CN109157679A - A kind of preparation method of nanometer hydroxyapatite-chitosan artificial bone - Google Patents
A kind of preparation method of nanometer hydroxyapatite-chitosan artificial bone Download PDFInfo
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Abstract
The invention discloses a kind of nanometer hydroxyapatite-chitosan artificial bone preparation methods, specifically, the present invention is using surface-modified nano hydroxyapatite and chitosan as raw material, artificial bone is prepared by mixing, extruding pelletization, injection molding, it is modified by the surface to nanometer hydroxyapatite, the dispersibility for improving nanometer hydroxyapatite improves its binding ability with chitosan, and finally obtained artificial bone is made to have better mechanical property and hydrophily.
Description
Technical field
The invention belongs to biological medicine Material Fields, and in particular to a kind of nanometer hydroxyapatite-chitosan artificial bone
Preparation method.
Background technique
The research of biological medicine material is the emerging cross discipline to grow up in recent decades, with global aged
Change trend development and bone wound frequently occurs, Bone Defect Repari and bone alternate material are increasingly becoming the emphasis in the field.With people
Material performance requirement is stepped up, the biomaterial of single kind is difficult to meet clinical requirement, thus uses dissimilarity
The material progress of matter is compound, is the hot spot studied at present to obtain the composite biological material with excellent clinical performance.
With the continuous deepening of research, for the research of nano-hydroxyapatite/chitosan composite material have been achieved with compared with
Big progress.It was verified that nano-hydroxyapatite/chitosan system composite material can get good osteoinductive, matched
Degradation rate.Chinese patent CN102276879 A " fibrous nano-hydroxyapatite/chitosan composite material and its preparation side
Method " discloses a kind of method for preparing composite material using fibrous nano hydroxyapatite and chitosan, provides a kind of anti-
The fibrous nano-hydroxyapatite/chitosan composite material and its system that Compressive Strength is high, nanometer hydroxyapatite content is suitable
Preparation Method.
But in actual application, however it remains nanometer hydroxyapatite and chitosan interface cohesion are not satisfactory, grain
The problems such as son dispersion is uneven, bracket or artificial bone brittleness made of resulting materials be big, poor mechanical property.Therefore, people pass through
Various means improve the bonding behavior of nanometer hydroxyapatite and chitosan, and Chinese patent CN101352585 A discloses " particle
The preparation method of the nano hydroxylapatite granule/chitosan stent aligned ", the hydroapatite particles in the bracket are poly- in shell
In glycosyl body it is well dispersed and formed between chitosan it is effective, stable be bonded, and present and align, thus in structure and
Functionally realization nanometer hydroxyapatite and chitosan is effective compound.
Further, since chitosan molecule in, it is intermolecular have strong hydrogen bond association so that chitosan be in close crystalline state knot
Structure does not melt, and is also insoluble in common organic solvent, causes processing difficulties, limits its popularization and application.
Summary of the invention
The present invention provides a kind of nanometer hydroxyapatite-chitosan artificial bone preparation method, this method uses surface
Modifted-nano-hydroxyapatite and Butyrylation chitosan, improve the dispersibility of nanometer hydroxyapatite, improve the combination of the two
Ability makes finally obtained artificial bone have better mechanical property and biocompatibility.
Specifically, the present invention adopts the following technical scheme:
A kind of preparation method of nano-hydroxyapatite/chitosan artificial bone, the nano hydroxyapatite for using surface modified
For the chitosan of lime stone and Butyrylation as raw material, specific method is the nanometer hydroxyapatite and Butyrylation for taking surface modified
Chitosan is uniformly mixed, and after 100~150 DEG C are dried in vacuo 2~24 hours, through injection molding after blending extrusion, obtains artificial aggregate
Material.
Preferably, the mass ratio of the surface-modified nano hydroxyapatite and Butyrylation chitosan is 7:1~7:9.
