CN103751839A - Polylactic acid-chitosan composite nerve conduit and preparation method thereof - Google Patents
Polylactic acid-chitosan composite nerve conduit and preparation method thereof Download PDFInfo
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Abstract
Belonging to the technical field of medical biomaterials, the invention in particular relates to a polylactic acid-chitosan composite nerve conduit. The composite nerve conduit is composed of oriented polylactic acid electrospun fiber and a chitosan layer wrapping the fiber. The invention also provides a preparation method of the polylactic acid/chitosan composite nerve conduit, and application of the nerve conduit in preparation of peripheral nerve defect repair materials. The polylactic acid-chitosan composite nerve conduit prepared by the invention has excellent biomechanical properties and superior hydrophilcity, also has good biological tissue compatibility, can significantly promote the attachment, migration and proliferation of Schwann cells, is easy to cut and preserve, and is simple to operate during clinical use, thus having good clinical application prospects in the peripheral nerve damage repair field.
Description
Technical field
The invention belongs to biomaterial for medical purpose technical field, be specifically related to a kind of polylactic acid/chitosan composite nerve conduit and preparation method thereof and application, this tube material has good biomechanical strength, hydrophilic and short Schwann Cell Increase effect, can be used as the Regeneration and Repair of peripheral nerve defection.
Background technology
Peripheral nerve injury is clinical common extremity severe trauma, at ordinary times, wartime is all more common.According to < < science Times > >, in the whole world, increase newly in wound case every year, peripheral nerve injury case accounts for 1.5%～4.0%.Every year newly-increased 600,000～900,000 examples of China's peripheral nerve injury case, wherein need to repair neural case by neural transplantation and are about 300,000～450,000 examples.The reparation of peripheral nerve defection, the damaged reparation of especially long distance is a comparatively thorny clinically difficult problem always.The most frequently used method is to utilize autologous less important neural transplantation to carry out the main neural broken ends of fractured bone of bridge joint reparation damage at present, promote impaired neuranagenesis, thereby the functional rehabilitation acquiring a certain degree, nerve autograft remains the neural goldstandard of repairing of peripheral nerve surgical field at present.Yet there is certain shortcoming in the restorative procedure of nerve autograft, such as: need operation to cut the nerve of transplanting, Origin of Innervation is limited, has sacrificed the function of less important nerve, for district neuroma, the formation of cicatrix and the risk of infection etc., these drawbacks limit its clinical practice.Nerve allograft and heterogenous allosome neural transplantation are owing to having certain immunoreation and the risk of communicate illness, and the application of immunosuppressant can cause immunity of organisms low, cause the generation of patient's secondary tumor and infectious disease, clinical practice has certain difficulty.
In recent years, along with developing rapidly of bio-medical material and tissue engineering, people turn to the emphasis of research with nerve trachea and promote peripheral nerve regeneration to replace nerve autograft.From the structure angle of nerve trachea, desirable nerve trachea should have porous and connective good tube wall, and inner surface will have the micro structure similar to n cell epimatrix, will have good pliability and the anti-ability of collapsing simultaneously.Traditional nerve trachea preparation technology can easier preparation have certain thickness tubing as solvent casting method, and after being combined with means such as lyophilizations, can control porosity and the connectedness of tube wall; But shortcoming is not have the micro structure similar with perineural n cell epimatrix.Electrostatic spinning technique is a kind of spinning technique of preparing polymer nanofiber that development in recent years is got up, its maximum feature is that resulting timbering material has the advantages such as porosity is high, fibre diameter is little, specific surface area is large, homogeneity is good, the more important thing is, prepared nanofiber can imitate n cell epimatrix from micro-scale, and this makes electrostatic spinning have advantageous advantage at nerve trachea aspect preparing.Existing studies confirm that, the membrane material obtaining with solvent casting method is compared, and fibrous material prepared by Electrospun can better promote schwann cell to attach and propagation.Meanwhile, can obtain at an easy rate the electricity spinning fibre of orientations by specific collection device, this anisotropic physical signalling has been proved effectively guidance and the promotion axon regeneration.
