CN107459634A - A kind of unsaturated aliphatic polyester and its preparation method and application - Google Patents
A kind of unsaturated aliphatic polyester and its preparation method and application Download PDFInfo
- Publication number
- CN107459634A CN107459634A CN201710667116.4A CN201710667116A CN107459634A CN 107459634 A CN107459634 A CN 107459634A CN 201710667116 A CN201710667116 A CN 201710667116A CN 107459634 A CN107459634 A CN 107459634A
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- Prior art keywords
- aliphatic polyester
- unsaturated aliphatic
- butyl
- succinic anhydride
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- 229920003232 aliphatic polyester Polymers 0.000 title claims abstract description 81
- 125000001931 aliphatic group Chemical group 0.000 title claims abstract description 74
- 238000002360 preparation method Methods 0.000 title claims description 28
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229940014800 succinic anhydride Drugs 0.000 claims abstract description 25
- YSUQLAYJZDEMOT-UHFFFAOYSA-N 2-(butoxymethyl)oxirane Chemical compound CCCCOCC1CO1 YSUQLAYJZDEMOT-UHFFFAOYSA-N 0.000 claims abstract description 19
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229920000728 polyester Polymers 0.000 claims abstract 3
- 239000000017 hydrogel Substances 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 239000000178 monomer Substances 0.000 claims description 20
- 238000007151 ring opening polymerisation reaction Methods 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 239000011259 mixed solution Substances 0.000 claims description 12
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 12
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 10
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- LZHUBCULTHIFNO-UHFFFAOYSA-N 2,4-dihydroxy-1,5-bis[4-(2-hydroxyethoxy)phenyl]-2,4-dimethylpentan-3-one Chemical compound C=1C=C(OCCO)C=CC=1CC(C)(O)C(=O)C(O)(C)CC1=CC=C(OCCO)C=C1 LZHUBCULTHIFNO-UHFFFAOYSA-N 0.000 claims description 9
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 9
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 claims description 8
- GNSFRPWPOGYVLO-UHFFFAOYSA-N 3-hydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCO GNSFRPWPOGYVLO-UHFFFAOYSA-N 0.000 claims description 8
- DPBJAVGHACCNRL-UHFFFAOYSA-N 2-(dimethylamino)ethyl prop-2-enoate Chemical compound CN(C)CCOC(=O)C=C DPBJAVGHACCNRL-UHFFFAOYSA-N 0.000 claims description 6
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 6
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 claims description 5
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 claims description 5
- VFHVQBAGLAREND-UHFFFAOYSA-N diphenylphosphoryl-(2,4,6-trimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 VFHVQBAGLAREND-UHFFFAOYSA-N 0.000 claims description 5
- DXPPIEDUBFUSEZ-UHFFFAOYSA-N 6-methylheptyl prop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C=C DXPPIEDUBFUSEZ-UHFFFAOYSA-N 0.000 claims description 4
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 4
- YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 claims description 4
- QZPSOSOOLFHYRR-UHFFFAOYSA-N 3-hydroxypropyl prop-2-enoate Chemical compound OCCCOC(=O)C=C QZPSOSOOLFHYRR-UHFFFAOYSA-N 0.000 claims description 3
- OEOIWYCWCDBOPA-UHFFFAOYSA-N 6-methyl-heptanoic acid Chemical compound CC(C)CCCCC(O)=O OEOIWYCWCDBOPA-UHFFFAOYSA-N 0.000 claims description 3
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 3
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- 239000010941 cobalt Substances 0.000 claims description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 3
- 239000004246 zinc acetate Substances 0.000 claims description 3
- ADJMNWKZSCQHPS-UHFFFAOYSA-L zinc;6-methylheptanoate Chemical compound [Zn+2].CC(C)CCCCC([O-])=O.CC(C)CCCCC([O-])=O ADJMNWKZSCQHPS-UHFFFAOYSA-L 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 230000003013 cytotoxicity Effects 0.000 abstract description 12
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 12
- 230000008961 swelling Effects 0.000 abstract description 12
- 239000000126 substance Substances 0.000 abstract description 3
- 229920001577 copolymer Polymers 0.000 abstract description 2
- 238000010276 construction Methods 0.000 abstract 2
- 230000001413 cellular effect Effects 0.000 abstract 1
- 238000007142 ring opening reaction Methods 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 56
- 238000000016 photochemical curing Methods 0.000 description 41
- 210000000629 knee joint Anatomy 0.000 description 29
- 230000005499 meniscus Effects 0.000 description 29
- 230000003833 cell viability Effects 0.000 description 26
- 230000021164 cell adhesion Effects 0.000 description 20
- 238000001514 detection method Methods 0.000 description 12
- 238000002156 mixing Methods 0.000 description 10
- 239000002994 raw material Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000004806 packaging method and process Methods 0.000 description 8
