CN109260524A - A kind of tissue repair nano short fiber material and its preparation method and application - Google Patents
A kind of tissue repair nano short fiber material and its preparation method and application 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/222—Gelatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Abstract
The present invention relates to a kind of tissue repair nano short fiber materials and its preparation method and application.The nano short fiber material includes nano short fiber, and the diameter of the nano short fiber is 200~800nm, and length is 10~200 μm, and at least one nano short fiber surface has porous structure.Nano short fiber material provided by the invention shortens the length of nanofiber, with preferable dispersion performance, and the nano short fiber material is made of the degradable biomaterial with good biocompatibility and tissue repair performance, it need not remove, without second operation, especially suitable for the tissue repair compared with small area or deep layer defect.In addition, nano short fiber material provided by the invention can not only be prepared into powder, injection etc., it is used alone, can also be used in combination with other materials in combining the modus operandis such as minimally invasive, laparoscope, injection.
Description
Technical field
The invention belongs to tissue renovation material fields, more particularly, to a kind of tissue repair nano short fiber material
And its preparation method and application.
Background technique
Minimally invasiveization has become a kind of new trend of surgical clinical at present.Compared to traditional operation, minimally invasiveization operation is caused
Notch it is small, patient restores fast, while the incidence for the complication such as infecting is significantly reduced.With minimally invasiveization perform the operation popularization,
Also the cooperation of corresponding minimally invasiveization medical instrument is required.Tissue repair products can be as the high-end consumptive material in medical instrument
Defect provides necessary support, wad act, while its microstructure is conducive to histiocytic adherency, migration and increases
It grows, has greatly accelerated the reparation of defect.
It is the one kind more innovated at present using tissue engineering bracket prepared by electrostatic spinning technique in tissue repair products
Tissue repair products.Electrostatic spinning (electrospinning) technology is a kind of highly effective method for preparing nanometer to micron order fiber,
Device simple, it is low-cost, and the tissue engineering bracket prepared have high-specific surface area, the diameter of controllable nano fiber and
Porosity, is widely used in organizational project at the advantages that tridimensional network of similar natural extracellular matrix especially can be obtained
The preparation of bracket.
The repair mechanisms of electrospinning tissue repair products mainly utilize micro nanometer fiber composition tridimensional network simulation day
Right extracellular matrix promotes the adherency, migration and proliferation of cell.But the electrospinning tissue repair products prepared at present are mostly continuous long
The sheet or bulk of fiber composition, can not adapt to the requirement of minimally invasiveization operation.
Therefore, the nano short fiber material for developing a kind of requirement of applicable minimally invasiveization operation has highly important meaning
Justice.
Summary of the invention
It is mostly the sheet or block of continuous fiber composition it is an object of the invention to overcome existing electrospinning tissue repair products
Shape can not adapt to the defect of the requirement of minimally invasiveization operation, provide a kind of tissue repair nano short fiber material.The present invention provides
Nano short fiber material shorten the length of nanofiber, improve the dispersibility of nanofiber and widened nano short fiber
The application range of material；It can be made into blocky, pulvis or injection, defect be delivered to by syringe, hysteroscope or interposing catheter,
The requirement of minimally invasiveization operation has been adapted to, and has remained the tissue repair effect of nanofiber.
Another object of the present invention is to provide the above-mentioned tissue repair preparation methods of nano short fiber material.
Another object of the present invention is to provide a kind of tissue repair of injectable nano short fiber materials.
Another object of the present invention is to provide above-mentioned tissue repair with nano short fiber material minimally invasiveization operation in
Using.
For realize foregoing invention purpose, the present invention adopts the following technical scheme:
A kind of tissue repair nano short fiber material, the nano short fiber material includes nano short fiber, and the nanometer is short
The diameter of fiber is 200~800nm, and length is 10~200 μm, and at least one nano short fiber surface has porous structure.
Compared with existing nano-fiber material, nano short fiber material provided by the invention shortens the length of nanofiber
Degree, distribution of lengths is between 10~200 μm.The present inventor is by repeatedly studies have shown that nano short fiber is distributed in this
In section, it is ensured that nano short fiber material provided by the invention has preferable dispersion performance, and can promote macrophage etc.
