CN107648671A - A kind of anti-infective high intensity artificial dura mater of multilayer and preparation method thereof - Google Patents

A kind of anti-infective high intensity artificial dura mater of multilayer and preparation method thereof Download PDF

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CN107648671A
CN107648671A CN201711094466.2A CN201711094466A CN107648671A CN 107648671 A CN107648671 A CN 107648671A CN 201711094466 A CN201711094466 A CN 201711094466A CN 107648671 A CN107648671 A CN 107648671A
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slice
layer
intermediate layer
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dura mater
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CN107648671B (en
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李瑞锋
王斐
李典
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Shaanxi Mechatronics Vocational And Technical College
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    • 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
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • 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
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • 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
    • A61L27/58Materials at least partially resorbable by the body
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0015Electro-spinning characterised by the initial state of the material
    • D01D5/003Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0061Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0069Electro-spinning characterised by the electro-spinning apparatus characterised by the spinning section, e.g. capillary tube, protrusion or pin
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0061Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0076Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0061Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0092Electro-spinning characterised by the electro-spinning apparatus characterised by the electrical field, e.g. combined with a magnetic fields, using biased or alternating fields
    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
    • 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
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/32Materials or treatment for tissue regeneration for nerve reconstruction

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Abstract

The invention provides a kind of anti-infective high intensity artificial dura mater of multilayer, comprising three layers, the cerebripetal hydrophobic internal layer in face, carries on the back cerebripetal water soluble chitosan outer layer and Weaving type intermediate layer.Present invention also offers a kind of preparation method of the anti-infective high intensity artificial dura mater of multilayer, comprise the following steps:Electrospun prepares hydrophobic inner layer;Prepare water soluble chitosan slice;Prepare hydrophobicity slice;Prepare Weaving type intermediate layer;Outer layer is prepared with orientation electrospinning process on the intermediate layer, finally obtains artificial dura mater.Artificial dura mater of the present invention efficiently solves the infection problems in endocranium repair process, while improves the dural intensity of Traditional Man, and can cut randomly as needed, securely and reliably, has a extensive future.

