CN105748171A - Biological type nerve conduit - Google Patents

Biological type nerve conduit Download PDF

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Publication number
CN105748171A
CN105748171A CN201610099523.5A CN201610099523A CN105748171A CN 105748171 A CN105748171 A CN 105748171A CN 201610099523 A CN201610099523 A CN 201610099523A CN 105748171 A CN105748171 A CN 105748171A
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fiber
layer
nerve
silk fibroin
duct according
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CN105748171B (en
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王国红
李颖虹
侯软玲
王树芳
徐红彦
赵红岗
李东亮
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Xinxiang Medical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/0077Special surfaces of prostheses, e.g. for improving ingrowth
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    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005Use of materials characterised by their function or physical properties
    • A61L33/0011Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/0077Special surfaces of prostheses, e.g. for improving ingrowth
    • A61F2002/0086Special 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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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2230/00Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
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    • A61L2300/414Growth factors
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/32Materials or treatment for tissue regeneration for nerve reconstruction

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Abstract

The invention discloses a biological type nerve conduit.The biological type nerve conduit comprises a fiber-felt inner layer composed of regenerated silk fibroin fibers mixed with vascular endothelial growth factors and alkaline fibroblast growth factors and having three-dimensional staggered network structure characteristics, wherein the outer surface of the fiber-felt inner layer is sequentially covered with a porous transition layer, an anticoagulation layer and an outer layer, a plurality of cavities for storing a bioactive factor solution is formed in the fiber-felt inner layer and are located between the outer surface of the fiber-felt inner layer and the inner surface of the porous transition layer, and the outer layer is a hydrophobic-fiber-felt outer layer composed of regenerated silk fibroin fibers mixed with copper ions and having three-dimensional staggered network structure characteristics.The biological type nerve conduit provides a three-dimensional space for neural recovery, it is ensured that the nerve conduit has appropriate strength, hardness and elasticity, bioactive factors can be loaded in a required mode before an operation, the product production quality can be easy to control, the survival rate of the bioactive factors can be greatly improved, and neural regeneration is more efficiently promoted.

Description

Biological nerve duct
Technical field
The present invention relates to bio-medical material and implantable medical devices field, be specifically related to a kind of biological nerve duct.
Background technology
Nervous system is one of topmost organ in human body, and it controls sensorimotor's function of human body.Various wounds such as compressing, drawing-off, tearing, cutting off and other factors such as ischemia, tumor etc. will cause neural part or all of damage, thus causing afunction and other nervous system disease.The reconstruction of the neural reparation of defect and function is one of mankind's difficult problem of waiting to capture.Perineural neuron axon can extend under proper condition, grew damaged region, reaches the purpose of neuranagenesis.By means of the development of neurosurgery particularly microneurosurgery, reparation and the regeneration of nerve injury are possibly realized.Research at present and the CO2 laser weld technology applied clinically mainly have three kinds, directly identical, neural transplantation (autologous or allosome) and nerve trachea reparation.Directly coincide is directly near end neural for dialysis, remote body end are carried out operation stitching, it is limited only to shorter neurotmesis (less than 8mm), this is not stretch function due to nerve, sew up the tension force produced and can affect the regeneration of nerve, therefore the neurologic defect of long pause is also helpless, and its curative effect acceptance rate is only 50%.Neural transplantation can cause losing for function of nervous system of district, to relatively big thicker neurologic defect supply source deficiency, and the problem having second operation.The solution immune-suppression problems and heteroplastic transplantation is still needed.Directly it coincide and neural transplantation there is also broken ends of fractured bone sensory nerve and the problem of Motor nerve fibre wrong position.Due in the traumatology department field, repairing of neural injury is to sew up by nerve end end, but owing to peripheral nerve is mixed nerve, and also lack the science discrimination method that can distinguish neural broken ends of fractured bone sensory nerve and Motor nerve fibre in operation quickly and accurately at present, even if applying fine microsurgical technique row perineurial suture, it is also difficult to avoid after nerve end end is sewed up, because of the misorientation docking of sensation, Motor nerve fibre, and affect the curative effect of nerve suture, affect the recovery of function of nervous system.
