CN110420355A - A kind of composite nerve repairs conduit and preparation method thereof - Google Patents
A kind of composite nerve repairs conduit and preparation method thereof Download PDFInfo
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- CN110420355A CN110420355A CN201910595225.9A CN201910595225A CN110420355A CN 110420355 A CN110420355 A CN 110420355A CN 201910595225 A CN201910595225 A CN 201910595225A CN 110420355 A CN110420355 A CN 110420355A
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Abstract
The present invention provides a kind of composite nerves to repair conduit and preparation method thereof.The composite nerve repairs the electrospun fibers layer that conduit includes hollow natural polymer conduit and is coated on outside natural polymer conduit；The natural polymer conduit is made of mass-volume concentration of the collagen slurries of 4%-7%, the electrospun fibers layer is made of the spinning solution comprising polylactic acid and chitosan, and the mass ratio of the polylactic acid and chitosan is (6-9.5): (0.5-4).The present invention is on the basis of keeping collagen catheter characteristic, hence it is evident that the mechanical strength for improving collagen catheter maintains good three-dimensional structure during neural restoration, avoids the occurrence of conduit avalanche phenomenon；Manufacture craft is simple, and material source enriches cheap, is easy to industrialize.
Description
Technical field
The invention belongs to biomaterial for medical purpose, medical instruments field, and in particular to a kind of composite nerve repair conduit and its
Preparation method and application.
Background technique
Nerve trachea is the principle and method using organizational engineering, with natural and/or synthesized degradable high molecular material
Preparation can establish the hollow tubular structures of bridge grafting nerves in the peripheral nerve injury broken ends of fractured bone, can provide for the nerve damaged suitable
Suitable nerve regneration microenvironment.Common natural material includes collagen, gelatin, chitosan, fibroin albumen etc., is all had good
Biocompatibility, low immunogenicity；Synthesized degradable high molecular material includes polylactic acid, polyhydroxybutyrate valeric acid copolyesters, gathers
(D, Pfansteihl-co- glycolic) etc., has the characteristics that good mechanical strength, degradability.
Neural restoration process is a complicated biological question, conduit in addition to good biocompatibility, it is nontoxic,
Outside low immunogenicity, suitable catheter configuration and mechanical strength equally play an important role to neural restoration.Currently, by grinding
Study carefully different structural pipe walls, no matter single layer, there are still some problems for double-deck or multilayered structure, cannot copy and provided naturally completely
The bracket of neuromechanism.The nerve trachea of the natural macromolecular material listed, although having good biocompatibility, low
Immunogenicity, but defect is mechanical strength deficiency, degrades too fast, and tear-resistant ability is poor during practical clinical, holds
Easily there is hollow conduit avalanche phenomenon and hinder neural restoration process.Although the nerve trachea of synthesized degradable high molecular material has
There are a relatively better mechanical strength, slower degradation property, but it still has the hydrophobicity of polyester itself and relatively poor
The shortcomings that biocompatibility, is unfavorable for the attachment of cell and migration and easily causes rejection.Therefore, preparing has completely
Three-dimensional structure, good biocompatibility, excellent mechanical strength, suitable biological degradability, and nerve regneration can be guided
Nerve trachea is of great significance.
Currently, have both simultaneously good biocompatibility, directional guide nerve regneration, it is degradable and can it is good support lead
The nerve trachea of pipe structure is still within the research and probe stage, and many patented technologies propose the various sides for preparing nerve trachea
Method, step is relatively cumbersome, poor operability.Therefore provide it is a kind of it is simple, feasible, be easy to industrialized nerve trachea production side
Method is of great significance for clinical application.
Summary of the invention
To solve defect existing in the prior art, the present invention provides a kind of composite nerves to repair conduit and its preparation side
Method and application.
On the one hand, the present invention provides a kind of composite nerves to repair conduit, and it includes hollow that the composite nerve, which repairs conduit,
Natural polymer conduit and the electrospun fibers layer that is coated on outside natural polymer conduit；The natural polymer is led
Pipe is made of mass-volume concentration of the collagen slurries of 4%-7%, and the electrospun fibers layer comprising polylactic acid and shell by gathering
The spinning solution of sugar is made, and the mass ratio of the polylactic acid and chitosan is (6-9.5): (0.5-4).
Further, the natural polymer conduit is preferably made of mass-volume concentration of 6% collagen slurries；It is preferred that
, the collagen is type i collagen.In one embodiment, the collagen slurries are after mixing collagen with acid solution
Collagen slurries are prepared.
