CN107459634B - 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
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- CN107459634B CN107459634B CN201710667116.4A CN201710667116A CN107459634B CN 107459634 B CN107459634 B CN 107459634B CN 201710667116 A CN201710667116 A CN 201710667116A CN 107459634 B CN107459634 B CN 107459634B
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- C08G63/52—Polycarboxylic acids or polyhydroxy compounds in which at least one of the two components contains aliphatic unsaturation
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- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
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Abstract
The present invention relates to a kind of unsaturated aliphatic polyesters, the polyester is polyester of the structural unit shown in structural unit shown in chemical formula (I) and chemical formula (II) by the linear random arrangement of molar ratio of 3:7~7:3, its number-average molecular weight is 5000~12000, and monodispersity index is 1.21~1.80；The unsaturated aliphatic polyester is by glycidyl methacrylate, and n-butyl glycidyl ether and succinic anhydride carry out ring opening copolymer and obtain.Unsaturated aliphatic polyester of the present invention can be used for preparing tissue engineering bracket, which has preferable elasticity modulus and swelling behavior, and cytotoxicity is low, good biocompatibility, and cellular affinity is high.
Description
Technical field
The present invention relates to organic high molecular compounds, and in particular to unsaturated aliphatic polyester, the unsaturated fat adoption
Ester is suitable for medical material.
Background technique
Its main chain of aliphatic polyester is formed by connecting by aliphatic structure unit by the ester bond of facile hydrolysis, and main chain is submissive,
It is easy under the action of microorganism, is degraded by the catalysis of enzyme.Therefore, aliphatic polyester is because it is with good life
Object compatibility and biodegradability are a kind of important bio-medical materials, are widely used in biomedicine field, such as drug
Sustained release, operation suture thread, bone immobilizing material, tissue engineering material etc..Common aliphatic polyester has polyglycolide (PGA), gathers
Lactide (PLA), glycolide-lactide copolymer (PLGA), polycaprolactone (PCL) etc..The synthesis side of aliphatic polyester at present
There are two types of methods.First is to be prepared using bifunctional monomer by condensation, such as be condensed and gathered with binary acid and dihydric alcohol
Conjunction obtains.Second is to use its ester compounds or lactone compound for monomer, carries out ring opening copolymer and obtains.But aliphatic poly
Ester is there are several biggish defects, and first, the hydrophily of aliphatic polyester is poor, bioactivity is low, affinity to cell and viscous
Attached power is weak.Second, the main chain of aliphatic polyester lacks reactivity site, limits the application of aliphatic polyester.
Unsaturated aliphatic polyester refers to the aliphatic polyester containing unsaturated double-bond, can be with the monomer containing unsaturated double-bond
Or prepolymer is solidified.Currently, the preparation method of unsaturated aliphatic polyester mainly uses condensation methods.Condensation methods be exactly by
Unsaturated dibasic aliphatic acid or dibasic aliphatic acid anhydrides are obtained with unsaturated dihydric alcohol polycondensation.The insatiable hunger of this method preparation
Contain unsaturated double-bond with aliphatic polyester main chain.Yang Qun etc. is with fumaric acid, diglycol and 1,4- butanediol
Raw material has synthesized unsaturated aliphatic polyester and copolyesters using melt-polycondensation, it is found that the unsaturated aliphatic polyester can be with
Biodegrade (apply chemical industry, 2013, the 3rd phase of volume 42,490).But the unsaturated fat adoption that above-mentioned document is reported
Unsaturated double-bond in ester is located at main chain, and reactivity is low, poor with other monomers containing unsaturated double-bond progress photocuring ability, no
Can apply is tissue engineering bracket.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of unsaturated aliphatic polyester, the unsaturated aliphatic polyester sides
Contain unsaturated double-bond on chain, there is good biocompatibility and low cytotoxicity with the photocuring hydrogel obtained by it.
