CN106512101A - Method for preparing bone tissue engineering scaffold with dual-mode pore structure by utilizing supercritical fluid technique - Google Patents
Method for preparing bone tissue engineering scaffold with dual-mode pore structure by utilizing supercritical fluid technique Download PDFInfo
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- CN106512101A CN106512101A CN201610969582.3A CN201610969582A CN106512101A CN 106512101 A CN106512101 A CN 106512101A CN 201610969582 A CN201610969582 A CN 201610969582A CN 106512101 A CN106512101 A CN 106512101A
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- tissue engineering
- bone tissue
- pore structure
- supercritical fluid
- engineering scaffold
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- 238000000034 method Methods 0.000 title claims abstract description 39
- 239000011148 porous material Substances 0.000 title claims abstract description 37
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 33
- 239000012530 fluid Substances 0.000 title claims abstract description 23
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 9
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims abstract description 9
- 238000004945 emulsification Methods 0.000 claims abstract description 8
- 239000004408 titanium dioxide Substances 0.000 claims abstract description 8
- 239000002105 nanoparticle Substances 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims abstract description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- 230000002902 bimodal effect Effects 0.000 claims description 27
- 229920000642 polymer Polymers 0.000 claims description 27
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 23
- 229920001577 copolymer Polymers 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 18
- 239000001569 carbon dioxide Substances 0.000 claims description 15
- 238000001816 cooling Methods 0.000 claims description 9
- 239000003995 emulsifying agent Substances 0.000 claims description 9
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 238000005119 centrifugation Methods 0.000 claims description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 229910000831 Steel Inorganic materials 0.000 claims description 6
- 238000005485 electric heating Methods 0.000 claims description 6
- 239000010959 steel Substances 0.000 claims description 6
- 238000009792 diffusion process Methods 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 4
- 238000011067 equilibration Methods 0.000 claims description 4
- 229920000954 Polyglycolide Polymers 0.000 claims description 3
- 239000004633 polyglycolic acid Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 239000004005 microsphere Substances 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 4
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 abstract 1
- 239000002808 molecular sieve Substances 0.000 abstract 1
- 239000002667 nucleating agent Substances 0.000 abstract 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 abstract 1
- 238000000935 solvent evaporation Methods 0.000 abstract 1
- 229910052719 titanium Inorganic materials 0.000 abstract 1
- 239000010936 titanium Substances 0.000 abstract 1
- 229960004424 carbon dioxide Drugs 0.000 description 13
- 238000005187 foaming Methods 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 210000000481 breast Anatomy 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910002090 carbon oxide Inorganic materials 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000009477 glass transition Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000006911 nucleation Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000005325 percolation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- 238000010146 3D printing Methods 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- HGWOWDFNMKCVLG-UHFFFAOYSA-N [O--].[O--].[Ti+4].[Ti+4] Chemical compound [O--].[O--].[Ti+4].[Ti+4] HGWOWDFNMKCVLG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000006261 foam material Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000001582 osteoblastic effect Effects 0.000 description 1
- 230000000278 osteoconductive effect Effects 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229920000307 polymer substrate Polymers 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
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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
-
- 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
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
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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
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- General Health & Medical Sciences (AREA)
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- Oral & Maxillofacial Surgery (AREA)
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Abstract
The invention discloses a method for preparing a bone tissue engineering scaffold with a dual-mode pore structure by utilizing a supercritical fluid technique. Polymeric microspheres synthetized by pre-adopting an emulsification/solvent evaporation method and submicron-scale or nanoscale particles (for example, hydroxyapatite, titanium silicalite molecular sieves or titanium dioxide) serving as a nucleating agent are mixed in advance, a cylindrical sheet is formed after the mixture is tableted and is put in a high-pressure kettle, pressure maintaining is performed under certain temperature and certain pressure for a period of time, and pressure release is performed at a certain pressure releasing rate to form the bone tissue engineering scaffold with the dual-mode pore structure. According to the method, the operating conditions are mild, the operating process is simple, the process is stable, no residual organic solvent is left, and the method can be used for preparation of the bone tissue engineering scaffold.
Description
Technical field
The present invention relates to a kind of method for preparing bimodal pore structure bone tissue engineering scaffold based on supercritical fluid technique.