Infiltration of the inflammatory cell to affected part, while nano short fiber is unlikely to be swallowed by macrophage, promotes inflammatory cell to affected part
Cell micro-environment carries out continuing improvement, histiocytic basic into microenvironment is provided for fibroblast etc..
The porous structure that staple fiber surface occurs, further increases the specific surface area of staple fiber.These porous structures
When staple fiber is mixed with other products (such as physiological saline, bio-ink or biogum), play the role of " handgrip ", increases
Staple fiber is dissociated difficulty, and the dispersibility of staple fiber is promoted, be conducive to product mix play it is multi-functional.Meanwhile porous structure
Occur, when also interacting staple fiber with cell, the attachment proteins of cell preferential at the porous structure, a large amount of can be enriched with, and be made thin
Adherency of the born of the same parents in staple fiber is more abundant.
Preferably, the relative standard deviation of the nano short fiber distribution of lengths is not more than 40%.
Preferably, the length of the nano short fiber is 30 ~ 50 μm.
Preferably, the nano short fiber hydrolyzes to obtain by fibrous raw material, and the fibrous raw material includes polylactic acid-based material
Expect, the mass fraction of polylactic acid is not less than 50% in the polylactic acid material.
Self-catalysis hydrolysis can occur for polylactic acid material, while polylactic acid is semi-crystalline polymer, acid fiber by polylactic
The generation site of hydrolysis is occurred by amorphous area to crystal region.Therefore, the amorphous area selective hydrolysis in fiber, amorphous area can be made
After hydrolysis, nanofiber is truncated substantially, and nano short fiber can be obtained, and nano short fiber surface after hydrolysis can generate not
With the porous structure of size, porous structure is to be not easy to hydrolyze facile hydrolysis part premature hydrolysis in paragraph (crystal region) on nanofiber
It is formed.
In order to guarantee in compound phase, polylactic acid chain rupture site formed continuous phase, the content of polylactic acid at least 50% with
On.Lower than 50% content, polylactic acid can not form continuous phase in composite fibre, when ammonolysis, even if polylactic acid is degradable, receive
Rice fiber also can not chain rupture formation staple fiber.
Preferably, the polylactic acid material includes polylactic acid, polylactide-polyglycolic acid copolymer, the poly- second two of polylactic acid-
One or more of alcohol copolymer or poly-epsilon-caprolactone-copolymer of poly lactic acid.
These polylactic acid materials have good biocompatibility and tissue repairing ability, while having good spin
Property, nanofiber is made by electrostatic spinning technique with can be convenient；Above-mentioned material contains lactic acid group simultaneously, can be used as at hydrolysis
The chain rupture site of reason.
Preferably, the fibrous raw material further includes functional filler；The quality of functional filler point in the fibrous raw material
Number is not more than 25%.
Preferably, the functional stuffing is polydioxanone, polyanhydride, gelatin, collagen, hyaluronic acid, chitosan, silk
Element, fibrin, pectin, starch and its derivative, cellulose and its etherate, polyoxyethylene, polyvinyl alcohol or polyethylene glycol
One or more of.
The addition of functional stuffing does not influence the crystal property of main material and hydrolysis property, and is embedded in non-hydrolyzable moiety master
Functional stuffing in material has facilitation to the tissue repair performance of nano short fiber.
The above-mentioned tissue repair preparation method of nano short fiber material, includes the following steps:
S1: polylactic acid material is prepared into nanofiber using electrostatic spinning technique；
S2: the nanofiber in step S1 being placed in ammonia spirit after being hydrolyzed, and is cleaned, filtering, and freeze-drying is
Obtain the nano short fiber.
By the nano short fiber of ammonium hydroxide hydrolysis process, in addition to axial length significantly shortens, it was found that in nanofiber
There are some porous structures in surface.These porous structures are the PLA molecule hydrolysis that fiber surface is distributed in hydrolytic process
It generates.