Description

A kind of anti-infective high intensity artificial dura mater of multilayer and preparation method thereof
Technical field
The present invention relates to anti-infective high intensity artificial dura mater of a kind of multilayer and preparation method thereof, belong to electrostatic spinning technique Field.
Background technology
Dura defect is common in neurosurgery clinical position, open craniocerebral injury (industry, traffic, war etc.), The erosion of tumour, congenital defect of meninges and other brain disorder reasons can trigger dura defect.Dura defect need and When repairing it is excessive to prevent cerebrospinal fluid, prevent the bulging of brain and the compressing of atmospheric pressure, otherwise will jeopardize human life.Dura defect The complication such as intracranial infection, brain adhesion, hypohydropses can also be triggered, often cause such as headache, brain disorder disease.
Oneself has artificial dura mater made of multiple material just in Clinical practice, to can be divided mainly into two major classes at present:Biology spreads out Green material and artificial synthesized high polymer material.Bio-derived material mainly have allogeneic human cerebral dura mater and xenogenesis pig/ Ox source pericardium, dermal matrix and biomembrane using the preparation of ox tendon forceps type i collagen etc..Artificial synthesized high polymer material is main Including polyesters degradable macromolecule, such as PLA, polyglycolic acid, polycaprolactone and polyurethane.Additionally include poly- four The non-degradable high polymer material such as PVF.
Meninx injury repair effect desirably multilayer artificial dura mater at present.This multilayer artificial dura mater passes through It is layered to reach the purpose of simulation meninx physiological function.This kind of artificial dura mater is typically made up of for two layers internal layer and outer layer.Wherein Internal layer is made up of hydrophobic material, and outer layer is made up of water wetted material.Because the hydrophobic hydrophilic nmature of materials at two layers is different, cause outer layer with The coupling reliability of internal layer is not high, there is the phenomenon of stripping, the life and health of the patient of serious threat.
Meninx is mainly distributed the collagenous fibres of fibroblast and its secretion.General fibroblast diameter is at 20-30 μm Between.Document report, when electrospun fibers footpath is between 50-1000nm, average pore size can reach 2 μm.Average pore size Below 3 μm, entering in electrospun fibers film for cell, the generation of effective brain adhesion can be effectively prevented.Work as fiber For diameter between 5-200 μm, average pore size reaches 20-100 μm.So be advantageous to it is fibroblastic move into, adhere to, breeding and Growth and Differentiation.
Chitosan is the unique a kind of alkaline polysaccharide with cation found in nature, has good bio-compatible Property, degradability and prevention tissue adhesive properties, it is often more important that numerous studies oneself confirm its there is excellent broad-spectrum antibacterial characteristic, Oneself is clinically widely applied, therefore is the ideal material for preparing anti-infective artificial dura mater.
Kyle Kurpinski etc. exist《Nanomedicine》In in an article delivering, describe a kind of double-deck Electrospinning film, material therefor are PLCL/PPG solution.Article utilizes rotating shaft collection device, obtains the electrospinning film of parallel arrangement, surveys The parallel and electrospinning film of vertical fibers arragement direction mechanical strength is tried, sample size is 6 × 1cm, is measured along both direction Maximum load be respectively 12.08 ± 1.15N and 3.01 ± 0.54N.It can be seen that on direction consistent with machine direction film it is strong Spend very poor.
Chinese invention patent CN 103480042 A, it is entitled:" a kind of artificial endorchis and preparation method thereof and make With method ", a kind of artificial endorchis with double-decker is disclosed, by PLA/ethanol copolymer fiber of orientation PLA/ethanol copolymer of film inner layer and non orientation-chitin fiber film outer layer composition.Although the artificial endorchis can Realize dura mater regeneration and prevent the purpose of paralysed trace and adhesion, but have the disadvantage that:(1) outer layer fiber uses PLA/ethanol Acid copolymer and chitosan are combined, and when chitosan content is relatively low, anti-infection activity will necessarily be restricted, and this is special This artificial dural anti-infection property energy is not referred in profit yet;(2) needed outer layer and inner fiber during Clinical practice It is separated while to also need to coated with adhesive between two layers again in defect of meninges position, Clinical practice process has been significantly greatly increased In inconvenience.
Chinese invention patent CN 103656749 A, a kind of entitled " the artificial hard brain of compound degradable antibacterial Film and preparation method thereof ", disclose a kind of comprising vancomycin or ofloxacin hydrochloride parenteral solution, chitosan and β-phosphoglycerol The antibacterial artificial dura mater of sodium, but the product mainly realizes antibacterial purpose, shell using the antibiotic medicine in combination of materials Glycan is only used as pharmaceutical carrier.Simultaneously there is the problems such as registration declaration difficulty in the artificial dura mater as medical instruments combination product, no Easily realize industrialization development and clinical practice.