Preferably, the main technologic parameters that the mixing squeezes out are 120~220 DEG C of processing temperature, screw speed 60~
100r/min, 3~10min of reaction time.
Preferably, the main technologic parameters of the injection-moulding step are 40~100 DEG C of mold temperature, injection pressure 40
~80MPa, 10~50MPa of dwell pressure, 8~24s of dwell time.
Preferably, the modified nanometer hydroxyapatite in the surface is poly ethyldiol modified nanometer hydroxyapatite.
Preferably, the preparation method of the modified nanometer hydroxyapatite in the surface be take concentration be 2~10% it is poly-
Nanometer hydroxyapatite is added in glycol water while stirring, 30~80 DEG C of 2~10h of insulated and stirred after addition, ultrasound
Disperse 1~5h, filtering, filter cake successively uses dehydrated alcohol, chloroform, after drying organic solvent, is dried in vacuo at 80~140 DEG C
8~40h grinds to get modifted-nano-hydroxyapatite.
It is further preferred that the polyethylene glycol used is polyethylene glycol 200, polyethylene glycol 400, Macrogol 600, poly- second
One or more of glycol 800, cetomacrogol 1000.
Preferably, the preparation method of Butyrylation chitosan is to take chitosan powder, methanesulfonic acid is added in ice-water bath, stirring makes
Chitosan is sufficiently swollen, and continues that butyric anhydride is slowly added dropwise under stirring, and after room temperature reaction 8 hours, -20 DEG C overnight, is taken out, filter
It crosses, distilled water suspends, and is 7 with ammonium hydroxide tune pH value, boils 2h, filter while hot, and ether washs, it is dried in vacuo 48h at 30~80 DEG C,
To obtain the final product.
It is further preferred that vacuum drying condition is to be dried in vacuo 48h at 60 DEG C.
The invention also discloses the artificial bone products that application this method obtains.
A kind of preparation method of nanometer hydroxyapatite-chitosan artificial bone, the nano hydroxyapatite for using surface modified
As raw material, specific method is that the nanometer hydroxyapatite for taking surface modified and the mixing of chitosan pellet are equal for lime stone and chitosan
Even, after 100~150 DEG C are dried in vacuo 2~24 hours, extruding pelletization, after gained pellet is vacuum dried, injection molding is required
Shape.
Preferably, the mass ratio of the modified nanometer hydroxyapatite in the surface and chitosan is 7:1~7:9.
Preferably, the main technologic parameters of the extruding pelletization step are 120~220 DEG C of extruder temperature, extrusion output
3.0~6.0kg/h.
Preferably, particle is dried in vacuo 5~15 hours at 60~110 DEG C after extrusion.
Preferably, the main technologic parameters of the injection-moulding step are 40~100 DEG C of mold temperature, melt temperature 200
~280 DEG C, 0.2~1.5s of filling time, dwell pressure (filling percentage) 50~110%, 3~15s of dwell time, when cooling
Between 3~15s.
Preferably, the modified nanometer hydroxyapatite in the surface is poly ethyldiol modified nanometer hydroxyapatite.
Preferably, the preparation method of the modified nanometer hydroxyapatite in the surface is that take concentration be 2~10% poly- second
Nanometer hydroxyapatite is added in two alcohol solutions while stirring, 30~80 DEG C of 2~10h of insulated and stirred after addition, ultrasound point
1~5h is dissipated, filtering, filter cake successively uses dehydrated alcohol, chloroform, after drying organic solvent, is dried in vacuo 8 at 80~140 DEG C
~40h grinds to get modifted-nano-hydroxyapatite.
It is further preferred that the polyethylene glycol used is polyethylene glycol 200, polyethylene glycol 400, Macrogol 600, poly- second
One of glycol 800, cetomacrogol 1000.
