CN109568667A - The preparation of the degradable bone-repairing composite material of high-intensitive and no inflammation reaction and product and application - Google Patents
The preparation of the degradable bone-repairing composite material of high-intensitive and no inflammation reaction and product and application Download PDFInfo
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- CN109568667A CN109568667A CN201811601413.XA CN201811601413A CN109568667A CN 109568667 A CN109568667 A CN 109568667A CN 201811601413 A CN201811601413 A CN 201811601413A CN 109568667 A CN109568667 A CN 109568667A
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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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
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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
- A61L27/58—Materials at least partially resorbable by the body
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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
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The present invention relates to preparation method of degradable bone-repairing composite material of a kind of high-intensitive and no inflammation reaction and products thereof and applications, surface chemical modification is carried out to calcium carbonate crystal whisker material using low molecular weight polyester as modifying agent, is then added in PLGA Bone Defect Repari matrix by the method for solution blending.The Bone Defect Repari is implanted into material, calcium carbonate crystal whisker can reach evenly dispersed in organic substrate, reach the mechanical strength of PLGA to be obviously improved, and since the presence of calcium carbonate substantially change implantation material surrounding tissue pH not, solves the problems, such as that PLGA material implants and easily cause inflammation.The present invention is simply controllable, and calcium carbonate crystal whisker additional amount is few, easy processing molding, high mechanical strength, and performance is stablized, and the bone renovating material that can be used as the more demanding load-bearing bony site of performance indicator uses.
Description
Technical field
The present invention relates to the preparation method of the degradable bone-repairing composite material of a kind of high-intensitive and no inflammation reaction and its
Product and application, and in particular to it is a kind of with degradable poly poly lactic coglycolic acid (PLGA) for matrix, with oligomer polyester
Calcium carbonate crystal whisker after modification is reinforcing agent, and preparation while the Bone Defect Repari that there is high-intensitive and no inflammation to react use filling multiple
Condensation material.The invention belongs to bio-medical composition fields.
Background technique
Absorbable high-molecular bone surgical implant is not because interfering children's bone growth and development, avoiding two with material absorbable
It is secondary to take out the advantages such as operation, pain and financial burden that patient be effectively reduced, it is widely used in Orthopedic Clinical.But it is absorbable
There is organize caused by intensity deficiency, degradation rate and organization healing mismatch, catabolite for macromolecule orthopedic implanting material
The problems such as reaction, seriously restricts absorbable implantation material in the practical application of China's clinic.Therefore single organic polymer
The application of material is restricted, and more and more researchers begin to focus on organic matter and the compound material of inorganic matter at present.
In the past ten years, the advanced composite material (ACM) of biologically absorbable polymer and bioceramic has been used for Bone Defect Repari
Material improves mechanical performance.Such as by hydroxyapatite, the inorganic fillers such as bata-tricalcium phosphate and calcium carbonate are added to biodegradable
The composite material of excellent in mechanical performance is prepared in copolymer matrix to improve mechanical performance.Hydroxyapatite and bata-tricalcium phosphate
It with excellent biology performance, has been widely studied, but they have brittle, mechanical strength is low and in fluid environment
The disadvantages of middle fatigue resistance is weak is restricted them in practical applications, also needs further to study.On the contrary, calcium carbonate crystal whisker
It is a kind of green material, there is excellent performance, such as high-intensitive, high-modulus, high chemical stability and nontoxicity etc., this
Outside, calcium carbonate degradation process has Ca2+The release of ion, these Ca2+Ion will participate in the sclerotin mineralization process of union.
Therefore, theoretically, which can promote to form good interface between material and bone, have certain synosteosis power and bone
Conductibility.It is widely studied in biomedical and biopolymer.So calcium carbonate crystal whisker can be used as biology
The reinforcing agent of medical polymer material uses.In addition, calcium carbonate crystal whisker is degradable, and catabolite is alkalinity, can neutralize PLGA
The acidity of matrix degradation, the surrounding materials that make to implant maintain always neutral range, reduce the generation of inflammatory reaction.But
Calcium carbonate crystal whisker is a kind of material that polarity is very big, and the interface compatibility between polymer substrate is poor and easily reunites.Cause
This, improve interfacial adhesion between calcium carbonate crystal whisker and polymeric matrix for prepare calcium carbonate whisker composite material and
Its is important.However, cause surface grafting rate relatively low due to the low reaction activity of calcium carbonate crystal whisker surface hydroxyl, it is more important
, the organic molecule being largely grafted more or less has rejection to human body.Therefore, seek nontoxic and and polymer substrate
The good calcium carbonate crystal whisker surface modifier of blending and have that efficient surface modifier grafting method is with higher grinds
Study carefully meaning and application value.