It is the study hotspot that current neuranagenesis is repaired that nerve trachea repairs (bridge joint art), is the big focus jointly paid close attention to of tissue engineering, materialogy, biology, medical circle.Chinese scholars has been proven that nerve trachea substitutes autotransplantation to repair the feasibility of neurologic defect in recent ten years.Owing to nerve has certain Regeneration and Repair ability, induced by conduit, put up a bridge for the near end of defect nerve, remote body end, guide neural direction of regeneration, it is possible to make the neuranagenesis reparation that defect length is shorter.In recent years, there is scholar to advocate to stay the gap of 2~3mm between the neural broken ends of fractured bone, due to neural chemotaxis, being conducive to making near-end Sensory nerve fibre and Motor nerve fibre nerve fiber corresponding to far-end respectively dock, thus improving restoration effect.Compared to the restorative procedure of other nerve injury, adopt nerve trachea can provide the multiple advantage of neuranagenesis: the two ends temporarily fixed in neuranagenesis and support defect neural;Guide neuronic aixs cylinder axial growth, it is to avoid external and formation neuroma;The microenvironment of one relative insulation is provided for neuranagenesis, the neurotrophic factor that enriching nerve regeneration is required, reduces cell entry, it is prevented that the formation of cicatrix;Be conducive to Sensory nerve fibre and Motor nerve fibre correctly nerve fiber corresponding to far-end to dock, improve restoration effect.Material for preparing nerve trachea is broadly divided into non-nervous tissue, non-biodegradable material and Biodegradable material.Non-nervous tissue's material mainly includes duct of Arantius, arterial, amniotic duct, skeleton pipe, musculomembranous tube etc., the main feature of these materials is similar to the cell based counterdie of schwann cell containing basement membrane, move into offer condition for schwann cell, but these materials easily subside after ischemia, hypoplasia, formation lock scar tissue, hypertrophy and adhesion etc..Non-biodegradation shaped material such as silica gel tube, polyethylene, polyvinyl fluoride etc. are once used to prepare nerve trachea research neuranagenesis situation, Nondegradable due to conduit, after neuranagenesis completes, regeneration site still intactly stayed by conduit, this is likely to make regenerated nervous fibers, causing chronic forms to oppress and cause inflammation, thus its long-term effect is not satisfactory, application clinically is restricted.Both of which is inadvisable.Degradation material is the focus of current nerve trachea research, present Research from current nerve trachea, mainly by various biocompatibility and degradable materials, such as bovine collagen albumen, polylactic acid, chitosan etc., it is processed as hollow pipe or the built-in fiber parallel with axle, sponge etc. wherein again, puts up a bridge at the neural near end of defect and remote body end, build a microenvironment being conducive to regeneration function to play, stoping growing into of surrounding connective tissue, inducing neural regenerates along duct direction.In repair process, tube material is also degraded gradually and is absorbed by organism.And with this type of material for matrix by the modes such as injection before physical absorption, microcyst, chemical bonding, use on material in conjunction with various neuranagenesis accelerator, such as adult albumen, Neural cell adhesion protein, nerve growth factor, ciliary neurotrophic factor, Brain Derived Neurotrophic Factor etc., to promote the regeneration of nerve;Or carry out schwann cell or stem cell cultivation, with constructing tissue through engineering approaches artificial nerve catheter.Although the research of nerve trachea bridge joint art is own obtains many progress, such as Chinese patent CN100479785C (the authorizing day 2009.4.22) preparation method disclosing a kind of double-layer artificial nerve catheter, the mode of employing reverse mould prepares the ectonexine of nerve trachea.But also have suitable distance from replacing nerve autograft reparation peripheral nerve defection clinically.It main reason is that the function that current tube material provides can't fully meet the requirement of this accurately complicated physiological process of axon regeneration.The bionical conduit of nanoscale can be prepared by electrostatic spinning technique.On the one hand, the fiber that method of electrostatic spinning is obtained it is nano level, the several orders of magnitude less of the non-woven fabrics diameter that traditional method obtains;The character such as the intensity of technical arrangement plan conduit, hardness, degradation speed, pipe thickness, diameter, the distribution of aperture hole, material can be passed through on the other hand.