- 238000007789 sealing Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000002522 swelling effect Effects 0.000 description 8
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 4
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- -1 ester compound Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000006068 polycondensation reaction Methods 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000031700 light absorption Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- XMLYCEVDHLAQEL-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-phenylpropan-1-one Chemical compound CC(C)(O)C(=O)C1=CC=CC=C1 XMLYCEVDHLAQEL-UHFFFAOYSA-N 0.000 description 1
- 239000012957 2-hydroxy-2-methyl-1-phenylpropanone Substances 0.000 description 1
- JHVNAMYDHIZUPY-UHFFFAOYSA-N CCC1C2CCCC1C2 Chemical compound CCC1C2CCCC1C2 JHVNAMYDHIZUPY-UHFFFAOYSA-N 0.000 description 1
- 229920001634 Copolyester Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000219000 Populus Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- MAHPNPYYQAIOJN-UHFFFAOYSA-N azimsulfuron Chemical compound COC1=CC(OC)=NC(NC(=O)NS(=O)(=O)C=2N(N=CC=2C2=NN(C)N=N2)C)=N1 MAHPNPYYQAIOJN-UHFFFAOYSA-N 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 238000012643 polycondensation polymerization Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/12—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from polycarboxylic acids and polyhydroxy compounds
- C08G63/52—Polycarboxylic acids or polyhydroxy compounds in which at least one of the two components contains aliphatic unsaturation
- C08G63/56—Polyesters derived from ester-forming derivatives of polycarboxylic acids or of polyhydroxy compounds other than from esters thereof
- C08G63/58—Cyclic ethers; Cyclic carbonates; Cyclic sulfites ; Cyclic orthoesters
-
- 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
- A61L27/16—Macromolecular materials obtained 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
- A61L27/14—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
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
- C08F283/01—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to unsaturated polyesters
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
-
- 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
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2210/00—Compositions for preparing hydrogels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2230/00—Compositions for preparing biodegradable polymers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Dispersion Chemistry (AREA)
- Macromonomer-Based Addition Polymer (AREA)
Abstract
The present invention relates to a kind of unsaturated aliphatic polyester, the polyester is the construction unit shown in chemical formula (I) and the construction unit shown in chemical formula (II) by 3:7~7:The polyester of the 3 linear random arrangement of mol ratio, its number-average molecular weight are 5000~12000, and monodispersity index is 1.21~1.80；Described unsaturated aliphatic polyester is that GMA, n-butyl glycidyl ether and succinic anhydride are carried out ring opening copolymer and obtained.Unsaturated aliphatic polyester of the present invention can be used for preparing tissue engineering bracket, and the support has preferable modulus of elasticity and swelling behavior, and cytotoxicity is low, good biocompatibility, and cellular affinity is high.
Description
Technical Field
The present invention relates to an organic polymer compound, and more particularly to an unsaturated aliphatic polyester which is suitable for medical materials.
Background
The main chain of the aliphatic polyester is formed by connecting aliphatic structural units through ester bonds which are easy to hydrolyze, is flexible and is easy to degrade under the action of microorganisms and catalysis of enzymes. Therefore, the aliphatic polyester is an important biomedical material due to good biocompatibility and biodegradability, and is widely applied to the biomedical field, such as drug sustained release, operation sutures, bone fixation materials, tissue engineering materials and the like. Examples of the aliphatic polyester generally used include Polyglycolide (PGA), Polylactide (PLA), glycolide-lactide copolymer (PLGA), and Polycaprolactone (PCL). At present, there are two methods for synthesizing aliphatic polyester. The first is prepared by condensation using difunctional monomers, for example, by condensation polymerization with dibasic acids and glycols. And secondly, the ester compound or the lactone compound is adopted as a monomer to carry out ring-opening copolymerization to obtain the compound. However, aliphatic polyesters have several major drawbacks, and first, aliphatic polyesters are poor in hydrophilicity, low in bioactivity, and weak in affinity and adhesion to cells. Second, the aliphatic polyester backbone lacks reactive sites, limiting the utility of the aliphatic polyester.