The mass ratio of the polylactic acid and chitosan is (7-9.5): (0.5-3), it is preferable that (8-9.5): (0.5-2), more
It is preferred that (9-9.5): (0.5-1), it is further preferred that 7:3,8:2,9:1 or 9.5:0.5.The spinning solution is to gather polylactic acid and shell
Sugar, which is dissolved in trifluoroacetic acid, to be prepared.
Further, natural polymer conduit aperture is 50-220 μm, 0.4 ± 0.3mm of wall thickness, the electrostatic spinning
Fibrous layer with a thickness of 0.05-0.15mm, fibre diameter 300-700nm.
On the other hand, the present invention provides the preparation method that composite nerve repairs conduit, the method includes hollow days
The step of preparation of right polymeric catheter and cladding electrospun fibers layer；It is suitable to select when preparing natural polymer conduit
The collagen slurries of mass-volume concentration inject in mold, freeze-drying, and high temperature is fixed-type；Then by hollow natural polymer
Sub- conduit coats electrospun fibers layer by electrospinning process and obtains composite nerve reparation conduit.
In other implementations, composite nerve repair the preparation method of conduit further include complex repairation conduit it is dry,
Packaging, sterilizing and etc..Preferably, the drying means be vacuum drying, condition are as follows: 30-60 DEG C of vacuum drying 12-48h or
It is air-dried at room temperature 48-96h, preferably 40 DEG C vacuum drying are for 24 hours.Preferably, sterilization method is eo sterilization or Co 60
Irradiation sterilization, optimization ethylene oxide gaseous sterilization.
In one embodiment, the preparation of the hollow natural polymer conduit includes the following steps:
(1) I-type collagen is extracted, is acidified 120- in 0.4-0.8M glacial acetic acid after collagen is ground
240min obtains homogeneous slurry；
(2) above-mentioned slurries are centrifuged, temperature is controlled at 5-20 DEG C, revolution 3000-5000rpm, time 40-
100min, it is filling into mold；
(3) after fixing mold, in axial direction slow sample introduction, gradient freezing molding, at the uniform velocity elevator speed are carried out
Turning/min, angular adjustment 5-10, time interval 1-10s for 5-15, temperature stops decline after being down to -60 DEG C, maintains 20-50min,
And in freezing chamber defrosting 1-5h；
(4) it is freeze-dried after shaped article being taken out axis, high-temperature vacuum is fixed.
Collagen concentration is 4-10% (mass volume ratio) in the slurries；It is preferred that 6-7% (mass volume ratio)；It is described
The preferred 0.5-0.6M of the molar concentration of glacial acetic acid；Preferably 12 DEG C of temperature, the preferred 4000rpm of revolution of slurries centrifugation, the time is preferred
80min。
It is 50-220 μm, internal diameter 2-5mm, 0.4 ± 0.3mm of wall thickness by the conduit aperture that the above method prepares.It is preferred that
Conduit long 15cm, internal diameter 4mm, wall thickness 0.5mm.
In one embodiment, the electrostatic spinning process is as follows: by polylactic acid, chitosan using trifluoroacetic acid as molten
Agent is mixed into uniform electrostatic spinning solution, polylactic acid in electrostatic spinning solution: chitosan (mass ratio)=(7-9.5): (0.5-
3)；It is preferred that polylactic acid: chitosan (mass ratio)=7:3；It is preferred that polylactic acid: chitosan (mass ratio)=8:2；It is preferred that polylactic acid:
Chitosan (mass ratio)=9:1；It is preferred that polylactic acid: chitosan (mass ratio)=9.5:0.5.Uniaxial electrostatic spinning, electrostatic high-pressure
15-30kV, fltting speed 0.8-2.4ml/h receive distance 15-30cm, spinning time 60-120min.It is preferred that electrostatic high-pressure
20kV, fltting speed 1.8ml/h receive distance 20cm, spinning time 90min.
The present invention also provides the composite nerves for using the method for the invention to prepare to repair conduit.
The present invention also provides the composite nerves to repair application of the conduit in neural restoration clinical operation.It is especially suitable
The peripheral nerve defection caused by the wound of a variety of causes and tumor resection, repair deficiency length 1.5cm.