By above technical solution, compared with prior art, the present invention having following outstanding feature:
1. the present invention, as raw material, is modified by surface using surface-modified nano hydroxyapatite, makes nano hydroxyapatite
The dispersibility of lime stone is significantly improved, and nanometer hydroxyapatite is made to have good dispersed in chitosan basal body
State, the two are capable of forming stable bonding state, conducive to the mechanical property and biocompatibility of artificial bone.
2. the present invention uses Butyrylation chitosan, there is certain liquid crystal liquid crystal property and good processing performance, be further ensured that
The interface binding power of nanometer hydroxyapatite and chitosan.
3. the present invention prepares artificial bone using the technique that mixing squeezes out injection molding, preparation process is simple, and technological parameter can
Control is suitable for industrial mass production, meanwhile, the method that the present invention takes can prepare the artificial bone of specific shape as needed.
Specific embodiment
Combined with specific embodiments below, the present invention is further illustrated.It should be noted that in following embodiment
Specific embodiment can not limit the invention.
In following embodiment, unless otherwise specified, the reagent being related to can be obtained from commodity channel.
The preparation of 1 nanometer hydroxyapatite of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 600 is configured to 5% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 55 DEG C insulated and stirred 6 hours, then ultrasonic disperse 3 hours, filtering, filter cake is successively
After dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 24 hours at 100 DEG C, grinding is modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 60 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:3 in mass ratio is uniformly mixed,
It after being dried in vacuo 8 hours at 110 DEG C, is added in extruder, sets 160 DEG C of processing temperature, screw speed 80r/min, instead
5min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
80 DEG C of temperature, injection pressure 60MPa, dwell pressure 30MPa, dwell time 15s.Material is added according to pre-set shape
Work is to get product.
The preparation of 2 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 800 is configured to 5% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 60 DEG C insulated and stirred 6 hours, then ultrasonic disperse 3.5 hours, filtering, filter cake according to
It is secondary to be dried organic solvent with after dehydrated alcohol, chloroform, be dried in vacuo 24 hours at 90 DEG C, it grinds modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 30 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 2:1 in mass ratio is uniformly mixed,
It after being dried in vacuo 8 hours at 110 DEG C, is added in extruder, sets 180 DEG C of processing temperature, screw speed 75r/min, instead
6min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
Temperature 70 C, injection pressure 70MPa, dwell pressure 40MPa, dwell time 10s.Material is added according to pre-set shape
Work is to get product.
The preparation of 3 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 1000 is configured to 10% aqueous solution, stirring
Lower addition nanometer hydroxyapatite, after adding, in 80 DEG C insulated and stirred 10 hours, then ultrasonic disperse 3 hours, filtering, filter cake
Successively with after dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 40 hours at 140 DEG C, is ground to get surface
Modifted-nano-hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 80 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:9 in mass ratio is uniformly mixed,
It after being dried in vacuo 24 hours at 150 DEG C, is added in extruder, sets 220 DEG C of processing temperature, screw speed 100r/min,
Reaction time 10min.
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
100 DEG C of temperature, injection pressure 80MPa, dwell pressure 50MPa, dwell time 24s.Material is carried out according to pre-set shape
Processing is to get product.
The preparation of 4 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 200 is configured to 3% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 30 DEG C insulated and stirred 10 hours, then ultrasonic disperse 5 hours, filtering, filter cake according to
It is secondary to be dried organic solvent with after dehydrated alcohol, chloroform, be dried in vacuo 8 hours at 80 DEG C, it grinds modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 30 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:1 in mass ratio is uniformly mixed,
It after being dried in vacuo 2 hours at 100 DEG C, is added in extruder, sets 120 DEG C of processing temperature, screw speed 60r/min, instead
3min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
40 DEG C of temperature, injection pressure 40MPa, dwell pressure 10MPa, dwell time 8s.Material is added according to pre-set shape
Work is to get product.