Summary of the invention
Present invention aims at, drops bad for the existing bone renovating material mechanical property using PLGA as load-bearing bony site
The deficiencies of solution product easily causes inflammation, it is an object of that present invention to provide a kind of degradable Bone Defect Reparis of high-intensitive and no inflammation reaction
The preparation method of composite material.
Another object of the present invention is: providing the degradable of a kind of high intensity of above method preparation and no inflammation reaction
Bone-repairing composite material product.
Another object of the present invention is to: a kind of application of the said goods is provided.
The object of the invention is realized by following proposal: a kind of degradable Bone Defect Repari composite wood of high-intensitive and no inflammation reaction
The preparation method of material, with degradable poly poly lactic coglycolic acid (PLGA) for matrix, with the calcium carbonate crystal whisker after modification
For reinforcing agent, using oligomer polyester as modifying agent, by monomer ring-opening polymerization method by polyester graft in calcium carbonate crystal whisker surface
On, preparation while the bone-repairing composite material with the reaction of high-intensitive and no inflammation, comprising the following steps:
(1) preparation of calcium carbonate crystal whisker: calcium chloride and sodium carbonate are dissolved separately in distilled water at room temperature, then in magnetic force
Two kinds of solution are slowly dropped in three neck round bottom flask simultaneously under stirring, the pH of mixture is made with 0.1M ammonium chloride buffer solution
It is maintained at 8-9, after being added dropwise, which stirs 1 ~ 10 h under 60 ~ 100 °C with 120 ~ 200 r/min, then old
Change 0.5 ~ 4 h, sediment is washed with distilled water three times, then with a large amount of ethanol washings, by obtained calcium carbonate crystal whisker (CCW)
Grain is dried in vacuo spare after 24 h under 120 °C；
(2) surface modification of calcium carbonate crystal whisker: dried calcium carbonate crystal whisker is added in xylene solvent, is put into water removal deoxygenation
Three-necked flask in, catalyst is added under nitrogen protection and magnetic agitation, which is preheating to 90 °C；Secondly, by polyester
In the xylene solvent that monomer is dissolved under 120 °C, after two kinds of solution dissolve respectively, monomer solution is added drop-wise to carbon dropwise
In sour calcium pyroborate mixed solution, in 120 °C of lower nitrogen protections, 12 ~ 48 h of magnetic agitation back flow reaction, wherein monomer and carbonic acid
Calcium pyroborate mass ratio between the two is 1/1 ~ 10/1；Then reactant is cooled to room temperature, product is under the conditions of 5000 rpm
Centrifuge separation is washed with a large amount of chloroforms and removes the non-grafted oligomer in calcium carbonate crystal whisker surface；Finally, that isolates is heavy
Shallow lake product is dried in vacuo 24 ~ 72 h under 50 °C and removes solvent；
(3) preparation of PLGA/ calcium carbonate crystal whisker composite material: composite material film passes through ultrasonic disperse and solution casting method system
Standby, detailed process is first to be dissolved in PLGA copolymer in dichloromethane solvent with the concentration of 5 ~ 20 w/v%, secondly, by pre-
Calcium carbonate crystal whisker dry particle after the modification first weighed is added in copolymer solution, passes through magnetic agitation and ultrasonication
It is transferred to natural volatile dry in quartzy box after being mixed uniformly, volatilizees and completes to solvent, membrane sample molding places it in often
Constant weight is dried under vacuum under temperature to get no inflammation response type high-strength composite bone renovating material is arrived.
The structure index of the calcium carbonate crystal whisker are as follows: width is 1 ~ 5 μm, and length is 5 ~ 50 μm, and draw ratio is 1 ~ 50.
Dressing agent polyester is one of polylactic acid, polyglycolic acid, poly lactide-glycolide acid.
The catalyst is one of stannous octoate, zinc, zinc oxide, zinc chloride.
The additive amount of calcium carbonate crystal whisker after the modified are as follows: 1-10 wt%.