Chinese patent CN101439205A (publication date 2009.5.27) discloses a kind of nerve trachea, and it has core-shell structure, and sandwich layer is bioactive ingredients, and shell is Biodegradable material, is prepared by coaxial electrostatic spinning method.This nerve trachea is along with the degraded of material, and active substance can controllably discharge, but in CO2 laser weld early stage, shell fiber can not be degraded as support, so that bioactie agent can not well discharge, does not reach the purpose of reparation.Chinese patent CN101507842A (publication date 2009.8.19) discloses the nerve trachea of the flexible compressive resistance of a kind of spiral type, acid fiber by polylactic wrapping is wound on stainless steel tube, and with it for receiving device, by electrostatic spinning, prepare described nerve trachea.
Chinese patent CN101543645A (publication date 2009.9.30) discloses a kind of polycaprolactone (PCL) static spinning nerve conduit, internal layer is the reticulate vessel that high molecular degradable fiber is made, and outer layer is the PCL Sub-micro Fibers adopting method of electrostatic spinning to prepare.These two patents simply prepare nerve trachea with synthesising biological material merely, although also have certain repairing effect, but poor for neural functional repairing effect, generally can only accomplish growing into of nerve fiber cell.
Although these patents all have employed electrostatic spinning technique prepares nerve trachea, but still difficulty becomes desirable nerve trachea.Desirable nerve trachea should possess following characteristics:
(1) what be necessary for nerve repairs the three dimensions providing required, namely to ensure that nerve trachea has suitable intensity, consistency and elasticity, make nerve have the passage of regeneration;
(2) can biodegradation: conduit transplantation site in vivo can exist long time, and neuranagenesis is degraded after completing, and does not need second operation to take out;
(3) material therefor must possess low cytotoxicity, slight local organization untoward reaction etc.;
(4) there is suitable degradation cycle: when nerve growth, keep corresponding intensity, hardness, with obstruction free nerve growth;On the other hand, require again after neuranagenesis completes, degrade as early as possible, in order to avoid pressuring nerve;
(5) nutrient substance, accelerator nerve reparation can be provided for nerve in degraded simultaneously;
(6) there is desirably double-deck or multiple structure: outer layer provides necessary intensity, simultaneously work as the tight structure preventing connective tissue from growing into and to play barrier action;Internal layer then needs to have macroporous structure and high voidage, is conducive to the infiltration of bioactie agent, grows into offer nutrition for blood capillary and fibrous tissue;
(7) in the conceived case, at nerve trachea internal layer implantable neural peripheral cell, such as, Schwann cell, so would be even more beneficial to CO2 laser weld, effect will be better.
In the process promoting nerve trachea bridge joint art clinical practice, it is highly desirable to the nerve trachea biomimetic material of a kind of similar neural matrix membrane function of research, material itself had both had good moulding processability, can provide for the regeneration of aixs cylinder longer again simultaneously and guide and Nutrition, to meet the requirement of nerve regeneration better.
Summary of the invention
For solving the problems referred to above, the invention provides a kind of biological nerve duct.
For achieving the above object, the technical scheme that the present invention takes is:
Biological nerve duct, including the fiber felt internal layer with three-dimensional staggered network structure feature that the regenerated silk fibroin fiber being mixed with VEGF and basic fibroblast growth factor is constituted, described fiber felt inner layer outer surface is coated with Porous transition layer successively, anticoagulation layer and outer layer, described fiber felt internal layer is provided with the cavity of some storage bioactie agent solution, described cavity is between the outer surface and the inner surface of Porous transition layer of fiber felt internal layer, described outer layer is 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.
Wherein, described VEGF and basic fibroblast growth factor are dispersed in regenerated silk fibroin fiber.
Wherein, described Porous transition layer is by hydrophilic polymer 40-60 part, hydrophobic polymer 40-60 part, nano silicon 20~30 parts, vanillin 0.1~0.2 part, and 0.1~0.2 part of mixed mixed solution of thymol adopts the connecting layer that method of electrostatic spinning is made.