The preparation of 5 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 600 is configured to 8% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 65 DEG C insulated and stirred 6 hours, then ultrasonic disperse 2 hours, filtering, filter cake is successively
After dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 18 hours at 110 DEG C, grinding is modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 55 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:4 in mass ratio is uniformly mixed,
It after being dried in vacuo 8 hours at 100 DEG C, is added in extruder, sets 160 DEG C of processing temperature, screw speed 90r/min, instead
10min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
80 DEG C of temperature, injection pressure 60MPa, dwell pressure 40MPa, dwell time 10s.Material is added according to pre-set shape
Work is to get product.
The preparation of 6 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 400 is configured to 6% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 55 DEG C insulated and stirred 6 hours, then ultrasonic disperse 3 hours, filtering, filter cake is successively
After dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 36 hours at 95 DEG C, grinding is received to get surface modification
Rice hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 55 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 1:1 in mass ratio is uniformly mixed,
It after being dried in vacuo 8 hours at 110 DEG C, is added in extruder, sets 180 DEG C of processing temperature, screw speed 90r/min, instead
6min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
Temperature 50 C, injection pressure 60MPa, dwell pressure 30MPa, dwell time 20s.Material is added according to pre-set shape
Work is to get product.
The preparation of 7 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 800 is configured to 8% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 75 DEG C insulated and stirred 7 hours, then ultrasonic disperse 4 hours, filtering, filter cake is successively
After dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 16 hours at 100 DEG C, grinding is modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 40 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:8 in mass ratio is uniformly mixed,
It after being dried in vacuo 8 hours at 100 DEG C, is added in extruder, sets 150 DEG C of processing temperature, screw speed 60r/min, instead
8min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
Temperature 60 C, injection pressure 75MPa, dwell pressure 45MPa, dwell time 18s.Material is added according to pre-set shape
Work is to get product.
The preparation of 8 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 600 is configured to 5% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 45 DEG C insulated and stirred 8 hours, then ultrasonic disperse 4 hours, filtering, filter cake is successively
After dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 24 hours at 100 DEG C, grinding is modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 55 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:2 in mass ratio is uniformly mixed,
It after being dried in vacuo 7 hours at 110 DEG C, is added in extruder, sets 1500 DEG C of processing temperature, screw speed 75r/min, instead
4min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
Temperature 60 C, injection pressure 50MPa, dwell pressure 30MPa, dwell time 15s.Material is added according to pre-set shape
Work is to get product.
The preparation of 9 nanometer hydroxyapatites of embodiment-chitosan artificial bone
1. preparing the modified nanometer hydroxyapatite in surface.Taking polyethylene glycol 800 is configured to 4% aqueous solution, under stirring
Nanometer hydroxyapatite is added, after adding, in 65 DEG C insulated and stirred 8 hours, then ultrasonic disperse 3 hours, filtering, filter cake is successively
After dehydrated alcohol, chloroform, organic solvent is dried, is dried in vacuo 18 hours at 100 DEG C, grinding is modified to get surface
Nanometer hydroxyapatite.
2. preparing Butyrylation chitosan.Chitosan powder is taken, methanesulfonic acid is added in ice-water bath, stirring keeps chitosan sufficiently molten
It is swollen, continue that butyric anhydride is slowly added dropwise under stirring, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, filtration, and distilled water is outstanding
It is floating, be 7 with ammonium hydroxide tune pH value, boil 2h, filter while hot, ether washing, at 80 DEG C vacuum drying 48h to get.
3. mixing squeezes out.Surface-modified nano hydroxyapatite and butyrylchitosan are taken, 7:3 in mass ratio is uniformly mixed,
It after being dried in vacuo 10 hours at 120 DEG C, is added in extruder, sets 150 DEG C of processing temperature, screw speed 85r/min, instead
8min. between seasonable
4. injection molding.It squeezes out obtained material to be added in automatic injection machine, injection molding machine running parameter is set are as follows: mold
65 DEG C of temperature, injection pressure 45MPa, dwell pressure 45MPa, dwell time 18s.Material is added according to pre-set shape
Work is to get product.
