CN105748171B - Biological nerve duct - Google Patents
Biological nerve duct Download PDFInfo
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- CN105748171B CN105748171B CN201610099523.5A CN201610099523A CN105748171B CN 105748171 B CN105748171 B CN 105748171B CN 201610099523 A CN201610099523 A CN 201610099523A CN 105748171 B CN105748171 B CN 105748171B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0077—Special surfaces of prostheses, e.g. for improving ingrowth
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/08—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0077—Special surfaces of prostheses, e.g. for improving ingrowth
- A61F2002/0086—Special surfaces of prostheses, e.g. for improving ingrowth for preferentially controlling or promoting the growth of specific types of cells or tissues
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0063—Three-dimensional shapes
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
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Abstract
The invention discloses a kind of biological nerve duct, including being mixed with the fibrofelt internal layer with three-dimensional staggered network structure feature that the regenerated silk fibroin fiber of VEGF and basic fibroblast growth factor is constituted, fibrofelt inner layer outer surface is successively covered with Porous transition layer, anticoagulation layer and outer layer, cavity of the fibrofelt internal layer provided with some storage bioactie agent solution, cavity is located between the inner surface of the outer surface of fibrofelt internal layer and Porous transition layer, outer layer is to be mixed with the hydrophobic fibre felt outer layer with three-dimensional staggered network structure feature that the regenerated silk fibroin fiber of copper ion is constituted.The present invention is the three dimensions needed for the recovery of nerve is provided, it ensure that nerve trachea has suitable intensity, consistency and elasticity, bioactie agent can be loaded in a desired fashion before surgery, not only make production quality easily controllable, and the survival rate of bioactie agent can be greatly improved, more efficiently promote the regeneration of nerve.
Description
Technical field
The present invention relates to bio-medical material and implantable medical devices field, and in particular to a kind of biological nerve is led
Pipe.
Background technology
Nervous system is one of topmost organ in human body, and it controls sensorimotor's function of human body.It is various outer
Wound such as compressing, drawing-off, tear, cut-out and other factors such as ischaemic, tumour will cause nervous system part or
All damages, so as to cause function to be lost and other neurogenic diseases.Defect nerve reparation and function reconstruction be the mankind still
One of problem to be captured.Perineural neuron axon can extend under proper condition, grew and be damaged region, reach
The purpose of nerve regneration.By means of the development of neurosurgery particularly microneurosurgery, the reparation and regeneration of neurotrosis are
It is possibly realized.The current CO2 laser weld technology studied and clinically applied mainly has three kinds, and direct identical, nerve-grafting is (certainly
Body or allosome) and nerve trachea reparation.It is that the near end of dialysis nerve, remote body end directly are carried out into operation stitching directly to coincide,
Shorter neurectmesis (being less than 8mm) is limited only to, this is due to that nerve can influence without function, the tension force that suture is produced is stretched
The regeneration of nerve, thus it is also helpless to the neurologic defect of long pause, and its curative effect acceptance rate is only 50%.Nerve-grafting meeting
Cause to lose for area's nervous function, the problem of originating to larger thicker neurologic defect supply not enough, and have second operation.And it is different
Body transplants solution immune-suppression problems of still needing.Directly it coincide and nerve-grafting also there is broken ends of fractured bone sensory nerve and kinesitherapy nerve is fine
The problem of tieing up wrong position.Because in traumatology department field, repairing of neural injury is sutured by nerve end end, but due to peripheral nerve
It is composite nerve, and also lacking can quickly and accurately distinguish that neural broken ends of fractured bone sensory nerve and kinesitherapy nerve are fine at present in operation
The science discrimination method of dimension, even if using fine microsurgical technique row perineurial suture, it is also difficult to avoid stitching at nerve end end
After conjunction, because of sensation, the misorientation docking of motor fibre, and the curative effect of nerve suture is influenceed, influence the recovery of nervous function.
