CN106110396A - A kind of nerve trachea containing microchannel and oriented nanofibers and preparation method thereof - Google Patents
A kind of nerve trachea containing microchannel and oriented nanofibers and preparation method thereof Download PDFInfo
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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
- A61L27/26—Mixtures of macromolecular compounds
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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
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
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- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/40—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
- D04H1/42—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
- D04H1/4382—Stretched reticular film fibres; Composite fibres; Mixed fibres; Ultrafine fibres; Fibres for artificial leather
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- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING 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
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/70—Non-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
- D04H1/72—Non-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
- D04H1/728—Non-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
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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 containing microchannel with the nerve trachea of oriented nanofibers, in " core-skin " structure." core " is that the bundle fiber being coiled into by the oriented nanofibers film roll containing microchannel is constituted.Microchannel is parallel with nanofiber orientation." skin " is to be composited by oriented nanofibers film and random nano fibrous membrane.Its preparation method is to utilize electrostatic spinning technique, uses high speed rotating collecting drum first to collect one layer of oriented nanofibers, then according to fibre orientation, the long filament of surface-coated arranged in parallel, electrostatic spinning sprays formation channel layer again, is hereafter taken out by long filament, forms the nano fibrous membrane containing microchannel.Spray finally by winding, cladding and electrostatic spinning, ultimately form containing microchannel and the nerve trachea of oriented nanofibers bundle.Preparation technology is simple for this conduit, it is easy to industrialization, its size adjustable, it is adaptable to the CO2 laser weld of impaired a length of 10 30mm.
Description
Technical field
The invention belongs to field of biomedical polymer materials, be specifically related to a kind of containing microchannel and oriented nanofibers
Nerve trachea and preparation method thereof.
Background technology
Nervous system regeneration is limited in one's ability, and the nerve injury that congenital malformation, wound, operation etc. cause all can cause arranging district
Sensory deprivation, the dyskinesia and neuropathic pain etc..Short distance neurologic defect, can sew up by Direct Surgery, but the length more than 1cm
Section peripheral nerve defection, need to use nerve autograft or by the auxiliary nervous regeneration of artificial nerve graft.Use autologous god
Although through skin grafing and mending effect still can, but have that source is limited, residual for district sensory disturbance, increase for district's wound, needs
The shortcomings such as Repeated Operation, the most artificial constructed nerve graft becomes the research emphasis of neuranagenesis.Nervous cell regenerating is
The premise of neurological functional recovery, the most important condition of nervous cell regenerating has been intended to suitable growing environment.It is developed many
Different materials composition and the graft of configuration, it is intended to guide axon growth, improve neuranagenesis ability, as long filament, fibre bundle,
Doughnut, multilayer pipe etc., wherein electrostatic spinning nano fiber applied research in CO2 laser weld is particularly subject to the concern of people.
Research in recent years finds for CO2 laser weld, Electrospun nano-fibers has the advantage that (1) nano-scale fiber has
Having high-specific surface area, add the contact area of cell and fiber, portability also discharges the multiple biologies such as medicine, albumen, nucleic acid
Chemical substance, the most beneficially nerve cell adhesion, migrate, breed, may additionally facilitate aixs cylinder and stretch；(2) unordered and orderly row is contrasted
Row nanofiber is seen, research at present is proved oriented nanofibers the most countershaft projection exhibition and has guiding function, and this is to nerve again
Raw significant with reparation；(3) nano fiber scaffold can imitate extracellular matrix, provides suitable for nervous cell regenerating
Growing environment, has high osmosis, beneficially nutrient substance, O2Infiltration and cellular uptake and metabolite are discharged.
Based on above advantage, people utilize nanofiber to build nerve trachea and graft thereof one after another.Early stage people are main
It is that the thin metal that electrostatic spinning nano fiber is collected in high speed rotating turns on rod, the fiber pipe directly formed.Such as patent CN
101439205A, CN 102091353A with CN 102671235A etc. are all to use different high polymers and packing material, utilize
Single spraying head or coaxial electrostatic spinning technology, directly spray nanofiber and turning on rod at a high speed, will turn after rod takes out and form nerve
Conduit.Utilizing nerve trachea prepared by the method, its greatest problem is that fibre orientation is axially vertical with conduit, is unfavorable for that guiding is subject to
Damage neural along conduit axial growth.Then utilize high speed transfer roller to collect and form oriented nanofibers film, be perpendicular to fibre orientation
This film roll being coiled into nerve trachea and becomes the selection of people, patent CN 102525689A and CN 103127548A etc. use exactly
The high oriented fibers film of different materials composition, defines nerve trachea by method for winding.But this rolling tube is further
Have also discovered problems in repairing research, outstanding behaviours exists: the nerve trachea only one of which lumen formed by winding, only exists
Pipe inner wall contains oriented nanofibers, and nerve is fascicular texture, it is difficult to efficiently guide injured nerve.Therefore, by fibrous membrane
Directly it is wound into pencil and will improve contact guidance efficiency.But, single winding will make fiber intermembranous shortage space, be unfavorable for god
Through growing into.In addition in operation and Post operation easily subsides gillies' graft, is unfavorable for that nutrition transmission is grown into nerve.Therefore design
New thin film-forming method and method for winding, build containing microchannel, microtubular, the composite structure of void layer, and be not only to contain
There is the tube of a lumen, the important development direction in this field will be become.
