CN110180023A - A kind of preparation method of high intensity biomass tissue engineering bracket material - Google Patents
A kind of preparation method of high intensity biomass tissue engineering bracket material Download PDFInfo
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- CN110180023A CN110180023A CN201910521210.8A CN201910521210A CN110180023A CN 110180023 A CN110180023 A CN 110180023A CN 201910521210 A CN201910521210 A CN 201910521210A CN 110180023 A CN110180023 A CN 110180023A
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- 239000000463 material Substances 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000002028 Biomass Substances 0.000 title claims abstract description 12
- 229920001661 Chitosan Polymers 0.000 claims abstract description 53
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000000661 sodium alginate Substances 0.000 claims abstract description 27
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 27
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 27
- 239000007864 aqueous solution Substances 0.000 claims description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 239000004626 polylactic acid Substances 0.000 claims description 18
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 8
- 238000006116 polymerization reaction Methods 0.000 claims description 8
- 238000009777 vacuum freeze-drying Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 claims description 6
- 230000006196 deacetylation Effects 0.000 claims description 5
- 238000003381 deacetylation reaction Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 4
- 229910021641 deionized water Inorganic materials 0.000 claims description 4
- 238000011010 flushing procedure Methods 0.000 claims description 4
- 238000002386 leaching Methods 0.000 claims description 4
- 230000010355 oscillation Effects 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 150000004676 glycans Chemical class 0.000 claims 1
- 239000007970 homogeneous dispersion Substances 0.000 claims 1
- 230000009977 dual effect Effects 0.000 abstract description 7
- 238000004132 cross linking Methods 0.000 abstract description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 abstract 1
- 230000002209 hydrophobic effect Effects 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 28
- 210000001519 tissue Anatomy 0.000 description 19
- 230000015556 catabolic process Effects 0.000 description 8
- 238000006731 degradation reaction Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 6
- 210000000988 bone and bone Anatomy 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229920002101 Chitin Polymers 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000512259 Ascophyllum nodosum Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000199919 Phaeophyceae Species 0.000 description 1
- 241000195474 Sargassum Species 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940058573 b-d glucose Drugs 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000007948 fast release tablet Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 125000005474 octanoate group Chemical group 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 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 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Chemical group 0.000 description 1
Classifications
-
- 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
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to the preparation methods of a kind of sodium alginate, chitosan-based high-intensitive biomass group engineering scaffold material, it is obtained after the dual network gel of second network struction of first network and the carboxymethyl chitosan crosslinking that the timbering material is formed by sodium alginate cross-linking is freeze-dried, the bracket has excellent intensity, resilience, macroporosity, good biocompatibility and certain surface hydrophobic feature, can be used for human tissue engineering field.
Description
Technical field
The invention belongs to the preparation method of biomass tissue engineering bracket material, more particularly to a kind of with high-intensitive,
The preparation method of the biomass-based bracket of good biocompatibility.
Background technique
Tissue engineering bracket material, which refers to, with tissue biopsy cell combination and can be implanted into the different tissues of organism, and root
According to the material for the function that specific substitution tissue has.In order to be proliferated seed cell and differentiation, it is desirable to provide one by biological material
Expect that constituted cytoskeleton, timbering material are equivalent to artificial extracellular matrix.Tissue engineering bracket material include: bone, cartilage,
Blood vessel, nerve, skin and artificial organs, such as the tissue stent material of liver,spleen,kidney, bladder.
The preparation of current tissue engineering material and raw material sources multiplicity, mainly include natural biodegradable polymer material and
Synthesized degradable high molecular material, but respectively have advantage and disadvantage.Such as natural biodegradable polymer material.Natural biodegradable macromolecule
Material refers to the high molecular degradable material by extracting in animal vegetable tissue.It itself is exactly being organized into for nature bone such as collagen
Point.Chitosan is the derivative of chitin.There are also gelatin, agar, glucan, hyaluronic acids.The characteristics of this kind of material is degradation
Product is easily absorbed by organisms, but intensity and processing performance are poor, and degradation speed can not be adjusted.Synthesized degradable high molecular material.