Background technology
Tissue engineering bracket is one of three elements of organizational project, in order to meet sticking, breed and breaking up for cell, favorably
In the transmission and the discharge of metabolite of nutriment, tissue engineering bracket is needed with double mode pore-size distribution, higher
Porosity and suitable mechanical strength (The Journal of Supercritical Fluids, 2012,69：97-107).Tool
There is the bone tissue engineering scaffold of bimodal pore structure, wherein should be big for the propagation of osteocyte, growth and the macropore diameter for breaking up
In 100 μm, and be used for nutriment transmission small aperture should between 1～50 μm (Biotechnology and
Bioengineering, 2011,108：963-976；Biomaterials, 2005,26：5474-91).It is full in order to prepare
The bone tissue engineering scaffold with bimodal pore structure that foot is required, selects suitable preparation method just to become extremely important.
The preparation method of support mainly has solvent cast/particle percolation, phase separation method, 3D printing, fusion-cast/particle
Leaching etc. (Current Opinion in Solid State and Materials Science, 2004,8:313-321).
Although these methods can prepare interconnected pore rate height and the larger support in aperture, but need using substantial amounts of organic solvent
Or operate at high temperature, it is unfavorable for the load of biotic factor in organizational project.Supercritical fluid foaming, it is particularly overcritical
Blown with carbon dioxide method, it is because which can avoid the use of organic solvent and high temperature, of increased attention.Overcritical two
Plastication of the carbonoxide foaming due to supercritical carbon dioxide to polymer, the glass transition temperature of polymer and melting
Temperature drop, so as to the blowing temperature of polymer can be substantially reduced so that supercritical carbon dioxide foaming can be in relatively low temperature
Degree is carried out.Supercritical carbon dioxide foaming process include carbon dioxide diffusion dissolution enter polymer substrate it is internal, overcritical two
Plastication of the carbonoxide to polymer reduces carbon dioxide during glass transition temperature and melt temperature, the pressure release of polymer
Supersaturation causes a large amount of gas cores to produce and grow, and final polymer solidification obtains the material with loose structure
(Biomaterials, 1996,17：1417-1422).
Nucleator is added in foaming process, more gas cores can be formed with the nucleation behavior of efficient hardening foaming process,
Under different pressure release speed, gas nucleus growth forms the pore structure of various modes.Prepared using supercritical fluid foaming and had
Orifice size (1～10 μm) and high-density cellular (109～1012cells/cm3) microcellular foam material during, relate to
The use of nucleator.Calcium stearate, talcum, zinc stearate, Sodium Benzoate, stearic acid, magnesium silicate and rubber grain etc. can use
Make nucleator in supercritical fluid foaming process (Journal of Applied Polymer Science, 2008,108：
3997-4003)。
Nucleator is also needed to meet certain requirement for preparing tissue engineering bracket, or is easy to remove, or nucleator
Presence to cell stick, grow and break up unrestraint effect, if having certain facilitation more preferably.Such as titanium dioxide
Titanium can prepare the nucleator of tissue engineering bracket as supercritical fluid method, it can not only strengthen it is osteoblastic stick, also
Can induce cell growth in living tissue (ACS Applied Materials＆Interfaces, 2014,6：16918-
16931)；Hydroxyapatite has good biocompatibility, can provide matrix for the deposition of new bone, with certain osteoconductive
(Biotechnology and Bioengineering, 2015,112：801-810)；Tricalcium phosphate has good biofacies
Capacitive and degradability, while conductibility (the Journal of Biomedical of bone can be increased with the stable tricalcium phosphate of silicon
Materials Research Part A, 2008,85:301-312).If by the sub-micron or nanoparticle of biocompatibility
Be used for supercritical carbon dioxide foaming process as nucleator, then the generation of a large amount of gas cores and the merging in hole when being conducive to pressure release,
Rupture, it is easy to form the tissue engineering bracket with Bimodal pore structure.During supercritical carbon dioxide foaming, foaming
Temperature, pressure, equilibration time and pressure release speed all can have different degrees of impact to the pore structure of support, therefore by regulation
Operating parameter is stated, the tissue engineering bracket with Different Pore Structures is prepared, is had great importance.
The content of the invention
It is an object of the invention to provide a kind of bone tissue engineer that bimodal pore structure is prepared based on supercritical fluid technique
The method of support.