Chinese invention patent CN106943634A, entitled " a kind of adsorbable artificial with anti-infective function is hard Meninx and preparation method and application ", one kind is disclosed by nano fibrous membrane by degradable poly-vinegar nano fibrous membrane and chitosan Nano fibrous membrane double-decker forms.There is the adsorbable artificial endocranium of the present invention good anti-infection property can effectively prevent art Intracranial infection afterwards, certain suture power can be born, do not torn, not off-clip.But two layers of the product is using roller orientation spinning work Prepared by skill, two layers of meninx is orientation nanofiber, and this fiber membrane intensity is well below non-oriented property fiber membrane.Together When the artificial dura mater only have two layers, the bond strength of two interlayers is inadequate.
Therefore, clinically there is an urgent need to a kind of intensity height at present to be resistant to brain high pressure, and internal layer is combined reliably with outer layer, resisted Infectious strong, easy to use artificial dura mater.
The content of the invention
For overcome the deficiencies in the prior art, it is an object of the present invention to provide a kind of artificial hard brain of the anti-infective high intensity of multilayer Film, the difference of the artificial dura mater and the anti-infective artificial dura mater of tradition are:
(1) artificial dura mater outer layer, it is prepared by chitosan by orientation electrostatic spinning process, there is reliable anti-sense Metachromia energy, while itself can degrade and nontoxic, securely and reliably.
(2) artificial dura mater internal layer, prepared using electrospinning process, obtain non-oriented property nano-fiber film.It is this kind thin Film tearing toughness is far longer than orientation film, improves artificial dura mater entirety tearing toughness.
(3)Increase Weaving type intermediate layer among the internal layer and outer layer of artificial dura mater, intermediate layer using hydrophobic material and Water wetted material braiding forms, according to " similar compatibility " principle, slice and artificial dura mater prepared by the hydrophobic material in braiding layer Internal layer(It is prepared by hydrophobic material Electrospun)Reliable connection, slice and artificial dura mater outer layer prepared by water wetted material(Water wetted material It is prepared by Electrospun)Reliable connection, and both slices are overlapping weave ins, the slice of hydrophilic material passes through hydrophobic material The space of the slice of matter is combined with outer layer, and the slice of hydrophobic material is combined through the space of the slice of hydrophilic material with internal layer, this Just reliably it is combined together for two layers inside and outside sample.In a word, the artificial dura mater of this structure, improves between internal layer and outer layer Adhesion, it is not easy that stripping between layers occurs in the presence of external force.
It is a further object of the present invention to provide a kind of preparation method of the anti-infective high intensity artificial dura mater of multilayer.
Technical scheme is used by the present invention solves the above problems:
A kind of anti-infective high intensity artificial dura mater of multilayer, comprising three layers, cerebripetal one layer of face is hydrophobic inner layer, backwards to big One layer of brain is water soluble chitosan outer layer, is Weaving type intermediate layer between two layers.
The hydrophily outer layer is made up of electrostatic spinning, i.e. outer layer is in order to effectively induce stem cell and fibroblastic move Entering, this layer then uses the water soluble chitosan using good biocompatibility, furthermore, adjusted, made average by electrospinning parameters Aperture reaches 20-100 μm, and general fibroblast diameter is between 20-30 μm.So be advantageous to it is fibroblastic move into, Adhesion, propagation and Growth and Differentiation.
The internal layer is to use hydrophobic material, prevents moving into for cell, so as to reach the purpose to prevent adhesion;Should to preparing The electrospinning parameters of layer material are adjusted, and make its hole aperture below nanometer, one to two orders of magnitude smaller than cell(One As fibroblast diameter between 20-30 μm), so as to prevent cell from entering, prevent brain adhesion from producing.
The intermediate layer is formed using hydrophobic material and the braiding of water soluble chitosan material.
A kind of anti-infective high intensity artificial dura mater of multilayer, including internal layer, intermediate layer, outer layer, its preparation method is by following Step is prepared:
(1) preparation of internal layer:Inner layer material composition is polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen), it is dissolved in In hexafluoroisopropanol (Suzhou Hao Fan Biological Co., Ltd.), concentration of dope 7%(wt), stir 4 hours, Electrospun ginseng Number be flow velocity be 0.9 ml/h, voltage 13kV, receive distance 20cm, electrostatic spinning 4h.