Summary of the invention
Goal of the invention: in order to solve the deficiencies in the prior art, the invention provides a kind of containing microchannel and orientation nano
Nerve trachea of fiber and preparation method thereof, it is possible to repairing more than the impaired distance of 1cm, perception is the most refreshing with motor function recovery
Through conduit, change the deficiency of existing nano-fiber tubular graft, and production efficiency can be improved.
Technical scheme: a kind of containing microchannel with the nerve trachea of oriented nanofibers, described conduit is to be tied by " skin-core "
Structure is constituted, and described " core " is that the bundle fiber being coiled into by the oriented nanofibers film roll containing microchannel is constituted, and described is micro-logical
The a diameter of 30-200um in road, parallel with nanofiber orientation, described nanofiber diameter is 80-450nm；Described " skin " is
By oriented nanofibers film roll around cladding, spray one layer of random nano fibrous membrane the most again and be composited.
As optimization: the material of described " core " is natural by one or more in fibroin, gelatin, laminin，LN, collagen
Polymer forms, or by polylactic acid (PLA), the polymer (PLGA) of hydroxyacetic acid and hydracrylic acid different copolymer ratio, poly-oneself
One or more compositions in the synthetic polymer such as lactone composition, it is also possible to be by above-mentioned natural with the one in synthetic high polymer
With multiple composition；By weight, the weight of " core " accounts for 85-90%.
As optimization: the material of described " skin " is polylactic acid (PLA), hydroxyacetic acid and hydracrylic acid different copolymer ratio
One or more compositions in the synthetic polymer compositions such as polymer (PLGA), polycaprolactone.
A kind of containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, comprise the steps:
(1) by by one or more in fibroin, gelatin, laminin，LN, collagen, or polylactic acid (PLA), hydroxyacetic acid
With one or more groups in the synthetic polymer composition such as the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
Become, or above-mentioned natural and in synthetic high polymer a kind of and multiple composition polymer is dissolved in volatile solvent, uses quiet
Electrospinning, utilizes the high speed transfer roller of a diameter of 200mm to collect, and rotating speed is 1000-3000rpm, forms highly oriented Nanowire
Dimension film, in this, as " basic unit " of microchannel nano fibrous membrane；
(2) it is parallel to nanofiber orientation, shows the length of a diameter of 32-210um arranged in parallel in established " basic unit "
Silk, spacing is 0.02-0.2mm；Described long filament uses aqueous polyurethane (PU) or polyvinyl alcohol (PVA) coating processing in advance；
(3) utilize high polymer and the process conditions of spinning basic unit, continue electrostatic spinning, arranging " basic unit " table of long filament
Bright formation " channel layer "；
(4) fibrous membrane is taken off from high speed transfer roller, according to the difference of filament surface coating material, fibrous membrane is put in 40-
The water of 95 DEG C or ethanol process in 10-30min, then long filament is extracted out from fibrous membrane, between " basic unit " and " channel layer "
Form the microchannel of a diameter of 30-200um；
(5) it is perpendicular to nanofiber direction, this fibrous membrane containing microchannel is cut into the strip of 10-30mm；
(6) " basic unit " of strip is attached in thin metal round roller, is then wound into the winding article of a diameter of 1-3mm,
Form the bundles of nanofibers " core " of nerve trachea；
(7) polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
One or more in forming Deng synthetic polymer are dissolved in volatile solvent, utilize the high speed transfer roller of a diameter of 200mm to receive
Collection, rotating speed is 1000-3000rpm, collects 4-6h, forms the high oriented fibers film that thickness is 15-25um；
(8) it is perpendicular to fibre orientation, the fibrous membrane in step (7) is cut into ratio strip of strip width 4mm in step (5),
Being wrapped in this winding article surface that step (6) is formed, wrap up 1-2 layer, two ends form " sheath " of 2mm；
(9) by the polymer solution electrostatic spinning in step (7), the winding article surface formed in step (8) sprays one layer
Random nano fibrous membrane, ultimately forms " skin " of nerve trachea；
(10) metal round roller is extracted out, formed containing microchannel and the nerve trachea of oriented nanofibers.