The nano short fiber with preferable dispersion performance can be successfully prepared in preparation method provided by the invention, and should
Method is quickly prepared using self-catalysis hydrolysis, maintains the biocompatibility and tissue repair of nano short fiber material
Energy.
Preferably, the mass fraction of the ammonia spirit is 5% ~ 25%.
Inventor has found that the rush hydrolysis effect of ammonium hydroxide is best, and when ammonia concn 5% ~ 25% during the test
With appropriate reaction rate, normal preparation demand can be met.
Preferably, the matter liquor ratio (g/ml) of nanofiber described in S2 and ammonia spirit is 1:5 ~ 1:50.
It is further preferable that the matter liquor ratio (g/ml) of nanofiber described in S2 and ammonia spirit is 1:5 ~ 1:10.
Signified matter liquor ratio (g/ml) of the invention refers to the ratio between the quality of nanofiber and the volume of ammonium hydroxide.
Preferably, the hydrolysis is terminated by following process after hydrolysis process in S2: adjusts pH=7 of hydrolysis process,
Or the mass fraction of ammonium hydroxide is adjusted less than 5%.
Preferably, further include the steps that deamination is handled before cleaning in S2, the deamination processing is the side for taking rotary distillation
Formula deamination.
It is further preferable that the temperature 45 C of the rotary distillation, pressure is 0.5 atmospheric pressure.
The effect of deamination processing is to remove unreacted ammonia, and the ammonia for rotating out can be again dissolved in water and form ammonia
Water, for next preparation process.
Preferably, the cleaning solution of cleaning described in S3 is pure water.
Preferably, the process of the filtering is to filter, 10 ~ 30 μm of filter paper aperture when the suction filtration.
The effect of cleaning and filtering is the hydrolysate for removing hydrolysis and generating, and removes the short fibre of the lesser nanometer of length
Dimension.The lesser nano short fiber of length is easy to be swallowed by macrophage, little to the effect of stimulation body reparation.
Above-mentioned tissue repair with nano short fiber material minimally invasiveization operation in application also in protection scope of the present invention
It is interior.
Preferably, the tissue repair is supplied in the form of pulvis, bulk or injection with nano short fiber material, and benefit
It is delivered with the mode of conduit, hysteroscope channel or injection.
Preferably, the tissue repair supplies seasonable, the infusion pump with nano short fiber material in the form of injection
Include the tissue repair nano short fiber material and dispersion liquid.
Compared with prior art, the invention has the following beneficial effects:
Nano short fiber material provided by the invention shortens the length of nanofiber, has preferable dispersion performance, and institute
It states nano short fiber material to be made of the degradable biomaterial with good biocompatibility and tissue repair performance, without going
It removes, second operation is not necessarily to, especially suitable for the tissue repair compared with small area or deep layer defect.In addition, nanometer provided by the invention
Short fiber material can not only be prepared into powder, injection etc., in combining the modus operandis such as minimally invasive, laparoscope, injection individually
Using can also be used in combination with other materials.The preparation method of nano short fiber material provided by the invention solves
Nano fibrous membrane or nanofiber gather more serious technical problem round and round in crushing process.This method is hydrolyzed anti-using self-catalysis
It should quickly prepare, maintain the biocompatibility and tissue repair performance of nano short fiber material.
Detailed description of the invention
Fig. 1 is the shape appearance figure for the tissue repair nano short fiber material that embodiment 1 provides；
Fig. 2 is the hydrolysis schematic diagram that embodiment 1 prepares tissue repair nano short fiber material；
Fig. 3 is the nano short fiber length and its distribution for the tissue repair nano short fiber material that embodiment 1 provides；
Fig. 4 is nano short fiber preparation :(a) pulvis；(b) injection；
Fig. 5 is the results of animal figure for the tissue repair nano short fiber material that embodiment 1 provides :(a) experimental group dissection
Figure；(b) control group internal anatomy；(c) experimental group pathological examination figure；(d) control group pathological examination figure.