(2) prepared by intermediate layer.
Use carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd)Film prepared by electrostatic spinning, film thickness are 40μm.Wide 3mm, long 1000mm slice is made in film.
Use polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen)Film prepared by electrostatic spinning, film thickness 40 μm.Wide 3mm, long 1000mm slice is made in film.
Two kinds of slice 3mmx1000mm are face-down, and hydrophily slice is transversely arranged, hydrophobicity slice longitudinal arrangement, using conspicuous Ge Lisi weavings are worked out, and obtain Weaving type intermediate layer.
(3)Before internal layer solidification, internal layer upper surface is put among Weaving type layer by layer.
Finally, intermediate layer is pressed down against with 50N pressure, keeps 1min.
(4) prepared by outer layer:
Cladding material is carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd), it is dissolved in pure water (Jinan sea industry Work Co., Ltd) in, concentration of dope 6%(wt), stir 1 hour, electrospinning parameters are:The .4ml/h of flow velocity 0, voltage 0.9kV, Receive distance 1mm, orientation electrostatic spinning process prepares 2h, obtains orientation layers of nanofibers, fiber direction with it is any one Side is parallel.
(5) artificial meninx takes out from culture dish by made from, is rinsed 3 times with distilled water, is vacuum-packed after freeze-dried, - 20 DEG C of Cord bloods after the sterilizing of 25kGy cobalts -60.
The thickness for every layer of multilayer electrostatic spinning artificial dura mater being prepared is:Internal layer thickness is 80 μm ± 10 μm, outside Thickness degree is 30 μm ± 10 μm, and intermediate layer thickness is 80 μm ± 20 μm.
When prepared by internal layer, for electrospun fibers diameter control between 50-1000nm, average pore size is 2 μm;
When prepared by outer layer, for electrospun fibers diameter control between 5-200 μm, average pore size is 20-100 μm.
The beneficial effects of the invention are as follows:
(1) artificial dura mater of the present invention uses three-decker, strengthens the bond strength of internal layer and outer layer by intermediate layer.
(2) artificial dura mater mechanical property of the present invention can meet indication to tensile strength and flexible requirement, tool There are reliable intensity and good pliability, elasticity;Suture needle can be supported, it is waterproof, it can be held in surgical repair and after repairing By certain power and it is deformed, without breakage, making cerebrospinal fluid be unlikely to seepage, plays a part of protecting brain tissue, and can root Cut randomly according to needs.
(3) the artificial dural medial surface (i.e. the cerebripetal one side in face) of the present invention is smooth, can prevent adhesion, can play very Isolating the effect of scalp soft tissue and brain tissue well, lateral surface (carrying on the back cerebripetal one side) and side are then loose structure, Cell is allowed to grow into;Autologous fibroblasts as early as possible and some undifferentiated cells can be promoted to soak into growth to collagen inside, Meninx is promoted to repair early.Beneficial to progress skull prosthesis in the future.
(4) material that endocranium of the invention uses is proved to be completely absorbed after cambium generation, It is carcinogenic to avoid diaphragm.
(5) material used in the present invention is to have confirmed the safe biologic material nontoxic to human body at present, is had Good biological tissue's compatibility, foreign rejection, non-toxic reaction, without carcinogenic, teratogenesis.Immune row will not be brought Reprimand, viral transmission, all multi-risk Systems of disease propagation, will not also bring other toxic actions.
(6) the preparation method processing step of artificial meninx of the invention simplifies, and the production time is short, can effectively avoid processing During product be contaminated, product quality is easily controllable, and product standard is easily realized, product can realize low cost, high efficiency Industrialization production.
(7) artificial meninx clinical practice prepared in accordance with the present invention is simple, due in processes without introducing glutaraldehyde etc. Toxicant, strict immersion and cleaning need not be carried out again in clinical practice, also therefore avoid and made due to soaking in advance Into pre-selected size not enough and make the situation of product rejection.
Brief description of the drawings
Fig. 1 is obtained artificial dura mater structural representation, wherein 1 is internal layer, 2 be intermediate layer, and 3 be outer layer.
Fig. 2 is interlayer structure schematic diagram.4 be the slice that carboxymethyl chitosan film is cut into, and 5 be polycaprolactone membrane The slice cut into.
Fig. 3 is orientation nanofiber design sketch.
Fig. 4 is non-tropism nanofiber design sketch.
Embodiment
Below by specific embodiment, the present invention will be described, but the invention is not limited in this.
Experimental method used in following embodiments is conventional method unless otherwise specified:Institute in following embodiments Reagent, material etc., unless otherwise specified, commercially obtain.
Embodiment 1