As optimization: membrane removal is contained within outside microchannel, at the intermembranous passage possibly together with 20-200um of fiber.
As optimization: the stitching strength of described " sheath " is 2-2.7N/ pin, the degradation speed of " core " is 3-12 week, " sheath "
Degradation speed is 8-20 week.
As optimization: its total length is 14-34mm, through bundles of nanofibers " core " a length of 10-30mm of winding, neural
Conduit two ends have the stitching sheath of a length of 2mm, can be used for the CO2 laser weld of impaired a length of 10-30mm.
Beneficial effect: construction method of the present invention is first compatible by having good biological high polymer electrostatic spinning, with at a high speed
Transfer roller is collected, and forms the highly oriented nano fibrous membrane of multichannel.Being perpendicular to fibre orientation, by various winding methods, formation contains
The fibre bundle of microchannel, in this, as " core " of nerve graft.1-2 layer oriented nanofibers film it is coated with again on the surface of core,
Forming the internal layer of " sheath ", last electrostatic sprays formation " sheath " outer layer.Concrete advantage is as follows:
(1) realize the nerve trachea containing bundles of nanofibers to build.The nerve containing oriented nanofibers built at present
Conduit mainly has two kinds, and one is directly to collect nanofiber by high speed transfer roller and form conduit, the orientation of this fiber and pipe
Axially vertical, it is unfavorable for guiding nerve growth；Another kind is the conduit containing only a lumen formed by winding, this conduit
It is only capable of guiding nerve growth by the oriented nanofibers of tube wall, and nerve is fascicular texture, it is difficult to efficiently guide.The present invention will
Utilizing oriented nanofibers film to be wound by various modes, form bundles of nanofibers, fibre orientation direction of growing into nerve is consistent,
Efficiently guide neuranagenesis.
(2) realize being contained within microchannel at graft.Traditional nano fibrous membrane is despite many holes, but stratiform winding
After, lack passage, be unfavorable for that nerve is grown into.The present invention, for improving this drawback, intends during electrostatic spinning, embeds and supports
Thing, spinning is extracted supporter after completing and is formed " in layer " microchannel, by forming " interlayer " passage after winding again, increases regeneration god
The growth of warp and guide space.
(3) rapid build is realized.The present invention is the most disposable spinning highly oriented nano fibrous membrane containing microchannel, then
According to injured nerve length, being perpendicular to fibre orientation, clip fibrous membrane, then winding forms bundles of nanofibers.Finally, winding is single
Layer oriented nanofibers film also sprays formation nonwoven nanofiber layer to improve its intensity by electrostatic.This constructing technology greatly carries
High originally utilize transfer roller to collect nanofiber to form the speed of production of conduit, it is simple to Mirae Corp.'s metaplasia is produced.
Accompanying drawing explanation
Fig. 1 be the present invention different rotating speeds under the presentation graphics schematic diagram of acid fiber by polylactic；
Fig. 2 is the present invention FFT figure for three motor speeds radially image pixel intensities；
Fig. 3 is nerve trachea cross-sectional scans Electronic Speculum electromicroscopic photograph of the present invention.
Detailed description of the invention
Below in conjunction with specific embodiment, the invention will be further described.
Embodiment 1
A kind of containing microchannel with the nerve trachea of oriented nanofibers, conduit is to be made up of " skin-core " structure.
" core " is that the bundle fiber being coiled into by the oriented nanofibers film roll containing microchannel is constituted, and microchannel diameter is
30um, parallel with nanofiber orientation, nanofiber diameter is 80nm.The material of " core " by fibroin, gelatin, laminin，LN,
These several natural polymers of collagen form；By weight, the weight of " core " accounts for 85%.
" skin " is around cladding by oriented nanofibers film roll, sprays one layer of random nano fibrous membrane the most again and is composited.
The material of " skin " is polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
Synthetic polymer forms.