Specific embodiment
Below with reference to embodiment, the present invention will be further described.These embodiments are retouched to typical case of the invention
It states, however, the present invention is not limited thereto.Test method as used in the following examples unless otherwise specified, is conventional method, is made
Raw material, reagent etc., unless otherwise specified, being can raw materials and reagents obtained from commercial sources such as regular market purchases.
In the present invention, the measurement of the nano short fiber length of material, the specific steps are as follows:
1. dispersing nano short fiber material in suitable quantity of water, it is added drop-wise on glass slide, covered and in 37 DEG C of baking ovens
Remove moisture removal；
2. using optical microphotograph sem observation nano short fiber, amplification factor 400X takes 3 visuals field to take pictures at random；
3. using the length of nano short fiber in Image Pro software measurement photo, 50 points of every photo random measurement；
4. the nano short fiber material of identical material selects 3 different batches, each batch takes 3 parts of samples, every part of sample at random
3 visuals field are taken to take pictures at random, each visual field takes 50 point measurements at random, then the nano short fiber material of every kind of material is available
1350 data have statistical significance；This 1350 data are subjected to statistical analysis to get the length of above-mentioned nano short fiber
Degree and distribution.
For this group of discrete data of nano short fiber length, the discrete journey that standard deviation characterizes its distribution of lengths can be used
Degree.But difference is organized other arithmetic average and is had differences, and standard deviation can not carry out across comparison, and therefore, present invention supplement is adopted
The length point of characterization nano short fiber is normalized with relative standard deviation (RSD, relative standard deviation)
The dispersion degree of cloth.Relative standard deviation just refers to: the ratio of standard deviation and calculated result arithmetic mean of instantaneous value.
Relative standard deviation calculation formula:
Relative standard deviation (RSD)=standard deviation (SD)/calculated result arithmetic mean of instantaneous value (X) * 100%.
The preparation of 1 polylactic acid nano short fiber material of embodiment
The present embodiment provides a kind of polylactic acid nano short fiber materials, are prepared via a method which to obtain.
S1. 0.8g polylactic acid is added in the hexafluoroisopropanol solution of 10ml, 8%(w/ is made until dissolution in stirring at normal temperature
V) spinning solution；
S2. spinning solution is added in syringe, front end of the syringe needle adds extension tube and connects the syringe needle of 20G, and syringe is placed in
On micro-injection pump, syringe needle is perpendicular to reception plate, receiver board lower ground；Setting injection rate be 6ml/h, when needle point have it is molten
When liquid squeezes out, the voltage of 22kv is loaded on needle point；There is nanofiber to spray at this time and be collected on receiver board, forms Nanowire
Tie up film；
S3. nano fibrous membrane vacuum drying 48h is removed into hexafluoroisopropanol, is then transferred to 15% ammonium hydroxide according to matter liquor ratio 1:5
In, 10min is stood to paste, and the stirring reprocessing 10min for loading 300rpm obtains uniform suspension；
S4. will be added in suspension in a certain amount of hydrochloric acid and, until pH=7；It is transferred in revolving bottle, is carried out using revolving instrument
Deamination processing, rotates temperature 45 C, 0.5 atmospheric pressure of pneumatics；
S5. a large amount of pure water are added in deamination treated suspension, are filtered by 10 ~ 30 μm of filter paper, collect filter cake and again
It filters, is repeated 3 times after adding water；
S6. a small amount of pure water of filtered filter cake addition will be cleaned, suspension is made, freezing solidification in low temperature refrigerator (- 80 DEG C), then it is cold
Jelly is dried to polylactic acid nano staple fiber.
Obtained polylactic acid nano short fiber material is powdery, and microstructure is as shown in Figure 1.The diameter of its nano short fiber
For 300 ~ 600nm, of length no more than 160 μm, surface has porous structure, and the relative standard deviation of distribution of lengths data is
28.45%, length and its distribution map such as Fig. 3.Hydrolytic process such as Fig. 2, wherein dark parts are not facile hydrolysis in nanofiber
Paragraph (generally crystal region), light color are facile hydrolysis paragraph (generally amorphous area), and fiber hydrolyzes control water by amorphous area
Staple fiber can be obtained in solution time and condition；Porous structure is to be not easy to hydrolyze facile hydrolysis part premature hydrolysis shape in paragraph (crystal region)
At.