The unsaturated aliphatic polyester is aliphatic polyester containing unsaturated double bonds, and can be solidified with monomer or prepolymer containing unsaturated double bonds. At present, the unsaturated aliphatic polyester is prepared mainly by a polycondensation method. The polycondensation method is that unsaturated dibasic aliphatic acid or dibasic aliphatic anhydride and unsaturated dibasic alcohol are polycondensed to obtain the product. The main chain of the unsaturated aliphatic polyester prepared by the method contains unsaturated double bonds. The poplar group and the like use fumaric acid, diethylene glycol and 1, 4-butanediol as raw materials to synthesize unsaturated aliphatic polyester and copolyester by a melt polycondensation method, and the unsaturated aliphatic polyester can be found to be biodegradable (applied to chemical industry, 2013, volume 42, stage 3, 490). However, the unsaturated double bond in the unsaturated aliphatic polyester reported in the above documents is located in the main chain, and the reaction activity is low, and the photocuring ability with other unsaturated double bond-containing monomers is poor, and thus the unsaturated aliphatic polyester cannot be applied as a tissue engineering scaffold.
Disclosure of Invention
The technical problem to be solved by the invention is to provide unsaturated aliphatic polyester, wherein the side chain of the unsaturated aliphatic polyester contains unsaturated double bonds, and the photocuring hydrogel prepared from the unsaturated aliphatic polyester has good biocompatibility and low cytotoxicity.
The technical scheme for solving the problems is as follows:
an unsaturated aliphatic polyester having a number average molecular weight (M for short) of a structural unit represented by the formula (I) and a structural unit represented by the formula (II) which are linearly and randomly arranged at a molar ratio of 3:7 to 7:3n) 5000 to 12000, and a dispersion index (PDI for short) of 1.21 to 1.80,
the unsaturated aliphatic polyester is obtained by ring-opening copolymerization of glycidyl methacrylate, n-butyl glycidyl ether and succinic anhydride.
The unsaturated aliphatic polyester is preferably one in which the molar ratio of the structural unit represented by the formula (I) to the structural unit represented by the formula (II) is 2:3 to 3:2, the number average molecular weight is 5000 to 10000, and the dispersibility index is preferably 1.21 to 1.60.
The specific preparation method of the unsaturated aliphatic polyester comprises the following steps:
adding glycidyl methacrylate, n-butyl glycidyl ether, ortho-tert-butyl hydroquinone and a catalyst into succinic anhydride, dissolving into a proper amount of mixed solution, carrying out ring-opening copolymerization reaction for 5-12 h at 90-120 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester; wherein,
the sum of the addition amount of the glycidyl methacrylate and the n-butyl glycidyl ether is equal to the molar amount of the succinic anhydride, and the molar ratio of the glycidyl methacrylate to the n-butyl glycidyl ether is 3: 7-7: 3;
the addition amount of the tert-butyl hydroquinone is 1-10% of the molar amount of the succinic anhydride;
the adding amount of the catalyst is 1-10% of the molar amount of the succinic anhydride;
the mixed solution consists of ethyl acetate and butyl acetate in equal volume ratio;
the catalyst is one of tetra-n-butylammonium bromide, zinc acetate, zinc isooctanoate and cobalt isooctanoate.
In the above method, the molar ratio of glycidyl methacrylate to n-butyl glycidyl ether is preferably 2:3 to 3:2, and more preferably 1: 1.
In the above method, the amount of the tert-butylhydroquinone added is preferably 2 to 8 mol% of the succinic anhydride, and more preferably 5 mol% of the succinic anhydride.
In the above process, the amount of the catalyst to be added is preferably 2 to 8% by mole of the succinic anhydride to be used, more preferably 5% by mole of the succinic anhydride to be used.