A kind of containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, comprise the steps:
(1) will be dissolved in volatile solvent by fibroin, gelatin, laminin，LN, these several polymer formed of collagen,
Using electrostatic spinning technique, utilize high speed transfer roller to collect, rotating speed is 1000rpm, and a diameter of 200mm forms highly oriented Nanowire
Dimension film, in this, as " basic unit " of microchannel nano fibrous membrane；
(2) it is parallel to nanofiber orientation, shows the long filament of a diameter of 32um arranged in parallel in established " basic unit ",
Away from for 0.02mm；Long filament uses aqueous polyurethane (PU) or polyvinyl alcohol (PVA) coating processing in advance；
(3) utilize high polymer and the process conditions of spinning basic unit, continue electrostatic spinning, arranging " basic unit " table of long filament
Bright formation channel layer；
(4), after collecting 6h, fibrous membrane is taken off from high speed transfer roller, according to the difference of filament surface coating material, by fiber
Film is put in the water of 40 DEG C or ethanol and processes in 10min, then long filament is extracted from fibrous membrane, in " basic unit " and " channel layer "
Between form the microchannel of a diameter of 30um；
(5) it is perpendicular to nanofiber direction, this fibrous membrane containing microchannel is cut into the strip of 10mm；
(6) " basic unit " of strip is attached in thin metal round roller, is then wound into the winding article of a diameter of 1mm, shape
Become the bundles of nanofibers " core " of nerve trachea；
(7) polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
Being dissolved in volatile solvent of synthetic polymer composition, utilizes high speed transfer roller to collect, and rotating speed is 1000rpm, and transfer roller is a diameter of
200mm, collects 4h, forms the high oriented fibers film that thickness is 15um；
(8) it is perpendicular to fibre orientation, the fibrous membrane in step (7) is cut into ratio strip of strip width 4mm in step (5),
Being wrapped in this winding article surface that step (6) is formed, wrap up 1 layer, two ends form " sheath " of 2mm；
(9) by the polymer solution electrostatic spinning in step (7), the winding article surface formed in step (8) sprays one layer
Random nano fibrous membrane, ultimately forms " skin " of nerve trachea；
(10) metal round roller is extracted out, formed containing microchannel and the nerve trachea of oriented nanofibers.
Wherein, membrane removal is contained within outside microchannel, at the intermembranous passage possibly together with 20um of fiber.The stitching strength of " sheath " is
2N/ pin, the degradation speed of " core " is 3 weeks, and the degradation speed of " sheath " is 8 weeks.Its total length is 14mm, through the Nanowire of winding
Dimension bundle " core " a length of 10mm, nerve trachea two ends have the stitching sheath of a length of 2mm, can be used for the god of impaired a length of 10mm
Repaired.
Embodiment 2
A kind of containing microchannel with the nerve trachea of oriented nanofibers, conduit is to be made up of " skin-core " structure.
" core " is that the bundle fiber being coiled into by the oriented nanofibers film roll containing microchannel is constituted, and microchannel diameter is
200um, parallel with nanofiber orientation, nanofiber diameter is 450nm.The material of " core " is by polylactic acid (PLA), hydroxyacetic acid
With the synthetic polymer composition such as the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone；By weight, " core "
Weight accounts for 90%.
" skin " is around cladding by oriented nanofibers film roll, sprays one layer of random nano fibrous membrane the most again and is composited.
The material of " skin " is polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
Form Deng synthetic polymer.
A kind of containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, comprise the steps:
(1) will by polylactic acid (PLA), the polymer (PLGA) of hydroxyacetic acid and hydracrylic acid different copolymer ratio, poly-oneself
Polymer in the synthetic polymer compositions such as lactone is dissolved in volatile solvent, uses electrostatic spinning technique, utilizes and turns at a high speed
Roller is collected, and rotating speed is 3000rpm, and a diameter of 200mm forms highly oriented nano fibrous membrane, in this, as microchannel nanofiber
" basic unit " of film；
(2) it is parallel to nanofiber orientation, shows the long filament of a diameter of 210um arranged in parallel in established " basic unit ",
Spacing is 0.2mm；Long filament uses aqueous polyurethane (PU) or polyvinyl alcohol (PVA) coating processing in advance；
(3) utilize high polymer and the process conditions of spinning basic unit, continue electrostatic spinning, arranging " basic unit " table of long filament
Bright formation channel layer；
(4), after collecting 12h, fibrous membrane is taken off from high speed transfer roller, according to the difference of filament surface coating material, by fiber
Film is put in the water of 95 DEG C or ethanol and processes in 30min, then long filament is extracted from fibrous membrane, in " basic unit " and " channel layer "
Between form the microchannel of a diameter of 200um；
(5) it is perpendicular to nanofiber direction, this fibrous membrane containing microchannel is cut into the strip of 30mm；
(6) " basic unit " of strip is attached in thin metal round roller, is then wound into the winding article of a diameter of 3mm, shape
Become the bundles of nanofibers " core " of nerve trachea；
(7) polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
The polymer formed Deng synthesis is dissolved in volatile solvent, utilizes high speed transfer roller to collect, and rotating speed is 3000rpm, transfer roller diameter
For 200mm, collect 6h, form the high oriented fibers film that thickness is 25um；
(8) it is perpendicular to fibre orientation, the fibrous membrane in step (7) is cut into ratio strip of strip width 4mm in step (5),
Being wrapped in this winding article surface that step (6) is formed, wrap up 1-2 layer, two ends form " sheath " of 2mm；
(9) by the polymer solution electrostatic spinning in step (7), the winding article surface formed in step (8) sprays one layer
Random nano fibrous membrane, ultimately forms " skin " of nerve trachea；
(10) metal round roller is extracted out, formed containing microchannel and the nerve trachea of oriented nanofibers.