Common degradable synthesized polymer material has polylactic acid, polyglycolic acid, polycaprolactone, polyethers, polycarbonate etc..This kind of material
Catabolite can be metabolized exclusion in vivo, harmless to body, plasticity is preferable.Wherein polylactic acid and polyglycolic acid are in a group weaver
It is most widely used in journey.But high molecular material equally exists drawback, such as lacks synosteosis ability, is not easy to clinical development, degrades
Rate is uncontrollable, cell adhesion difficulty etc..
The preparation of timbering material can be freeze-dried by gel rubber material and is prepared.Gel refers to the height of three-dimensional net structure
The system of molecular compound and solvent composition, macromolecule therein is with Van der Waals force, chemical bond force, physical entanglement power, hydrogen bond force
Deng connection.Since it is a kind of three-dimensional network stereochemical structure, it is not dissolved in solvent, but swellable.The preparation and composition of gel
The polymer material and biological material predominantly synthesized, wherein biological material include cellulose, chitosan, chitin,
Sodium alginate, gelatin, hyaluronic acid etc..Biomass gel has the unexistent advantage of synthesized gel rubber, such as has good biology
Compatibility, low cytotoxicity, degradability etc..The difficulty that the main needs that biomass gel rubber material prepares timbering material overcome is
Intensity is improved, controls degradation time etc. really to realize the preparation of excellent timbering material.
It in the present invention, will take sodium alginate and chitosan as basic material to prepare hydrogel material and then prepare tissue
Engineering scaffold material.
Involved chitosan is that the chitin being widely present by nature is obtained by deacetylation, and chemical name is
Chitosan (1-4) -2- amino-B-D glucose.Chitosan has good antibiotic property, machinability.Also because it is good
Mouldability can be used for the preparation of tissue engineering bracket material.As the compound of chitosan and calcium phosphate can be used as the substitution of bone
Object, for the repairing of bone and the filler of tooth, the composite material of chitosan derivatives and polyester can be used as artificial blood vessel.It is related
Sodium alginate is the by-product after extracting iodine and mannitol in the kelp or sargassum of brown algae, and molecule is by β-D- sweet dew
Uronic acid (β-D-mannuronic, M) and α-L- guluronic acid (α-L-guluronic, G) are keyed by (1 → 4),
It is a kind of natural polysaccharide.Traditionally, sodium alginate is used as the adhesive of tablet or the disintegrating agent of fast-release tablet.In recent years, alginic acid
It is contained in the application constantly extension of different biomedicine fields, generates gel when pH is less than 3 using Na-alginate or in chlorination
Ion exchange occurs in the presence of calcium to generate the characteristic of gel, sodium alginate gel is more and more widely used,
Such as it is used as three-dimensional rack, simulated skin tissue.But either sodium alginate gel or the bracket material of chitosan gel rubber preparation
Expect that its intensity is unable to reach the requirement of practical application.In the present invention, this is solved the problems, such as using multiple technologies.First is that structure
Built Multi net voting structure, and introduced hyper-branched group such as graft copolymer in a network etc., another is then to use one kind newly
The nanometer POSS electrolyte of type, the substitute as traditional sodium alginate cross-linking agent calcium chloride.Polyhedral oligomeric silsesquioxane
(Polyhedral oligomeric silsesquioxane, POSS) is a kind of novel organic-inorganic nano particle,
It was synthesized for the first time in 1946.The general molecular formula of POSS is (RSiO1.5)8, the R in formula is organic substituent, Ke Yiwei
H, the inertia groups such as alkyl, aryl and vinyl, amino isoreactivity group, while molecule has inorganic skeleton and molecular dimension
Between 1 ~ 3nm.It is lazy and in recent years, POSS has been widely used in biological field, and is found to have extraordinary bio-compatible
Property.Meanwhile POSS is also employed for being used to improve the mechanical property of gel, solution swelling rate in hydrogel or draws functionality
Enter in hydrogel.
