CN103751839B - A kind of polylactic acid and chitosan composite nerve conduit and preparation method thereof - Google Patents
A kind of polylactic acid and chitosan composite nerve conduit and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to medical biomaterial technical field, be specifically related to a kind of polylactic acid and chitosan composite nerve conduit, this composite nerve conduit is made up of orientation polylactic acid electrospinning fibre and the chitosan layer being wrapped in fibrous external.Present invention also offers the preparation method of above-mentioned polylactic acid/chitosan composite nerve conduit, and this nerve trachea is preparing the application in peripheral nerve defection repair materials.Polylactic acid prepared by the present invention and chitosan composite nerve conduit have excellent biomechanical property and splendid hydrophilic, the attaching that simultaneously biological tissue's compatibility is good, significantly can promote schwann cell, migration and propagation, be easy to cut out and preserve and Clinical practice is simple to operate, injury repairing field neural around has good potential applicability in clinical practice.
Description
Technical field
The invention belongs to medical biomaterial 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, and at ordinary times, wartime is all more common.According to " science Times ", in the whole world every year newly-increased wound case, peripheral nerve injury case accounts for 1.5% ~ 4.0%.China's peripheral nerve injury case is newly-increased 600,000 ~ 900,000 examples every year, wherein need to repair neural case by neural transplantation and are about 300,000 ~ 450,000 examples.The reparation of peripheral nerve defection, the reparation of especially long distance defect is a difficult problem comparatively thorny clinically always.Method the most frequently used is at present the major nerve broken ends of fractured bone utilizing autologous secondary neural transplantation to carry out bridge joint reparation damage, promote impaired neuranagenesis, thus the functional rehabilitation acquired a certain degree, nerve autograft remains the goldstandard of peripheral nerve surgical field CO2 laser weld at present.But 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, sacrifices the function of secondary nerve, for district's neuroma, the formation of cicatrix and the risk etc. of infection, these shortcomings limit its clinical practice.Owing to there is certain immunoreation and the risk of communicate illness in nerve allograft and heterogenous allosome neural transplantation, 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, the emphasis of research turns to and uses nerve trachea to promote that peripheral nerve regeneration is to replace nerve autograft by people.From the structural point of nerve trachea, desirable nerve trachea should have porous and connective good tube wall, and inner surface will have the micro structure similar to natural extracellular matrix, will have good pliability and anti-ability of collapsing simultaneously.Traditional nerve trachea preparation technology such as solvent casting method easier preparation can have certain thickness tubing, and can control porosity and the connectedness of tube wall after being combined with means such as lyophilizations; But shortcoming is not have the micro structure similar with perineural natural extracellular matrix.Electrostatic spinning technique is a kind of spinning technique preparing polymer nanofiber that development in recent years is got up, its maximum feature is that obtained 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, obtained nanofiber can imitate natural extracellular matrix from micro-scale, and this makes electrostatic spinning have advantageous advantage in prepared by nerve trachea.Existing research confirms, compared with the membrane material obtained with solvent casting method, fibrous material prepared by Electrospun can better promote schwann cell to attach and propagation.Meanwhile, can be obtained the electricity spinning fibre of orientations by specific collection device easily, this anisotropic physical signalling has been proved can effective 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 diseased nervus lateralis defect of rat is repaired, within postoperative 8 weeks, find that the seriality of aixs cylinder and muscle function obtain reconstruction (Yoo et.al., End-to-side neurorrhaphy using an electrospun PCL/collagennerve conduit for complex peripheral motor nerve regeneration, Biomaterials, 2012,33,9027-9036).But due to high porosity and the specific surface area of electricity spinning fibre film, make fibrous membrane quality comparatively soft, lower by the mechanical strength rolling or directly collect the nerve trachea obtained, resistance to extraneous compressive load hardly, very easily to collapse after implanting phenomenon, thus cause aixs cylinder epitaxial growth difficulty.Pure polylactic acid (PLA) nerve trachea prepared by Ramakrishna etc. is behind implantation peripheral nerve defect in rats place, the conduit finding that there is 50% there occurs collapses, thus had a strong impact on Regeneration and Repair (the Ramakrishna et.al. of defect nerve, In vivo study of novel nanofibrous intra-luminal guidancechannels 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 attach and propagation on its surface, 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 natural extracellular matrix similar and conveniently, the appearance of safe and effective peripheral nerve patching material.