Wherein, membrane removal is contained within outside microchannel, at the intermembranous passage possibly together with 200um of fiber.The stitching strength of " sheath " is
2.7N/ pin, the degradation speed of " core " is 12 weeks, and the degradation speed of " sheath " is 20 weeks.Its total length is 34mm, through receiving of winding
Rice fibre bundle " core " a length of 30mm, nerve trachea two ends have the stitching sheath of a length of 2mm, can be used for impaired a length of 30mm
CO2 laser weld.
Embodiment 3
A kind of containing microchannel with the nerve trachea of oriented nanofibers, conduit is to be made up of " skin-core " structure.
" core " is that the bundle fiber being coiled into by the oriented nanofibers film roll containing microchannel is constituted, and microchannel diameter is
130um, parallel with nanofiber orientation, nanofiber diameter is 380nm.The material of " core " is by fibroin, gelatin, layer adhesion egg
In vain, the natural polymer of collagen, with by polylactic acid (PLA), the polymer of hydroxyacetic acid and hydracrylic acid different copolymer ratio
(PLGA), the polymer composition of the synthesis such as polycaprolactone；By weight, the weight of " core " accounts for 87%.
" skin " is around cladding by oriented nanofibers film roll, sprays one layer of random nano fibrous membrane the most again and is composited.
The material of " skin " is polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
Form Deng synthetic polymer.
A kind of containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, comprise the steps:
(1) by by fibroin, gelatin, laminin，LN, the natural polymer of collagen, with by polylactic acid (PLA), hydroxyacetic acid
It is dissolved in volatile solvent with the polymer of the synthesis such as the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
In, using electrostatic spinning technique, utilize high speed transfer roller to collect, rotating speed is 1900rpm, and a diameter of 200mm forms highly oriented nanometer
Fibrous membrane, in this, as " basic unit " of microchannel nano fibrous membrane；
(2) it is parallel to nanofiber orientation, shows the long filament of a diameter of 133um arranged in parallel in established " basic unit ",
Long filament spacing is 0.13mm；Long filament uses aqueous polyurethane (PU) or polyvinyl alcohol (PVA) coating processing in advance；
(3) utilize high polymer and the process conditions of spinning basic unit, continue electrostatic spinning, arranging " basic unit " table of long filament
Bright formation channel layer；
(4), after collecting 9h, fibrous membrane is taken off from high speed transfer roller, according to the difference of filament surface coating material, by fiber
Film is put in the water of 77 DEG C or ethanol and processes in 19min, then long filament is extracted from fibrous membrane, in " basic unit " and " channel layer "
Between form the microchannel of a diameter of 130um；
(5) it is perpendicular to nanofiber direction, this fibrous membrane containing microchannel is cut into the strip of 14mm；
(6) " basic unit " of strip is attached in thin metal round roller, is then wound into the winding article of a diameter of 2mm, shape
Become the bundles of nanofibers " core " of nerve trachea；
(7) polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
Being dissolved in volatile solvent Deng synthetic polymer, utilize high speed transfer roller to collect, rotating speed is 1600rpm, and transfer roller is a diameter of
200mm, collects 5h, forms the high oriented fibers film that thickness is 19um；
(8) it is perpendicular to fibre orientation, the fibrous membrane in step (7) is cut into ratio strip of strip width 4mm in step (5),
Being wrapped in this winding article surface that step (6) is formed, wrap up 2 layers, two ends form " sheath " of 2mm；
(9) by the polymer solution electrostatic spinning in step (7), the winding article surface formed in step (8) sprays one layer
Random nano fibrous membrane, ultimately forms " skin " of nerve trachea；
(10) metal round roller is extracted out, formed containing microchannel and the nerve trachea of oriented nanofibers.