A kind of biology with excellent mechanical performance, biocompatibility and slow degradability has been obtained by above strategy
Matter tissue engineering bracket material.
Summary of the invention
The purpose of the invention is to provide a kind of preparation method of tissue engineering bracket material, it is provided in particular in a kind of tool
There is high-intensitive, tissue engineering bracket material.
The purpose of the present invention is what is be achieved through the following technical solutions:
(1) 20oUnder C, a certain amount of chitosan is added in 0.1mol/L concentration acetum and the grafting of O- hydroxyethyl chitosan is poly-
Lactic acid is stirred to get water solution A for 4-8 hours, and the mass concentration of chitosan is between 2-3% in water solution A, in water solution A
The mass ratio of chitosan and O- hydroxyethyl chitosan grafted polylactic acid is between 2:1-3:1；
(2) the sodium alginate aqueous solution B that mass concentration is 2-3.5% is added in water solution A, stirs evenly to form aqueous solution
The volume ratio of C, water solution A and sodium alginate aqueous solution B are between 2:1-3:1；
(3) the sodium β-glycerophosphate aqueous solution that 1g/mL is persistently instilled in aqueous solution C is mixing uniformly to form pre-polymerization liquid D, in advance
The mass ratio of sodium β-glycerophosphate and chitosan is between 4:1-6:1 in poly- liquid D；
(4) pre-polymerization liquid D is warming up to 38oC is simultaneously placed 30 minutes, forms gel A；
(5) after by gel A with clear water repeated flushing, in -40oVacuum freezedrying 24 hours in C, obtain aeroge B；
(6) 20oA certain amount of eight ammoniums caged silsesquioxane is added in deionized water under C, sonic oscillation is simultaneously stirred to equal
Even dispersion obtains aqueous solution B, and buffer is added in aqueous solution B and reconciles pH value of water solution between 8-8.5, eight in aqueous solution B
The mass concentration of ammonium caged silsesquioxane is 1.5-2%；
(7) by aeroge B 20oLeaching in aqueous solution B is completely immersed under C to set 48 hours, it is rear to take out the acetic acid for immersing a large amount of pH=3
It is impregnated 12 hours in aqueous solution, gel C is obtained, by gel C in -40oVacuum freezedrying 24 hours, obtain final products in C.
Further, for the viscosity average molecular weigh of the chitosan between 250000-500000, deacetylation is greater than 95%,
Viscosity are as follows: 20 DEG C, be 150-200 mPa.s under 10g/L concentration.
Further, the sodium alginate is 20oUnder C mass fraction be 1% Aqueous Solution Viscosity between 500-600 mPa.s it
Between.
Further, the O- hydroxyethyl chitosan grafted polylactic acid based on polylactic acid and O- hydroxyethyl chitosan mass ratio
The grafting rate of calculation is between 120-210%.