In the above method, the catalyst is preferably tetra-n-butylammonium bromide.
In the above method, the temperature of the ring-opening copolymerization reaction is preferably 100 to 120 ℃, and more preferably 110 ℃; the time of the ring-opening copolymerization reaction is preferably 5 to 10 hours, and preferably 6 to 8 hours.
The unsaturated aliphatic polyester has good biocompatibility and biodegradability, contains unsaturated double bonds on side chains, can be further subjected to functional modification or photocuring to form gel, and is used for preparing biodegradable photocuring hydrogel.
The photocuring hydrogel consists of unsaturated aliphatic polyester, hydrophilic unsaturated monomer, soft unsaturated monomer and photoinitiator, wherein the content of the hydrophilic unsaturated monomer is 40-60% of the weight of the unsaturated aliphatic polyester, the content of the soft unsaturated monomer is 40-60% of the weight of the unsaturated aliphatic polyester, and the content of the photoinitiator is 0.5-1% of the weight of the unsaturated aliphatic polyester;
the hydrophilic unsaturated monomer is one or more than two of hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and N, N-dimethylamino ethyl acrylate;
the soft unsaturated monomer is one or two of butyl acrylate, 2-ethylhexyl acrylate and isooctyl acrylate;
the photoinitiator is one or more than two of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone, 2-hydroxy-2-methyl-1-phenyl acetone, 2,4, 6-trimethylbenzoyl-diphenyl phosphine oxide and thiopropoxy thioxanthone.
In the above photocurable hydrogel, the content of the hydrophilic unsaturated monomer is preferably 50% by weight of the unsaturated aliphatic polyester.
In the above photocurable hydrogel, the content of the soft unsaturated monomer is preferably 50% by weight of the unsaturated aliphatic polyester.
The photo-curing hydrogel disclosed by the invention is stored in a light-closed manner, when the photo-curing hydrogel is used, the photo-initiation conditions of the photo-curing hydrogel are that the light intensity of ultraviolet light is 200-600 mJ/sq cm, and the photo-initiation reaction time is 1-5 min.
The tissue engineering scaffold prepared from the photocuring hydrogel has the advantages of good elastic modulus and swelling performance, low cytotoxicity, good biocompatibility and high cell affinity.
Detailed Description
The production method and effects of the present invention will be described in further detail with specific examples.
Example 1
(1) Preparation of unsaturated aliphatic polyesters
Taking 10g (100mmol) of succinic anhydride, 7.1g (50mmol) of glycidyl methacrylate, 6.5g (50mmol) of n-butyl glycidyl ether, 0.83g (5mmol) of o-tert-butylhydroquinone and 1.755g (5mmol) of zinc isooctanoate, adding 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate to 1:1, carrying out ring-opening copolymerization reaction for 8h at 110 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The weight average molecular weight and the number average molecular weight of the obtained unsaturated aliphatic polyester were measured by Jasco Gulliver system (PU-980, CO-965, RI-930, and UV-1570) gel permeation chromatography. Polystyrene gel columns (Shodex columns K804, K805, and J806) were prepared, using THF as eluent and polystyrene as standard calibration, and measured at 30 ℃ with the following results: mw＝16432,Mn＝11255,PDI＝1.46。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of unsaturated aliphatic polyester prepared in the step 1, 1g of hydroxypropyl acrylate, 1g of hydroxyethyl methacrylate, 1g of butyl acrylate, 1g of isooctyl acrylate, and 0.025g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 4min by ultraviolet light with the light intensity of 300 mJ/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
Drying the prepared knee joint meniscus in a 60 ℃ oven for 24h to ensure that the knee joint meniscus is fully dehydrated and dried, measuring the weight of the dry tissue engineering scaffold, then soaking the knee joint meniscus in deionized water at room temperature until the swelling of the knee joint meniscus is balanced, wiping off excessive moisture on the surface of the tissue engineering scaffold by using filter paper, measuring the mass of the tissue engineering scaffold again, and finally calculating the swelling ratio.
The swelling ratio of the tissue engineering scaffold prepared in the step 2 is 943% according to the method.
2. Modulus of elasticity
The prepared knee menisci were tested in a Zwick/Roell 2202 universal materials tester (Zwick, Germany).