Wherein, membrane removal is contained within outside microchannel, at the intermembranous passage possibly together with 150um of fiber.The stitching strength of " sheath " is
2.3N/ pin, the degradation speed of " core " is 9 weeks, and the degradation speed of " sheath " is 12 weeks.Its total length is 22mm, through receiving of winding
Rice fibre bundle " core " a length of 18mm, nerve trachea two ends have the stitching sheath of a length of 2mm, can be used for impaired a length of 19mm
CO2 laser weld.
The present invention passes through scanning electron microscopic observation and Mechanics Performance Testing, demonstrates the feasibility of this nerve trachea, by outward
Portion has stimulated with histological observation restoration effect.
1, the morphologic observation of nano fibrous membrane characterizes with orientation:
Utilize scanning electron microscopic observation fibre morphology, and utilize Photoshop software test fibre diameter, utilize ImageJ soft
Part and Oval Profile plug-in unit characterize fibre orientation, i.e. by Fourier transformation (FFT), stereoscan photograph are converted to picture
Sketch map, then utilizes Oval Profile plug-in unit, with pixel map center as the center of circle, with 1 ° for interval, along radius backwards calculation picture
Element intensity and, fibre orientation is the highest, and pixel and difference are the biggest, and the peak of formation is the narrowest more high.
2, ultimate strength test
Use the miniature strength machine of MTS-Tytron 250, along parallel and vertical fibers orientation, test fibrous membrane mechanics
Performance, a length of 70mm of fibrous membrane, width 5mm, clamping length 30mm, draw speed is 0.05cm/s, each sample testing 5
Secondary.First testing the surface density of film, calculate specific stress and engineering stress the most successively, concrete formula is as follows:
Tex fiber linear density unit, refers to the weight that the fiber of 1000m length is had, ρpolymerDensity polymer.
3, strength test is sewed up
Sewing up at end 2mm in distance, utilize the test of MTS-Tytron 250 strength machine to sew up strength, draw speed is
0.05cm/s, each sample testing 3 times.
4, internal transplanting
SD rat claims 10% chloral hydrate (300mL/kg) intraperitoneal injection of anesthesia after quality, takes left hind stock posteriolateral incision
Being about 4cm, after stock, spatium intermusculare finds sciatic nerve, excises the sciatic nerve of 8mm length below piriformis at about 5mm so that it is
Broken ends of fractured bone retraction causes the long neurologic defect of 10mm.Then, the nerve broken ends of fractured bone is inserted in respectively nerve graft " sheath " interior 1mm, microscope
Epineurium is sewed up two or three pin with nerve graft " sheath " layer and is fixed by lower 7-0 noinvasive suture.
5, PLA nanofiber form is observed with orientation
Now there are some researches show, the neurite length substantially ratio on oriented nanofibers is on unordered nanofiber
Long, oriented nanofibers can guide axon growth.Therefore, first we have studied this impact fibre of electrostatic spinning transfer roller rotating speed
The most important factor of dimension orientation.Fig. 1 shows the stereoscan photograph and Fourier transformation photo thereof obtained under different rotating speeds,
With 1 ° for interval, image pixel intensities and statistics along radial direction show in FIG.Result shows, obtains when rotating speed is 1000rpm
Fiber stereoscan photograph after Fourier transformation, in 0-180 °, (181-360 ° of symmetry) image pixel intensities is almost identical, shows
Fiber is that unordered shape arranges.And when rotating speed reaches 1500rpm, intuitively observe from scanning electron microscope, or along fibre orientation, pixel and
Significantly improve, obvious crest image pixel intensities figure be can be observed in Fig. 2, illustrate can obtain consistent orientation under this rotating speed.
Under high-pressure electrostatic effect, the spiral type Quick extension of injection stream is considered as nanofiber unordered shape reason with differentiation, works as receipts
When collection roll surface line rotating speed is equal to or more than electrostatic spinning speed, it is possible to stretch injection stream therefore preferable fiber can be obtained and take
To.But when rotating speed reaches 2000rpm, from Fig. 1, Fig. 2, can find again that the orientation of fiber declines, this is probably and turns at a high speed
Caused by the air-flow on roller surface.