It is the study hotspot that current nerve regneration is repaired that nerve trachea, which repairs (bridge joint art), be organizational engineering, materialogy,
The big focus that biology, medical field are paid close attention to jointly.Domestic and foreign scholars have confirmed that nerve trachea is substituted certainly in recent ten years
Body is transplanted to repair the feasibility of neurologic defect.Because nerve has certain Regeneration and Repair ability, induced by conduit, be scarce
Damage the near end of nerve, remote body end to put up a bridge, guide the direction of regeneration of nerve, the nerve regneration that defect length can be made shorter is repaiied
It is multiple.In recent years, there is scholar to advocate to stay 2-3mm gap between the neural broken ends of fractured bone, due to the chemotaxis of nerve, be conducive to making near-end
Nerve fibre corresponding to distal end is docked respectively for Sensory nerve fibre and motor fibre, so as to improve restoration effect.Phase
Than in the restorative procedure of other neurotrosises, a variety of advantages of nerve regneration can be provided using nerve trachea：In nerve
Two ends that are temporarily fixed and supporting defect nerve in regeneration；Guide the aixs cylinder axial growth of neuron, it is to avoid external and formation god
Through knurl；The microenvironment of a relative insulation is provided for nerve regneration, the neurotrophic factor needed for enriching nerve regeneration is reduced thin
Born of the same parents invade, and prevent the formation of scar；Being conducive to Sensory nerve fibre and motor fibre, correctly nerve corresponding to distal end is fine
Dimension docking, improves restoration effect.Non-nervous tissue, non-biodegradation material are broadly divided into for preparing the material of nerve trachea
Material and Biodegradable material.Non-nervous tissue's material mainly includes duct of Arantius, arterial, amniotic duct, bone pipe, musculomembranous tube
Deng the characteristics of these materials are main is similar to the cell basilar memebrane of schwann cell containing basilar memebrane, is that schwann cell is moved into and carried
For condition, but these materials are easily collapsed after ischemic, hypoplasia, form lock scar tissue, hyperplasia and adhesion etc..It is abiotic
Degradation-type material such as silicone tube, polyethylene, polyvinyl fluoride etc. are once used to prepare nerve trachea research nerve regneration situation, due to
The nondegradation of conduit, after nerve regneration is completed, conduit still intactly stays in regeneration site, and this may make regenerating nerve fine
Dimensionization, causes chronic forms to be oppressed and triggers inflammation, thus its long-term effect is not satisfactory, and clinically application is restricted.
Both of which is inadvisable.Degradation material is the focus of current nerve trachea research, in terms of the present Research of current nerve trachea,
Mainly by various biocompatibilities and degradable materials, such as bovine collagen albumen, PLA, chitosan, in being processed as
Blank pipe or the again built-in fiber parallel with axle, sponge etc. wherein, put up a bridge in the near end and remote body end of defect nerve, build one
The individual microenvironment for being conducive to regeneration function to play, prevents growing into for surrounding connective tissue, inducing neural regenerates along duct direction.
In repair process, tube material is also gradually degraded to be absorbed by organism.And by matrix of such material by physical absorption, micro-
Packing, chemical bonding, using it is preceding injection etc. mode on material combine various nerve regneration accelerator, such as adult albumen, nerve
CAP, nerve growth factor, CNTF, BDNF etc., to promote nerve
Regeneration；Or schwann cell or stem cell culture are carried out, artificial nerve catheter is engineered with constructing tissue.Although nerve trachea is bridged
Oneself obtains many progress for the research of art, and such as Chinese patent CN100479785C (grant date 2009.4.22) discloses a kind of bilayer
The preparation method of artificial nerve catheter, prepares the ectonexine of nerve trachea by the way of reverse mould.But it is autologous from clinically replacing
Nerve-grafting repairs peripheral nerve defection and also has suitable distance.It is main reason is that the function that tube material is provided at present
The requirement of this accurate complicated physiology course of axon regeneration can't be fully met.It can be prepared and received by electrostatic spinning technique
The bionical conduit of meter level.On the one hand, it is nonwoven that is nano level, being obtained than traditional method by the fiber obtained by method of electrostatic spinning
The small several orders of magnitude of cloth diameter；On the other hand the intensity of technical arrangement plan conduit, hardness, degradation speed, thickness of pipe wall can be passed through
The properties such as degree, diameter, the distribution of aperture hole, material.