Technical proposal that the invention solves the above-mentioned problems is:
A kind of unsaturated aliphatic polyester, the polyester are shown in structural unit shown in chemical formula (I) and chemical formula (II)
Structural unit by 3:7~7:3 the linear random arrangement of molar ratio polyester, number-average molecular weight (abbreviation Mn) be 5000~
12000, monodispersity index (abbreviation PDI) is 1.21~1.80,
The unsaturated aliphatic polyester is by glycidyl methacrylate, n-butyl glycidyl ether and fourth two
Acid anhydrides carries out ring opening copolymer and obtains.
Above-mentioned unsaturated aliphatic polyester, wherein shown in structural unit shown in the chemical formula (I) and chemical formula (II)
The molar ratio of structural unit be preferably 2:3~3:2, number-average molecular weight is 5000~10000, monodispersity index preferably 1.21
~1.60.
Above-mentioned unsaturated aliphatic polyester specific the preparation method is as follows:
Succinic anhydride is taken, glycidyl methacrylate, n-butyl glycidyl ether, tert-butylhydroquinone is added
And catalyst, it is dissolved into suitable mixed solution, under nitrogen protection, 90~120 DEG C of ring opening copolymers react 5~12h, remove
Solvent obtains the unsaturated aliphatic polyester；Wherein,
The sum of described additional amount of glycidyl methacrylate and n-butyl glycidyl ether is equal to taken fourth two
The mole of acid anhydrides, first base propylene acid glycidyl ester ester ︰ n-butyl glycidyl ether=3 ︰, 7~7 ︰ 3 molar ratio；
The additional amount of the tert-butylhydroquinone for taken succinic anhydride mole 1~10%；
The additional amount of the catalyst for taken succinic anhydride mole 1~10%；
The mixed solution is made of the ethyl acetate and butyl acetate of isometric ratio；
The catalyst is one of tetra-n-butyl ammonium bromide, zinc acetate, zinc Isoocatanoate and cobalt iso-octoate.
In the above method, the molar ratio of the first base propylene acid glycidyl ester ester ︰ n-butyl glycidyl ether is preferably
2 ︰, 3~3 ︰ 2, preferably 1 ︰ 1.
In the above method, the additional amount of the tert-butylhydroquinone is preferably the mole of taken succinic anhydride
2~8%, the 5% of the mole of preferably taken succinic anhydride.
In the above method, the additional amount of the catalyst is preferably the 2~8% of the mole of taken succinic anhydride, most
It is the 5% of the mole of taken succinic anhydride well.
In the above method, the preferred tetra-n-butyl ammonium bromide of the catalyst.
In the above method, the temperature of the ring opening copolymer reaction is preferably 100~120 DEG C, and preferably 110 DEG C；It is described
Ring opening copolymer reaction time be preferably 5~10h, preferably 6~8h.
Unsaturated aliphatic polyester of the present invention has good biocompatibility and biodegradability, and
Contain unsaturated double-bond on side chain, can be to its further functional modification or photocuring plastic, being used to prepare biological can drop
The photocuring hydrogel of solution.
Above-mentioned photocuring hydrogel by unsaturated aliphatic polyester, hydrophily unsaturated monomer, soft unsaturated monomer and
Photoinitiator composition, wherein the content of hydrophily unsaturated monomer is the 40~60% of unsaturated aliphatic polyester weight, soft
The content of unsaturated monomer is the 40~60% of unsaturated aliphatic polyester weight, and the content of photoinitiator is unsaturated aliphatic
The 0.5~1% of weight polyester；
The hydrophily unsaturated monomer is hydroxypropyl acrylate, hydroxy propyl methacrylate, hydroxyethyl methacrylate second
Ester, hydroxy-ethyl acrylate and acrylic acid-N, one of TMSDMA N dimethylamine base ethyl ester or two or more；
The soft unsaturated monomer is in butyl acrylate, acrylic acid-2-ethyl caproite and Isooctyl acrylate monomer
It is one or two kinds of；
The photoinitiator is 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone, 2- hydroxy-2-methyl -
One of 1- phenylacetone, 2,4,6- trimethylbenzoy-dipheny phosphine oxide and thio propoxyl group thioxanthone or
It is two or more.