Owing to having good machinability and biodegradability, polyesters macromolecule (comprising polycaprolactone, polylactic acid, poly-hydroxyl ethanol acid etc.) becomes the synthetic macromolecular material that a class is used widely.Yoo etc. have prepared the composite nerve conduit of polycaprolactone (PCL) and type i collagen blending by Electrospinning, the damaged reparation of diseased nervus lateralis to rat, seriality and the muscle function of within postoperative 8 weeks, finding aixs cylinder have obtained reconstruction (Yoo et.al., End-to-side neurorrhaphy using an electrospun PCL/collagen nerve conduit for complex peripheral motor nerve regeneration, Biomaterials, 2012,33,9027-9036).But high porosity and specific surface area due to electricity spinning fibre film, make fibrous membrane quality comparatively soft, lower by rolling or directly collect the mechanical strength of the nerve trachea obtain, resistance to extraneous compressive load hardly, the phenomenon of very easily collapsing after implanting, thus aixs cylinder epitaxial growth difficulty caused.Prepared pure polylactic acid (PLA) nerve trachea such as Ramakrishna is after implanting peripheral nerve defect in rats place, finding that there is 50% conduit has occurred to collapse, thereby had a strong impact on Regeneration and Repair (the Ramakrishna et.al. of damaged nerve, In vivo study of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration, J.Neural Eng., 2010,7,046003).In addition, the hydrophilic of polyesters macromolecular fibre film is poor, has bibliographical information to reach as high as 138.2 °, causes its cellular affinity poor, and cell is difficult to echo propagation at its surface label, is unfavorable for the Regeneration and Repair to axonal injury.
Therefore, earnestly hope for a long time clinically a kind of preparation process simple, anti-collapse and hydrophilicity is good, short Schwann Cell Increase ability is strong, microstructure with n cell epimatrix is similar and conveniently, the appearance of safe and effective peripheral nerve patching material.
Summary of the invention
The object of the invention is to overcome the deficiency of existing nerve trachea, for clinically providing a kind of and there is the good anti-ability of collapsing and hydrophilic, can on micro-scale, simulate n cell epimatrix structure, can significantly promote schwann cell attaching and propagation, be easy to cut out and preservation and clinical use polylactic acid/chitosan composite nerve conduit simple to operate.Another object of the present invention is to provide preparation method and the application of described polylactic acid/chitosan composite nerve conduit.
Chitosan is a kind of natural polysaecharides material, has nontoxic, the advantage such as histocompatibility good, biodegradable, also can obviously suppress the formation of scar tissue, clinical, is used widely.In chitosan molecule chain, contain a large amount of hydroxyls and the amino hydrophilic radical that waits, can give the wettability that material is good, be conducive to cell in its surface adhesion.In addition research shows, the vivo degradation product oligochitosan of chitosan has the effect of obvious promotion Schwann Cell Increase.
The present invention attempts polylactic acid and this bi-material of chitosan to prepare composite by specific mode combination, makes it to possess both advantages, thereby is the clinical nerve trachea that a kind of excellent performance is provided, to be used as better the Regeneration and Repair of peripheral nerve injury.
A first aspect of the present invention, a kind of polylactic acid and chitosan composite nerve conduit have been to provide, this nerve trachea is comprised of acid fiber by polylactic and chitosan, described acid fiber by polylactic, selecting molecular weight is 50,000 to 500,000 polylactic acid, be height-oriented arrangement, diameter is 100-2000nm, and between fiber, aperture size is 100-5000nm;
Described chitosan, be wrapped in the outside of acid fiber by polylactic and and the fiber of acid fiber by polylactic between, its compound quantity is between 1-40%;
The height-oriented arrangement of described acid fiber by polylactic, refers to that the fiber number of arranging in the same direction accounts for the more than 95% of fiber total quantity.
The compound quantity of described chitosan, refers to that the weight of chitosan accounts for the percentage ratio of acid fiber by polylactic and chitosan weight sum.
The wall thickness of nerve trachea of the present invention is between 0.05-0.5mm, and caliber is between 0.5-5mm, and porosity is between 50-90%.