Chinese patent CN101439205A (publication date 2009.5.27) discloses a kind of nerve trachea, and it has shell-core knot
Structure, sandwich layer is bioactive ingredients, and shell is Biodegradable material, is prepared by coaxial electrostatic spinning method.The nerve is led
Pipe can controllably discharge with the degraded of material, active material, but in CO2 laser weld early stage, shell fiber can not as support
Degraded, so that bioactie agent can not discharge well, does not reach the purpose of reparation.Chinese patent CN101507842A is (public
Open a day 2009.8.19) nerve trachea of the flexible compressive resistance of spiral shape a kind of is disclosed, acid fiber by polylactic wrapping is wound on stainless
On steel pipe, and using it as reception device, by electrostatic spinning, the nerve trachea is prepared.
Chinese patent CN101543645A (publication date 2009.9.30) discloses a kind of polycaprolactone (PCL) static spinning god
Through conduit, internal layer is the reticulate vessel that high molecular degradable fiber is made, and outer layer is the PCL sub-micros prepared using method of electrostatic spinning
Meter level fiber.This two patents are to prepare nerve trachea with synthesising biological material merely, although also have certain repairing effect,
But it is poor for the feature repairing effect of nerve, it can only typically accomplish growing into for nerve fibre cell.
Although these patents all employ electrostatic spinning technique and prepare nerve trachea, still hardly possible is led as preferable nerve
Pipe.Preferable nerve trachea should possess following characteristics：
(1) be necessary for nerve reparation provide needed for three dimensions, i.e., to ensure nerve trachea have suitable intensity,
Consistency and elasticity, makes nerve have the passage of regeneration；
(2) can be biodegradable：Transplantation site can have long time to conduit in vivo, occur after the completion of nerve regneration
Degraded, is not required to second operation taking-up；
(3) material therefor must possess low cytotoxicity, slight local organization adverse reaction etc.；
(4) there is suitable degradation cycle：In nerve growth, corresponding intensity, hardness are kept, it is raw with obstruction free nerve
It is long；On the other hand, require after the completion of nerve regneration, degrade as early as possible again, in order to avoid pressuring nerve；
(5) nutriment, accelerans reparation can be provided for nerve simultaneously in degraded；
(6) there is preferably double-deck or sandwich construction：Outer layer provides necessary intensity, while playing prevents connective tissue long
Enter and rise the tight structure of barrier action；Internal layer then needs to possess macroporous structure and high voidage, is conducive to bioactie agent
Infiltration, be that capillary and fibr tissue grow into offer nutrition；
(7) in the conceived case, neural peripheral cell is implanted into nerve trachea internal layer, such as, Schwann cell, this
Sample would be even more beneficial to CO2 laser weld, and effect will be more preferable.
During nerve trachea bridge joint art clinical practice is promoted, it is also very desirable to a kind of similar neural matrix membrane work(of research
The nerve trachea biomimetic material of energy, material both has good moulding processability in itself, while can be longer again aixs cylinder
Regeneration provides guiding and trophism, preferably to meet the requirement of nerve regeneration.
The content of the invention
To solve the above problems, the invention provides a kind of biological nerve duct.
To achieve the above object, the technical scheme taken of the present invention is：
Biological nerve duct, including it is mixed with VEGF and basic fibroblast growth factor again
The fibrofelt internal layer with three-dimensional staggered network structure feature that fibroin azelon is constituted, the fibrofelt inner layer outer surface
Successively covered with Porous transition layer, anticoagulation layer and outer layer, the fibrofelt internal layer is provided with some storage bioactie agents
The cavity of solution, the cavity is located between the inner surface of the outer surface of fibrofelt internal layer and Porous transition layer, and the outer layer is
Outside the hydrophobic fibre felt with three-dimensional staggered network structure feature for being mixed with the regenerated silk fibroin fiber of copper ion composition
Layer.