In above-mentioned photocuring hydrogel, the content of the hydrophily unsaturated monomer is preferably unsaturated aliphatic polyester
The 50% of weight.
In above-mentioned photocuring hydrogel, the content of the soft unsaturated monomer is preferably unsaturated aliphatic polyester weight
The 50% of amount.
Photocuring hydrogel of the present invention answers black out to save, in use, the light-initiated condition of photocuring hydrogel is
Ultraviolet light light intensity is 200~600 millijoules/square centimeter, and the Photoinitiated reactions time is 1~5min.
The tissue engineering bracket of photocuring hydrogel preparation of the present invention has preferable elasticity modulus and swellability
Can, cytotoxicity is low, good biocompatibility, the high advantage of cellular affinity.
Specific embodiment
Preparation method and its effect of the invention are described in further detail with specific embodiment below.
Embodiment 1
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride 10g (100mmol), glycidyl methacrylate 7.1g (50mmol), normal-butyl is taken to shrink sweet
Oily ether 6.5g (50mmol), tert-butylhydroquinone 0.83g (5mmol) and zinc Isoocatanoate 1.755g (5mmol) are added
100mL ethyl acetate: the dissolution of butyl acetate=1:1 volume ratio mixed solution, under nitrogen protection, 110 DEG C of ring opening copolymers are anti-
8h is answered, solvent is removed and obtains unsaturated aliphatic polyester.
The weight average molecular weight for obtaining unsaturated aliphatic polyester and number-average molecular weight are used into Jasco Gulliver system
(PU-980, CO-965, RI-930, and UV-1570) gel permeation chromatograph is measured.It is equipped with Aquapak A-440 column
(Shodex col umns K804, K805, and J806) uses THF as eluant, eluent, and polystyrene is as standard correction, and 30
It is measured at DEG C, measurement result are as follows: Mw=16432, Mn=11255, PDI=1.46.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g, hydroxypropyl acrylate 1g, hydroxyethyl methacrylate 1g prepared by step 1, propylene
Acid butyl ester 1g, Isooctyl acrylate monomer 1g, 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone 0.025g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 300 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
4min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
Prepared meniscus of knee joint is placed in drying in 60 DEG C of baking oven for 24 hours, to be dehydrated it sufficiently, measures it
The weight of stem organization's engineering rack, is then soaked in deionized water at room temperature, is reached swelling equilibrium to it, is wiped with filter paper
The moisture that tissue engineering bracket surface is extra is removed, the quality of tissue engineering bracket is measured again, finally calculates swelling ratio.
The swelling ratio of tissue engineering bracket according to the preparation of above method detecting step 2 is 943%.
2. elasticity modulus
By 2202 universal testing machine of Zwick/Roell on prepared meniscus of knee joint (German Zwick company)
It is detected.
It is detected according to the above method, the elasticity modulus of prepared tissue engineering bracket is 3.27MPa
3. cell experiment
3.1. cell inoculation
Prepared meniscus of knee joint is rinsed with deionized water repeatedly, is then impregnated 1 hour and is rinsed with PBS, repeat 3
It is secondary.Bracket is transferred in 24 orifice plates, addition DMEM cell culture fluid, which is put into incubator, prewets.The people liver of culture is normally thin
Born of the same parents HL-7702 is inoculated with (2.0 × 10 on bracket6Cell/100uL/ bracket), 37 DEG C, 5%CO2Culture 4 is small in incubator
When make cell preferably adherent.Then add the culture solution of 1mL, 37 DEG C, 5%CO in each culture hole2It is cultivated in incubator, 2d is more
It is primary to change culture solution.