On the other hand, the present invention also provides composite nerves to repair conduit in the neural restoration of preparation stretch-proof and degradation resistant
Application in material；Preferably, described to be degraded to one of proteasome degradation, acid degradation or alkaline degradation or a variety of.
Further, the stretch-proof is to be imposed a condition using MED-01 medical packaging ability meter as 10mm/min,
Extension test is carried out to material, the average maximum pull of material is not less than 29N, it is preferable that is not less than 34N, it is further preferred that being not less than
42N, it is further preferred that being not less than 48N, it is further preferred that being not less than 50N.
The beneficial effects of the present invention are:
1, the present invention combines a step electrospinning process by the Freeze Drying Technique of collagen catheter, and acquisition is more suitable for mind
The composite nerve of repaired process repairs conduit；On the basis of keeping collagen catheter characteristic, hence it is evident that improve collagen catheter
Mechanical strength maintains good three-dimensional structure during neural restoration, avoids the occurrence of conduit avalanche phenomenon；Manufacture craft letter
Singly, material source enriches cheap, is easy to industrialize.
2, freeze-drying obtain have orienting stephanoporate natural polymer collagen catheter, have good biocompatibility and
Porosity communication is simultaneously arranged along duct direction, can guide nerve cell oriented growth, promotes nerve regneration；External sheath is unordered
Electrospun fibers, due to the incompatibility of polylactic acid and chitosan, the waving with spin solvent during electrostatic spinning
It sends out and occurs mutually to separate, polycation chitosan dissociates outward, to directly form core-shell structure；Certainly due to electrostatic spinning technique
The high porosity of body, Large ratio surface feature can simulate human body cell epimatrix structure, be conducive to cell attachment, migration and life
Long, in addition, the fiber film component is selected as, internal layer is synthesized degradable polylactic acid and outer layer is natural polymer chitosan, gathers cream
Acid has good spinnability so that it is guaranteed that the excellent mechanical strength of tunica fibrosa, outer layer chitosan improve the biofacies of polylactic acid
Capacitive and hydrophily；Guiding role, and unordered nucleocapsid knot can not only be provided during neural restoration for axon growth
The cladding of structure electrospun fibers is capable of providing isotropic excellent mechanical strength, improves conduit in surgical operation use
Tear-resistant ability and gradient layer-by-layer degradation from inside to outside can ensure to keep nerve trachea three-dimensional in nerve regeneration
The integrality and plasticity of structure.
Detailed description of the invention
The drawings described herein are used to provide a further understanding of the present application, constitutes part of this application, this Shen
Illustrative embodiments and their description please are not constituted an undue limitation on the present application for explaining the application.In the accompanying drawings:
Fig. 1 is scanning electron microscope (SEM) figure that the present invention prepares resulting composite nerve conduit internal layer cross section；
Fig. 2 is the scanning electron microscope (SEM) that the present invention prepares that resulting composite nerve repairs conduit internal layer lateral incision face
Figure；
Fig. 3 is the scanning electron microscope (SEM) that the present invention prepares resulting compound repaired catheter outer spinning fibre
Figure；
Fig. 4 is the transmission electron microscope that the present invention prepares that resulting composite nerve repairs catheter outer spinning fibre
(TEM) figure；
Fig. 5 is that the present invention prepares resulting composite nerve reparation catheter outer spinning fibre marked by fluorescein isothiocyanate
Laser scanning co-focusing microscope (CLSM) figure afterwards；
Fig. 6 is that the present invention prepares resulting composite nerve reparation conduit cross section appearance photo；
Fig. 7 is that the present invention prepares resulting composite nerve reparation conduit overall appearance photo；
State of 1 collagen tube of embodiment in degradation solution when Fig. 8 is enzyme degradation 20min；
State of the 2 complex repairation pipe of embodiment in degradation solution when Fig. 9 is enzyme degradation 20min；
State of 1 collagen tube of embodiment in degradation solution when Figure 10 is enzyme degradation 40min；
State of the 2 complex repairation pipe of embodiment in degradation solution when Figure 11 is enzyme degradation 40min；
State of 1 collagen tube of embodiment in degradation solution when Figure 12 is enzyme degradation 60min；
State of the 2 complex repairation pipe of embodiment in degradation solution when Figure 13 is enzyme degradation 60min；
Vertical face figure of the 2 complex repairation pipe of embodiment in degradation solution when Figure 14 is enzyme degradation 60min；
State of the complex repairation pipe in degradation solution when Figure 15 is 120min；
1 collagen tube deflated state of embodiment when Figure 16 is acid degradation 0min；
2 complex repairation tubulose state of embodiment when Figure 17 is acid degradation 180min；
2 complex repairation pipe of embodiment stretches observation when Figure 18 is acid degradation 60min；
Figure 19 is 2 complex repairation conduit state of embodiment during alkaline degradation.