6, neural transplantation physical performance
In traditional sense, nerve graft is designed to tubulose mostly, in order to the neural broken ends of fractured bone is sewed up and grows into.But, as
Fruit directly utilizes thin transfer roller and collects nanofiber formation gillies' graft, and fiber is radial parallel arrangement, rather than axially in parallel, this
The contact guidance of nerve will be unfavorable for.For overcoming this not enough, we devise the construction method that first spinning winds again, the method
The mode of appearance of the nerve graft formed, its length and diameter can be adjusted according to the size of injured nerve, in this reality
Testing the middle a length of 10mm of graft fibre bundle, a diameter of 3mm, a diameter of 3.2mm of whole graft, about length 15mm.Fig. 3
A (), (b), (c) are graft stereoscan photograph, amplification is respectively 50 (a), 500 (b), and 5000 (c) is again by Fig. 3 (b)
Can be further observed that this graft is made up of ten hundreds of parallel nanofiber with Fig. 3 (c), fibre diameter 480 ± 75nm, this is
Injured nerve provides more contact guidance may.Additionally, the fibre bundle formed by winding also to produce more interlayer empty
Gap, this moves into being easy to cell and the transfer of nutrition and metabolite again.
In sum, under the conditions of suitable electrostatic spinning process, high speed transfer roller is utilized to be obtained in that the PLA of ideal orientation
Nano fibrous membrane, Mechanics Performance Testing finds that this film has good pliability in parallel fiber direction.By twice winding and
" core sheath " the formula nerve graft containing bundles of nanofibers formed after one time electrostatic spinning sprays, has and meets clinical operation
Sewing up strength, find that, far-end near at injured nerve all has regenerating nerve and Schwann cell to grow into after transplanting, the nerve of regeneration can
Through impaired spacing, consistent with fibre orientation, show the feasibility that this graft builds and internal Nerve Graft is repaired.
Construction method of the present invention is first compatible by having good biological high polymer electrostatic spinning, collects with high speed transfer roller,
Form the highly oriented nano fibrous membrane of multichannel.It is perpendicular to fibre orientation, by various winding methods, forms the fibre containing microchannel
Dimension bundle, in this, as " core " of nerve graft.It is coated with 1-2 layer oriented nanofibers film on the surface of core again, forms " sheath "
Internal layer, last electrostatic sprays formation " sheath " outer layer.Concrete advantage is as follows:
(1) realize the nerve trachea containing bundles of nanofibers to build.The nerve containing oriented nanofibers built at present
Conduit mainly has two kinds, and one is directly to collect nanofiber by high speed transfer roller and form conduit, the orientation of this fiber and pipe
Axially vertical, it is unfavorable for guiding nerve growth；Another kind is the conduit containing only a lumen formed by winding, this conduit
It is only capable of guiding nerve growth by the oriented nanofibers of tube wall, and nerve is fascicular texture, it is difficult to efficiently guide.The present invention will
Utilizing oriented nanofibers film to be wound by various modes, form bundles of nanofibers, fibre orientation direction of growing into nerve is consistent,
Efficiently guide neuranagenesis.
(2) realize being contained within microchannel at graft.Traditional nano fibrous membrane is despite many holes, but stratiform winding
After, lack passage, be unfavorable for that nerve is grown into.The present invention, for improving this drawback, intends during electrostatic spinning, embeds and supports
Thing, spinning is extracted supporter after completing and is formed " in layer " microchannel, by forming " interlayer " passage after winding again, increases regeneration god
The growth of warp and guide space.
(3) rapid build is realized.The present invention is the most disposable spinning highly oriented nano fibrous membrane containing microchannel, then
According to injured nerve length, being perpendicular to fibre orientation, clip fibrous membrane, then winding forms bundles of nanofibers.Finally, winding is single
Layer oriented nanofibers film also sprays formation nonwoven nanofiber layer to improve its intensity by electrostatic.This constructing technology greatly carries
High originally utilize transfer roller to collect nanofiber to form the speed of production of conduit, it is simple to Mirae Corp.'s metaplasia is produced.
Claims (7)
1. one kind contains microchannel and the nerve trachea of oriented nanofibers, it is characterised in that: described conduit is to be tied by " skin-core "
Structure is constituted, and described " core " is that the bundle fiber being coiled into by the oriented nanofibers film roll containing microchannel is constituted, and described is micro-logical
The a diameter of 30-200um in road, parallel with nanofiber orientation, described nanofiber diameter is 80-450nm；Described " skin " is
By oriented nanofibers film roll around cladding, spray one layer of random nano fibrous membrane the most again and be composited.
It is the most according to claim 1 containing microchannel with the nerve trachea of oriented nanofibers, it is characterised in that: described
The material of " core " is made up of one or more natural polymers in fibroin, gelatin, laminin，LN, collagen, or by polylactic acid
(PLA), in the synthetic polymer such as hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone composition
One or more compositions, it is also possible to natural be made up of with multiple with the one in synthetic high polymer above-mentioned；By weight,
The weight of " core " accounts for 85-90%.