3.2. cell viability is evaluated
24 well culture plates are taken out in 1d, 3d, 7d respectively, every hole is added 80uL MTT solution, is put into incubator and is further continued for training
Support 4h.It inhales and abandons culture solution, every hole adds 750uL hydrochloric acid aqueous isopropanol (0.4mol/L), in being incubated for 15min in incubator, blows and beats
Every hole takes 200uL to move into 96 well culture plates after mixing, detects each hole absorbance value (OD at 540nm with full-automatic microplate reader
Value).
Cell viability %=((cell OD- blank OD to be measured)/(control cell OD- blank OD)) × 100
It is detected according to the above method, the cell viability of prepared tissue engineering bracket is as shown in table 1.
The cell viability of 1 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 102 | 117 | 106 |
By table 1 it is known that the tissue engineering bracket cytotoxicity of preparation is small, cellular affinity is high, influences on cell activity
It is small.
3.3. cell adherence
The infiltration and adherency of cell are by gross examination of skeletal muscle (MTT dyeing).People's normal cell lines of human liver HL-7702 kind plant on bracket
In vitro culture 3 days, culture solution is sucked out, PBS is rinsed 3 times, every time 10 minutes.80uL MTT solution is added in every hole, is put into incubator
Continue to cultivate 4h.It inhales and abandons culture solution, every hole adds 750uL hydrochloric acid aqueous isopropanol (0.4mol/L), in being incubated in incubator
15min, every hole takes 200uL to move into 96 well culture plates after piping and druming mixes, and each Kong Guang is detected at 540nm with full-automatic microplate reader
Absorption value (OD value).
Cell adherence rate %=((cell OD- blank OD to be measured)/(control cell OD- blank OD)) × 100
It is detected according to the above method, the cell adherence rate of prepared tissue engineering bracket is 98%.By cell adherence
For rate as it can be seen that prepared tissue engineering bracket cell adhesion is good, cellular affinity is high.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 2
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (50mmol, 7.1g), normal-butyl is taken to shrink
Glycerin ether (50mmol, 6.5g), tert-butylhydroquinone (0.33g, 2mmol) and tetrabutylammonium bromide (0.64g, 2mmol),
100mL ethyl acetate: butyl acetate=1:1 volume ratio mixed solution dissolution, under nitrogen protection, 90 DEG C of ring opening copolymers is added
5h is reacted, solvent is removed and obtains unsaturated aliphatic polyester.
Gained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=6028, Mn
=4982, PDI=1.21.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g prepared by step 1, hydroxy propyl methacrylate 0.5g, hydroxyethyl methacrylate
0.5g, hydroxy-ethyl acrylate 0.8g, acrylic acid-N, TMSDMA N dimethylamine base ethyl ester 1.2g, butyl acrylate 1g, acrylic acid-2-ethyl
Own ester 2g, 2,4,6- trimethylbenzoy-dipheny phosphine oxide 0.02g, thio propoxyl group thioxanthone 0.02g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 200 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
5min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 864%.
2. elasticity modulus
It is detected by 1 the method for embodiment, the elasticity modulus of prepared tissue engineering bracket is 2.99MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 2.
The cell viability of 2 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 97 | 109 | 118 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 105%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 3
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (40mmol, 5.68g), normal-butyl is taken to shrink
Glycerin ether (60mmol, 7.8g), tert-butylhydroquinone (1.33g, 8mmol) and zinc acetate (0.98g, 8mmol) are added
100mL ethyl acetate: the dissolution of butyl acetate=1:1 volume ratio mixed solution, under nitrogen protection, 120 DEG C of ring opening copolymers are anti-
12h is answered, solvent is removed and obtains unsaturated aliphatic polyester.
Obtained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=
21611,Mn=12006, PDI=1.80.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g prepared by step 1, hydroxy propyl methacrylate 0.5g, hydroxyethyl methacrylate
0.5g, hydroxy-ethyl acrylate 0.8g, acrylic acid-N, TMSDMA N dimethylamine base ethyl ester 1.2g, butyl acrylate 1g, acrylic acid-2-ethyl
Own ester 2g, 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone 0.025g, thio propoxyl group thioxanthone 0.025g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 600 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
1min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 686%.