A kind of method that bimodal pore structure bone tissue engineering scaffold is prepared based on supercritical fluid technique, including following step
Suddenly：
1) raw polymer is dissolved in organic solution, is then added in the aqueous solution of emulsifying agent, high-speed stirred 1～
3 minutes, the solution of emulsification is formed, volatilize at 30 DEG C, polymer microballoon is collected by centrifugation；
2) polymer microballoon is mixed with nucleator, takes mixture compressing tablet, obtains cylinder thin slice；
3) cylinder thin slice is put in the autoclave of supercritical fluid foamed system, titanium dioxide is passed through in autoclave
Carbon, under conditions of 35～70 DEG C of temperature, 6～20MPa of pressure and equilibration time were more than 30 minutes, carbon dioxide diffusion dissolution enters
Enter in polymer；Pressure release is carried out with the pressure release speed of 0.1～20MPa/min, as carbon dioxide is diffused out from polymer,
Obtain the bone tissue engineering scaffold with bimodal pore structure；
The supercritical fluid foamed system includes CO2Steel cylinder, hand-operated valve, check valve, heat exchanger, flowmeter, high pressure
Pump, cooling bath, heat exchanger, pressure gauge, controllable electric heating jacket, autoclave and relief valve；CO2It is steel cylinder and hand-operated valve, unidirectional
Valve, the tube side of heat exchanger, flowmeter, high-pressure pump, heat exchanger, autoclave, relief valve are sequentially connected, the shell of heat exchanger
Journey, cooling bath, high-pressure pump constitute cooling circuit, and controllable electric heating jacket is provided with around autoclave, and autoclave is connected with pressure gauge.
Preferably, described polymer is PLA, polyglycolic acid and lactic acid-ethanol copolymer.
Preferably, described organic solvent is dichloromethane or chloroform；Emulsifying agent is polyvinyl alcohol；Emulsifying agent is water-soluble
Liquid concentration is 0.5%～2% (w/w), and volumetric usage is 10～50 times of organic solvent.
Preferably, described nucleator consumption for polymer 1%～20%.
Preferably, described nucleator is submicron order or nano-scale particle, described submicron order or nano-scale particle
For one or more in hydroxyapatite, HTS or titanium dioxide.
The present invention utilizes super critical CO 2 technology, and various nucleators can be adopted to prepare with bimodal pore structure
Bone tissue engineering scaffold, to solve the problems, such as that existing bone tissue engineering scaffold preparation method is related to high temperature or organic solvent.From
The nucleator not only ability with nucleation in foaming process, and there is good biocompatibility and biologically active, have
The sticking, breed and breaking up on tissue engineering bracket beneficial to cell, and need not remove after expanding.Therefore, with traditional
Grain percolation is compared, in supercritical CO2Adding nucleator in foaming process not only operates simpler, operating condition gentle, a step
The support with double mode pore-size distribution is prepared, and if selecting bioactivator effectively can strengthen as nucleator
The function of support, makes support have good biologically active.
Description of the drawings
Fig. 1 is supercritical fluid foamed system structural representation；
Fig. 2 shows for the electron scanning of bone tissue engineering scaffold prepared under the pressure release speed of 14MPa/min in embodiment 1
Micro mirror photo；
Fig. 3 shows for the electron scanning of bone tissue engineering scaffold prepared under the pressure release speed of 1MPa/min in embodiment 1
Micro mirror photo.
Specific embodiment
A kind of method that bimodal pore structure bone tissue engineering scaffold is prepared based on supercritical fluid technique, including following step
Suddenly：
1) raw polymer is dissolved in organic solution, is then added in the aqueous solution of emulsifying agent, high-speed stirred 1～
3 minutes, the solution of emulsification is formed, volatilize at 30 DEG C, polymer microballoon is collected by centrifugation；
2) polymer microballoon is mixed with nucleator, takes mixture compressing tablet, obtains cylinder thin slice；
3) cylinder thin slice is put in the autoclave of supercritical fluid foamed system, titanium dioxide is passed through in autoclave
Carbon, under conditions of 35～70 DEG C of temperature, 6～20MPa of pressure and equilibration time were more than 30 minutes, carbon dioxide diffusion dissolution enters
Enter in polymer；Pressure release is carried out with the pressure release speed of 0.1～20MPa/min, as carbon dioxide is diffused out from polymer,
Obtain the bone tissue engineering scaffold with bimodal pore structure；
As described in Figure 1, the supercritical fluid foamed system includes CO2Steel cylinder 1, hand-operated valve 2, check valve 3, heat exchanger
4th, flowmeter 5, high-pressure pump 6, cooling bath 7, heat exchanger 8, pressure gauge 9, controllable electric heating jacket 10, autoclave 11 and relief valve
12；CO2Steel cylinder 1 and hand-operated valve 2, check valve 3, the tube side of heat exchanger 4, flowmeter 5, high-pressure pump 6, heat exchanger 8, autoclave
11st, relief valve 12 is sequentially connected, and the shell side of heat exchanger 4, cooling bath 7, high-pressure pump 6 constitute cooling circuit, around autoclave 11
Controllable electric heating jacket 10 is provided with, autoclave 11 is connected with pressure gauge 9.