The concentration ratio of the calcium chloride and sodium carbonate are as follows: 1/1 ~ 1/2.
The present invention provides a kind of preparation method of the degradable bone-repairing composite material of high-intensitive and no inflammation reaction, special
Sign is, 3.33 g calcium chloride and 3.18 g sodium carbonate are dissolved separately at room temperature in 150 mL and 100 mL distilled water,
Then two kinds of solution are slowly dropped in three neck round bottom flask under magnetic stirring simultaneously, are made with 0.1M ammonium chloride buffer solution
The pH of mixture is maintained at 8-9, and after being added dropwise, which stirs 4 h, subsequent aging under 80 °C with 120 r/min
1 h, sediment are washed with distilled water three times, then with a large amount of ethanol washings, by obtained calcium carbonate crystal whisker particle at 120 °C
It is spare after 24 h of lower vacuum drying；
It is added in 20 mL xylene solvents secondly, weighing the dried calcium carbonate crystal whisker of 2 g, is put into three mouthfuls of water removal deoxygenation
In flask, 0.002 mL Sn (Oct) is added under nitrogen protection and magnetic agitation2, which is preheating to 90 °C, secondly,
In the 10 mL xylene solvents that 2 g glycolides are dissolved under 120 °C, after two kinds of solution dissolve respectively, by monomer solution
It is added drop-wise in calcium carbonate crystal whisker mixed solution dropwise, in 120 °C of lower nitrogen protections, 18 h of magnetic agitation back flow reaction.Then will
Reactant is cooled to room temperature, and product is centrifugated under the conditions of 5000 rpm, with a large amount of chloroforms wash remove it is non-grafted in
The oligomer on calcium carbonate crystal whisker surface；
Finally, prepare composite material film by ultrasonic disperse and solution casting method, detailed process is, by PLGA copolymer, with
The concentration of 10 w/v% is dissolved in dichloromethane solvent, then that mass fraction is dry for the calcium carbonate crystal whisker after 5 wt% modification
Particle is added in copolymer solution, is transferred in quartzy box after being mixed uniformly by magnetic agitation and ultrasonication certainly
Right volatile dry volatilizees to solvent and completes, and membrane sample molding places it in and is dried under vacuum to constant weight under room temperature and repairs to get to bone
Multiple composite material.
The present invention provides a kind of degradable bone-repairing composite material of high-intensitive and no inflammation reaction, according to any of the above-described institute
The method of stating is prepared.
The present invention provides a kind of degradable bone-repairing composite material the answering in Bone Defect Repari of high-intensitive and no inflammation reaction
With.
The composite material obtained by this method, calcium carbonate crystal whisker are uniformly dispersed in PLGA, and two-phase interface compatibility is good,
Not only the mechanical property of PLGA is highly improved, and is not easy to cause inflammatory reaction.Gained composite material is able to satisfy clinical application
Demand.The Bone Defect Repari is implanted into material, and calcium carbonate crystal whisker can reach evenly dispersed in organic substrate, makes the mechanical strength of PLGA
Reach and be obviously improved, and since the presence of calcium carbonate substantially change implantation material surrounding tissue pH not, solves PLGA material
Material, which implants, easily causes the problem of inflammation.
It is calcium carbonate crystal whisker material modification agent that the present invention, which selects the polyester consistent with matrix composition, is passed through chemical bond
Whisker surface is grafted on, plasticiser can be played the role of by grafting on the short chain of the polyester on whisker surface, help to weaken PLGA points
Stress between subchain, and then the toughness of composite material is improved, caused by overcoming the loss of material molten process middle-molecular-weihydroxyethyl
The shortcomings that performance declines；And the aobvious alkalinity of calcium carbonate crystal whisker degradation, the acidity generated in PLGA degradation process can be neutralized, ensure that
Stable pH value is maintained around implant material.The present invention is simply controllable, and inorganic crystal whisker additional amount is few, easy processing at
Type, high mechanical strength, performance are stablized, and the bone renovating material that can be used as the more demanding load-bearing bony site of performance indicator uses.