Wherein, described bioactie agent is the mixture of one or more in neurotrophic factor, neurogliocyte or medicine.
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 accounts for the 1.7 × 10 of described regenerated silk fibroin total fiber mass~3~4.7 × 10~3%.
Wherein, described hydrophobic polymer is any one or a few mixture in hydrophobic polyurethane, pla-pcl, polyglycolic acid, polyhydroxy-alkanoate class, polyurethanes or Merlon.
Wherein, described hydrophilic polymer is Polyethylene Glycol, poly butyric alkyl caproate, poly phosphate, polyvinyl alcohol, polyethylene oxide, collagen protein, gelatin, chitosan, modification of chitosan, cellulose, modified cellulose, gelatin, fibrin, fibroin, the peptide polymer of elastin mimicry, alginic acid, chondroitin sulfate, heparin, agar, glucosan or any one or a few mixture in alginic acid.
Wherein, the diameter range of described regenerated silk fibroin fiber is 300nm~7 μm.
Wherein, described anticoagulant property medicine is heparin.
The method have the advantages that
The present invention is the neural required three dimensions of recovering to provide, it is ensured that nerve trachea has suitable intensity, consistency and elasticity, makes nerve have the passage of regeneration;The material used is to it turned out the safe biologic material that human non-toxic is harmless at present, is artificial material, namely will not bring all multi-risk Systems of immunologic rejection, virus disseminating, disease propagation, without bringing other toxic action;The nerve trachea integral material of the present invention is semipermeability, do not allow cell to pass through, it is allowed to nutrient substance passes through, it is to avoid the fibrosis that cell brings, and nutrition is by accelerating again axon growth, CO2 laser weld;The nerve trachea of the present invention has good mechanical strength, supports suture needle, and automatic safe is degraded, it is ensured that during nerve obtains and repairs, material keeps intensity and hardness, the phenomenons such as this makes CO2 laser weld be normally carried out, it is to avoid fibrosis, nerve compression;The nerve trachea of the present invention has micro-cavities, compared with the nerve trachea product of traditional structure, operation consent can be passed through in a desired fashion as injection, immersion etc. load bioactie agent, 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.
Accompanying drawing explanation
Fig. 1 is the structural representation of embodiment of the present invention biological nerve duct.
Detailed description of the invention
In order to make objects and advantages of the present invention clearly understand, below in conjunction with embodiment, the present invention is further elaborated.Should be appreciated that specific embodiment described herein is only in order to explain the present invention, is not intended to limit the present invention.
As shown in Figure 1, embodiments provide a kind of biological nerve duct, including the fiber felt internal layer 1 with three-dimensional staggered network structure feature that the regenerated silk fibroin fiber being mixed with VEGF and basic fibroblast growth factor is constituted, described fiber felt internal layer 1 outer surface is coated with Porous transition layer 2 successively, anticoagulation layer 3 and outer layer 4, described fiber felt internal layer 1 is provided with the cavity 5 of some storage bioactie agent solution, described cavity 5 is between the outer surface and the inner surface of Porous transition layer 2 of fiber felt internal layer 1, described outer layer 4 is 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.
Described VEGF and basic fibroblast growth factor are dispersed in regenerated silk fibroin fiber.
Described Porous transition layer 2 is by hydrophilic polymer 40-60 part, hydrophobic polymer 40-60 part, nano silicon 20~30 parts, vanillin 0.1~0.2 part, and 0.1~0.2 part of mixed mixed solution of thymol adopts the connecting layer that method of electrostatic spinning is made.
Described bioactie agent is the mixture of one or more in neurotrophic factor, neurogliocyte or medicine.
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 described regenerated silk fibroin total fiber mass~3~4.7 × 10~3%.
Described hydrophobic polymer is any one or a few mixture in hydrophobic polyurethane, pla-pcl, polyglycolic acid, polyhydroxy-alkanoate class, polyurethanes or Merlon.