Preferably, described polymer is PLA, polyglycolic acid and lactic acid-ethanol copolymer.
Preferably, described organic solvent is dichloromethane or chloroform；Emulsifying agent is polyvinyl alcohol；Emulsifying agent is water-soluble
Liquid concentration is 0.5%～2% (w/w), and volumetric usage is 10～50 times of organic solvent.
Preferably, described nucleator consumption for polymer 1%～20%.
Preferably, described nucleator is submicron order or nano-scale particle, described submicron order or nano-scale particle
For one or more in hydroxyapatite, HTS or titanium dioxide.
Embodiment 1：Bimodal pore structure PLGA bone tissue engineering scaffold is prepared by nucleator of titanium dioxide
First by lactic acid-ethanol copolymer (lactic acid：Glycolic=85:15, Mw=140K) it is dissolved in dichloromethane to obtain
To the lactic acid-ethanol copolymer solution of mass volume ratio 10%, resulting solution is added to the aqueous solution of 1% polyvinyl alcohol
In, high-speed stirred forms the solution of emulsification, volatilizes dichloromethane, and centrifugation obtains lactic acid-ethanol copolymer microsphere.With breast
Acid-ethanol copolymer：Titanium dioxide=95:The cylindrical sheets for obtaining are put into height by 5 mass ratio, compressing tablet after mixing
In pressure kettle, CO is passed through2, the temperature setting of autoclave is arranged on into 9MPa in 45 DEG C, pressure.After 2 hours, with certain pressure release speed
Rate pressure release, obtains the bone tissue engineering scaffold with Bimodal pore structure.What pressure release speed was prepared when being 14MPa/min
The electron microscope in the tissue engineering bracket section of bimodal pore structure is as shown in Figure 2.Although it can be seen that due to pressure release speed
Rate is very fast, and the support aperture for preparing is less, respectively less than 100 μm, but inside 30～40 μm of hole occurs in that 10 μm
Aperture, defines with preferable connective pore structure.Pressure release speed be 1MPa/min when prepare with bimodal pore
The electron microscope in the tissue engineering bracket section of structure is as shown in Figure 3.It can be seen that average pore size is 38 μm of aperture going out
Aperture is more than inside 100 μm of macropore now, is formed with preferably connective pore structure, complies fully with bone tissue engineering scaffold
Requirement to aperture, can be used as bone tissue engineering scaffold.
Embodiment 2：Bimodal pore structure PLGA bone tissue engineering scaffold is prepared by nucleator of HTS
First by lactic acid-ethanol copolymer (lactic acid：Glycolic=85:15, Mw=140K) it is dissolved in dichloromethane
The lactic acid-ethanol copolymer solution of mass volume ratio 10% is obtained, resulting solution is added to the aqueous solution of 1% polyvinyl alcohol
In, high-speed stirred forms the solution of emulsification, volatilizes dichloromethane, and centrifugation obtains lactic acid-ethanol copolymer microsphere.With breast
Acid-ethanol copolymer：HTS=95:The cylindrical sheets for obtaining are put into by 5 mass ratio, compressing tablet after mixing
In autoclave, CO is passed through2, the temperature setting of autoclave is arranged on into 9MPa in 35 DEG C, pressure.After 2 hours, with 1MPa/min's
Pressure release speed pressure release, obtains the tissue engineering bracket with Bimodal pore structure.
Embodiment 3：Bimodal pore structure PLGA bone tissue engineering scaffolds are prepared by nucleator of hydroxyapatite
First by lactic acid-ethanol copolymer (lactic acid：Glycolic=85:15, Mw=140K) it is dissolved in dichloromethane
The lactic acid-ethanol copolymer solution of mass volume ratio 10% is obtained, resulting solution is added to the aqueous solution of 1% polyvinyl alcohol
In, high-speed stirred forms the solution of emulsification, volatilizes dichloromethane, and centrifugation obtains lactic acid-ethanol copolymer microsphere.With breast
Acid-ethanol copolymer：Hydroxyapatite=95:The cylindrical sheets for obtaining are put into by 5 mass ratio, compressing tablet after mixing
In autoclave, CO is passed through2, the temperature setting of autoclave is arranged on into 9MPa in 55 DEG C, pressure.After 2 hours, with 0.1MPa/min
Pressure release speed pressure release, obtains the tissue engineering bracket with Bimodal pore structure.The porosity of support is 75.6%, compresses mould
Measure as 18.15 ± 5.16MPa, the requirement of cartilage and os osseum can be met.