Wherein, the VEGF and basic fibroblast growth factor are in regenerated silk fibroin fiber
It is dispersed.
Wherein, the Porous transition layer is by 40-60 parts of hydrophilic polymer, 40-60 parts of hydrophobic polymer, nano-silica
20~30 parts of SiClx, 0.1~0.2 part of vanillic aldehyde, 0.1~0.2 part of mixed mixed solution of thymol use method of electrostatic spinning
The connecting layer being made.
Wherein, described bioactie agent is one or more in neurotrophic factor, Deiter's cells or medicine
Mixture.
Wherein, the quality of VEGF accounts for the 3 × 10 of regenerated silk fibroin total fiber mass~5~7 × 10~5%.
Wherein, the quality of basic fibroblast growth factor account for the regenerated silk fibroin total fiber mass 1.7 ×
10~3~4.7 × 10~3%.
Wherein, the hydrophobic polymer is hydrophobic polyurethane, polycaprolactone, polyglycolic acid, poly- hydroxy alkyl acid
The mixture of any one or a few in esters, polyurethanes or makrolon.
Wherein, the hydrophilic polymer be polyethylene glycol, it is poly butyric capronate, polyphosphate, polyvinyl alcohol, poly-
Oxidative ethane, collagen, gelatin, chitosan, modification of chitosan, cellulose, modified cellulose, fibrin, silk-fibroin, elastic force
Any one or a few in peptide polymer, alginic acid, chondroitin sulfate, heparin, agar, glucan or the alginic acid of albumen mimicry
Mixture.
Wherein, the diameter range of described regenerated silk fibroin fiber is 300nm~7 μm.
Wherein, the anticoagulant property medicine is heparin.
The invention has the advantages that：
The present invention for nerve recovery provide needed for three dimensions, it is ensured that nerve trachea have suitable intensity, firmly
Degree and elasticity, make nerve have the passage of regeneration；Used material is to have confirmed the safety nontoxic to human body at present
Biomaterial, is artificial material, i.e., will not bring all multi-risk Systems of immunological rejection, viral transmission, disease propagation, will not also bring
Other toxic actions；The nerve trachea integral material of the present invention is in semipermeability, does not allow cell to pass through, it is allowed to which nutriment leads to
Cross, it is to avoid the fibrosis that cell is brought, nutrition by accelerating axon growth, CO2 laser weld again；The nerve trachea of the present invention
With good mechanical strength, suture needle, automatic safe degraded, it is ensured that during nerve has obtained repairing again, material holding are supported
Intensity and hardness, this causes CO2 laser weld to be normally carried out, it is to avoid fibrosis, the phenomenon such as neurothlipsis；The nerve trachea of the present invention
, can be by operation consent in a desired fashion such as injection, immersion compared with the nerve trachea product of traditional structure with micro-cavities
Deng loading bioactie agent, not only make production quality easily controllable, and depositing for bioactie agent can be greatly improved
Motility rate, more efficiently promotes the regeneration of nerve.
Brief description of the drawings
Fig. 1 is the structural representation of biological nerve duct of the embodiment of the present invention.
Embodiment
In order that objects and advantages of the present invention are more clearly understood, the present invention is carried out with reference to embodiments further
Describe in detail.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to limit this hair
It is bright.
As shown in figure 1, the embodiments of the invention provide a kind of biological nerve duct, including it is mixed with vascular endothelial growth
What the regenerated silk fibroin fiber of the factor and basic fibroblast growth factor was constituted has three-dimensional staggered network structure feature
Fibrofelt internal layer 1, the outer surface of fibrofelt internal layer 1 is successively covered with Porous transition layer 2, anticoagulation layer 3 and outer layer 4, institute
Cavity 5 of the fibrofelt internal layer 1 provided with some storage bioactie agent solution is stated, the cavity 5 is located at fibrofelt internal layer 1
Between the inner surface of outer surface and Porous transition layer 2, the outer layer 4 is that the regenerated silk fibroin fiber for being mixed with copper ion is constituted
The hydrophobic fibre felt outer layer with three-dimensional staggered network structure feature.