2. elasticity modulus
It is detected by 1 the method for embodiment, the elasticity modulus of prepared tissue engineering bracket is 3.48MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 3.
The cell viability of 3 tissue engineering bracket of table
| Time (day) | 1d | 3d | 7d |
| Cell viability % | 112 | 98 | 108 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 91%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 4
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (60mmol, 8.52g), normal-butyl is taken to shrink
Glycerin ether (40mmol, 5.2g), tert-butylhydroquinone (1.0g, 6mmol) and cobalt iso-octoate (1.38g, 4mmol) are added
100mL ethyl acetate: the dissolution of butyl acetate=1:1 volume ratio mixed solution, under nitrogen protection, 100 DEG C of ring opening copolymers are anti-
10h is answered, solvent is removed and obtains unsaturated aliphatic polyester.
Obtained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=
15902,Mn=9756, PDI=1.63.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g, acrylic acid-N, TMSDMA N dimethylamine base ethyl ester 1.5g prepared by step 1, five polyethylene glycol
Methyl ether acetate 1.0g, acrylic acid-2-ethyl caproite 2.4g, 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone
0.005g, 2- hydroxy-2-methyl -1- phenylacetone 0.015g, 2,4,6- trimethylbenzoy-dipheny phosphine oxides
0.015g。
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 300 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
3min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 11228%.
2. elasticity modulus
It is detected by 1 the method for embodiment, the elasticity modulus of prepared tissue engineering bracket is 3.44MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 4.
The cell viability of 4 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 109 | 116 | 110 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 98%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 5
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (30mmol, 4.26g), normal-butyl is taken to shrink
Glycerin ether (70mmol, 9.1g), tert-butylhydroquinone (0.664g, 4mmol) and tetra-n-butyl ammonium bromide (0.966g,
3mmol), 100mL ethyl acetate: butyl acetate=1:1 volume ratio mixed solution dissolution, under nitrogen protection, 90 DEG C is added
Ring opening copolymer reacts 5h, removes solvent and obtains unsaturated aliphatic polyester.
Obtained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=
7451,Mn=5867, PDI=1.27.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g prepared by step 1, hydroxy propyl methacrylate 2.2g, acrylic acid-2-ethyl caproite
2.8g, 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone 0.01g, 2- hydroxy-2-methyl -1- phenylacetone
0.01g, 2,4,6- trimethylbenzoy-dipheny phosphine oxide 0.01g, thio propoxyl group thioxanthone 0.01g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 500 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
4min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 1042%.
2. elasticity modulus
It is detected by 1 the method for embodiment, the elasticity modulus of prepared tissue engineering bracket is 2.86MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 5.
The cell viability of 5 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 114 | 98 | 110 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 102%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 6
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (70mmol, 9.94g), normal-butyl is taken to shrink
Glycerin ether (30mmol, 3.9g), tert-butylhydroquinone (0.664g, 4mmol) and tetra-n-butyl ammonium bromide (1.61g,
5mmol), 100mL ethyl acetate: butyl acetate=1:1 volume ratio mixed solution dissolution, under nitrogen protection, 105 DEG C is added
Ring opening copolymer reacts 7h, removes solvent and obtains unsaturated aliphatic polyester.
Obtained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=
10218,Mn=7683, PDI=1.33.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g prepared by step 1, hydroxyethyl methacrylate 0.2g, hydroxy propyl methacrylate
0.8g, hydroxy-ethyl acrylate 1g, acrylic acid-N, TMSDMA N dimethylamine base ethyl ester 0.6g, acrylic acid-2-ethyl caproite 2.3g, 4- (2- hydroxyl
Base oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone 0.03g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 350 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
2.5min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 985%.