(1) preparation of internal layer:Inner layer material composition is polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen), it is dissolved in In hexafluoroisopropanol (Suzhou Hao Fan Biological Co., Ltd.), concentration of dope 5%(wt), stir 1 hour, Electrospun ginseng Number be flow velocity be 1 .0ml/h, voltage 12kV, receive distance 15cm, electrostatic spinning 2h.
(2) prepared by intermediate layer.
Use carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd)Film prepared by electrostatic spinning, film thickness are 40μm.Wide 3mm, long 1000mm slice is made in film.
Use polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen)Film prepared by electrostatic spinning, film thickness 40 μm.Wide 3mm, long 1000mm slice is made in film.
Two kinds of slice 3mmx1000mm are face-down, and hydrophily slice is transversely arranged, hydrophobicity slice longitudinal arrangement, using conspicuous Ge Lisi weavings are worked out, and obtain Weaving type intermediate layer.
(3)Before internal layer solidification, internal layer upper surface is put among Weaving type layer by layer.
Finally, intermediate layer is pressed down against with 50N pressure, keeps 1min.
(4) prepared by outer layer:
Cladding material is carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd), it is dissolved in pure water (Jinan sea industry Work Co., Ltd) in, concentration of dope 6%(wt), stir 1 hour, electrospinning parameters are:The .2ml/h of flow velocity 0, voltage 0.8kV, Receive distance 1mm, orientation electrostatic spinning process prepares 3h, obtains orientation layers of nanofibers, fiber direction with it is any one Side is parallel.
(5) artificial meninx takes out from culture dish by made from, is rinsed 3 times with distilled water, is vacuum-packed after freeze-dried, - 20 DEG C of Cord bloods after the sterilizing of 25kGy cobalts -60.
Embodiment 2
(1) preparation of internal layer:Inner layer material composition is polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen), it is dissolved in In hexafluoroisopropanol (Suzhou Hao Fan Biological Co., Ltd.), concentration of dope 7%wt, stir 4 hours, Electrospun parameter Be 0.9 ml/h for flow velocity, voltage 13kV, receive distance 20cm, electrostatic spinning 4h.
(2) prepared by intermediate layer.
Use carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd)Film prepared by electrostatic spinning, film thickness are 40μm.Wide 3mm, long 1000mm slice is made in film.
Use polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen)Film prepared by electrostatic spinning, film thickness 40 μm.Wide 3mm, long 1000mm slice is made in film.
Two kinds of slice 3mmx1000mm are face-down, and hydrophily slice is transversely arranged, hydrophobicity slice longitudinal arrangement, using conspicuous Ge Lisi weavings are worked out, and obtain Weaving type intermediate layer.
(3)Before internal layer solidification, internal layer upper surface is put among Weaving type layer by layer.
Finally, intermediate layer is pressed down against with 50N pressure, keeps 1min.
(4) prepared by outer layer:
Cladding material is carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd), it is dissolved in pure water (Jinan sea industry Work Co., Ltd) in, concentration of dope 6%(wt), stir 1 hour, electrospinning parameters are:The .4ml/h of flow velocity 0, voltage 0.9kV, Receive distance 1mm, orientation electrostatic spinning process prepares 2h, obtains orientation layers of nanofibers, fiber direction with it is any one Side is parallel.
(5) artificial meninx takes out from culture dish by made from, is rinsed 3 times with distilled water, is vacuum-packed after freeze-dried, - 20 DEG C of Cord bloods after the sterilizing of 25kGy cobalts -60.
Embodiment 3
(1) preparation of internal layer:Inner layer material composition is polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen), it is dissolved in In hexafluoroisopropanol (Suzhou Hao Fan Biological Co., Ltd.), concentration of dope 5%wt, stir 4 hours, Electrospun parameter Be 1 .0ml/h for flow velocity, voltage 15kV, receive distance 25cm, electrostatic spinning 5h.
(2) prepared by intermediate layer.
Use carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd)Film prepared by electrostatic spinning, film thickness are 40μm.Wide 3mm, long 1000mm slice is made in film.
Use polycaprolactone(Bo Li biomaterials Co., Ltd of Shenzhen)Film prepared by electrostatic spinning, film thickness 40 μm.Wide 3mm, long 1000mm slice is made in film.
Two kinds of slice 3mmx1000mm are face-down, and hydrophily slice is transversely arranged, hydrophobicity slice longitudinal arrangement, using conspicuous Ge Lisi weavings are worked out, and obtain Weaving type intermediate layer.
(3)Before internal layer solidification, Weaving type intermediate layer is put in internal layer upper surface.
Finally, intermediate layer is pressed down against with 50N pressure, keeps 1min.
(4) prepared by outer layer:
Cladding material is carboxymethyl chitosan(Nantong Lv Shen bioengineering Co., Ltd), it is dissolved in pure water (Jinan sea industry Work Co., Ltd) in, concentration of dope 6%(wt), stir 1 hour, electrospinning parameters are:The .6ml/h of flow velocity 0, voltage 1kV, connect Receipts distance 2mm, orientation electrostatic spinning process prepare 3h, obtain orientation layers of nanofibers, fiber direction and any one side It is parallel.
(5) artificial meninx takes out from culture dish by made from, is rinsed 3 times with distilled water, is vacuum-packed after freeze-dried, - 20 DEG C of Cord bloods after the sterilizing of 25kGy cobalts -60.