Detailed description of the invention
Fig. 1 be embodiment 1 prepared by polyglycolic acid modification front and back calcium carbonate crystal whisker SEM figure (a modification before, b modification
Afterwards)；
Fig. 2 is PLGA prepared by embodiment 1 and adds the compound of the calcium carbonate crystal whisker particle after the modification of 2% content polyglycolic acid
The pH variation diagram of medium in 45 weeks degradation processes of material；
Fig. 3 is the composite material table of the calcium carbonate crystal whisker particle after the modification of 2% content polyglycolic acid of addition prepared by embodiment 1
Live/Dead experimental result after face culture MC3T3-E1 cell 14 days；
Fig. 4 dispersibility SEM in PLGA matrix for the calcium carbonate crystal whisker before and after the modification of polyglycolic acid prepared by Examples 1 and 2
Comparison diagram；
Calcium carbonate before Fig. 5 is pure PLGA prepared by Examples 1 and 2 and the polyglycolic acid modification of 2% content of addition and after modification
The stress-strain diagram of metal whisker composite.
Specific embodiment
Below by way of specific embodiment, the technical scheme of the present invention will be further described.Embodiment below is to this
The further explanation of invention, and do not limit the scope of the invention.
Embodiment 1
A kind of degradable bone-repairing composite material of high-intensitive and no inflammation reaction, with the copolymerization of degradable poly lactic-co-glycolic acid
Object (PLGA) is that matrix, using oligomer polyester as modifying agent, is opened using the calcium carbonate crystal whisker after modification as reinforcing agent by monomer
Cyclopolymerization method on calcium carbonate crystal whisker surface, prepares polyester graft according to the following steps:
Firstly, 3.33 g calcium chloride and 3.18 g sodium carbonate are dissolved separately in 150 mL and 100 mL distilled water at room temperature
In, then two kinds of solution are slowly dropped in three neck round bottom flask simultaneously under magnetic stirring, it is molten with 0.1M chloride buffer
Liquid makes the pH of mixture be maintained at 8-9, and after being added dropwise, which stirs 4 h under 80 °C with 120 r/min, then
1 h of aging, sediment are washed with distilled water three times, then with a large amount of ethanol washings, by obtained calcium carbonate crystal whisker particle 120
It is dried in vacuo under °C spare after 24 h.
It is added in 20 mL xylene solvents secondly, weighing the dried calcium carbonate crystal whisker of 2 g, is put into water removal deoxygenation
In three-necked flask, 0.002 mL Sn (Oct) is added under nitrogen protection and magnetic agitation2, which is preheating to 90 °C, so
Afterwards, after two kinds of solution dissolve respectively, monomer is molten in 10 mL xylene solvents 2 g glycolides being dissolved under 120 °C
Liquid is added drop-wise to dropwise in calcium carbonate crystal whisker mixed solution, in 120 °C of lower nitrogen protections, 18 h of magnetic agitation back flow reaction.Then
Reactant is cooled to room temperature, product is centrifugated under the conditions of 5000 rpm, and it is non-grafted to wash removing with a large amount of chloroforms
Oligomer in calcium carbonate crystal whisker surface.
Finally, preparing composite material film, detailed process by ultrasonic disperse and solution casting method are as follows: by PLGA copolymer
It is dissolved in dichloromethane solvent with the concentration of 10 w/v%, is calcium carbonate crystal whisker dry after 5 wt% modification by mass fraction
Grain is added in copolymer solution, is transferred to after being mixed uniformly by magnetic agitation and ultrasonication natural in quartzy box
Volatile dry volatilizees to solvent and completes, membrane sample molding, places it under room temperature and is dried under vacuum to constant weight to get Bone Defect Repari is arrived
Composite material.
The reaction equation 1 that polyglycolic acid modifies calcium carbonate crystal whisker is as follows:
。
Fig. 1 is the SEM figure (before a modification, after b modification) of the calcium carbonate crystal whisker of polyglycolic acid modification front and back, as seen from the figure, carbon
The dimension width of sour calcium pyroborate is 1 ~ 5 μm, the hexagonal cylindrical shape that length is 5 ~ 50 μm, its pattern of modification front and back does not change
Become.
Fig. 2 was the composite material of the calcium carbonate crystal whisker particle after PLGA is modified with 5% content polyglycolic acid of addition at 45 weeks
The pH variation of medium in degradation process, as seen from the figure, PLGA pH value in 45 weeks degradation processes was substantially on a declining curve, by 45 weeks
After, pH value is down to 6.83, the pH value of the degradation solution of the composite material containing the calcium carbonate crystal whisker material after polyglycolic acid modification
Start to occur slightly rising after dropping at the 25th week 7.0 or so, 25 weeks, pH value remains unchanged substantially.