Specific embodiment
For the clearer general idea for illustrating the application, it is described in detail by way of examples below.Under
In the description of text, gives a large amount of concrete details and more thoroughly understand in order to provide to the application.However, for this field
It is readily apparent that the application may not need one or more of these details and be carried out for technical staff.In others
In example, in order to avoid obscuring with the application, some technical characteristics well known in the art are not described.
Embodiment 1: the preparation of composite nerve reparation conduit internal layer collagen catheter
It is prepared as example with 6% concentration collagen slurries with internal layer collagen catheter, inner conductor preparation step is as follows:
(1) I-type collagen after being ground according to 0.6g: the ratio mixing of 10ml (0.6M acetum), acidification
200min obtains the uniform collagen slurries that concentration is 6% (mass volume ratio)；
(2) be centrifuged step (1) collagen slurries: temperature is controlled at 10 ± 2 DEG C, revolution 4000rpm, time 60min；
(3) be filled to mold after being centrifuged: taking diameter is 6mm, and length is the hollow stainless steel cylindrical mold of 30mm, injects glue
Virgin pulp liquid, middle shaft diameter are 4mm, are inserted into mold；
(4) be freeze-dried: gradient freezing: mold is placed in elevator, decrease speed be 10 turns/min, angular adjustment 9,
Time interval 1.5s, temperature are down to -60 DEG C of closing elevators, in -80 DEG C~-60 DEG C maintenance 40min, -20 DEG C of freezing chamber~-
Thaw 2h under the conditions of 30 DEG C, opens the locking cap of both mold ends, takes out axis, wherein lyophilization program is as follows:
(5) high-temperature vacuum is fixed: pressure is -0.09MPa, and temperature is 105 ± 2 DEG C, and the set time is for 24 hours.
Following example 2-6 prepares composite nerve and repairs internal layer collagen catheter used in conduit to be all made of embodiment 1 identical
Method.
Embodiment 2: composite nerve repairs catheter outer preparation method one
(1) electrostatic spinning process: 0.95g polylactic acid and 0.05g chitosan are dissolved in trifluoroacetic acid, are formed uniform
The spinning solution that chitosan mass content is 5%, polylactic acid: chitosan=9.5:0.5 (mass ratio)；It prepared by embodiment 1
Collagen catheter is placed in electrostatic field, electrostatic high-pressure 20kV, receives distance 20cm, fltting speed 1.8ml/h, spinning time 90min；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
Embodiment 3: composite nerve repairs catheter outer preparation method two
(1) electrostatic spinning process: 0.9g polylactic acid and 0.1g chitosan are dissolved in trifluoroacetic acid, form uniform shell
The spinning solution of glycan quality 10%, polylactic acid: chitosan=9:1 (mass ratio)；Collagen catheter prepared by embodiment 1 is placed in
In electrostatic field, electrostatic high-pressure 20kV receives distance 20cm, fltting speed 1.8ml/h, spinning time 90min；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
Embodiment 4: composite nerve repairs catheter outer preparation method three
(1) electrostatic spinning process: 0.8g polylactic acid and 0.2g chitosan are dissolved in trifluoroacetic acid, form uniform shell
The spinning solution that glycan mass content is 20%, polylactic acid: chitosan=8:2 (mass ratio)；Collagen prepared by embodiment 1 is led
Pipe is placed in electrostatic field, electrostatic high-pressure 22kV, receives distance 25cm, fltting speed 1.5ml/h, spinning time 90min；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
Embodiment 5: composite nerve repairs catheter outer preparation method four
(1) electrostatic spinning process: 0.7g polylactic acid and 0.3g chitosan are dissolved in trifluoroacetic acid, form uniform spin
Silk solution, chitosan mass content are 30%, polylactic acid: chitosan=7:3 (mass ratio)；Collagen prepared by embodiment 1 is led
Pipe is placed in electrostatic field, electrostatic high-pressure 20kV, receives distance 22cm, fltting speed 1.8ml/h, spinning time 90min；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
Embodiment 6: composite nerve repairs catheter outer preparation method five
(1) electrostatic spinning process: 0.6g polylactic acid and 0.4g chitosan are dissolved in trifluoroacetic acid, form uniform spin
Silk solution, chitosan mass content are 40%, polylactic acid: chitosan=6:4 (mass ratio)；Collagen prepared by embodiment 1 is led