The preparation of comparative example nano hydroxylapatite granule/chitosan stent
This comparative example refers to the Chinese patent CN101352585 A " nano-hydroxyapatite/chitosan of particle direction-arrangement
Embodiment 1 in the preparation method of bracket " specification, specifically:
Step 1: the preparation of nano hydroxyapatite colloidal sols
(1) with polyvinylpyrrolidone (PVP K15) simultaneously for template, dispersing agent, modifying agent；
(2) using deionized water prepare 0.01mol/L containing calcium nitrate, the solution of diammonium hydrogen phosphate 0.006mol/L, then
0.1gPVP K15 is added in above-mentioned calcium nitrate solution and is sufficiently dissolved；
(3) use 100 revs/min of high speed disperser, under the conditions of ammonium hydroxide control system pH value is 10.6, by above-mentioned (1),
(2) material is sufficiently mixed, and is formed nanometer hydroxyapatite (HA) colloidal sol, is made in the nano hydroxyapatite colloidal sols system
Calcium phosphorus molar ratio is up to 1.6: 1, and polyvinyl pyrrolidone content is 0.01% by mass percentage；
Step 2: the ageing of nano hydroxyapatite colloidal sols
Above-mentioned nano hydroxyapatite colloidal sols 20 DEG C at a temperature of, naturally place ageing 24 hours, then use deionization
Water sufficiently washs colloidal sol and obtains the nano hydroxyapatite colloidal sols of particle direction-arrangement；
Step 3: the molding of nano hydroxylapatite granule/chitosan stent
(1) with mass percent concentration be 2% acetum prepare mass percent be 1% chitosan solution；
(2) high speed disperser for using 100 revs/min of speed, according to nano hydroxyapatite colloidal sols: chitosan solute
The nano hydroxyapatite colloidal sols of chitosan solution and step 2 are sufficiently mixed by the ratio that mass ratio is 9: 1, obtain a nanometer hydroxyl
Base apatite/chitosan mixed liquor；
(3) mixed liquor of nano-hydroxyapatite/chitosan is stood to injection model after removing bubble, is placed in -5 DEG C super
Freezed 24 hours in low temperature refrigerator, be then transferred in freeze drier be freeze-dried 24 hours to get to nanometer hydroxyapatite/
Chitosan stent；
Step 4: the post-processing of nano hydroxylapatite granule/chitosan stent
(1) ammonium hydroxide that nano hydroxylapatite granule/chitosan stent mass percent concentration is 0.5% is impregnated 1 first
Hour, it is then impregnated 3 hours with deionized water again, changes a water every half an hour；
(2) timbering material after cleaning is put back into model, be placed again into after being freezed 24 hours in -5 DEG C of ultra low temperature freezer
It is transferred in freeze drier and is freeze-dried 24 hours again, finally obtain the nano-hydroxyapatite/chitosan of particle direction-arrangement
Bracket.
1 artificial bone Mechanics Performance Testing of test example
Artificial bone or bracket prepared by the method for taking the embodiment of the present invention 1, embodiment 2 and comparative example is adopted as sample
It is surveyed with three-point bending resistance method with universal testing machine measurement artificial bone/timbering material tensile strength, bending strength and elasticity modulus
The span that examination is given directions is 25mm, loading speed 5.00mm/min.It the results are shown in Table 1.
1 mechanical experimental results table (n=10) of table
Seen from table 1, the artificial bone of method disclosed by the invention preparation has a preferable mechanical property, and according to data,
The elasticity modulus of skeleton is 17-18.9GPa, bending strength 160MPa, and artificial bone prepared by the present invention is extremely close
This data.
The test of 2 hydrophily of test example
Artificial bone or bracket prepared by the method for taking the embodiment of the present invention 1, embodiment 2 and comparative example makes as sample
Water and sample and the contact angle compareed are measured with contact angle tester, to evaluate the hydrophily of sample.