The VEGF and basic fibroblast growth factor are uniform in regenerated silk fibroin fiber
It is scattered.
The Porous transition layer 2 is by 40-60 parts of hydrophilic polymer, 40-60 parts of hydrophobic polymer, nano silicon
20~30 parts, 0.1~0.2 part of vanillic aldehyde, 0.1~0.2 part of mixed mixed solution of thymol are made of method of electrostatic spinning
Connecting layer.
Described bioactie agent is mixing one or more of in neurotrophic factor, Deiter's cells or medicine
Thing.
The quality of VEGF accounts for the 3 × 10 of regenerated silk fibroin total fiber mass~5~7 × 10~5%.
The quality of basic fibroblast growth factor accounts for the 1.7 × 10 of the regenerated silk fibroin total fiber mass~3~
4.7×10~3%.
The hydrophobic polymer be hydrophobic polyurethane, polycaprolactone, polyglycolic acid, polyhydroxy-alkanoate class,
The mixture of any one or a few in polyurethanes or makrolon.
The hydrophilic polymer is polyethylene glycol, poly butyric capronate, polyphosphate, polyvinyl alcohol, polyoxy second
Alkane, collagen, gelatin, chitosan, modification of chitosan, cellulose, modified cellulose, fibrin, silk-fibroin, elastin
Any one or a few in peptide polymer, alginic acid, chondroitin sulfate, heparin, agar, glucan or the alginic acid of mimicry it is mixed
Compound.
The diameter range of described regenerated silk fibroin fiber is 300nm~7 μm.
The anticoagulant property medicine is heparin.
Originally it is embodied as the three dimensions needed for the recovery offer of nerve, it is ensured that nerve trachea has suitable strong
Degree, consistency and elasticity, make nerve have the passage 6 of regeneration；Used material be at present have confirmed it is nontoxic to human body
Safe biologic material, be artificial material, i.e., will not bring all multi-risk Systems of immunological rejection, viral transmission, disease propagation, also not
Other toxic actions can be brought；The nerve trachea integral material of the present invention is in semipermeability, does not allow cell to pass through, it is allowed to nutrition
Material passes through, it is to avoid the fibrosis that cell is brought, and nutrition by accelerating axon growth, CO2 laser weld again；The god of the present invention
There is good mechanical strength through conduit, suture needle, automatic safe degraded, it is ensured that during nerve has obtained repairing again, material is supported
Material keeps intensity and hardness, and this causes CO2 laser weld to be normally carried out, it is to avoid fibrosis, the phenomenon such as neurothlipsis；The god of the present invention
There are micro-cavities through conduit, can be by operation consent in a desired fashion as noted compared with the nerve trachea product of traditional structure
The loading bioactie agent such as penetrate, soak, not only making production quality easily controllable, and can greatly improve bioactivity because
The survival rate of son, more efficiently promotes the regeneration of nerve, with important clinical value.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (10)
1. biological nerve duct, it is characterised in that including being mixed with VEGF and basic fibroblast life
The fibrofelt internal layer (1) with three-dimensional staggered network structure feature that the regenerated silk fibroin fiber of the long factor is constituted, the fibre
Felt internal layer (1) outer surface is tieed up successively covered with Porous transition layer (2), anticoagulation layer (3) and outer layer (4), the fibrofelt internal layer
(1) cavity (5) provided with some storage bioactie agent solution, the cavity (5) is located at the appearance of fibrofelt internal layer (1)
Between the inner surface of face and Porous transition layer (2), the outer layer (4) is that the regenerated silk fibroin fiber for being mixed with copper ion is constituted
The hydrophobic fibre felt outer layer with three-dimensional staggered network structure feature.