2. elasticity modulus
It is detected by 1 the method for embodiment, the elasticity modulus of prepared tissue engineering bracket is 3.41MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 6.
The cell viability of 6 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 99 | 98 | 96 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 91%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 7
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (50mmol, 7.1g), normal-butyl is taken to shrink
Glycerin ether (50mmol, 6.5g), tert-butylhydroquinone (0.83g, 5mmol) and tetrabutylammonium bromide (0.83g, 5mmol),
100mL ethyl acetate is added: the dissolution of butyl acetate=1:1 volume ratio mixed solution, under nitrogen protection, 115 DEG C of open loops are total
Poly- reaction 6h, removes solvent and obtains unsaturated aliphatic polyester.
Obtained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=
15074,Mn=8764, PDI=1.72.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g prepared by step 1, hydroxy propyl methacrylate 2.5g, acrylic acid-2-ethyl caproite
2.8g, 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone 0.045g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 450 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
4min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 869%.
2. elasticity modulus
It is detected by 1 the method for embodiment, the elasticity modulus of prepared tissue engineering bracket is 2.86MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 7.
The cell viability of 7 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 97 | 99 | 95 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 91%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Embodiment 8
(1) preparation of unsaturated aliphatic polyester
Succinic anhydride (10g, 100mmol), glycidyl methacrylate (50mmol, 7.1g), normal-butyl is taken to shrink
Glycerin ether (50mmol, 6.5g), tert-butylhydroquinone (0.83g, 5mmol) and tetrabutylammonium bromide (0.83g, 5mmol),
100mL ethyl acetate is added: the dissolution of butyl acetate=1:1 volume ratio mixed solution, under nitrogen protection, 100 DEG C of open loops are total
Poly- reaction 8h, removes solvent and obtains unsaturated aliphatic polyester.
Obtained unsaturated aliphatic polyester is detected by 1 the method for embodiment, testing result are as follows: Mw=
11558,Mn=7362, PDI=1.57.
(2) preparation and its performance of photocuring hydrogel
(a) formula of photocuring hydrogel
Unsaturated aliphatic polyester 5g, hydroxy propyl methacrylate 2.6g, Isooctyl acrylate monomer 2.4g prepared by step 1,
4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone 0.015g, thio propoxyl group thioxanthone 0.025g.
(b) preparation of photocuring hydrogel
Above-mentioned steps (a) raw material is uniformly mixed, black out encapsulates to get the photocuring hydrogel.
(c) photocuring hydrogel performance
For the performance for verifying photocuring hydrogel of the present invention, above-mentioned photocuring hydrogel is filled into first transparent
It is then 600 millijoules/square centimeter ultraviolet light by the meniscus of knee joint mold light intensity in meniscus of knee joint mold
1min is irradiated, tissue engineering bracket meniscus of knee joint is obtained after demoulding.
1. swelling behavior
It is detected by 1 the method for embodiment, the swelling ratio of prepared tissue engineering bracket is 916%.
2. elasticity modulus
1 the method for embodiment is detected, and the elasticity modulus of prepared tissue engineering bracket is 2.49MPa
3. cell experiment
It is detected by 1 the method for embodiment, the cell viability of prepared tissue engineering bracket is as shown in table 8.
The cell viability of 8 tissue engineering bracket of table
| Time (day) | 1 | 3 | 7 |
| Cell viability % | 103 | 97 | 108 |
It is detected by 1 the method for embodiment, the cell adherence rate of prepared tissue engineering bracket is 97%.
The above results show that prepared bracket cytotoxicity is low, and cell adhesion is good, and cellular affinity is high.
Claims (7)
1. a kind of unsaturated aliphatic polyester, which is shown in structural unit shown in chemical formula (I) and chemical formula (II)
Structural unit is by the polyester of the linear random arrangement of molar ratio of 3:7~7:3, and number-average molecular weight is 5000~12000, dispersibility
Index is 1.21~1.80,
The unsaturated aliphatic polyester is by glycidyl methacrylate, n-butyl glycidyl ether and succinic anhydride
Ring opening copolymer is carried out to obtain.