The elastic modulus of the prepared tissue engineering scaffold is 3.27MPa by detection according to the method
3. Cell experiments
3.1. Cell seeding
Repeatedly washing the prepared knee joint meniscus with deionized water, soaking in PBS for 1 hr, washing, repeating for 3 times, transferring the scaffold to 24-well plate, adding DMEM cell culture solution, placing in incubator, pre-wetting, inoculating cultured human liver normal cell HL-7702 on the scaffold (2.0 × 10)6Cells/100 uL/scaffold), 37 ℃ 5% CO2The cells were allowed to adhere better by culturing in an incubator for 4 hours. Then, 1mL of the culture medium was added to each well, and 5% CO was added at 37 ℃2Culturing in an incubator, and replacing the culture solution once 2 d.
3.2. Evaluation of cell viability
Taking out 24-well culture plates at 1d, 3d and 7d respectively, adding 80uL MTT solution into each well, putting into an incubator, and culturing for 4 h. Absorbing the culture solution, adding 750uL (0.4mol/L) isopropanol hydrochloride solution into each hole, incubating for 15min in an incubator, uniformly mixing by blowing, taking 200uL of each hole, transferring into a 96-hole culture plate, and detecting the light absorption value (OD value) of each hole at 540nm by using a full-automatic enzyme labeling instrument.
Cell viability%
The cell viability of the prepared tissue engineering scaffold is shown in table 1.
TABLE 1 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 102 | 117 | 106 |
As can be seen from Table 1, the prepared tissue engineering scaffold has low cytotoxicity, high cell affinity and small influence on cell activity.
3.3. Cell adhesion
The infiltration and adhesion of cells were observed by gross observation (MTT staining). Human liver normal cells HL-7702 were planted on the scaffolds and cultured in vitro for 3 days, the culture medium was aspirated, and the cells were washed 3 times with PBS, 10 minutes each time. 80uL of MTT solution was added to each well and placed in an incubator for further incubation for 4 h. Absorbing the culture solution, adding 750uL (0.4mol/L) isopropanol hydrochloride solution into each hole, incubating for 15min in an incubator, uniformly mixing by blowing, taking 200uL of each hole, transferring into a 96-hole culture plate, and detecting the light absorption value (OD value) of each hole at 540nm by using a full-automatic enzyme labeling instrument.
Cell adhesion rate = ((test cell OD-blank OD)/(control cell OD-blank OD)) × 100
The cell adhesion rate of the prepared tissue engineering scaffold is 98 percent by detection according to the method. The cell adhesion rate shows that the prepared tissue engineering scaffold has good cell adhesion and high cell affinity.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 2
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (50mmol, 7.1g), n-butyl glycidyl ether (50mmol, 6.5g), ortho-tert-butylhydroquinone (0.33g, 2mmol) and tetrabutylammonium bromide (0.64g, 2mmol), 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate to 1:1, carrying out ring-opening copolymerization reaction for 5h at 90 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The obtained unsaturated aliphatic polyester was tested as described in example 1, and the test results were: mw＝6028,Mn＝4982,PDI＝1.21。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of unsaturated aliphatic polyester prepared in step 1, 0.5g of hydroxypropyl methacrylate, 0.5g of hydroxyethyl methacrylate, 0.8g of hydroxyethyl acrylate, 1.2g of N, N-dimethylaminoethyl acrylate, 1g of butyl acrylate, 2g of 2-ethylhexyl acrylate, 0.02g of 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide and 0.02g of thiopropoxythioanthrone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 5min by ultraviolet light with the light intensity of 200 mJ/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold tested by the method described in example 1 was 864%.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested according to the method of example 1 is 2.99MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 2.