The preparation of 2 PLGA/ gelatin nano short fiber material of embodiment
The present embodiment provides a kind of PLGA/ gelatin nano short fiber materials, are prepared via a method which to obtain.
S1. 1gPLGA is added in the hexafluoroisopropanol solution of 10ml, stirring at normal temperature adds 0.2g's until dissolution
10%(w/v is made after dissolution in gelatin) spinning solution；
S2. spinning solution is added in syringe, front end of the syringe needle adds extension tube and connects the syringe needle of 23G, and syringe is placed in
On micro-injection pump, syringe needle is perpendicular to reception plate, receiver board lower ground；Setting injection rate be 2ml/h, when needle point have it is molten
When liquid squeezes out, the voltage of 30kv is loaded on needle point；There is nanofiber to spray at this time and be collected on receiver board, forms Nanowire
Tie up film；
S3. nano fibrous membrane vacuum drying 48h is removed into hexafluoroisopropanol, is then transferred to 10 % ammonia according to matter liquor ratio 1:10
In water, 10min is stood to paste, the stirring reprocessing 10min for loading 300rpm obtains uniform suspension；
S4. a large amount of pure water weak ammonia will be added in suspension；It is transferred in revolving bottle, is carried out at deamination using revolving instrument
Reason rotates temperature 45 C, 0.5 atmospheric pressure of pneumatics；
S5. a large amount of pure water are added in deamination treated suspension, are filtered by 10 ~ 30 μm of filter paper, collect filter cake and again
It filters, is repeated 3 times after adding water；
S6. a small amount of pure water of filtered filter cake addition will be cleaned, suspension is made, freezing solidification in low temperature refrigerator (- 80 DEG C), then it is cold
Jelly is dried to polylactic acid nano staple fiber.
Obtained polylactic acid nano short fiber material is powdery, and microstructure is as shown in Figure 2.The diameter of its nano short fiber
For 200 ~ 800nm, of length no more than 200 μm, the relative standard deviation of distribution of lengths data is 35.11%.
Embodiment 3
The present embodiment provides a kind of polylactic acid nano short fiber materials, are prepared via a method which to obtain.
S1. 0.8g polylactic acid is added in the hexafluoroisopropanol solution of 10ml, 8%(w/ is made until dissolution in stirring at normal temperature
V) spinning solution；
S2. spinning solution is added in syringe, front end of the syringe needle adds extension tube and connects the syringe needle of 20G, and syringe is placed in
On micro-injection pump, syringe needle is perpendicular to reception plate, receiver board lower ground；Setting injection rate be 6ml/h, when needle point have it is molten
When liquid squeezes out, the voltage of 22kv is loaded on needle point；There is nanofiber to spray at this time and be collected on receiver board, forms Nanowire
Tie up film；
S3. nano fibrous membrane vacuum drying 48h is removed into hexafluoroisopropanol, is then transferred to 25% ammonium hydroxide according to matter liquor ratio 1:50
In, 10min is stood to paste, and the stirring reprocessing 10min for loading 300rpm obtains uniform suspension；
S4. will be added in suspension in a certain amount of hydrochloric acid and, until pH=7；It is transferred in revolving bottle, is carried out using revolving instrument
Deamination processing, rotates temperature 45 C, 0.5 atmospheric pressure of pneumatics；
S5. a large amount of pure water are added in deamination treated suspension, are filtered by 10 ~ 30 μm of filter paper, collect filter cake and again
It filters, is repeated 3 times after adding water；
S6. a small amount of pure water of filtered filter cake addition will be cleaned, suspension is made, freezing solidification in low temperature refrigerator (- 80 DEG C), then it is cold
Jelly is dried to polylactic acid nano staple fiber.The diameter of its nano short fiber is 300 ~ 600nm, and of length no more than 100 μm, length is divided
The relative standard deviation of cloth data is 12.39%.
Embodiment 4
The present embodiment provides a kind of polylactic acid-polycaprolactone co-polymer nano short fiber materials, are prepared via a method which to obtain.