The results show that the contact angle of embodiment 1, the obtained artificial bone of embodiment 2 is respectively 45.3 ° and 47.2 °, control
I.e. the contact angle determination result of the artificial bone of comparative example is 68.4 °.
The hydrophily of biomaterial to cell sticking on the surface of the material, be proliferated, differentiation capability has great influence, be body
The important indicator of biocompatibility is evaluated in outer experiment.Contact angle is also known as hydrophilic angle, refers in gas, liquid, solid three-phase intersection point place
Angle theta of the tangent line of the liquid-vapor interface of work across liquid and solid-liquid boundary line, is the measurement to material hydrophilic performance.This
Test the result shows that method provided by the invention significantly improves nanometer hydroxyapatite-chitosan material hydrophily, can
To infer that artificial bone has preferable biocompatibility.
3 cell in vitro biocompatibility test of test example
Utilize the cell biological compatibility of mouse embryo stem cell detection artificial bone.Main experimental material and step are such as
Under:
1. cell secondary culture: it takes C57 mouse embryo stem cell (MESCs) 2nd generation passage cell to suspend and cultivates 5d, warp
Single cell suspension is made after 0.05% pancreatin+0.02%EDTA digestion, it is spare.
2. artificial bone prepares: the artificial bone of the method for the embodiment of the present invention 1, embodiment 2 and comparative example preparation or
Thick 0.2cm is made in bracket, and the square sheet of wide 0.5cm cleans 45min under distilled water ultrasound, and it is dry to be put into drying box
For 24 hours, autoclave sterilization is spare.3. the single cell suspension in step 1 is divided into test group, blank group, control group, wherein testing
The artificial bone that group is prepared with embodiment 1, embodiment 2 is mixed, and the artificial bone of control group and comparative example preparation is mixed, empty
MESCs cell is cultivated merely in white group of continuation.Cell-proliferation activity is detected respectively at the 2nd, 4,6,8 day row mtt assay.Select 490nm
Wavelength detects OD value with enzyme-linked immunosorbent assay instrument.
4. test result:
The proliferative conditions of mtt assay detection MESCs cell the results are shown in Table 2 in culture period.
2 mtt assay of table detect MESCs cell proliferation results (N=5)
| Group | 2d | 4d | 6d | 8d* |
| Test group 1 (embodiment 1) | 0.192±0.026 | 0.401±0.029* | 0.465±0.033* | 0.565±0.027** |
| Test group 2 (embodiment 2) | 0.194±0.018 | 0.405±0.022 | 0.458±0.042* | 0.566±0.032* |
| Control group | 0.191±0.020 | 0.389±0.031 | 0.449±0.018* | 0.534±0.016 |
| Blank group | 0.192±0.013 | 0.392±0.017 | 0.428±0.034 | 0.507±0.042 |
Note: * indicate compared to the blank group, P < 0.05；* indicates the P < 0.01 compared with blank group.
By upper table result it is found that experimental group, control group are compared with blank group, cell proliferative conditions cultivate early stage nothing in adherency
Significant difference shows that artificial bone of the invention does not generate adverse effect to MESCs proliferation in adherency culture early stage；Viscous
Attached late stage of culture, experimental group cell Proliferation data are apparently higher than control group and blank group, show later period artificial aggregate of the invention
Material has facilitation to MESCs proliferation.Result above prompt, artificial bone of the invention have good cell biological
Compatibility, cell proliferation are free of toxic effects.
Claims (10)
1. a kind of preparation method of nano-hydroxyapatite/chitosan artificial bone, the nano-hydroxy-apatite for using surface modified
For the chitosan of stone and Butyrylation as raw material, specific method is the nanometer hydroxyapatite for taking surface modified and the shell of Butyrylation
Glycan is uniformly mixed, and after 100~150 DEG C are dried in vacuo 2~24 hours, through injection molding after blending extrusion, obtains artificial bone.