Pipe is placed in electrostatic field, electrostatic high-pressure 22kV, receives distance 20cm, fltting speed 1.5ml/h, spinning time 90min；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
Embodiment 7: composite nerve repairs catheter outer preparation method six
Collagen concentration is 4% in embodiment 1, and other conditions are constant:
(1) electrostatic spinning process: 0.9g polylactic acid and 0.1g chitosan are dissolved in trifluoroacetic acid, form uniform shell
The spinning solution of glycan quality 10%, polylactic acid: chitosan=9:1 (mass ratio)；Using the method for embodiment 1, with 4% (matter
Measure volume ratio) uniform collagen slurries prepare 4% collagen catheter, then 4% collagen catheter is placed in electrostatic field, electrostatic high-pressure
20kV receives distance 20cm, fltting speed 1.8ml/h, spinning time 90min；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
Embodiment 8: composite nerve repairs catheter outer preparation method seven
Collagen concentration is 10% in embodiment 1, and other conditions are constant:
(1) electrostatic spinning process: 0.9g polylactic acid and 0.1g chitosan are dissolved in trifluoroacetic acid, form uniform shell
The spinning solution of glycan quality 10%, polylactic acid: chitosan=9:1 (mass ratio).Using the method for embodiment 1, with 10% (matter
Measure volume ratio) uniform collagen slurries prepare 10% collagen catheter, then 10% collagen catheter is placed in electrostatic field, electrostatic is high
20kV is pressed, distance 20cm, fltting speed 1.8ml/h, spinning time 90min are received；
(2) 40 DEG C of vacuum drying are for 24 hours；
(3) eo sterilization after just packing.
In order to more illustrate to visual pattern the core-shell structures of outer layer electrospun fibers, internal layer main component is the present invention
Polylactic acid outer layer main component is chitosan, is characterized using the method for marked by fluorescein isothiocyanate chitosan, in fiber
Surface shows apparent yellowish green fluorescence, as shown in the CLSM figure of the fluorescent staining of Fig. 5 outer layer electrospun fibers.
Embodiment 9: composite nerve is repaired ducting effect and is compared
1, Analysis of tensile strength
It using MED-01 medical packaging ability meter, imposes a condition as 10mm/min, stretching experiment is carried out to material, it is real
It is as follows to test result:
2, enzyme degradation analysis
100ml purified water, 0.833ml concentrated hydrochloric acid are added in Xiao Te bottles each, 1g pepsin mixes 10 points in shaking table
37 DEG C of water-baths preheat 30min after clock, and test specimen is added, and shaking table temperature is set as 37 DEG C, revolving speed 150r/min, concussion observation
Degradation situation.
3, acid degradation is analyzed
6M hydrochloric acid is configured, experiment product is respectively put into, is stood in 60 DEG C of baking ovens, different time is observed.
| Degradation time | 6% collagen catheter (embodiment 1) | Embodiment 2 |
| 0min | It reduces rapidly, deformation | It reduces rapidly, deformation |
| 5min | Volume reduces | Volume is gradually reduced, and keeps tubular structure |
| 10min | It is degradable, solution clarification | Volume is gradually reduced, and keeps tubular structure |
| 60min | - | Volume is gradually reduced, and keeps tubular structure |
| 180min | - | Volume is gradually reduced, still visible tubular structure |
In 60min, the conduit of embodiment 2 is stretched, still there is preferable mechanical property.
4, alkaline degradation is analyzed
2.5% sodium hydroxide solution is configured, experiment product is respectively put into, is stood in 60 DEG C of baking ovens, different time is seen
It examines.
| Degradation time | 6% collagen catheter (embodiment 1) | Embodiment 2 |
| 0min | Without significant change | It reduces rapidly, deformation |
| 5min | Volume reduces | Volume reduces |
| 15min | It is degradable | Volume reduces, and solution has wadding fibrous |
| 20min | - | Volume reduces, and solution has wadding fibrous |
| 50min | - | Degradable, solution is muddy |
To sum up comparing can find, 6% collagen catheter of internal layer, and outer layer polylactic acid and chitosan mass ratio are 9.5:0.5, spinning
Condition: electrostatic high-pressure 20kV receives distance 20cm, can get under conditions of fltting speed 1.8ml/h, spinning time 90min compared with
Ideal composite nerve collagen catheter.Composite nerve collagen catheter can be preferably kept within a certain period of time compared to collagen catheter
The integrality and plasticity of structure, would be even more beneficial to neural restoration.