S1. 1g polylactic acid-polycaprolactone co-polymer is added in the trifluoroacetic acid solution of 10ml, stirring at normal temperature is until molten
Solution, 10%(w/v is made) spinning solution；
S2. spinning solution is added in syringe, front end of the syringe needle adds extension tube and connects the syringe needle of 23G, and syringe is placed in
On micro-injection pump, syringe needle is perpendicular to reception plate, receiver board lower ground；Setting injection rate be 2ml/h, when needle point have it is molten
When liquid squeezes out, the voltage of 18kv is loaded on needle point；There is nanofiber to spray at this time and be collected on receiver board, forms Nanowire
Tie up film；
S3. nano fibrous membrane vacuum drying 48h is removed into trifluoroacetic acid, is then transferred to 20% ammonium hydroxide according to matter liquor ratio 1:40
In, 15min is stood to paste, and the gentle agitation reprocessing 10min for loading 100rpm obtains uniform suspension；
S4. will be added in suspension in a certain amount of hydrochloric acid and, until pH=7；It is transferred in revolving bottle, is carried out using revolving instrument
Deamination processing, rotates temperature 45 C, 0.5 atmospheric pressure of pneumatics；
S5. a large amount of pure water are added in deamination treated suspension, are filtered by 10 ~ 30 μm of filter paper, collect filter cake and again
It filters, is repeated 3 times after adding water；
S6. a small amount of pure water of filtered filter cake addition will be cleaned, suspension is made, freezing solidification in low temperature refrigerator (- 80 DEG C), then it is cold
Jelly is dried to polylactic acid-polycaprolactone co-polymer nano short fiber.The diameter of its nano short fiber is 100 ~ 500nm, and length is not
More than 150 μm, the relative standard deviation of distribution of lengths data is 18.94%.
The application mode for the nano short fiber material being prepared in 5 embodiment 1,2 of embodiment
For the application mode for showing made nano short fiber in the present invention, spy is herein for example, specific as follows:
A1: prepared polylactic acid nano staple fiber pulvis in Example 1, as shown in Figure 4 (a)；By its directly filling, smearing
Until filling up at tissue defect, wound is sutured to or is directly covered gauze.
A2: prepared PLGA/ gelatin nano short fiber material 0.5g in Example 2 is added into the 1%(w/ of 10ml
V) nano short fiber-hyaluronic acid injection liquid is made, as shown in Figure 4 (b) in hyaluronic acid aqueous solution；Slowly by injection
It is injected at tissue defect, defect point surrounding tissue is rubbed while injecting, injection is promoted to be uniformly distributed, until injection
Fill up defect.
6 zoopery of embodiment
For the actual tissue repairing effect for verifying nano short fiber material, the mode of muscular grafting is selected to carry out zoopery, joined
National standard " the 6th part of GB/T 16886.6-1997 BiologicalEvaluationofMedicalDevice: local reaction is tested after implantation " is examined,
Using nano short fiber material prepared in embodiment 1 as laboratory sample, commercially available tissue repair film is control sample, detailed process
It is as follows:
1. taking healthy SD rat 6, anesthesia, preserved skin, prostrate are fixed；
2. using Iodophor alcohol disinfecting rat buttocks, in rat two sides, gluteus does the defect each one of long 3cm, wide 1cm, depth 2cm respectively；
3. defect is implanted into proper amount of nano short fiber material in side, other side defect is implanted into control sample；
4. suturing muscle and skin；
5. normal raising, optionally gives a certain amount of antibiotic；It puts to death and is dissected and observed after 2 weeks, take a wherein rat at random
Implant site and its surrounding tissue, utilize HE decoration method carry out pathological analysis.
It is dissected and observed shown in result such as Fig. 5 (a) and Fig. 5 (b), wherein Fig. 5 (a) is experimental group (nano short fiber material)
Photo is dissected, Fig. 5 (b) is the dissection photo of control group (commercially available tissue repair film).It is found after dissection, experimental group and control group can
See apparent cellular infiltration, wherein experimental group material is shown in obvious new capillary vessel structure, as shown in Fig. 5 (a)；The two is along flesh
There is certain deformation in meat direction, and the deformation of control group is significantly greater than experimental group, as shown in Fig. 5 (b).