Fig. 3 is the composite material surface culture MC3T3- for adding the calcium carbonate crystal whisker particle after the modification of 5% content polyglycolic acid
Live/Dead experimental result after E1 cell 14 days, as seen from the figure, during entire culture, living cells quantity increases, dead cell
Quantity it is seldom, it was demonstrated that composite material used in the experiment all has good biocompatibility.
Embodiment 2
A kind of degradable bone-repairing composite material of high-intensitive and no inflammation reaction, it is approximate with implementation column 1, it makes according to the following steps
It is standby:
Firstly, 3.33 g calcium chloride and 3.18 g sodium carbonate are dissolved separately in 150 mL and 100 mL distilled water at room temperature
In, then two kinds of solution are slowly dropped in three neck round bottom flask simultaneously under magnetic stirring, it is molten with 0.1M chloride buffer
Liquid makes the pH of mixture be maintained at 8-9, and after being added dropwise, which stirs 4 h under 80 °C with 120 r/min, then
1 h of aging, sediment are washed with distilled water three times, then with a large amount of ethanol washings, by obtained calcium carbonate crystal whisker particle 120
It is dried in vacuo under °C spare after 24 h.
Secondly, preparing composite material film, detailed process by ultrasonic disperse and solution casting method are as follows: PLGA to be copolymerized
Object is dissolved in dichloromethane solvent with the concentration of 10 w/v%, is then that the untreated calcium carbonate of 5 wt% is brilliant by mass fraction
Palpus dry particle is added in copolymer solution, is transferred to quartz after being mixed uniformly by magnetic agitation and ultrasonication
Natural volatile dry in box, volatilizees to solvent and completes, membrane sample molding, place it under room temperature be dried under vacuum to constant weight to get
To bone-repairing composite material.
Embodiment 2 is compared with embodiment 1, studies influence of the surface treatment to composite property of calcium carbonate crystal whisker.
As shown in calcium carbonate crystal whisker dispersibility SEM comparison diagram in PLGA matrix of Fig. 4 polyglycolic acid modification front and back, repaired through polyglycolic acid
Calcium carbonate crystal whisker (a) after decorations is more uniformly dispersed in PLGA matrix than unmodified calcium carbonate crystal whisker (b).
Calcium carbonate crystal whisker composite material before being pure PLGA and the polyglycolic acid modification of 5% content of addition such as Fig. 5 and after modification
Stress-strain diagram, as seen from the figure, polyglycolic acid modification after calcium carbonate crystal whisker composite material mechanical performance it is best, draw
Stretch intensity, Young's modulus and the purer PLGA of elongation at break and it is unmodified after composite material be respectively increased 36.4%,
30.9% and 22% and 25%, 20.8% and 8.7%.
Embodiment 3
A kind of degradable bone-repairing composite material of high-intensitive and no inflammation reaction, it is approximate with implementation column 1, it makes according to the following steps
It is standby:
Firstly, 3.33 g calcium chloride and 3.18 g sodium carbonate are dissolved separately in 150 mL and 100 mL distilled water at room temperature
In.Then two kinds of solution are slowly dropped in three neck round bottom flask simultaneously under magnetic stirring, it is molten with 0.1M chloride buffer
Liquid makes the pH of mixture be maintained at 8-9, and after being added dropwise, which stirs 4 h under 80 °C with 120 r/min, then
1 h of aging, sediment are washed with distilled water three times, then with a large amount of ethanol washings, by obtained calcium carbonate crystal whisker particle 120
It is dried in vacuo under °C spare after 24 h.
It is added in 20 mL xylene solvents secondly, weighing the dried calcium carbonate crystal whisker of 2 g, is put into water removal deoxygenation
In three-necked flask, 0.002 mL Sn (Oct) is added under nitrogen protection and magnetic agitation2, which is preheating to 90 °C, so
Afterwards, after two kinds of solution dissolve respectively, monomer is molten in 10 mL xylene solvents 2 g lactides being dissolved under 120 °C
Liquid is added drop-wise to dropwise in calcium carbonate crystal whisker mixed solution, in 120 °C of lower nitrogen protections, 18 h of magnetic agitation back flow reaction.Then
Reactant is cooled to room temperature, product is centrifugated under the conditions of 5000 rpm, and it is non-grafted to wash removing with a large amount of chloroforms
Oligomer in calcium carbonate crystal whisker surface.