Claims (10)

1. a kind of anti-infective high intensity artificial dura mater of multilayer, includes three layers:The cerebripetal internal layer in face, carry on the back cerebripetal outer layer and Intermediate layer between two layers.
A kind of 2. anti-infective high intensity artificial dura mater of multilayer according to claim 1, it is characterised in that the inner-layer thick Spend for 80 μm ± 10 μm, be prepared by hydrophobic material by electrostatic spinning process.
A kind of 3. anti-infective high intensity artificial dura mater of multilayer according to claim 1, it is characterised in that the outer thickness Spend for 30 μm ± 10 μm, be prepared by water soluble chitosan with orientation electrostatic spinning process.
A kind of 4. anti-infective high intensity artificial dura mater of multilayer according to claim 1, it is characterised in that the intermediate layer Thickness is 80 μm ± 20 μm, is formed by slice braiding.
5. intermediate layer according to claim 4, it is characterised in that the intermediate layer have hydrophilic material prepare width be The slice braiding that width prepared by 3mm slice and hydrophobic material is 3mm forms.
6. slice according to claim 5, it is characterised in that the first layer slice, electrospinning is passed through by hydrophobic material It is 40 μm of ± 10 μm of films that silk technique, which is prepared into thickness, and rear cutting forms;Second layer slice, passed through by water soluble chitosan material It is 40 μm of ± 10 μm of films that electrospinning process, which is prepared into thickness, and rear cutting forms.
7. intermediate layer according to claim 4, it is characterised in that the slice braiding, two kinds of slice 3mmx1000mm faces Down, hydrophily slice is transversely arranged, hydrophobicity slice longitudinal arrangement, is worked out using He Gelisi weavings.
8. intermediate layer according to claim 5, it is characterised in that the intermediate layer placement process, it should solidify in internal layer Complete before.
9. intermediate layer according to claim 5, it is characterised in that the intermediate layer put is pressed down against with 50N pressure, Keep 1min.
10. a kind of a kind of method of the anti-infective high intensity artificial dura mater of multilayer prepared any one of claim 1-9, Comprise the steps:
(1) preparation of internal layer:Inner layer material is polycaprolactone, is dissolved in hexafluoroisopropanol, concentration of dope 7%(wt), stir Mix 4 hours, Electrospun parameter be flow velocity be 0.9 ml/h, voltage 13kV, receive distance 20cm, electrostatic spinning 4h.
(2) prepared by intermediate layer.
Carboxymethyl chitosan is prepared into film by electrostatic spinning process, and film thickness is 40 μm.Wide 3mm is made in film, it is long 1000mm slice.
Polycaprolactone crosses electrostatic spinning process and is prepared into film, and film thickness is 40 μm.Wide 3mm, long 1000mm is made in film Slice.
Two kinds of slice 3mmx1000mm are face-down, and hydrophily slice is transversely arranged, hydrophobicity slice longitudinal arrangement, using He Geli This weaving is worked out, and obtains Weaving type intermediate layer.
(3)Before internal layer solidification, Weaving type intermediate layer is put in internal layer upper surface.
Finally, the intermediate layer that top is put is extruded vertically downward with 50N pressure, keeps 1min.
(4) prepared by outer layer:
Cladding material is carboxymethyl chitosan, is dissolved in pure water, concentration of dope 6%(wt), stir 1 hour, electrospinning ginseng Number is:The .4ml/h of flow velocity 0, voltage 0.9kV, distance 1mm is received, orientation electrostatic spinning process prepares 2h, obtains orientation nanometer Fibrous layer, fiber direction are parallel with any one side.
(5) artificial meninx takes out from culture dish by made from, is rinsed 3 times with distilled water, is vacuum-packed, passes through after freeze-dried After 25kGy cobalts -60 sterilize, -20 DEG C of Cord bloods.
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CN112516368A (en) * 2020-11-27 2021-03-19 佛山仙湖实验室 Composite fiber membrane and preparation method and application thereof

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CN103418031A (en) * 2012-05-17 2013-12-04 天津市康尔医疗器械有限公司 Absorbable endocranium healing patch and preparation method thereof
CN106390204A (en) * 2016-11-16 2017-02-15 浙江省人民医院 Composite type artificial dura mater and preparation method

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CN101507661A (en) * 2009-03-10 2009-08-19 广州迈普再生医学科技有限公司 Nano artificial dura mater with multi functional-layers and preparation method thereof
CN103418031A (en) * 2012-05-17 2013-12-04 天津市康尔医疗器械有限公司 Absorbable endocranium healing patch and preparation method thereof
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CN112516368A (en) * 2020-11-27 2021-03-19 佛山仙湖实验室 Composite fiber membrane and preparation method and application thereof
CN112516368B (en) * 2020-11-27 2022-05-03 佛山仙湖实验室 Composite fiber membrane and preparation method and application thereof

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