Preferably, polylactic acid/chitosan composite nerve conduit of the present invention, the diameter of acid fiber by polylactic is at 630 ± 100nm, and between fiber, aperture size is 1000 ± 100nm;
Preferably, polylactic acid/chitosan composite nerve conduit of the present invention, the compound quantity of chitosan is 20-30%; Best complex amount is 26.2%.
Preferably, polylactic acid/chitosan composite nerve conduit of the present invention, the wall thickness of nerve trachea is at 0.2mm, and caliber is 2mm, and porosity is 80%.
Preferably, described acid fiber by polylactic, selects Poly-L-lactic acid, and weight average molecular weight is 10-40 ten thousand, and the best is 300,000.
Preferably, described chitosan, number-average molecular weight is 10-100 ten thousand, and deacetylation is greater than 70%, and best for number-average molecular weight is 500,000, deacetylation is more than 90%.
A second aspect of the present invention, is to provide the preparation method of above-mentioned polylactic acid and chitosan composite nerve conduit, and the method comprises the following steps:
(A) spinning solution of preparation polylactic acid: polylactic acid is added and obtains spinning solution in solvent, in spinning solution, the concentration of polylactic acid is 1-30%(grams per milliliter), wherein solvent can be selected one or more in hexafluoroisopropanol, DMF, oxolane, dichloromethane, acetone, chloroform, trifluoroacetic acid;
(B) spinning solution of polylactic acid steps A being made packs Electrospun liquid supplying device into, and the supply flow rate that regulates and controls Electrospun liquid by flow pump is 0.1-20ml/h;
(C) by rotating speed, be that the cylinder that 2000-4000 rev/min, diameter are 2-20cm is connected with earth terminal, as the collection substrate of Electrospun process;
(D) by high tension generator, to Electrospun process, provide high pressure, between 0.1-40kv, regulation and control regulate, and high pressure end occurs and with the distance of collecting between substrate, is set as 3cm-30cm;
(E) on cylinder, collecting acquisition thickness is the acid fiber by polylactic film of 0.05-0.5 millimeter;
(F) the resulting acid fiber by polylactic film of step e is immersed in the chitosan dilute acetic acid solution that concentration is 0.1-10%, after taking out, natural drying obtains polylactic acid and chitosan composite fiber film, and wherein chitosan compound quantity is 1-40%;
(G) resulting polylactic acid in step F and chitosan composite fiber film edge are curled into polylactic acid and the chitosan composite nerve conduit that diameter is 0.5-5mm perpendicular to acid fiber by polylactic differently-oriented directivity, and utilize the chitosan dilute acetic acid solution of 1-10% to bond to junction.
The polylactic acid that said method makes and chitosan composite nerve conduit, first at room temperature place an evening, and the vacuum drying oven that continues to put under 37-100 degree is placed more than 12 hours to remove residual solvent.
The polylactic acid that said method makes and chitosan composite nerve conduit, before clinical use, can be cut into the required length of operation, soaks after an evening standby in 75% ethanol.
Described Electrospun liquid supplying device, can be WZ-50C66T and WZ-50C6 (T) the type micro-injection pump of commercially available Zhejiang Prov Smith medicine instrument Co., Ltd, and the LSP01-1A of Baoding LanGe constant flow pump Co., Ltd and LSP01-2A type micro-injection pump etc.
In said method, preferred embodiment:
In step (A), select hexafluoroisopropanol as solvent, solution concentration is 8%(grams per milliliter);
In step (B), supply flow rate is 5ml/h;
In step (C), the drum rotation speed using is 3000 revs/min, and diameter is 8 centimetres;
In step (D), voltage is set as 15kv, and distance is set as 15cm;
In step (E), the acquisition time on swing roller is 4 hours, and fibrous membrane thickness is 0.2mm;
In step (F), the concentration of chitosan dilute acetic acid solution is 0.6%, and chitosan compound quantity is 26.2%;
In step (G), the diameter of polylactic acid/chitosan composite nerve conduit is 2mm, and the concentration of chitosan dilute acetic acid solution is 1.5%.
A third aspect of the present invention, is to provide the application in preparing peripheral nerve defection repair materials of above-mentioned polylactic acid and chitosan composite nerve conduit.