TABLE 2 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 97 | 109 | 118 |
The prepared tissue engineering scaffold has a cell adhesion rate of 105% according to the detection method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 3
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (40mmol, 5.68g), n-butyl glycidyl ether (60mmol, 7.8g), ortho-tert-butylhydroquinone (1.33g, 8mmol) and zinc acetate (0.98g, 8mmol), 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate to 1:1, carrying out ring-opening copolymerization reaction for 12h at 120 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The unsaturated aliphatic polyester obtained was examined as described in example 1, and the examination results were: mw＝21611,Mn＝12006,PDI＝1.80。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of unsaturated aliphatic polyester prepared in step 1, 0.5g of hydroxypropyl methacrylate, 0.5g of hydroxyethyl methacrylate, 0.8g of hydroxyethyl acrylate, 1.2g of N, N-dimethylaminoethyl acrylate, 1g of butyl acrylate, 2g of 2-ethylhexyl acrylate, 0.025g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone and 0.025g of thiopropoxy thioxanthone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 1min by ultraviolet light with the light intensity of 600 mJ/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold tested according to the method described in example 1 was 686%.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested according to the method described in example 1 is 3.48MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 3.
TABLE 3 cell viability of tissue engineering scaffolds
| Time (sky) | 1d | 3d | 7d |
| Cell viability% | 112 | 98 | 108 |
The prepared tissue engineering scaffold has a cell adhesion rate of 91% by performing the detection according to the method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 4
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (60mmol, 8.52g), n-butyl glycidyl ether (40mmol, 5.2g), o-tert-butylhydroquinone (1.0g, 6mmol) and cobalt isooctanoate (1.38g, 4mmol), adding 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate being 1:1, carrying out ring-opening copolymerization reaction for 10h at 100 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The unsaturated aliphatic polyester obtained was examined as described in example 1, and the examination results were: mw＝15902,Mn＝9756,PDI＝1.63。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of unsaturated aliphatic polyester prepared in step 1, 1.5g of N, N-dimethylaminoethyl acrylate, 1.0g of penta-polyethylene glycol methyl ether acrylate, 2.4g of 2-ethylhexyl acrylate, 0.005g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone, 0.015g of 2-hydroxy-2-methyl-1-phenyl acetone, and 0.015g of 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 3min by ultraviolet light with the light intensity of 300 millijoules/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold tested according to the method described in example 1 was 11228%.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested according to the method described in example 1 is 3.44MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 4.
TABLE 4 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 109 | 116 | 110 |
The prepared tissue engineering scaffold has a cell adhesion rate of 98% according to the detection method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 5
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (30mmol, 4.26g), n-butyl glycidyl ether (70mmol, 9.1g), ortho-tert-butylhydroquinone (0.664g, 4mmol) and tetra-n-butylammonium bromide (0.966g, 3mmol), 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate to 1:1, carrying out ring-opening copolymerization reaction for 5h at 90 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The unsaturated aliphatic polyester obtained was examined as described in example 1, and the examination results were: mw＝7451,Mn＝5867,PDI＝1.27。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of the unsaturated aliphatic polyester prepared in step 1, 2.2g of hydroxypropyl methacrylate, 2.8g of 2-ethylhexyl acrylate, 0.01g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone, 0.01g of 2-hydroxy-2-methyl-1-phenylpropanone, 0.01g of 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide, and 0.01g of thiopropoxythlucanthone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 4min by ultraviolet light with the light intensity of 500 millijoules/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold is 1042% by the detection method in example 1.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested according to the method of example 1 is 2.86MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 5.
TABLE 5 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 114 | 98 | 110 |
The prepared tissue engineering scaffold has a cell adhesion rate of 102% according to the detection method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 6
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (70mmol, 9.94g), n-butyl glycidyl ether (30mmol, 3.9g), ortho-tert-butylhydroquinone (0.664g, 4mmol) and tetra-n-butylammonium bromide (1.61g, 5mmol), 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate to 1:1, carrying out ring-opening copolymerization reaction for 7h at 105 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The unsaturated aliphatic polyester obtained was examined as described in example 1, and the examination results were: mw＝10218,Mn＝7683,PDI＝1.33。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of unsaturated aliphatic polyester prepared in step 1, 0.2g of hydroxyethyl methacrylate, 0.8g of hydroxypropyl methacrylate, 1g of hydroxyethyl acrylate, 0.6g of N, N-dimethylaminoethyl acrylate, 2.3g of 2-ethylhexyl acrylate, and 0.03g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 2.5min by ultraviolet light with the light intensity of 350 mJ/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold tested by the method described in example 1 was 985%.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested according to the method described in example 1 is 3.41MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 6.