Summary of the invention
The object of the invention is the deficiency overcoming existing nerve trachea, for clinically providing a kind of there is the good anti-ability of collapsing and hydrophilic, natural extracellular matrix structure can be simulated on a microscopic scale, significantly can promote the attaching of schwann cell and propagation, be easy to cut out and preserve and Clinical practice 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 obviously can suppress the formation of scar tissue, be used widely clinical.Wait hydrophilic radical containing a large amount of hydroxyls and amino in chitosan molecule chain, the wettability that material is good can be given, be conducive to cell in its surface adhesion.In addition research shows, the vivo degradation product oligochitosan of chitosan has the effect significantly promoting Schwann Cell Increase.
The present invention attempts polylactic acid and this bi-material of chitosan to be combined by specific mode to prepare composite, makes it the advantage possessing both, thus is the clinical nerve trachea providing a kind of excellent performance, to be used as the Regeneration and Repair of peripheral nerve injury better.
A first aspect of the present invention, there is provided a kind of polylactic acid and chitosan composite nerve conduit, this nerve trachea is made up of acid fiber by polylactic and chitosan, described acid fiber by polylactic, select molecular weight be 5 ten thousand to 50 ten thousand polylactic acid, in height-oriented arrangement, diameter is 100-2000nm, and between fiber, aperture size is 100-5000nm;
Described chitosan, be wrapped in acid fiber by polylactic outside 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 arranged in the same direction accounts for 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%, best for number-average molecular weight be 500,000, deacetylation is more than 90%.
A second aspect of the present invention, be to provide above-mentioned polylactic acid and the preparation method of chitosan composite nerve conduit, the method comprises the following steps:
(A) spinning solution of polylactic acid is prepared: added in solvent by polylactic acid and obtain spinning solution, in spinning solution, the concentration of polylactic acid is 1-30%(grams per milliliter), wherein solvent can select one or more in hexafluoroisopropanol, DMF, oxolane, dichloromethane, acetone, chloroform, trifluoroacetic acid;
(B) spinning solution of polylactic acid steps A obtained loads Electrospun liquid supplying device, is 0.1-20ml/h by the supply flow rate of flow pump regulation and control Electrospun liquid;
(C) be 2000-4000 rev/min by rotating speed, diameter is that the cylinder of 2-20cm is connected with earth terminal, as the collection substrate of electro-spinning process;
(D) provide high pressure by high tension generator to electro-spinning process, between 0.1-40kv, regulation and control regulate, and high pressure end occurs and is set as 3cm-30cm with the distance of collecting between substrate;
(E) on cylinder, the polylactic acid fiber membrane that acquisition thickness is 0.05-0.5 millimeter is collected;
(F) it is in the chitosan dilute acetic acid solution of 0.1-10% that polylactic acid fiber membrane step e obtained immerses concentration, and after taking out, namely natural drying obtains polylactic acid and chitosan composite fiber film, and wherein chitosan compound quantity is 1-40%;
(G) polylactic acid obtained in step F and chitosan composite fiber film edge are curled into perpendicular to acid fiber by polylactic differently-oriented directivity the polylactic acid and chitosan composite nerve conduit that diameter is 0.5-5mm, and utilize the chitosan dilute acetic acid solution of 1-10% to bond to junction.
The polylactic acid that said method is obtained and chitosan composite nerve conduit, first at room temperature place an evening, and the vacuum drying oven under continuing to put into 37-100 degree places more than 12 hours to remove residual solvent.
The polylactic acid that said method is obtained and chitosan composite nerve conduit, before Clinical practice, can be cut into the length needed for operation, for subsequent use soak an evening in 75% ethanol after.
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 Baoding LanGe constant flow pump Co., Ltd LSP01-1A 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 used is 3000 revs/min, and diameter is 8 centimetres;
In step (D), voltage sets is 15kv, and distance is set as 15cm;
In step (E), acquisition time is on a rotating drum 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 above-mentioned polylactic acid and chitosan composite nerve conduit is preparing the application in peripheral nerve defection repair materials.
Polylactic acid/chitosan composite nerve conduit that the present invention obtains is used as peripheral nerve defection patching material, has following beneficial effect:
1, there is higher hot strength, do not tear when sewing up in surgical operation, not off-clip; Can bear compressive load in certain body after surgery, anti-ability excellence of collapsing, can keep aixs cylinder recovery passage clock through.
2, have good hydrophilic, the schwann cell required for neuranagenesis etc. can carry out good attaching and propagation at catheter surface.
The catabolite oligochitosan of the chitosan component 3, in composite nerve conduit has the function significantly promoting Schwann Cell Increase; Chitosan can effectively be suppressed to fibrocellular adhesion simultaneously, avoids the formation of operative site scar tissue.