The above description is only an example of the present application, is not intended to limit this application.For those skilled in the art
For, various changes and changes are possible in this application.All any modifications made within the spirit and principles of the present application are equal
Replacement, improvement etc., should be included within the scope of the claims of this application.
Claims (10)
1. a kind of composite nerve repairs conduit, which is characterized in that it includes hollow natural polymer that the composite nerve, which repairs conduit,
Sub- conduit and the electrospun fibers layer being coated on outside natural polymer conduit；The natural polymer conduit is by mass body
Product concentration is made of the collagen slurries of 4%-7%, and the electrospun fibers layer is molten by the spinning comprising polylactic acid and chitosan
Liquid is made, and the mass ratio of the polylactic acid and chitosan is (6-9.5): (0.5-4).
2. composite nerve according to claim 1 repairs conduit, which is characterized in that the natural polymer conduit is by quality
Volumetric concentration is made of 6% collagen slurries；Preferably, the collagen is type i collagen.
3. composite nerve according to claim 1 repairs conduit, which is characterized in that the quality of the polylactic acid and chitosan
Ratio is (7-9.5): (0.5-3), it is preferable that (8-9.5): (0.5-2), it is further preferred that (9-9.5): (0.5-1), it is further preferred that 7:3,
8:2,9:1 or 9.5:0.5.
4. composite nerve according to claim 1 to 3 repairs conduit, which is characterized in that the natural polymer conduit
Aperture be 50-220 μm, 0.4 ± 0.3mm of wall thickness, the electrospun fibers layer with a thickness of 0.05-0.15mm, fibre diameter
For 300-700nm.
5. a kind of method for preparing any composite nerve of claim 1-4 and repairing conduit, which is characterized in that including following step
It is rapid:
(1) preparation of hollow natural polymer conduit: the collagen slurries of preparation appropriate mass volumetric concentration inject in mold,
Freeze-drying, high temperature are fixed-type；
(2) it coats electrospun fibers layer: preparing spinning solution using polylactic acid and chitosan, step (1) is obtained hollow
Natural polymer conduit by electrospinning process coat electrospun fibers layer obtain composite nerve repair conduit.
6. according to the method described in claim 5, it is characterized in that, the electrospinning process includes the following steps: that single shaft is quiet
Electrospun, electrostatic high-pressure 15-30kV, fltting speed 0.8-2.4ml/h receive distance 15-30cm, spinning time 60-120min；
It is preferred that electrostatic high-pressure 20kV, fltting speed 1.8ml/h, receive distance 20cm, spinning time 90min.
7. according to the method described in claim 5, it is characterized in that, the collagen slurries are to mix collagen with acid solution
After collagen slurries are prepared, it is preferred that the acid solution be acetum.
8. according to the method described in claim 5, it is characterized in that, the spinning solution is that polylactic acid and chitosan are dissolved in three
It is prepared in fluoroacetic acid；Preferably, the molecular weight of polylactic acid is 100000-200000Da, and the molecular weight of chitosan is 3000-
5000Da。
9. any composite nerve of claim 1-4 repairs conduit in the nerve repair material of preparation stretch-proof and degradation resistant
In application.