TABLE 6 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 99 | 98 | 96 |
The prepared tissue engineering scaffold has a cell adhesion rate of 91% by performing the detection according to the method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 7
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (50mmol, 7.1g), n-butyl glycidyl ether (50mmol, 6.5g), ortho-tert-butylhydroquinone (0.83g, 5mmol) and tetrabutylammonium bromide (0.83g, 5mmol), 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate to 1:1, carrying out ring-opening copolymerization reaction for 6h at 115 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The unsaturated aliphatic polyester obtained was examined as described in example 1, and the examination results were: mw＝15074,Mn＝8764,PDI＝1.72。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of the unsaturated aliphatic polyester prepared in step 1, 2.5g of hydroxypropyl methacrylate, 2.8g of 2-ethylhexyl acrylate, and 0.045g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 4min by ultraviolet light with the light intensity of 450 millijoules/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold is 869 percent according to the detection of the method in the example 1.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested according to the method of example 1 is 2.86MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 7.
TABLE 7 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 97 | 99 | 95 |
The prepared tissue engineering scaffold has a cell adhesion rate of 91% by performing the detection according to the method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Example 8
(1) Preparation of unsaturated aliphatic polyesters
Taking succinic anhydride (10g, 100mmol), glycidyl methacrylate (50mmol, 7.1g), n-butyl glycidyl ether (50mmol, 6.5g), ortho-tert-butylhydroquinone (0.83g, 5mmol) and tetrabutylammonium bromide (0.83g, 5mmol), 100mL of ethyl acetate: dissolving the mixed solution with the volume ratio of butyl acetate being 1:1, carrying out ring-opening copolymerization reaction for 8h at 100 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester.
The unsaturated aliphatic polyester obtained was examined as described in example 1, and the examination results were: mw＝11558,Mn＝7362,PDI＝1.57。
(2) Preparation and Properties of Photocurable hydrogels
(a) Formulation of photo-curable hydrogels
5g of unsaturated aliphatic polyester prepared in the step 1, 2.6g of hydroxypropyl methacrylate, 2.4g of isooctyl acrylate, 0.015g of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone and 0.025g of thiopropoxy thioxanthone.
(b) Preparation of Photocurable hydrogels
And (c) uniformly mixing the raw materials in the step (a), and sealing and packaging in a closed light manner to obtain the photocuring hydrogel.
(c) Properties of photo-curing hydrogels
In order to verify the performance of the photo-curing hydrogel, the photo-curing hydrogel is firstly poured into a transparent knee joint meniscus mould, then the knee joint meniscus mould is irradiated for 1min by ultraviolet light with the light intensity of 600 mJ/square centimeter, and the tissue engineering scaffold knee joint meniscus is obtained after demoulding.
1. Swelling Properties
The swelling ratio of the prepared tissue engineering scaffold is 916 percent by the detection method of the embodiment 1.
2. Modulus of elasticity
The elastic modulus of the prepared tissue engineering scaffold tested by the method described in example 1 is 2.49MPa
3. Cell experiments
The tissue engineering scaffolds prepared by the method described in example 1 were examined for cell viability as shown in Table 8.
TABLE 8 cell viability of tissue engineering scaffolds
| Time (sky) | 1 | 3 | 7 |
| Cell viability% | 103 | 97 | 108 |
The prepared tissue engineering scaffold has a cell adhesion rate of 97% by performing the detection according to the method described in example 1.
The results show that the prepared scaffold has low cytotoxicity, good cell adhesion and high cell affinity.
Claims (7)
1. An unsaturated aliphatic polyester which is a polyester having a structure unit represented by the formula (I) and a structure unit represented by the formula (II) which are linearly and randomly arranged at a molar ratio of 3:7 to 7:3, and which has a number average molecular weight of 5000 to 12000 and a dispersibility index of 1.21 to 1.80,
the unsaturated aliphatic polyester is obtained by ring-opening copolymerization of glycidyl methacrylate, n-butyl glycidyl ether and succinic anhydride.
2. The unsaturated aliphatic polyester according to claim 1, wherein the molar ratio of the structural unit represented by the formula (I) to the structural unit represented by the formula (II) is 2:3 to 3:2, the number average molecular weight is 5000 to 10000, and the dispersibility index is preferably 1.21 to 1.60.