Resulting polylactic acid/the chitosan composite nerve conduit of the present invention, as peripheral nerve defection patching material, has following beneficial effect:
1, there is higher hot strength, while sewing up in surgical operation, do not tear, off-clip not; After operation, can bear compressive load in certain body, the anti-ability excellence of collapsing, can keep axon regeneration channel clock to connect.
2, have good hydrophilic, the needed schwann cell of neuranagenesis etc. can carry out good attaching and propagation at catheter surface.
3, the catabolite oligochitosan of the chitosan component in composite nerve conduit has the function of obvious promotion Schwann Cell Increase; Chitosan can effectively be suppressed to fibrocellular adhesion simultaneously, avoids the formation of operative site scar tissue.
4, have and the similar micro structure of n cell epimatrix, be conducive to migration and the propagation of schwann cell, axon regeneration is had to facilitation.
5, there is good biocompatibility, after implanting, do not cause inflammatory reaction; Not containing living cells composition, do not use extrinsic protein simultaneously, avoided the immunological rejection bringing therefrom and the risk catching.
6, can repair well peripheral nerve defection, promote axon regeneration.
7, material source is abundant, composition is lower, and preparation technology and product form simply simultaneously, and product quality is easy to control, and can realize the industrialization of high-efficiency and low-cost and produce.
Therefore polylactic acid/chitosan composite nerve conduit that the present invention introduces is a kind of new medical biomaterial, and the fields such as Regeneration and Repair of neurologic defect have a good application prospect around.
Accompanying drawing explanation
Fig. 1 is the digital photograph of polylactic acid/chitosan composite nerve conduit;
Fig. 2 is the stereoscan photograph of pure polylactic acid and polylactic acid/chitosan composite nerve conduit surface and section, and wherein a is pure polylactic acid nano fiber; B, c, d is respectively the stereoscan photograph (in figure, scale is 5 μ m) that is immersed in resulting polylactic acid in 0.2%, 0.4% and 0.6% chitosan solution/chitosan composite nerve conduit surface and section;
Fig. 3 is the tensile stress-strain curve of the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantities;
Fig. 4 is the compressive stress-strain curve of the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantities;
Fig. 5 is the water contact angle of polylactic acid/chitosan composite nerve conduit and the relation curve of time of different chitosan compound quantities, wherein a be water droplet at the time dependent optical photograph of form on pure polylactic acid and composite nerve conduit surface, b is the time dependent relation curve of the water contact angle of pure polylactic acid and composite nerve conduit;
Fig. 6 is that schwann cell is cultivated the proliferation experiment result after 1,3 and 7 day at the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantities.
The specific embodiment
Now in conjunction with the embodiments and accompanying drawing, the invention will be further described, but enforcement of the present invention is not limited in this.
Following embodiment if no special instructions method therefor is conventional method.
The polylactic acid of using in embodiment, is Poly-L-lactic acid, and weight average molecular weight is 300,000, purchased from Jinan Dai Gang biological engineering company limited.
The chitosan of using in embodiment, number-average molecular weight is 500,000, deacetylation 90%, purchased from Qisheng Biopreparations Co., Ltd., Shanghai.
Embodiment 1: the preparation of polylactic acid/chitosan composite nerve conduit
(1) 0.8 gram of polylactic acid is dissolved in 10 milliliters of hexafluoroisopropanols, at room temperature stirs the solution of evening formation stable homogeneous.
(2) polylactic acid solution is put into syringe, syringe needle place connects high voltage power supply.Solution supply flow rate is controlled at 5ml/h by miniflow pump, and the voltage applying is 15kv, and high-pressure side is 15cm with the distance of earth terminal, and the diameter of the cylinder that uses is 8cm, and rotary speed is 3000rpm.By this process, can collect diameter is 630nm left and right, the polylactic acid nano fiber film of thickness about 0.2mm.
(3) polylactic acid nano fiber film being immersed respectively to concentration is 0.2%, (chitosan number-average molecular weight is 500,000 to 0.4% and 0.6% chitosan dilute acetic acid solution, deacetylation 90%, in solution, acetic acid content is 1%) in, after taking out, natural drying can obtain polylactic acid/chitosan composite fiber film, and wherein chitosan compound quantity is respectively 5.4%, 12.5% and 26.2% left and right (code name is respectively PLLA/CS-1, PLLA/CS-2, PLLA/CS-3).