10. application according to claim 9, which is characterized in that described to be degraded to proteasome degradation, acid degradation or alkaline degradation
One of or it is a variety of.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110975008A (en) * | 2019-12-18 | 2020-04-10 | 武汉理工大学 | Preparation method of nerve repair drug delivery system with electrical stimulation and angiogenesis promotion effects |
| CN111028983A (en) * | 2019-12-16 | 2020-04-17 | 天新福（北京）医疗器材股份有限公司 | Conductive composite material and preparation method and application thereof |
| CN111214709A (en) * | 2020-03-27 | 2020-06-02 | 中国医科大学 | Novel double-layer nerve conduit and preparation method thereof |
| CN115154666A (en) * | 2022-07-18 | 2022-10-11 | 上海市养志康复医院（上海市阳光康复中心） | Degradable artificial ligament capable of being used for repairing nerve loop and preparation method thereof |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843307A (en) * | 2005-04-07 | 2006-10-11 | 首都医科大学北京神经科学研究所 | Double-layer artificial nerve catheter and preparation method thereof |
| CN102688110A (en) * | 2012-06-13 | 2012-09-26 | 北京天新福医疗器材有限公司 | Multi-aperture nerve repairing tube and preparation method and application thereof |
| CN103751839A (en) * | 2013-12-17 | 2014-04-30 | 中国人民解放军第二军医大学 | Polylactic acid-chitosan composite nerve conduit and preparation method thereof |
| CN103750919A (en) * | 2014-01-20 | 2014-04-30 | 北京天新福医疗器材有限公司 | Method for freezing and forming artificial nerve sheath |
| CN103753747A (en) * | 2014-01-20 | 2014-04-30 | 北京天新福医疗器材有限公司 | Mold of artificial neurolemma tube, mold fixing device and demolding method |
| CN104382672A (en) * | 2014-11-14 | 2015-03-04 | 东华大学 | Double-layer multichannel nerve conduit and preparation method thereof |
| BR102014032548A2 (en) * | 2014-12-23 | 2016-08-16 | Fundação Universidade Fed De São Carlos | bioactive and bioresorbable fiberglass-based tubular conduit for regeneration of peripheral nervous tissue and process for obtaining same |
| CN109364303A (en) * | 2019-01-02 | 2019-02-22 | 沈阳尚贤微创医疗器械股份有限公司 | A kind of bionical nerve repair material and preparation method thereof with double-layer structure |
-
2019
- 2019-07-03 CN CN201910595225.9A patent/CN110420355A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843307A (en) * | 2005-04-07 | 2006-10-11 | 首都医科大学北京神经科学研究所 | Double-layer artificial nerve catheter and preparation method thereof |
| CN102688110A (en) * | 2012-06-13 | 2012-09-26 | 北京天新福医疗器材有限公司 | Multi-aperture nerve repairing tube and preparation method and application thereof |
| CN103751839A (en) * | 2013-12-17 | 2014-04-30 | 中国人民解放军第二军医大学 | Polylactic acid-chitosan composite nerve conduit and preparation method thereof |
| CN103750919A (en) * | 2014-01-20 | 2014-04-30 | 北京天新福医疗器材有限公司 | Method for freezing and forming artificial nerve sheath |
| CN103753747A (en) * | 2014-01-20 | 2014-04-30 | 北京天新福医疗器材有限公司 | Mold of artificial neurolemma tube, mold fixing device and demolding method |
| CN104382672A (en) * | 2014-11-14 | 2015-03-04 | 东华大学 | Double-layer multichannel nerve conduit and preparation method thereof |
| BR102014032548A2 (en) * | 2014-12-23 | 2016-08-16 | Fundação Universidade Fed De São Carlos | bioactive and bioresorbable fiberglass-based tubular conduit for regeneration of peripheral nervous tissue and process for obtaining same |
| CN109364303A (en) * | 2019-01-02 | 2019-02-22 | 沈阳尚贤微创医疗器械股份有限公司 | A kind of bionical nerve repair material and preparation method thereof with double-layer structure |
Non-Patent Citations (4)
| Title |
|---|
| XIE FENG: "In vitro and in vivo evaluation of a biodegradable chitosan-PLA composite peripheral nerve guide conduit material", 《MICROSURGERY》 * |
| 刘赣东: "泊洛沙姆188对静电纺PLA_CS神经导管性能的影响", 《上海纺织科技》 * |
| 杨洪阳: "核壳_海岛结构复合纳米纤维的制备及其性能研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
| 汪多仁: "《有机食品表面活性剂》", 30 April 2009, 北京：科学技术文献出版社 * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111028983A (en) * | 2019-12-16 | 2020-04-17 | 天新福（北京）医疗器材股份有限公司 | Conductive composite material and preparation method and application thereof |
| CN111028983B (en) * | 2019-12-16 | 2021-07-30 | 天新福（北京）医疗器材股份有限公司 | Conductive composite material and preparation method and application thereof |
| CN110975008B (en) * | 2019-12-18 | 2021-06-08 | 武汉理工大学 | Preparation method of nerve repair drug delivery system with electrical stimulation and angiogenesis promotion effects |
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| CN115487363A (en) * | 2022-09-26 | 2022-12-20 | 华瑞（福建）生物科技有限公司 | Degradable stent containing high-biocompatibility coating |
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