2. biological nerve duct according to claim 1, it is characterised in that the VEGF and alkalescence
Fibroblast growth factor is dispersed in regenerated silk fibroin fiber.
3. biological nerve duct according to claim 1, it is characterised in that the Porous transition layer (2) is by hydrophily
40-60 parts of polymer, 40-60 parts of hydrophobic polymer, 20~30 parts of nano silicon, 0.1~0.2 part of vanillic aldehyde, in hundred
0.1~0.2 part of mixed mixed solution of phenol uses the connecting layer that method of electrostatic spinning is made.
4. biological nerve duct according to claim 1, it is characterised in that described bioactie agent is sought for nerve
Support mixtures one or more of in the factor, Deiter's cells or medicine.
5. biological nerve duct according to claim 1, it is characterised in that the quality of VEGF is accounted for again
The 3 × 10 of fibroin azelon gross mass~5~7 × 10~5%.
6. biological nerve duct according to claim 1, it is characterised in that the matter of basic fibroblast growth factor
Amount accounts for the 1.7 × 10 of the regenerated silk fibroin total fiber mass~3~4.7 × 10~3%.
7. biological nerve duct according to claim 3, it is characterised in that the hydrophobic polymer is poly- for hydrophobicity
Any one or a few in urethane, pla-pcl, polyglycolic acid, polyhydroxy-alkanoate class, polyurethanes or makrolon
Mixture.
8. biological nerve duct according to claim 3, it is characterised in that the hydrophilic polymer is poly- second two
Alcohol, poly butyric capronate, polyphosphate, polyvinyl alcohol, polyethylene oxide, collagen, gelatin, chitosan, modified shell gather
Sugar, cellulose, modified cellulose, fibrin, silk-fibroin, the peptide polymer of elastin mimicry, alginic acid, chondroitin sulfate
The mixture of any one or a few in element, heparin, agar, glucan or alginic acid.
9. biological nerve duct according to claim 1, it is characterised in that described regenerated silk fibroin fiber it is straight
Footpath scope is 300nm~7 μm.
10. biological nerve duct according to claim 1, it is characterised in that the anticoagulant property medicine is heparin.
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| CN109513041B (en) * | 2018-12-29 | 2023-10-03 | 南通纺织丝绸产业技术研究院 | Nerve conduit with magnesium silk composite woven structure and preparation method thereof |
| CN113648013A (en) * | 2021-08-25 | 2021-11-16 | 心凯诺医疗科技(上海)有限公司 | Close net support of blood flow direction |
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| US6334872B1 (en) * | 1994-02-18 | 2002-01-01 | Organogenesis Inc. | Method for treating diseased or damaged organs |
| TW528600B (en) * | 1996-11-20 | 2003-04-21 | Yasuhiko Shimizu | Artificial neural canal |
| KR100592587B1 (en) * | 2004-07-15 | 2006-06-26 | 이진호 | Porous nerve guided conduit having hydrophilicity and selective permeability and its manufacturing method |
| CN101579246B (en) * | 2009-05-31 | 2010-12-08 | 苏州大学 | Artificial silk fibroin nano-fiber nerve repair conduit and preparation method thereof |
| KR101116237B1 (en) * | 2009-08-12 | 2012-03-09 | 서울대학교산학협력단 | Nanofibrous silk nerve conduit for the regeneration of injured nerve and preparation method thereof |
| CN102688076B (en) * | 2011-03-25 | 2014-09-10 | 广州迈普再生医学科技有限公司 | Nerve conduit and preparation method thereof |
| CN103920194B (en) * | 2011-03-25 | 2015-06-10 | 广州迈普再生医学科技有限公司 | Nerve conduit and preparation method thereof |
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| CN103127548B (en) * | 2013-01-31 | 2014-09-10 | 东南大学 | Manufacture method of artificial nerve conduit for promoting nerve defect repair |
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