2. the preparation method of artificial bone as described in claim 1, which is characterized in that the surface-modified nano hydroxyapatite
Mass ratio with Butyrylation chitosan is 7:1~7:9.
3. the preparation method of artificial bone as described in claim 1, which is characterized in that the main technologic parameters that the mixing squeezes out
For, 120~220 DEG C of processing temperature, 60~100r/min of screw speed, 3~10min of reaction time.
4. the preparation method of artificial bone as described in claim 1, which is characterized in that the main technique of the injection-moulding step
Parameter is 40~100 DEG C of mold temperature, 40~80MPa of injection pressure, 10~50MPa of dwell pressure, 8~24s of dwell time.
5. the preparation method of artificial bone as described in claim 1, which is characterized in that the modified nano-hydroxy-apatite in the surface
Stone is poly ethyldiol modified nanometer hydroxyapatite.
6. the preparation method of artificial bone as described in claim 1, which is characterized in that the modified nano-hydroxy-apatite in the surface
Preparation Method made of stones is to take concentration for 2~10% Aqueous Solutions of Polyethylene Glycol, and nanometer hydroxyapatite is added while stirring, is added
After 30~80 DEG C of 2~10h of insulated and stirred, 1~5h of ultrasonic disperse, filtering, filter cake successively uses dehydrated alcohol, chloroform,
After drying organic solvent, it is dried in vacuo 8~40h at 80~140 DEG C, grinds to get modifted-nano-hydroxyapatite.
7. the preparation method of artificial bone as claimed in claim 6, which is characterized in that the polyethylene glycol be polyethylene glycol 200,
One or more of polyethylene glycol 400, Macrogol 600, polyethylene glycol-800, cetomacrogol 1000.
8. the preparation method of artificial bone as described in claim 1, which is characterized in that the Butyrylation method for preparing chitosan
To take chitosan powder, methanesulfonic acid being added in ice-water bath, stirring is swollen chitosan sufficiently, continues to be slowly added dropwise under stirring
Butyric anhydride, after room temperature reaction 8 hours, -20 DEG C are overnight, take out, and filtration, distilled water suspends, and are 7 with ammonium hydroxide tune pH value, boil 2h,
Filter while hot, ether washing, at 30~80 DEG C vacuum drying 48h to get.
9. the preparation method of artificial bone as claimed in claim 8, which is characterized in that vacuum drying condition is vacuum at 60 DEG C
Dry 48h.
10. a kind of product that the preparation method of -9 described in any item artificial bones according to claim 1 obtains.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115678117A (en) * | 2022-12-16 | 2023-02-03 | 湖南师范大学 | Preparation method of sisal fiber reinforced nano hydroxyapatite/chitosan composite material |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19852027A1 (en) * | 1998-11-11 | 2000-05-18 | Fraunhofer Ges Forschung | Process for the production of a thermoplastically processable compound material from natural polymers |
| US20030040695A1 (en) * | 2001-03-16 | 2003-02-27 | The Procter & Gamble Company | Flushable tampon applicators |
| WO2006034128A8 (en) * | 2004-09-17 | 2006-06-15 | Angiotech Biomaterials Corp | Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use |
| CN101209355A (en) * | 2007-12-25 | 2008-07-02 | 暨南大学 | Preparation of material for bone plate, bone peg and bone block |