(4) by the polylactic acid obtaining/chitosan complex film along being curled into perpendicular to fiber orientation directions the nerve trachea that diameter is 2mm, and utilize 1.5% chitosan dilute acetic acid solution to bond to junction.
Polylactic acid/chitosan composite nerve conduit that said method makes, first at room temperature places an evening, and the vacuum drying oven that continues to put under 37 degree is placed more than 12 hours to remove residual solvent.Polylactic acid/chitosan composite nerve conduit the exterior appearance finally obtaining as shown in Figure 1.
Embodiment 2: the microscopic appearance of polylactic acid/chitosan composite nerve conduit is observed
Adopt field emission scanning electron microscope (JSM-6700F, JEOL, Japan) to analyze the surface of the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantities and cross-section morphology, accelerating potential is 10kV.
Result as shown in Figure 2, can see, pure polylactic acid (Fig. 2 a) and polylactic acid/chitosan composite fiber (Fig. 2 b, c, d) be height-oriented arrangement; Pure acid fiber by polylactic surface has no chitosan parcel, and aperture size is large, and porosity is high; Along with the increase of chitosan compound quantity, can obviously observe chitosan and be wrapped in the space between acid fiber by polylactic surface and fiber, porosity declines gradually.From cross-section morphology, can find out, pure acid fiber by polylactic is single ordered arrangement, and polylactic acid/chitosan composite fiber presents fibre bundle pattern, and chitosan is by several acid fiber by polylactic parcel bunchys, and along with chitosan compound quantity increases, fibre bundle chap gradually (d).
Embodiment 3: the biomechanical property research of polylactic acid/chitosan composite nerve conduit
Polylactic acid/chitosan composite fiber film is cut into the sample of long and the wide 40 * 4mm of being, and two limits prunings of sample are smooth, prevent crackle, then adopt spiral micrometer to measure the thickness of each sample, choose different parts measurement and average for three times.Then by omnipotent mechanics tester, carry out tensile mechanical properties mensuration, the rate of climb of crosshead is 2mm/min.Polylactic acid/chitosan composite nerve conduit is lain in a horizontal plane on testing stand, by omnipotent mechanics tester, carry out resistance to compression mechanics performance determining, the decrease speed of crosshead is 0.5mm/min.
Result demonstration, the stretching mechanical intensity of polylactic acid/chitosan composite fiber film is apparently higher than pure acid fiber by polylactic, and the raising gradually along with the increase of chitosan compound quantity.When chitosan compound quantity is 26.2%, the hot strength of composite cellulosic membrane is 23MPa, than the hot strength of pure acid fiber by polylactic (11MPa) be more than doubled (Fig. 3).Pure polylactic acid nerve trachea tolerates outside compressive load hardly, and when deflection is 50%, outside compressive stress is still 0.Along with the increase of chitosan compound quantity, the anti-pressure ability of polylactic acid/chitosan composite nerve conduit strengthens.When compound quantity is 26.2%, composite conduit is after reaching 50% deflection, and its outside compressive stress can be increased to 5 newton, and this shows the anti-ability of collapsing of composite nerve conduit improve a lot (Fig. 4).
Embodiment 4: the moistened surface Journal of Sex Research of polylactic acid/chitosan composite nerve conduit
Polylactic acid/chitosan composite fiber film is placed on to smooth slide surface, adopts drip method, use contact angle instrument to measure surface static water contact angle.
Result shows, the water contact angle of pure acid fiber by polylactic is 128 degree, and temporal evolution not.And after recombination chitosan, the water contact angle of composite cellulosic membrane extends in time gradually and reduces.When compound quantity is 26.2%, the water contact angle of composite cellulosic membrane reduced to rapidly 0 in 2.5 seconds, showed excellent hydrophilic (Fig. 5).