Shown in Pathological experiment result such as Fig. 5 (c) and Fig. 5 (d), wherein Fig. 5 (c) is experimental group (nano short fiber material)
Pathological experiment is as a result, Fig. 5 (d) is the Pathological experiment result of control group (commercially available tissue repair film).The two pathological examination is similar, disease
Reason result is shown: 1, being implanted into material in filament shape, internal defect, it is seen that a small amount of fibroblast grows into material internal.Residual
Material area percentage is about are as follows: obvious gap is had no between 40-50%, with surrounding tissue.2, implantation material peripheral is visible compared with multi-fiber
Hyperblastosis is tieed up, therebetween visible a small amount of lymphocytic infiltration (≤25/HPF), a small amount of plasmocyte infiltrating (≤25/HPF) is few
Macrophages infiltration (1-4/HPF) are measured, a large amount of multinucleate giant cells infiltrate (> 5/HPF).Wherein, experimental group is with a large amount of hairs
Thin blood vessel hyperplasia (8-20/HPF), control group are also with local rouge with blood capillary proliferation (4-7/HPF), control group
Fat cellular infiltration (< 20%).
From the above it is found that experimental group and control group are all demonstrated by good bioactivity at implantation initial stage, it is shown that
Tissue irritation promotes inflammatory cell infiltration material, establishes relevant cell environment, fibroblast is promoted to grow into, fiber occur
Hyperblastosis and blood capillary proliferation, it is seen that process of tissue reparation has been started up, it is anticipated that the achievable tissue of final material is repaired
Multiple process, test results are slightly better than control group.Meanwhile dissecting photo and showing, compared with the control group, experimental group has better
Ability of anti-deformation and support performance.
Obviously, the above embodiment of the present invention be only to clearly illustrate example of the present invention, and not be pair
The restriction of embodiments of the present invention.For those of ordinary skill in the art, may be used also on the basis of the above description
To make other variations or changes in different ways.There is no necessity and possibility to exhaust all the enbodiments.It is all this
Made any modifications, equivalent replacements, and improvements etc., should be included in the claims in the present invention within the spirit and principle of invention
Protection scope within.
Claims (15)
1. a kind of tissue repair nano short fiber material, the nano short fiber material includes nano short fiber, and feature exists
In the diameter of the nano short fiber is 200~800nm, and length is 10~200 μm, and at least one nano short fiber surface
With porous structure；Preferably, the length of the nano short fiber is 30 ~ 50 μm.
2. tissue repair nano short fiber material according to claim 1, which is characterized in that the nano short fiber
The relative standard deviation of distribution of lengths is not more than 40%.
3. tissue repair nano short fiber material according to claim 1, which is characterized in that the nano short fiber
It hydrolyzes to obtain by fibrous raw material, the fibrous raw material includes polylactic acid material, polylactic acid in the polylactic acid material
Mass fraction is not less than 50%.
4. tissue repair nano short fiber material according to claim 2, which is characterized in that the polylactic acid material packet
Include polylactic acid, polylactide-polyglycolic acid copolymer, PLA-PEG copolymer or poly-epsilon-caprolactone-copolymer of poly lactic acid
One or more of.
5. tissue repair nano short fiber material according to claim 1, which is characterized in that the fibrous raw material further includes
Functional filler；The mass fraction of functional filler is not more than 25% in the fibrous raw material.
6. tissue repair nano short fiber material according to claim 5, which is characterized in that the functional filler is poly-
Dioxane ketone, polyanhydride, gelatin, collagen, hyaluronic acid, chitosan, fibroin, fibrin, pectin, starch and its derivative
One or more of object, cellulose and its etherate, polyoxyethylene, polyvinyl alcohol or polyethylene glycol.