It is the most according to claim 1 containing microchannel with the nerve trachea of oriented nanofibers, it is characterised in that: described
The material of " skin " is polylactic acid (PLA), hydroxyacetic acid and the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone
One or more compositions in forming Deng synthetic polymer.
4. the preparation method of the nerve trachea containing microchannel and oriented nanofibers, it is characterised in that: include walking as follows
Rapid:
(1) by by one or more in fibroin, gelatin, laminin，LN, collagen, or polylactic acid (PLA), hydroxyacetic acid and hydroxyl
One or more compositions in the synthetic polymer compositions such as the polymer (PLGA) of base propanoic acid different copolymer ratio, polycaprolactone,
Or above-mentioned natural with synthetic high polymer in a kind of be dissolved in volatile solvent with multiple composition polymer, use Static Spinning
Silk technology, utilizes the high speed transfer roller of a diameter of 200mm to collect, and rotating speed is 1000-3000rpm, forms highly oriented nano fibrous membrane,
" basic unit " in this, as microchannel nano fibrous membrane；
(2) it is parallel to nanofiber orientation, shows the long filament of a diameter of 32-210um arranged in parallel in established " basic unit ",
Away from for 0.02-0.2mm；Described long filament uses aqueous polyurethane (PU) or polyvinyl alcohol (PVA) coating processing in advance；
(3) utilize high polymer and the process conditions of spinning basic unit, continue electrostatic spinning, show shape in " basic unit " arranging long filament
Become " channel layer "；
(4) fibrous membrane prepared by (3) is taken off from high speed transfer roller, according to the difference of filament surface coating material, by fibrous membrane
Be put in the water of 40-95 DEG C or ethanol in immersion treatment 10-30min, then long filament extracted out from fibrous membrane, " basic unit " with
The microchannel of a diameter of 30-200um is formed between " channel layer "；
(5) it is perpendicular to nanofiber direction, this fibrous membrane containing microchannel is cut into the strip of 10-30mm；
(6) " basic unit " of strip is attached in the thin metal round roller of a diameter of 0.5mm, is then wound into a diameter of 1-3mm's
Winding article, forms the bundles of nanofibers " core " of nerve trachea；
(7) polylactic acid (PLA), hydroxyacetic acid close with the polymer (PLGA) of hydracrylic acid different copolymer ratio, polycaprolactone etc.
Become one or more in polymer composition to be dissolved in volatile solvent, utilize the high speed transfer roller of a diameter of 200mm to collect, turn
Speed is 1000-3000rpm, collects 4-6h, forms the high oriented fibers film that thickness is 15-25um；
(8) it is perpendicular to fibre orientation, the fibrous membrane in step (7) is cut into ratio strip of strip width 4mm in step (5), parcel
In the winding article surface that step (6) is formed, wrapping up 1-2 layer, two ends form " sheath " of 2mm；
(9) by the polymer solution electrostatic spinning in step (7), one layer is sprayed in the winding article surface that step (8) is formed randomly
Nano fibrous membrane, forms " skin " of nerve trachea；
(10) metal round roller is extracted out, formed containing microchannel and the nerve trachea of oriented nanofibers.
The most according to claim 4 containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, its feature
It is: membrane removal is contained within outside microchannel, in the intermembranous microchannel possibly together with 20-200um of fiber.
The most according to claim 4 containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, its feature
Being: the stitching strength of described " sheath " is 2-2.7N/ pin, the degradation speed of " core " is 3-12 week, and the degradation speed of " sheath " is 8-
20 weeks.
The most according to claim 4 containing microchannel with the preparation method of the nerve trachea of oriented nanofibers, its feature
Being: its total length is 14-34mm, through bundles of nanofibers " core " a length of 10-30mm of winding, nerve trachea two ends have
The stitching sheath of a length of 2mm, it is adaptable to the CO2 laser weld of impaired a length of 10-30mm.
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| CN114681688A (en) * | 2022-04-15 | 2022-07-01 | 东南大学 | Tissue regeneration membrane for promoting vascularization by using micro-channel and preparation method thereof |
| CN115463251A (en) * | 2022-09-09 | 2022-12-13 | 四川大学 | Optogenetic nerve repair scaffold compounded with up-conversion nanoparticles and preparation method thereof |
| CN115449936A (en) * | 2022-09-15 | 2022-12-09 | 青岛大学 | High-performance film roll micro-nanofiber yarn and preparation process thereof |
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