Embodiment 5: the biocompatibility in vitro research of polylactic acid/chitosan composite nerve conduit
Polylactic acid/chitosan composite fiber film is cut to the disk into diameter 1cm, the alcohol-pickled sterilization with 75% 15 minutes, then with aseptic PBS phosphate buffer flushing material and prewet with cell culture fluid.Subsequently composite membrane is placed in to 48 well culture plates, by second filial generation rat schwann cell born of the same parents according to 1.5 * 10
4the density of cells/well is planted above composite membrane.Within in incubation every two days, change one time cell culture fluid.Cell was cultivated after 1,3,7 days on material, adopted mtt assay test material superficial cell optical density.
Result shows, after cultivating 3 days, the cell quantity on polylactic acid/chitosan composite fiber film surface of containing 5.4wt% and 12.6wt% chitosan is suitable with pure PLLA, and the cell quantity on polylactic acid/chitosan composite fiber film surface of containing 26.2wt% nano wire is apparently higher than pure PLLA material (p<0.05).Under same culture conditions, along with the prolongation of incubation time, on composite, the quantity of cell proliferation all constantly increases, and the cell quantity of cultivating after 7 days will be apparently higher than the cell quantity of cultivating 3d.After cultivating 7 days, the cell quantity on the composite that contains 26.2wt% is also apparently higher than pure PLLA material (p<0.05).In addition, these results show, compare with pure poly-lactic acid material, and the polylactic acid/chitosan composite fiber film that is compounded with chitosan more can promote attaching and the propagation of schwann cell.
More than show and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; that in above-described embodiment and description, describes just illustrates principle of the present invention; the present invention also has various changes and modifications without departing from the spirit and scope of the present invention, and these changes and improvements all fall in the claimed scope of the invention.The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (10)
1. a polylactic acid and chitosan composite nerve conduit, it is characterized in that, this nerve trachea is comprised of acid fiber by polylactic and chitosan, described acid fiber by polylactic, selecting molecular weight is 50,000 to 500,000 polylactic acid, be height-oriented arrangement, diameter is 100-2000nm, and between fiber, aperture size is 100-5000nm;
Described chitosan, be wrapped in the outside of acid fiber by polylactic and and the fiber of acid fiber by polylactic between, its compound quantity is between 1-40%.
2. a kind of polylactic acid according to claim 1 and chitosan composite nerve conduit, is characterized in that, the wall thickness of this nerve trachea is 0.05-0.5mm, and caliber is 0.5-5mm, and porosity is 50-90%.
3. a kind of polylactic acid according to claim 1 and chitosan composite nerve conduit, is characterized in that, the diameter of described acid fiber by polylactic is at 630 ± 100nm, and between fiber, aperture size is 1000 ± 100nm.
4. a kind of polylactic acid according to claim 1 and chitosan composite nerve conduit, is characterized in that, the compound quantity of chitosan is 20-30%.
5. a kind of polylactic acid according to claim 1 and chitosan composite nerve conduit, is characterized in that, the wall thickness of this nerve trachea is at 0.2mm, and caliber is 2mm, and porosity is 80%.
6. a kind of polylactic acid according to claim 1 and chitosan composite nerve conduit, is characterized in that, described acid fiber by polylactic is Poly-L-lactic acid, and weight average molecular weight is 10-40 ten thousand.
7. a kind of polylactic acid according to claim 1 and chitosan composite nerve conduit, is characterized in that, described chitosan, and number-average molecular weight is 10-100 ten thousand, deacetylation is greater than 70%.
8. a preparation method for polylactic acid as claimed in claim 1 and chitosan composite nerve conduit, the method comprises the following steps:
(A) spinning solution of preparation polylactic acid: polylactic acid is added and obtains spinning solution in solvent, in spinning solution, the concentration of polylactic acid is 1-30% grams per milliliter, wherein solvent can be selected one or more in hexafluoroisopropanol, DMF, oxolane, dichloromethane, acetone, chloroform, trifluoroacetic acid;
(B) spinning solution of polylactic acid steps A being made packs Electrospun liquid supplying device into, and the supply flow rate that regulates and controls Electrospun liquid by flow pump is 0.1-20ml/h;
(C) by rotating speed, be that the cylinder that 2000-4000 rev/min, diameter are 2-20cm is connected with earth terminal, as the collection substrate of Electrospun process;
(D) by high tension generator, to Electrospun process, provide high pressure, between 0.1-40kv, regulation and control regulate, and high pressure end occurs and with the distance of collecting between substrate, is set as 3cm-30cm;
(E) on cylinder, collecting acquisition thickness is the acid fiber by polylactic film of 0.05-0.5 millimeter;
(F) the resulting acid fiber by polylactic film of step e is immersed in the chitosan dilute acetic acid solution that concentration is 0.1-10%, after taking out, natural drying obtains polylactic acid and chitosan composite fiber film, and wherein chitosan compound quantity is 1-40%;
(G) resulting polylactic acid in step F and chitosan composite fiber film edge are curled into polylactic acid and the chitosan composite nerve conduit that diameter is 0.5-5mm perpendicular to acid fiber by polylactic differently-oriented directivity, and utilize the chitosan dilute acetic acid solution of 1-10% to bond to junction.