Described hydrophilic polymer is Polyethylene Glycol, poly butyric alkyl caproate, poly phosphate, polyvinyl alcohol, polyethylene oxide, collagen protein, gelatin, chitosan, modification of chitosan, cellulose, modified cellulose, gelatin, fibrin, fibroin, the peptide polymer of elastin mimicry, alginic acid, chondroitin sulfate, heparin, agar, glucosan or any one or a few mixture in alginic acid.
The diameter range of described regenerated silk fibroin fiber is 300nm~7 μm.
Described anticoagulant property medicine is heparin.
What be originally embodied as nerve recovers to provide required three dimensions, it is ensured that nerve trachea has suitable intensity, consistency and elasticity, makes nerve have the passage 6 of regeneration;The material used is to it turned out the safe biologic material that human non-toxic is harmless at present, is artificial material, namely will not bring all multi-risk Systems of immunologic rejection, virus disseminating, disease propagation, without bringing other toxic action;The nerve trachea integral material of the present invention is semipermeability, do not allow cell to pass through, it is allowed to nutrient substance passes through, it is to avoid the fibrosis that cell brings, and nutrition is by accelerating again axon growth, CO2 laser weld;The nerve trachea of the present invention has good mechanical strength, supports suture needle, and automatic safe is degraded, it is ensured that during nerve obtains and repairs, material keeps intensity and hardness, the phenomenons such as this makes CO2 laser weld be normally carried out, it is to avoid fibrosis, nerve compression;The nerve trachea of the present invention has micro-cavities, compared with the nerve trachea product of traditional structure, operation consent can be passed through in a desired fashion as injection, immersion etc. load bioactie agent, 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, there is important clinical value.
The above is only the preferred embodiment of the present invention; it should be pointed out that, for those skilled in the art, under the premise without departing from the principles of the invention; can also making some improvements and modifications, these improvements and modifications also should be regarded as protection scope of the present invention.

Claims (10)

1. biological nerve duct, it is characterized in that, including the fiber felt internal layer (1) with three-dimensional staggered network structure feature that the regenerated silk fibroin fiber being mixed with VEGF and basic fibroblast growth factor is constituted, described fiber felt internal layer (1) outer surface is coated with Porous transition layer (2) successively, anticoagulation layer (3) and outer layer (4), described fiber felt internal layer (1) is provided with the cavity (5) of some storage bioactie agent solution, described cavity (5) is positioned between the outer surface of fiber felt internal layer (1) and the inner surface of Porous transition layer (2), described outer layer (4) is 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.
2. biological nerve duct according to claim 1, it is characterised in that described VEGF and basic fibroblast growth factor are dispersed in regenerated silk fibroin fiber.
3. biological nerve duct according to claim 1, it is characterized in that, described Porous transition layer (2) is by hydrophilic polymer 40-60 part, hydrophobic polymer 40-60 part, nano silicon 20~30 parts, vanillin 0.1~0.2 part, and 0.1~0.2 part of mixed mixed solution of thymol adopts 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 the mixture of one or more in neurotrophic factor, neurogliocyte or medicine.
5. biological nerve duct according to claim 1, it is characterised in that the quality of VEGF accounts for the 3 × 10 of regenerated silk fibroin total fiber mass~5~7 × 10~5%.
6. biological nerve duct according to claim 1, it is characterised in that the quality of basic fibroblast growth factor accounts for the 1.7 × 10 of described regenerated silk fibroin total fiber mass~3~4.7 × 10~ 3%.
7. biological nerve duct according to claim 3, it is characterized in that, described hydrophobic polymer is any one or a few mixture in hydrophobic polyurethane, pla-pcl, polyglycolic acid, polyhydroxy-alkanoate class, polyurethanes or Merlon.
8. biological nerve duct according to claim 3, it is characterized in that, described hydrophilic polymer is Polyethylene Glycol, poly butyric alkyl caproate, poly phosphate, polyvinyl alcohol, polyethylene oxide, collagen protein, gelatin, chitosan, modification of chitosan, cellulose, modified cellulose, gelatin, fibrin, fibroin, the peptide polymer of elastin mimicry, alginic acid, chondroitin sulfate, heparin, agar, glucosan or any one or a few mixture in alginic acid.