2. unsaturated aliphatic polyester according to claim 1, which is characterized in that structure shown in the chemistry formula (I)
The molar ratio of structural unit shown in unit and chemical formula (II) is 3:7~7:3, and number-average molecular weight is 5000~10000, dispersion
Sex index is 1.21~1.60.
3. unsaturated aliphatic polyester according to claim 1 or 2, which is characterized in that the unsaturated aliphatic polyester by
Following methods are made:
Succinic anhydride is taken, glycidyl methacrylate, n-butyl glycidyl ether, tert-butylhydroquinone is added and is urged
Agent is dissolved into suitable mixed solution, and under nitrogen protection, 90~120 DEG C of ring opening copolymers react 5~12h, removes solvent
Obtain the unsaturated aliphatic polyester；Wherein,
The sum of described additional amount of glycidyl methacrylate and n-butyl glycidyl ether is equal to taken succinic anhydride
Mole, first base propylene acid glycidyl ester ester ︰ n-butyl glycidyl ether=3 ︰, 7~7 ︰ 3 molar ratio；
The additional amount of the tert-butylhydroquinone for taken succinic anhydride mole 1~10%；
The additional amount of the catalyst for taken succinic anhydride mole 1~10%；
The mixed solution is made of the ethyl acetate and butyl acetate of isometric ratio；
The catalyst is one of tetra-n-butyl ammonium bromide, zinc acetate, zinc Isoocatanoate and cobalt iso-octoate.
4. a kind of unsaturated aliphatic polyester according to claim 3, which is characterized in that
The molar ratio of the first base propylene acid glycidyl ester ester ︰ n-butyl glycidyl ether is 3 ︰, 7~7 ︰ 3；
The additional amount of the tert-butylhydroquinone is the 2~8% of the mole of taken succinic anhydride；
The additional amount of the catalyst is the 2~8% of the mole of taken succinic anhydride；
The catalyst is tetra-n-butyl ammonium bromide；
The temperature of the ring opening copolymer reaction is 100~120 DEG C；
The time of the ring opening copolymer reaction is 5~10h.
5. a kind of photocuring hydrogel, the photocuring hydrogel is by unsaturated aliphatic polyester of any of claims 1 or 2, parent
Aqueous unsaturated monomer, soft unsaturated monomer and photoinitiator composition, wherein the content of hydrophily unsaturated monomer is insatiable hunger
With the 40~60% of aliphatic polyester weight, the content of soft unsaturated monomer be unsaturated aliphatic polyester weight 40~
60%, the content of photoinitiator is the 0.5~1% of unsaturated aliphatic polyester weight；
The hydrophily unsaturated monomer is hydroxypropyl acrylate, hydroxy propyl methacrylate, hydroxyethyl methacrylate, third
Olefin(e) acid hydroxyl ethyl ester and acrylic acid-N, one of TMSDMA N dimethylamine base ethyl ester or two or more；
The soft unsaturated monomer is one of butyl acrylate and Isooctyl acrylate monomer or two kinds；
The photoinitiator is 4- (2- hydroxyl-oxethyl) phenyl-(2- hydroxyl -2- propyl) ketone, 2- hydroxy-2-methyl -1- benzene
One of benzylacetone, 2,4,6- trimethylbenzoy-dipheny phosphine oxide and thio propoxyl group thioxanthone or two kinds
More than.
6. a kind of photocuring hydrogel according to claim 5, it is characterised in that the hydrophily unsaturated monomer
Content is the 50% of unsaturated aliphatic polyester weight, and the content of the soft unsaturated monomer is unsaturated aliphatic polyester
The 50% of weight.
7. photocuring hydrogel described in claim 5 or 6 is preparing the application in tissue engineering bracket.
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