4, there is the micro structure similar with natural extracellular matrix, be conducive to migration and the propagation of schwann cell, to axon regeneration, there is facilitation.
5, there is good biocompatibility, after implanting, do not cause inflammatory reaction; Simultaneously not containing living cells composition, do not use extrinsic protein, avoid the immunological rejection brought therefrom and the risk caught.
6, peripheral nerve defection can be repaired well, promote axon regeneration.
7, material source is abundant, composition is lower, and simply, product quality is easy to control for preparation technology and product composition simultaneously, and the industrialization that can realize high-efficiency and low-cost is produced.
Therefore polylactic acid/chitosan composite nerve conduit that the present invention introduces is a kind of new medical biomaterial, and the field such as Regeneration and Repair of neurologic defect has 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 are the stereoscan photograph (in figure, scale is 5 μm) being immersed in polylactic acid/chitosan composite nerve conduit surface and the section obtained in 0.2%, 0.4% and 0.6% chitosan solution respectively;
Fig. 3 is the tensile stress-strain curve of the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantity;
Fig. 4 is the compressive stress-strain curve of the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantity;
Fig. 5 is the water contact angle of polylactic acid/chitosan composite nerve conduit and the relation curve of time of different chitosan compound quantity, the wherein a time dependent optical photograph of form that is water droplet on pure polylactic acid and composite nerve conduit surface, b is the time dependent relation curve of water contact angle of pure polylactic acid and composite nerve conduit;
Fig. 6 is the proliferation experiment result of schwann cell after the polylactic acid/chitosan composite nerve conduit of different chitosan compound quantity cultivates 1,3 and 7 day.
Detailed description of the invention
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 used 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 used in embodiment, number-average molecular weight is 500,000, and 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 that one forms stable homogeneous evening.
(2) PLA solution is put into syringe, syringe needle place connects high voltage power supply.Solution supply flow rate controls at 5ml/h by miniflow pump, and the voltage of applying is 15kv, and high-pressure side is 15cm with the distance of earth terminal, use the diameter of cylinder for 8cm, rotary speed is 3000rpm.By this process, can collect diameter is that about 630nm, thickness are at the polylactic acid nano fiber film of about 0.2mm.
(3) polylactic acid nano fiber film being immersed respectively concentration is 0.2%, (chitosan number-average molecular weight is 500,000 to the chitosan dilute acetic acid solution of 0.4% and 0.6%, 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 about 5.4%, 12.5% and 26.2% (code name is respectively PLLA/CS-1, PLLA/CS-2, PLLA/CS-3).
(4) polylactic acid obtained/chitosan complex film edge is curled into perpendicular to fiber orientation directions the nerve trachea that diameter is 2mm, and utilizes the chitosan dilute acetic acid solution of 1.5% to bond to junction.
Polylactic acid/chitosan composite nerve conduit that said method is obtained, first at room temperature places an evening, and continues the vacuum drying oven put under 37 degree and place more than 12 hours to remove residual solvent.The polylactic acid finally obtained/chitosan composite nerve conduit exterior appearance 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 quantity and cross-section morphology, accelerating potential is 10kV.
Result as shown in Figure 2, can be seen, pure polylactic acid (Fig. 2 a) and polylactic acid/chitosan composite fiber (Fig. 2 b, c, d) be height-oriented arrangement; Pure polylactic acid fiber 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 in space that chitosan is wrapped between polylactic acid fiber surface and fiber, porosity declines gradually.As can be seen from cross-section morphology, pure acid fiber by polylactic is single ordered arrangement, and polylactic acid/chitosan composite fiber then presents fibre bundle pattern, and chitosan is by several acid fiber by polylactic parcel bunchys, and along with the increase of chitosan compound quantity, fibre bundle is thicker (d) gradually.
Embodiment 3: the biomechanical property research of polylactic acid/chitosan composite nerve conduit
Being cut into by polylactic acid/chitosan composite fiber film long and wide is the sample of 40 × 4mm, and prunes smooth by sample two limits, and prevent crackle, then the thickness of each sample measured by employing spiral micrometer, chooses different parts and measures three times and average.Then carry out tensile mechanical properties mensuration by omnipotent mechanics tester, the rate of climb of crosshead is 2mm/min.Lie in a horizontal plane on testing stand by polylactic acid/chitosan composite nerve conduit, carry out compressive mechanical property mensuration by omnipotent mechanics tester, the decrease speed of crosshead is 0.5mm/min.