Embodiment 4：Bimodal pore structure PLGA bone tissue work is prepared as nucleator with hydroxyapatite and HTS
Engineering support
First by lactic acid-ethanol copolymer (lactic acid：Glycolic=85:15, Mw=140K) it is dissolved in dichloromethane
The lactic acid-ethanol copolymer solution of mass volume ratio 10% is obtained, resulting solution is added to the aqueous solution of 1% polyvinyl alcohol
In, high-speed stirred forms the solution of emulsification, volatilizes dichloromethane, and centrifugation obtains lactic acid-ethanol copolymer microsphere.With breast
Acid-ethanol copolymer：(hydroxyapatite：HTS=1:1)=95:5 mass ratio, compressing tablet after mixing, will
To cylindrical sheets be put in autoclave, be passed through CO2, the temperature setting of autoclave is arranged on into 15MPa in 55 DEG C, pressure.2
After hour, with the pressure release speed pressure release of 3MPa/min, the bone tissue engineering scaffold with bimodal pore structure is obtained.
Claims (5)
1. a kind of method that bimodal pore structure bone tissue engineering scaffold is prepared based on supercritical fluid technique, it is characterised in that bag
Include following steps：
1) raw polymer is dissolved in organic solvent, is then added in the aqueous solution of emulsifying agent, 1～3 point of high-speed stirred
Clock, forms the solution of emulsification, volatilizees, polymer microballoon is collected by centrifugation at 30 DEG C；
2) polymer microballoon is mixed with nucleator, takes mixture compressing tablet, obtains cylinder thin slice；
3) cylinder thin slice is put in the autoclave of supercritical fluid foamed system, carbon dioxide is passed through in autoclave,
Under conditions of 35～70 DEG C of temperature, 6～20MPa of pressure and equilibration time were more than 30 minutes, carbon dioxide diffusion dissolution enters poly-
In compound；Pressure release is carried out with the pressure release speed of 0.1～20MPa/min, as carbon dioxide is diffused out from polymer, is obtained
Bone tissue engineering scaffold with bimodal pore structure；
The supercritical fluid foamed system includes CO2Steel cylinder (1), hand-operated valve (2), check valve (3), heat exchanger (4), flow
Meter (5), high-pressure pump (6), cooling bath (7), heat exchanger (8), pressure gauge (9), controllable electric heating jacket (10), autoclave (11)
With relief valve (12)；CO2Steel cylinder (1) and hand-operated valve (2), check valve (3), the tube side of heat exchanger (4), flowmeter (5), high pressure
Pump (6), heat exchanger (8), autoclave (11), relief valve (12) are sequentially connected, the shell side of heat exchanger (4), cooling bath (7),
High-pressure pump (6) to be constituted and be provided with controllable electric heating jacket (10), autoclave (11) and pressure gauge around cooling circuit, autoclave (11)
(9) it is connected.
2. one kind according to claim 1 prepares bimodal pore structure bone tissue engineering scaffold based on supercritical fluid technique
Method, it is characterised in that described polymer be PLA, polyglycolic acid and lactic acid-ethanol copolymer.
3. one kind according to claim 1 prepares bimodal pore structure bone tissue engineering scaffold based on supercritical fluid technique
Method, it is characterised in that described organic solvent is dichloromethane or chloroform；Emulsifying agent is polyvinyl alcohol；Emulsifying agent water
Solution concentration is 0.5%～2% (w/w), and volumetric usage is 10～50 times of organic solvent.
4. one kind according to claim 1 prepares bimodal pore structure bone tissue engineering scaffold based on supercritical fluid technique
Method, it is characterised in that described nucleator consumption for polymer 1%～20%.
5. one kind according to claim 1 prepares bimodal pore structure bone tissue engineering scaffold based on supercritical fluid technique
Method, it is characterised in that described nucleator is submicron order or nano-scale particle, described submicron order or nanoscale
Grain is one or more in hydroxyapatite, HTS or titanium dioxide.
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| CN116354336A (en) * | 2023-03-03 | 2023-06-30 | 苏州纳微先进微球材料应用技术研究所有限公司 | Device for regulating and controlling pore canal structure of carbon microsphere by supercritical carbon dioxide and preparation method |
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