Finally, preparing composite material film by ultrasonic disperse and solution casting method.Detailed process is to be copolymerized PLGA
Object is dissolved in dichloromethane solvent with the concentration of 10 w/v%, then that mass fraction is brilliant for the calcium carbonate after 5 wt% modification
Palpus dry particle is added in copolymer solution, is transferred to quartz after being mixed uniformly by magnetic agitation and ultrasonication
Natural volatile dry in box, volatilizees to solvent and completes, membrane sample molding, place it under room temperature be dried under vacuum to constant weight to get
To bone-repairing composite material.
The reaction equation 2 of polylactic acid modified calcium carbonate crystal whisker is as follows:
。
Embodiment 4
A kind of degradable bone-repairing composite material of high-intensitive and no inflammation reaction, it is approximate with implementation column 1, it makes according to the following steps
It is standby:
Firstly, 3.33 g calcium chloride and 3.18 g sodium carbonate are dissolved separately in 150 mL and 100 mL distilled water at room temperature
In, then two kinds of solution are slowly dropped in three neck round bottom flask simultaneously under magnetic stirring, it is molten with 0.1M chloride buffer
Liquid makes the pH of mixture be maintained at 8-9.After being added dropwise, which stirs 4 h under 80 °C with 120 r/min, then
1 h of aging.Sediment is washed with distilled water three times, then with a large amount of ethanol washings, by obtained calcium carbonate crystal whisker particle 120
It is dried in vacuo under °C spare after 24 h.
It is added in 20 mL xylene solvents secondly, weighing the dried calcium carbonate crystal whisker of 2 g, is put into water removal deoxygenation
In three-necked flask, 0.002 mL Sn (Oct) is added under nitrogen protection and magnetic agitation2, which is preheating to 90 °C, so
Afterwards, it in 10 mL xylene solvents 1 g lactide and 1 g glycolide being dissolved under 120 °C, is dissolved respectively to two kinds of solution
Afterwards, monomer solution is added drop-wise to dropwise in calcium carbonate crystal whisker mixed solution, in 120 °C of lower nitrogen protections, magnetic agitation reflux is anti-
Answer 18 h.Then reactant is cooled to room temperature, product is centrifugated under the conditions of 5000 rpm, is washed with a large amount of chloroforms
Remove the non-grafted oligomer in calcium carbonate crystal whisker surface.
Finally, preparing composite material film by ultrasonic disperse and solution casting method.Detailed process is to be copolymerized PLGA
Object is dissolved in dichloromethane solvent with the concentration of 10 w/v%, then that mass fraction is brilliant for the calcium carbonate after 5 wt% modification
Palpus dry particle is added in copolymer solution, is transferred to quartz after being mixed uniformly by magnetic agitation and ultrasonication
Natural volatile dry in box, volatilizees to solvent and completes, membrane sample molding, place it under room temperature be dried under vacuum to constant weight to get
To bone-repairing composite material.