Further, the typical production of the O- hydroxyethyl chitosan grafted polylactic acid can be following processes:
Weigh certain mass chitosan, 5% mass concentration sodium hydrate aqueous solution be added and adjusts pH value to 13, after 60oC is next time
60h is flowed and reacted, is added to 60oAfter C, the aqueous solution of ethylene oxide that partial volume score is 15%, chitosan is added within every 20 minutes
The ratio that aqueous solution of ethylene oxide is added in total is every g chitosan/2-3ml aqueous solution of ethylene oxide, and solid is all after dissolution
Reaction is terminated, 5% mass concentration HCL aqueous solution regulation system pH value is added into system to 5, until solution clear.By solution
It is precipitated after filtering and being concentrated using dehydrated alcohol, centrifugation obtains solid, the filtering, dense with distilled water dissolved solid and more than repeating
Contracting, precipitation process, up to no insoluble solids.After final obtained solid is dissolved with water, dialysed by bag filter with a large amount of water, thoroughly
Liquid freezing is dry after analysis, and obtained solid is water solubility O-- hydroxyethyl chitosan.D is added by a certain percentage in flask,
L- lactide and water solubility O-- hydroxyethyl chitosan, are added the octoate catalyst stannous that lactide molar ratio is 0.1%, and vacuum is de-
In in oil bath pan 140 after hermetic sealoIt is stirred to react under C 24 hours and obtains crude product, through acetone stirring, drawer, after purification is added
Solid product is obtained, is used after dry.According to the different D of addition, the dosage of L- lactide and water solubility O-- hydroxyethyl chitosan
Than the grafting rate that can regulate and control polylactic acid.The feed ratio of D in the present invention, L- lactide and water solubility O-- hydroxyethyl chitosan
Between 20:1-40:1.
Further, the eight ammoniums caged silsesquioxane (OaPOSS) is the modified product of POSS.This POSS monomer
Because there is the presence of a large amount of ammoniums, so that monomer has good water solubility.Its structural formula is as follows:
Wherein, eight ammoniums in the corner OaPOSS are easier to dissociate under certain acidity and alkalinity environment, cation are formed, in He Hai
Play the role of similar calcium ion after mosanom mixing, cross-linking effect is formed by ion exchange, so that gel is formed, this friendship
Connection mode is other than having ion exchange, and there is also certain physical crosslinking effects.
Further, the quality of the aqueous solution D and aqueous acetic acid is more than 30 times of aeroge B, the quality of aqueous solution D
To guarantee the ion-exchange for thering are enough POSS ions to enter realization sodium alginate in aeroge B；The matter of aqueous acetic acid
Amount is for guaranteeing enough acidity to improve the crosslinking of sodium alginate to realize consistent internal structure.
Further, the realization of technical characterstic of the invention and advantage are as follows:
(1) the dual network structure of chitosan network and sodium alginate network is constructed, chitosan network plays flexibility in dual network
Chain effect, crossslinked sodium alginate network are that rigid network cooperates to cooperate with more preferably mechanical property；
(2) wherein chitosan network is master network in the Grafting Structure for wherein introducing O- hydroxyethyl chitosan grafted polylactic acid,
Significantly more efficient three-dimensional is connected to chitosan network, to effectively increase intensity and improve porosity；
(3) OaPOSS has more obvious performance advantage as the more traditional calcium ion crosslinking of cross-linking agents sodium alginate, can
Significantly more efficient offer intensity and resilience also can provide biological attachment point.
Each performance of tissue engineering bracket material of the present invention, including mechanical property, porosity, rheological behavior etc. can lead to
Overregulate monomer concentration, the ratio of dosage of crosslinking agent, OaPOSS dosage and dual network content is adjusted.
A kind of dual network sodium alginate Quito responsiveness aquagel with superior bio compatibility of the present invention just like
Lower performance characteristics:
In the scope of the invention, the performance of gel is as follows:
Compressive load (70%): 4.2-5.8N
Porosity: 85.7%-93.4%
Elasticity modulus: 10.5-22.7MPa
Maximum tension strain: 44%-56%
Aperture: 50-100 microns
Degradation cycle (50% degradation): 5-10 weeks
Specific embodiment
The specific embodiment of form combined with specific embodiments below remakes above content of the invention and further explains in detail
It states, but should not be construed as following each embodiments is the limitation to range involved by the above-mentioned theme of the present invention, it is all based in the present invention
It states the technology that content is realized and belongs to the scope of the invention.
