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Publication number Priority date Publication date Assignee Title
CN101507842A (en) * 2009-03-20 2009-08-19 东华大学 Preparation method of helical flexible pressure-resistance nerve conduit
IE20100460A1 (en) * 2010-07-22 2012-03-28 Cork Inst Technology A biomaterial to assist growth of a tissue

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CN104667351A (en) * 2015-03-09 2015-06-03 盐城工业职业技术学院 Nerve growth factor loaded silk fibroin nanofiber scaffold and preparation method
GB201506381D0 (en) * 2015-04-15 2015-05-27 Isis Innovation Embolization particle

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101507842A (en) * 2009-03-20 2009-08-19 东华大学 Preparation method of helical flexible pressure-resistance nerve conduit
IE20100460A1 (en) * 2010-07-22 2012-03-28 Cork Inst Technology A biomaterial to assist growth of a tissue

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