7. the preparation method of any tissue repair nano short fiber material of claim 1 ~ 6, which is characterized in that including such as
Lower step:
S1: polylactic acid material is prepared into nanofiber using electrostatic spinning technique；
S2: the nanofiber in step S1 being placed in ammonia spirit after being hydrolyzed, and is cleaned, filtering, and freeze-drying is
Obtain the nano short fiber.
8. preparation method according to claim 7, which is characterized in that the mass fraction of the ammonia spirit is 5% ~ 25%.
9. preparation method according to claim 7, which is characterized in that the matter liquor ratio of nanofiber described in S2 and ammonia spirit
It (g/ml) is 1:5 ~ 1:50, preferably 1:5 ~ 1:10.
10. preparation method according to claim 7, which is characterized in that terminate institute by following process after hydrolysis process in S2
It states hydrolysis: adjusting pH=7 of hydrolysis process, or adjust the mass fraction of ammonium hydroxide less than 5%.
11. preparation method according to claim 7, which is characterized in that further include the steps that deamination is handled before cleaning in S2, institute
Stating deamination processing is the mode deamination for taking rotary distillation；Preferably, the temperature 45 C of the rotary distillation, pressure are 0.5
Atmospheric pressure.
12. preparation method according to claim 7, which is characterized in that the cleaning solution of cleaning described in S2 is pure water；The mistake
The process of filter is to filter, 10 ~ 30 μm of filter paper aperture when the suction filtration.
13. application of any tissue repair of claim 1 ~ 6 with nano short fiber material in minimally invasiveization operation.
14. 3 application according to claim 1, which is characterized in that the tissue repair with nano short fiber material with pulvis,
Blocky or injection form supply, and delivered in the way of conduit, hysteroscope channel or injection.
15. 4 application according to claim 1, which is characterized in that the tissue repair is with nano short fiber material with injection
Form for seasonable, the injection includes the tissue repair nano short fiber material and dispersion liquid.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114712564A (en) * | 2021-01-05 | 2022-07-08 | 绍兴柯桥德沐服业有限公司 | Degradable nano short fiber material for tissue repair and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101781815A (en) * | 2010-02-03 | 2010-07-21 | 东华大学 | Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold |
| CN103820943A (en) * | 2014-03-11 | 2014-05-28 | 武汉大学 | Macropore three-dimensional ordered-orientation silk fibroin nano-fiber support and preparation method thereof |
| CN104945640A (en) * | 2015-07-02 | 2015-09-30 | 武汉工程大学 | Method for preparing polylactic acid microsphere by utilizing hydrolysis of moniliform nanofiber |
| CN106075568A (en) * | 2016-06-13 | 2016-11-09 | 广州迈普再生医学科技有限公司 | A kind of tissue repair degradable nano short fiber material and its preparation method and application |
| CN106924171A (en) * | 2017-03-02 | 2017-07-07 | 泉州威可赛机械科技有限公司 | A kind of injectable nano short fiber of carried anticancer medicine thing and its preparation method and application |
-
2018
- 2018-09-19 CN CN201811095518.2A patent/CN109260524B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101781815A (en) * | 2010-02-03 | 2010-07-21 | 东华大学 | Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold |
| CN103820943A (en) * | 2014-03-11 | 2014-05-28 | 武汉大学 | Macropore three-dimensional ordered-orientation silk fibroin nano-fiber support and preparation method thereof |
| CN104945640A (en) * | 2015-07-02 | 2015-09-30 | 武汉工程大学 | Method for preparing polylactic acid microsphere by utilizing hydrolysis of moniliform nanofiber |
| CN106075568A (en) * | 2016-06-13 | 2016-11-09 | 广州迈普再生医学科技有限公司 | A kind of tissue repair degradable nano short fiber material and its preparation method and application |
| CN106924171A (en) * | 2017-03-02 | 2017-07-07 | 泉州威可赛机械科技有限公司 | A kind of injectable nano short fiber of carried anticancer medicine thing and its preparation method and application |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114712564A (en) * | 2021-01-05 | 2022-07-08 | 绍兴柯桥德沐服业有限公司 | Degradable nano short fiber material for tissue repair and preparation method thereof |
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