3. The unsaturated aliphatic polyester according to claim 1 or 2, which is produced by the following method:
adding glycidyl methacrylate, n-butyl glycidyl ether, ortho-tert-butyl hydroquinone and a catalyst into succinic anhydride, dissolving into a proper amount of mixed solution, carrying out ring-opening copolymerization reaction for 5-12 h at 90-120 ℃ under the protection of nitrogen, and removing the solvent to obtain the unsaturated aliphatic polyester; wherein,
the sum of the addition amount of the glycidyl methacrylate and the n-butyl glycidyl ether is equal to the molar amount of the succinic anhydride, and the molar ratio of the glycidyl methacrylate to the n-butyl glycidyl ether is 3: 7-7: 3;
the addition amount of the tert-butyl hydroquinone is 1-10% of the molar amount of the succinic anhydride;
the adding amount of the catalyst is 1-10% of the molar amount of the succinic anhydride;
the mixed solution consists of ethyl acetate and butyl acetate in equal volume ratio;
the catalyst is one of tetra-n-butylammonium bromide, zinc acetate, zinc isooctanoate and cobalt isooctanoate.
4. An unsaturated aliphatic polyester according to claim 3,
the molar ratio of glycidyl methacrylate to n-butyl glycidyl ether is 2: 3-3: 2;
the addition amount of the tert-butyl hydroquinone is 2-8% of the molar amount of the succinic anhydride;
the adding amount of the catalyst is 2-8% of the molar amount of the succinic anhydride;
the catalyst is tetra-n-butylammonium bromide;
the temperature of the ring-opening copolymerization reaction is 100-120 ℃;
the time of the ring-opening copolymerization reaction is 5-10 h.
5. A photo-curable hydrogel, which comprises the unsaturated aliphatic polyester, the hydrophilic unsaturated monomer, the soft unsaturated monomer and the photoinitiator according to claim 1 or 2, wherein the content of the hydrophilic unsaturated monomer is 40-60% of the weight of the unsaturated aliphatic polyester, the content of the soft unsaturated monomer is 40-60% of the weight of the unsaturated aliphatic polyester, and the content of the photoinitiator is 0.5-1% of the weight of the unsaturated aliphatic polyester;
the hydrophilic unsaturated monomer is one or more than two of hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and N, N-dimethylamino ethyl acrylate;
the soft unsaturated monomer is one or two of butyl acrylate, 2-ethylhexyl acrylate and isooctyl acrylate;
the photoinitiator is one or more than two of 4- (2-hydroxyethoxy) phenyl- (2-hydroxy-2-propyl) ketone, 2-hydroxy-2-methyl-1-phenyl acetone, 2,4, 6-trimethylbenzoyl-diphenyl phosphine oxide and thiopropoxy thioxanthone.
6. A photocurable hydrogel according to claim 5 wherein said hydrophilic unsaturated monomer is present in an amount of 50% by weight of the unsaturated aliphatic polyester and said soft unsaturated monomer is present in an amount of 50% by weight of the unsaturated aliphatic polyester.
7. Use of the photo-curable hydrogel of claim 5 or 6 for the preparation of a scaffold for tissue engineering.
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| CN110776599A (en) * | 2019-10-31 | 2020-02-11 | 南方医科大学南方医院 | Antibacterial hydrogel |
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| CN103890659A (en) * | 2011-08-26 | 2014-06-25 | 罗门哈斯电子材料韩国有限公司 | Photopolymerizable unsaturated resin, photosensitive resin composition comprising the same, and light shielding spacer and liquid crystal display device formed therefrom |
| US20140171568A1 (en) * | 2012-12-18 | 2014-06-19 | Reichhold, Inc. | Vinyl-containing compounds with high heat distortion |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110746547A (en) * | 2019-10-31 | 2020-02-04 | 南方医科大学南方医院 | Photo-curing hydrogel for preparing cell scaffold |
| CN110776599A (en) * | 2019-10-31 | 2020-02-11 | 南方医科大学南方医院 | Antibacterial hydrogel |
| CN110776599B (en) * | 2019-10-31 | 2021-12-24 | 南方医科大学南方医院 | Antibacterial hydrogel |
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