Result shows, and the stretching mechanical intensity of polylactic acid/chitosan composite fiber film apparently higher than pure acid fiber by polylactic, and improves 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, is more than doubled (Fig. 3) than the hot strength (11MPa) of pure acid fiber by polylactic.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 the deflection of 50%, and its outside compressive stress can be increased to 5 newton, and this shows that the anti-ability of collapsing of composite nerve conduit improves 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 smooth slide surface, adopts drip method, use contact angle instrument to measure surperficial Static water contact angles.
Result shows, and the water contact angle of pure acid fiber by polylactic is 128 degree, and does not change in time.And after recombination chitosan, the water contact angle of composite cellulosic membrane extends in time and reduces gradually.When compound quantity is 26.2%, the water contact angle of composite cellulosic membrane reduced to 0 rapidly 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 the disk into diameter 1cm, the alcohol-pickled sterilization with 75% 15 minutes, then prewet with cell culture fluid with aseptic PBS phosphate buffer flushing material.Subsequently composite membrane is placed in 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 a cell culture fluid.Cell cultivates 1,3 on material, after 7 days, adopts mtt assay test material superficial cell optical density.
Result shows, in cultivation after 3 days, the cell quantity on the polylactic acid containing 5.4wt% and 12.6wt% chitosan/chitosan composite fiber film surface and pure PLLA are suitable, and the cell quantity on polylactic acid/chitosan composite fiber film surface 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 cultivating the cell quantity after 7 days will apparently higher than the cell quantity cultivating 3d.When cultivation is after 7 days, containing the cell quantity on the composite of 26.2wt% also apparently higher than pure PLLA material (p<0.05).In addition, these results show, compared with pure poly-lactic acid material, the polylactic acid/chitosan composite fiber film being compounded with chitosan more can promote attaching and the propagation of schwann cell.
More than show and describe 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; what describe in above-described embodiment and description 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.Application claims protection domain 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 made up of acid fiber by polylactic and chitosan, described acid fiber by polylactic, select molecular weight be 5 ten thousand to 50 ten thousand polylactic acid, in height-oriented arrangement, diameter is 100-2000nm, and between fiber, aperture size is 100-5000nm;
Described chitosan, be wrapped in acid fiber by polylactic outside 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, and 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 polylactic acid is prepared: added in solvent by polylactic acid and obtain spinning solution, in spinning solution, the concentration of polylactic acid is 1-30% grams per milliliter, wherein one or more in hexafluoroisopropanol, DMF, oxolane, dichloromethane, acetone, chloroform, trifluoroacetic acid selected by solvent;
(B) spinning solution of polylactic acid steps A obtained loads Electrospun liquid supplying device, is 0.1-20ml/h by the supply flow rate of flow pump regulation and control Electrospun liquid;
(C) be 2000-4000 rev/min by rotating speed, diameter is that the cylinder of 2-20cm is connected with earth terminal, as the collection substrate of electro-spinning process;
(D) provide high pressure by high tension generator to electro-spinning process, between 0.1-40kv, regulation and control regulate, and high pressure end occurs and is set as 3cm-30cm with the distance of collecting between substrate;
(E) on cylinder, the polylactic acid fiber membrane that acquisition thickness is 0.05-0.5 millimeter is collected;
(F) it is in the chitosan dilute acetic acid solution of 0.1-10% that polylactic acid fiber membrane step e obtained immerses concentration, and after taking out, namely natural drying obtains polylactic acid and chitosan composite fiber film, and wherein chitosan compound quantity is 1-40%;
(G) polylactic acid obtained in step F and chitosan composite fiber film edge are curled into perpendicular to acid fiber by polylactic differently-oriented directivity the polylactic acid and chitosan composite nerve conduit that diameter is 0.5-5mm, 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 used is 3000 revs/min, and diameter is 8 centimetres;
In step (D), voltage sets is 15kv, and distance is set as 15cm;
In step (E), acquisition time is on a rotating drum 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. one kind as arbitrary in claim 1-7 as described in polylactic acid and chitosan composite nerve conduit preparing the application in peripheral nerve defection repair materials.
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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 |
| 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 |
| CN109847104B (en) * | 2019-03-07 | 2022-05-03 | 宁波光远致信生物科技有限公司 | Nerve repair membrane and preparation method and application thereof |
| 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 |
| CN111632193B (en) * | 2020-05-15 | 2022-05-13 | 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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| CN103751839A (en) | 2014-04-30 |
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