| CN101352585A (en) * | 2008-07-31 | 2009-01-28 | 华南理工大学 | Method for preparing directionally arranged nano hydroxylapatite granule/chitosan stent |
| CN101376038A (en) * | 2008-10-07 | 2009-03-04 | 浙江大学 | Method for preparing composite bone repair stent material containing chitosan and hydroxylapatite |
| CN102120871A (en) * | 2011-03-22 | 2011-07-13 | 暨南大学 | Preparation method of chitosan fiber reinforced polylactic acid composite material |
| CN102153713A (en) * | 2010-12-03 | 2011-08-17 | 北京化工大学 | Photopolymeric composite material containing polyethylene glycol grafted hydroxyapatite and preparation method thereof |
| CN103980386A (en) * | 2014-05-07 | 2014-08-13 | 中国海洋大学 | Acylated chitin fiber and preparation method thereof, and application of acylated chitin fiber in preparation of surgical suture |
| CN106147164A (en) * | 2015-04-23 | 2016-11-23 | 上海微创医疗器械（集团）有限公司 | A kind of medical composite material and preparation method thereof |
-
2018
- 2018-10-26 CN CN201811261850.1A patent/CN109157679B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19852027A1 (en) * | 1998-11-11 | 2000-05-18 | Fraunhofer Ges Forschung | Process for the production of a thermoplastically processable compound material from natural polymers |
| US20030040695A1 (en) * | 2001-03-16 | 2003-02-27 | The Procter & Gamble Company | Flushable tampon applicators |
| WO2006034128A8 (en) * | 2004-09-17 | 2006-06-15 | Angiotech Biomaterials Corp | Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use |
| CN101209355A (en) * | 2007-12-25 | 2008-07-02 | 暨南大学 | Preparation of material for bone plate, bone peg and bone block |
| CN101352585A (en) * | 2008-07-31 | 2009-01-28 | 华南理工大学 | Method for preparing directionally arranged nano hydroxylapatite granule/chitosan stent |
| CN101376038A (en) * | 2008-10-07 | 2009-03-04 | 浙江大学 | Method for preparing composite bone repair stent material containing chitosan and hydroxylapatite |
| CN102153713A (en) * | 2010-12-03 | 2011-08-17 | 北京化工大学 | Photopolymeric composite material containing polyethylene glycol grafted hydroxyapatite and preparation method thereof |
| CN102120871A (en) * | 2011-03-22 | 2011-07-13 | 暨南大学 | Preparation method of chitosan fiber reinforced polylactic acid composite material |
| CN103980386A (en) * | 2014-05-07 | 2014-08-13 | 中国海洋大学 | Acylated chitin fiber and preparation method thereof, and application of acylated chitin fiber in preparation of surgical suture |
| CN106147164A (en) * | 2015-04-23 | 2016-11-23 | 上海微创医疗器械（集团）有限公司 | A kind of medical composite material and preparation method thereof |
Non-Patent Citations (7)
| Title |
|---|
| CORRELO, VM等: "Water absorption and degradation characteristics of chitosan-based polyesters and hydroxyapatite composites", 《MACROMOLECULAR BIOSCIENCE》 * |
| MOHAMMAD SHAKIR等: "Synthesis and characterization of a nano-hydroxyapatite/chitosan/polyethylene glycol nanocomposite for bone tissue engineering", 《POLYMERS FOR ADVANCED TECHNOLOGIES》 * |
| 刘宾元等: "丁酰化壳聚糖的制备及结构性能表征", 《高分子材料科学与工程》 * |
| 唐文琼等: "基于壳聚糖的先进材料Ⅲ.生物组织修复和其它领域", 《纤维素科学与技术》 * |
| 孙凯莹等: "纳米羟基磷灰石-壳聚糖复合材料对细胞粘附的影响", 《临床口腔医学杂志》 * |
| 尚可超: "《金工实习教程》", 31 August 2016, 西北：西北工业大学出版社 * |
| 庞桂花等: "纳米羟基磷灰石的制备及改性", 《中国组织工程研究》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115678117A (en) * | 2022-12-16 | 2023-02-03 | 湖南师范大学 | Preparation method of sisal fiber reinforced nano hydroxyapatite/chitosan composite material |
| CN115678117B (en) * | 2022-12-16 | 2023-09-19 | 湖南师范大学 | Preparation method of sisal fiber reinforced nano hydroxyapatite/chitosan composite material |
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