The reaction equation 3 that poly lactide-glycolide acid modifies calcium carbonate crystal whisker is as follows:
。
Claims (7)
1. the preparation method of the degradable bone-repairing composite material of a kind of high-intensitive and no inflammation reaction, which is characterized in that with can
Poly lactide-glycolide acid (PLGA) is degraded for matrix, using the calcium carbonate crystal whisker after modification as reinforcing agent, with oligomer
Polyester is modifying agent, by monomer ring-opening polymerization method by polyester graft on calcium carbonate crystal whisker surface, comprising the following steps:
(1) preparation of calcium carbonate crystal whisker: calcium chloride and sodium carbonate are dissolved separately in distilled water at room temperature, make calcium chloride and
The concentration ratio of sodium carbonate are as follows: 1/1 ~ 1/2, two kinds of solution are then slowly dropped to three neck round bottom flask simultaneously under magnetic stirring
In mixture, so that the pH of mixture is maintained at 8-9 with ammonium chloride buffer solution, after being added dropwise, stir the mixed solution, with
Afterwards aging, wash, be dried to obtain calcium carbonate crystal whisker (CCW) particle；
(2) surface modification of calcium carbonate crystal whisker: dried calcium carbonate crystal whisker particle is added in xylene solvent, is put into and removes
In the three-necked flask of water deoxygenation, catalyst is added under nitrogen protection and magnetic agitation, which is preheating to 90 °C, obtains carbon
Sour calcium pyroborate mixed solution；Secondly, monomer solution is obtained in the xylene solvent that polyester monocase is dissolved under 120 °C, to two kinds
After solution dissolves respectively, monomer solution is added drop-wise to dropwise in calcium carbonate crystal whisker mixed solution, monomer and calcium carbonate crystal whisker two are made
Mass ratio between person is 1/1 ~ 10/1, in 120 °C of lower nitrogen protections, 12 ~ 48 h of magnetic agitation back flow reaction；It then will be anti-
Object is answered to be cooled to room temperature, product is centrifugated under the conditions of 5000 rpm, and it is non-grafted in carbon to wash removing with a large amount of chloroforms
The oligomer on sour calcium pyroborate surface；Finally, the precipitated product isolated is dried in vacuo 24 ~ 72 h under 50 °C removes solvent；
(3) preparation of PLGA/ calcium carbonate crystal whisker composite material: composite material film passes through ultrasonic disperse and solution casting method system
Standby, detailed process is first to be dissolved in PLGA copolymer in dichloromethane solvent with the concentration of 5 ~ 20 w/v%, secondly, will add
Dosage is that the calcium carbonate crystal whisker dry particle after the modification of 1-10 wt% is added in copolymer solution, by magnetic agitation and is surpassed
Sonicated is transferred to natural volatile dry in quartzy box after being mixed uniformly, volatilize and complete to solvent, and membrane sample molding will
It, which is placed under room temperature, is dried under vacuum to constant weight to get no inflammation response type high-strength composite bone renovating material is arrived.
2. preparation method according to claim 1, it is characterised in that the structure index of the calcium carbonate crystal whisker are as follows: width
It is 1 ~ 5 μm, length is 5 ~ 50 μm, and draw ratio is 1 ~ 50.
3. preparation method according to claim 1, it is characterised in that dressing agent polyester is polylactic acid, polyglycolic acid, poly- cream
One of acid-co-glycolic acid.
4. preparation method according to claim 1, it is characterised in that the catalyst be stannous octoate, zinc, zinc oxide,
One of zinc chloride.
5. preparation method according to claim 1, which is characterized in that by 3.33 g calcium chloride and 3.18 g sodium carbonate in room
It is dissolved separately under temperature in 150 mL and 100 mL distilled water, is then under magnetic stirring slowly dropped to two kinds of solution simultaneously
In three neck round bottom flask, the pH of mixture is set to be maintained at 8-9 with 0.1M ammonium chloride buffer solution, after being added dropwise, the mixing is molten
Liquid stirs 4 h under 80 °C with 120 r/min, and subsequent 1 h of aging, sediment is washed with distilled water three times, then with a large amount of second
Obtained calcium carbonate crystal whisker particle is dried in vacuo spare after 24 h by alcohol washing under 120 °C；
It is added in 20 mL xylene solvents secondly, weighing the dried calcium carbonate crystal whisker of 2 g, is put into three mouthfuls of water removal deoxygenation
In flask, 0.002 mL Sn (Oct) is added under nitrogen protection and magnetic agitation2, which is preheating to 90 °C, secondly,
In the 10 mL xylene solvents that 2 g glycolides are dissolved under 120 °C, after two kinds of solution dissolve respectively, by monomer solution
It is added drop-wise in calcium carbonate crystal whisker mixed solution dropwise, in 120 °C of lower nitrogen protections, 18 h of magnetic agitation back flow reaction.Then will
Reactant is cooled to room temperature, and product is centrifugated under the conditions of 5000 rpm, with a large amount of chloroforms wash remove it is non-grafted in
The oligomer on calcium carbonate crystal whisker surface；
Finally, prepare composite material film by ultrasonic disperse and solution casting method, detailed process is, by PLGA copolymer, with
The concentration of 10 w/v% is dissolved in dichloromethane solvent, then that mass fraction is dry for the calcium carbonate crystal whisker after 5 wt% modification
Particle is added in copolymer solution, is transferred in quartzy box after being mixed uniformly by magnetic agitation and ultrasonication certainly
Right volatile dry volatilizees to solvent and completes, and membrane sample molding places it in and is dried under vacuum to constant weight under room temperature and repairs to get to bone
Multiple composite material.