Embodiment 1
A kind of high-intensitive biology of dual network sodium alginate with superior bio compatibility, chitosan-based multiple response of the present invention
The preparation of matter tissue engineering bracket material is as follows:
(1) 20oIt is that 2.3g chitosan and the O- ethoxy of 1.02g are added in 0.1mol/L acetum in 100ml concentration under C
Chitosan grafted polylactic acid stirred to get water solution A through 5 hours；
(2) the sodium alginate aqueous solution B that 40ml mass concentration is 2.5% is added in water solution A, stirs evenly water-soluble to be formed
Liquid C；
(3) the sodium β-glycerophosphate aqueous solution that 11.5ml concentration is 1g/mL is persistently instilled in aqueous solution C, after mixing evenly shape
At pre-polymerization liquid D；
(4) pre-polymerization liquid D is warming up to 38oC is simultaneously placed 30 minutes, forms gel A；
(5) after by gel A with clear water repeated flushing, in -40oVacuum freezedrying 24 hours in C obtain 9.6g aeroge B；
(6) 20oEight ammonium caged silsesquioxane of 5.76g is added in 320g deionized water under C, sonic oscillation simultaneously stirs extremely
It is evenly dispersed, aqueous solution B is obtained, buffer is added in aqueous solution B and reconciles pH value of water solution to 8.2；
(7) by aeroge B 20oLeaching in aqueous solution B is completely immersed under C to set 48 hours, it is rear to take out the acetic acid for immersing pH=3 400g
It is impregnated 12 hours in aqueous solution, gel C is obtained, by gel C in -40oVacuum freezedrying 24 hours, obtain final products in C.
The viscosity average molecular weigh of the chitosan is 426000, deacetylation 95.5%, viscosity are as follows: 20 DEG C, 10g/L is dense
Lower degree is 175mPa.s.
The sodium alginate is 20oUnder C, mass fraction is that 1% Aqueous Solution Viscosity is 550 mPa.s.
The O- hydroxyethyl chitosan grafted polylactic acid is connect by polylactic acid with what O- hydroxyethyl chitosan mass ratio calculated
Branch rate is 155%.
The performance of the present embodiment gel is as follows:
Compressive load (70%): 4.75N
Porosity: 91.4%
Elasticity modulus: 18.6MPa
Maximum tension strain: 52.4%
Aperture: 50-100 microns
Degradation cycle (50% degradation): 6.5 weeks
Embodiment 2
A kind of high-intensitive biology of dual network sodium alginate with superior bio compatibility, chitosan-based multiple response of the present invention
The preparation of matter tissue engineering bracket material is as follows:
(1) 20oIt is that 2.6g chitosan and the O- ethoxy of 1.14g are added in 0.1mol/L acetum in 100ml concentration under C
Chitosan grafted polylactic acid stirred to get water solution A through 6 hours；
(2) the sodium alginate aqueous solution B that 45ml mass concentration is 2.5% is added in water solution A, stirs evenly water-soluble to be formed
Liquid C；
(3) the sodium β-glycerophosphate aqueous solution that 13.2ml concentration is 1g/mL is persistently instilled in aqueous solution C, after mixing evenly shape
At pre-polymerization liquid D；
(4) pre-polymerization liquid D is warming up to 38oC is simultaneously placed 30 minutes, forms gel A；
(5) after by gel A with clear water repeated flushing, in -40oVacuum freezedrying 24 hours in C obtain 10.04g aeroge B；
(6) 20oEight ammonium caged silsesquioxane of 5.5g is added in 350g deionized water under C, sonic oscillation simultaneously stirs extremely
It is evenly dispersed, aqueous solution B is obtained, buffer is added in aqueous solution B and reconciles pH value of water solution to 8.4；
(7) by aeroge B 20oLeaching in aqueous solution B is completely immersed under C to set 48 hours, it is rear to take out the acetic acid for immersing pH=3 350g
It is impregnated 12 hours in aqueous solution, gel C is obtained, by gel C in -40oVacuum freezedrying 24 hours, obtain final products in C.