9. according to the preparation method of polylactic acid as claimed in claim 8 and chitosan composite nerve conduit, it is characterized in that,
In step (A), select hexafluoroisopropanol as solvent, solution concentration is 8% grams per milliliter;
In step (B), supply flow rate is 5ml/h;
In step (C), the drum rotation speed using is 3000 revs/min, and diameter is 8 centimetres;
In step (D), voltage is set as 15kv, and distance is set as 15cm;
In step (E), the acquisition time on swing roller is 4 hours, and fibrous membrane thickness is 0.2mm;
In step (F), the concentration of chitosan dilute acetic acid solution is 0.6%, and chitosan compound quantity is 26.2%;
In step (G), the diameter of polylactic acid/chitosan composite nerve conduit is 2mm, and the concentration of chitosan dilute acetic acid solution is 1.5%.
10. polylactic acid and the application of chitosan composite nerve conduit in preparing peripheral nerve defection repair materials as described in as arbitrary in claim 1-7.
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| CN107349473A (en) * | 2017-07-24 | 2017-11-17 | 武汉理工大学 | A kind of degradable poly lactic acid/fibroin/chitosan composite nerve conduit and preparation method thereof |
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| CN109847104A (en) * | 2019-03-07 | 2019-06-07 | 宁波光远致信生物科技有限公司 | A kind of neural restoration film and its preparation method and application |
| CN110420355A (en) * | 2019-07-03 | 2019-11-08 | 天新福（北京）医疗器材股份有限公司 | A kind of composite nerve repairs conduit and preparation method thereof |
| CN111632193A (en) * | 2020-05-15 | 2020-09-08 | 中国科学院深圳先进技术研究院 | Chitosan-based nerve fiber membrane, preparation method, nerve conduit and application |
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| CN106400314A (en) * | 2016-09-10 | 2017-02-15 | 华南理工大学 | Composite nanofiber film of structure bionic skin extracellular matrix and producing method and application thereof |
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| CN107349473B (en) * | 2017-07-24 | 2020-01-14 | 武汉理工大学 | Degradable polylactic acid/fibroin/chitosan composite nerve conduit and preparation method thereof |
| CN108992714A (en) * | 2018-08-15 | 2018-12-14 | 费宇奇 | A kind of preparation method of hydrophilic medical conduit |
| CN109847104A (en) * | 2019-03-07 | 2019-06-07 | 宁波光远致信生物科技有限公司 | A kind of neural restoration film and its preparation method and application |
| CN109758617A (en) * | 2019-03-11 | 2019-05-17 | 宁波光远致信生物科技有限公司 | A kind of neural restoration film and its preparation method and application |
| CN109758617B (en) * | 2019-03-11 | 2022-06-03 | 宁波光远致信生物科技有限公司 | Nerve repair membrane and preparation method and application thereof |
| CN110420355A (en) * | 2019-07-03 | 2019-11-08 | 天新福（北京）医疗器材股份有限公司 | A kind of composite nerve repairs conduit and preparation method thereof |
| CN111632193A (en) * | 2020-05-15 | 2020-09-08 | 中国科学院深圳先进技术研究院 | Chitosan-based nerve fiber membrane, preparation method, nerve conduit and application |
| CN114699560A (en) * | 2021-04-16 | 2022-07-05 | 中国人民解放军总医院 | Double-layer tubular product for promoting defective nerve regeneration |
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