9. biological nerve duct according to claim 1, it is characterised in that the diameter range of described regenerated silk fibroin fiber is 300nm~7 μm.
10. biological nerve duct according to claim 1, it is characterised in that described anticoagulant property medicine is heparin.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108273138A (en) * 2018-02-05 2018-07-13 北京诺康达医药科技有限公司 A kind of absorbable peripheral nerve of intelligent control repairs conduit and preparation method thereof
WO2020133668A1 (en) * 2018-12-29 2020-07-02 南通纺织丝绸产业技术研究院 Nerve conduit of magnesium filament and silk compositely woven structure and preparation method for nerve conduit
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

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1237914A (en) * 1996-11-20 1999-12-08 清水庆彦 Artificial neural canal
US20020019663A1 (en) * 1994-02-18 2002-02-14 Termin Paul L. Method for treating diseased or damaged organs
KR20060006295A (en) * 2004-07-15 2006-01-19 이진호 Porous nerve guided conduit having hydrophilicity and selective permeability and its manufacturing method
CN101579246A (en) * 2009-05-31 2009-11-18 苏州大学 Artificial silk fibroin nano-fiber nerve repair conduit and preparation method thereof
EP2465472A2 (en) * 2009-08-12 2012-06-20 SNU R&DB Foundation Silk nanofiber nerve conduit and method for producing thereof
CN102688076A (en) * 2011-03-25 2012-09-26 广州迈普再生医学科技有限公司 Nerve conduit and preparation method thereof
CN103127548A (en) * 2013-01-31 2013-06-05 东南大学 Manufacture method of artificial nerve conduit for promoting nerve defect repair
CN103841839A (en) * 2011-07-15 2014-06-04 捷通国际有限公司 Multicarotenoid beadlets and related method
CN103920194A (en) * 2011-03-25 2014-07-16 广州迈普再生医学科技有限公司 Nerve conduit and preparation method thereof
CN104689376A (en) * 2015-03-17 2015-06-10 邹蓉 Nerve conduit and preparation method thereof
CN205007321U (en) * 2015-01-28 2016-02-03 五石医疗科技(苏州)有限公司 Darkness pipe

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020019663A1 (en) * 1994-02-18 2002-02-14 Termin Paul L. Method for treating diseased or damaged organs
CN1237914A (en) * 1996-11-20 1999-12-08 清水庆彦 Artificial neural canal
KR20060006295A (en) * 2004-07-15 2006-01-19 이진호 Porous nerve guided conduit having hydrophilicity and selective permeability and its manufacturing method
CN101579246A (en) * 2009-05-31 2009-11-18 苏州大学 Artificial silk fibroin nano-fiber nerve repair conduit and preparation method thereof
EP2465472A2 (en) * 2009-08-12 2012-06-20 SNU R&DB Foundation Silk nanofiber nerve conduit and method for producing thereof
CN102688076A (en) * 2011-03-25 2012-09-26 广州迈普再生医学科技有限公司 Nerve conduit and preparation method thereof
CN103920194A (en) * 2011-03-25 2014-07-16 广州迈普再生医学科技有限公司 Nerve conduit and preparation method thereof
CN103841839A (en) * 2011-07-15 2014-06-04 捷通国际有限公司 Multicarotenoid beadlets and related method
CN103127548A (en) * 2013-01-31 2013-06-05 东南大学 Manufacture method of artificial nerve conduit for promoting nerve defect repair
CN205007321U (en) * 2015-01-28 2016-02-03 五石医疗科技(苏州)有限公司 Darkness pipe
CN104689376A (en) * 2015-03-17 2015-06-10 邹蓉 Nerve conduit and preparation method thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108273138A (en) * 2018-02-05 2018-07-13 北京诺康达医药科技有限公司 A kind of absorbable peripheral nerve of intelligent control repairs conduit and preparation method thereof
WO2020133668A1 (en) * 2018-12-29 2020-07-02 南通纺织丝绸产业技术研究院 Nerve conduit of magnesium filament and silk compositely woven structure and preparation method for nerve conduit
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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