The viscosity average molecular weigh of the chitosan is 482000, deacetylation 95.5%, viscosity are as follows: 20 DEG C, 10g/L is dense
Lower degree is 190mPa.s.
The sodium alginate is 20oUnder C, mass fraction is that 1% Aqueous Solution Viscosity is 550mPa.s.
The O- hydroxyethyl chitosan grafted polylactic acid is connect by polylactic acid with what O- hydroxyethyl chitosan mass ratio calculated
Branch rate is 172%.
The performance of the present embodiment gel is as follows:
Compressive load (70%): 5.045N
Porosity: 92.2%
Elasticity modulus: 19.2MPa
Maximum tension strain: 48.2%
Aperture: 50-100 microns
Degradation cycle (50% degradation): 7.2 weeks.
Claims (5)
1. a kind of preparation method of high intensity biomass tissue engineering bracket material, it is characterized in that:
Material is prepared by following step:
(1) 20oUnder C, a certain amount of chitosan and the poly- cream of O- hydroxyethyl chitosan grafting are added in 0.1mol/L concentration acetum
Acid is stirred to get water solution A for 4-8 hours, and the mass concentration of chitosan is between 2-3% in water solution A, shell in water solution A
The mass ratio of glycan and O- hydroxyethyl chitosan grafted polylactic acid is between 2:1-3:1；
(2) the sodium alginate aqueous solution B that mass concentration is 2-3.5% is added in water solution A, stirs evenly to form aqueous solution
The volume ratio of C, water solution A and sodium alginate aqueous solution B are between 2:1-3:1；
(3) the sodium β-glycerophosphate aqueous solution that 1g/mL is persistently instilled in aqueous solution C is mixing uniformly to form pre-polymerization liquid D, in advance
The mass ratio of sodium β-glycerophosphate and chitosan is between 4:1-6:1 in poly- liquid D；
(4) pre-polymerization liquid D is warming up to 38oC is simultaneously placed 30 minutes, forms gel A；
(5) after by gel A with clear water repeated flushing, in -40oVacuum freezedrying 24 hours in C, obtain aeroge B；
(6) 20oA certain amount of eight ammoniums caged silsesquioxane is added in deionized water under C, sonic oscillation is simultaneously stirred until homogeneous
Dispersion, obtains aqueous solution D, and buffer is added in aqueous solution D and reconciles pH value of water solution between 8-8.5, eight ammonia in aqueous solution D
The mass concentration of alkali caged silsesquioxane is 1.5-2%；
(7) by aeroge B 20oLeaching in aqueous solution D is completely immersed under C to set 48 hours, it is rear to take out the acetic acid water for immersing a large amount of pH=3
It is impregnated 12 hours in solution, gel C is obtained, by gel C in -40oVacuum freezedrying 24 hours, obtain final products in C.
2. a kind of preparation method of high-intensitive biomass tissue engineering bracket material according to claim 1, feature exist
In: for the viscosity average molecular weigh of the chitosan between 250000-500000, deacetylation is greater than 95%.
3. a kind of preparation method of high-intensitive biomass tissue engineering bracket material according to claim 1, feature exist
In: the sodium alginate is 20oMass fraction is 1% Aqueous Solution Viscosity between 500-600 mPa.s under C.
4. a kind of preparation method of high-intensitive biomass tissue engineering bracket material according to claim 1, feature exist
In: the grafting rate of the O- hydroxyethyl chitosan grafted polylactic acid calculated by polylactic acid and O- hydroxyethyl chitosan mass ratio is situated between
Between 120-210%.
5. a kind of preparation method of high-intensitive biomass tissue engineering bracket material according to claim 1, feature exist
In: the quality of the aqueous solution D and aqueous acetic acid is more than 30 times of aeroge B.
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| CN112048079A (en) * | 2020-09-08 | 2020-12-08 | 西北大学 | Carboxymethyl chitosan-alginate injectable double-network temperature-sensitive hydrogel and preparation method and application thereof |
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