6. the degradable bone-repairing composite material of a kind of high-intensitive and no inflammation reaction, it is characterised in that according to claim 1-5
Any the method is prepared.
7. a kind of degradable bone-repairing composite material of the reaction of high-intensitive and no inflammation according to claim 6 is in Bone Defect Repari
Application.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111437440A (en) * | 2020-04-02 | 2020-07-24 | 杭州鹿扬科技有限公司 | Controllable degradable bone implantation composite material and preparation method thereof |
| CN113663136A (en) * | 2021-09-29 | 2021-11-19 | 南京市中医院 | Degradable polymer-calcium carbonate composite bone repair material and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1944529A (en) * | 2006-10-19 | 2007-04-11 | 上海大学 | Process for preparing biologically degradable SiO2/poly lactic acid nano composite material |
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
| CN101461963A (en) * | 2009-01-07 | 2009-06-24 | 华南理工大学 | Multiplex composite bone tissue engineering bracket material capable of degrading gradiently and preparation method thereof |
| CN103059274A (en) * | 2013-01-07 | 2013-04-24 | 四川大学 | Aliphatic polyester/calcium carbonate composite material and its preparation method |
| US8936805B2 (en) * | 2005-09-09 | 2015-01-20 | Board Of Trustees Of The University Of Arkansas | Bone regeneration using biodegradable polymeric nanocomposite materials and applications of the same |
| CN104606718A (en) * | 2015-01-23 | 2015-05-13 | 上海大学 | Preparation method of composite material bionic bone scaffold containing drug carrying microsphere |
| CN106730023A (en) * | 2016-12-20 | 2017-05-31 | 上海纳米技术及应用国家工程研究中心有限公司 | A kind of polyphosphoric acids calcium is modified IPDI PCLLA PEG PCLLA porous supports and preparation and application |
| CN106963984A (en) * | 2017-03-02 | 2017-07-21 | 复旦大学 | A kind of preparation method of gelatin/carboxy apatite composite coating |
-
2018
- 2018-12-26 CN CN201811601413.XA patent/CN109568667A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8936805B2 (en) * | 2005-09-09 | 2015-01-20 | Board Of Trustees Of The University Of Arkansas | Bone regeneration using biodegradable polymeric nanocomposite materials and applications of the same |
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
| CN1944529A (en) * | 2006-10-19 | 2007-04-11 | 上海大学 | Process for preparing biologically degradable SiO2/poly lactic acid nano composite material |
| CN101461963A (en) * | 2009-01-07 | 2009-06-24 | 华南理工大学 | Multiplex composite bone tissue engineering bracket material capable of degrading gradiently and preparation method thereof |
| CN103059274A (en) * | 2013-01-07 | 2013-04-24 | 四川大学 | Aliphatic polyester/calcium carbonate composite material and its preparation method |
| CN104606718A (en) * | 2015-01-23 | 2015-05-13 | 上海大学 | Preparation method of composite material bionic bone scaffold containing drug carrying microsphere |
| CN106730023A (en) * | 2016-12-20 | 2017-05-31 | 上海纳米技术及应用国家工程研究中心有限公司 | A kind of polyphosphoric acids calcium is modified IPDI PCLLA PEG PCLLA porous supports and preparation and application |
| CN106963984A (en) * | 2017-03-02 | 2017-07-21 | 复旦大学 | A kind of preparation method of gelatin/carboxy apatite composite coating |
Non-Patent Citations (2)
| Title |
|---|
| JIELIN WANG等: "Composites of poly(L-lactide-trimethylene carbonate-glycolide) and surface modified calcium carbonate whiskers as a potential bone substitute material", 《RSC ADVANCES》 * |
| JIELIN WANG等: "Fabrication and characterization of composites composed of a bioresorbable polyester matrix and surface modified calcium carbonate whisker for bone regeneration", 《POLYMERS ADVANCED TECHNOLOGIES》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111437440A (en) * | 2020-04-02 | 2020-07-24 | 杭州鹿扬科技有限公司 | Controllable degradable bone implantation composite material and preparation method thereof |
| CN113663136A (en) * | 2021-09-29 | 2021-11-19 | 南京市中医院 | Degradable polymer-calcium carbonate composite bone repair material and preparation method thereof |
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