CN107236135A - Gelatin hydrogel and preparation method and application thereof - Google Patents
Gelatin hydrogel and preparation method and application thereof Download PDFInfo
- Publication number
- CN107236135A CN107236135A CN201710552351.7A CN201710552351A CN107236135A CN 107236135 A CN107236135 A CN 107236135A CN 201710552351 A CN201710552351 A CN 201710552351A CN 107236135 A CN107236135 A CN 107236135A
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- China
- Prior art keywords
- gelatin
- hydrogel
- network
- cross
- modified
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229920000159 gelatin Polymers 0.000 title claims abstract description 120
- 235000019322 gelatine Nutrition 0.000 title claims abstract description 120
- 108010010803 Gelatin Proteins 0.000 title claims abstract description 119
- 235000011852 gelatine desserts Nutrition 0.000 title claims abstract description 119
- 239000008273 gelatin Substances 0.000 title claims abstract description 117
- 239000000017 hydrogel Substances 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000004132 cross linking Methods 0.000 claims abstract description 47
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 44
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 44
- 125000004386 diacrylate group Chemical group 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000012986 modification Methods 0.000 claims abstract description 12
- 230000004048 modification Effects 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 7
- GJKGAPPUXSSCFI-UHFFFAOYSA-N 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Chemical compound CC(C)(O)C(=O)C1=CC=C(OCCO)C=C1 GJKGAPPUXSSCFI-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
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- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- -1 methyl Acrylamido Chemical group 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims 1
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- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 abstract description 10
- 238000006731 degradation reaction Methods 0.000 abstract description 10
- 230000003197 catalytic effect Effects 0.000 abstract description 2
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- 239000000243 solution Substances 0.000 description 19
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- 238000000034 method Methods 0.000 description 9
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- 230000000052 comparative effect Effects 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
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- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 4
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- 102000008186 Collagen Human genes 0.000 description 3
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- IBFYXTRXDNAPMM-BVTMAQQCSA-N Geniposide Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=CC2)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O IBFYXTRXDNAPMM-BVTMAQQCSA-N 0.000 description 2
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- 230000009286 beneficial effect Effects 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
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- 125000005641 methacryl group Chemical group 0.000 description 2
- 229960000282 metronidazole Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
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- 230000009471 action Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
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- 230000007613 environmental effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
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- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
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- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
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- 108090000765 processed proteins & peptides Proteins 0.000 description 1
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- 239000002994 raw material Substances 0.000 description 1
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- 230000008719 thickening Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
Classifications
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Abstract
The invention discloses a gelatin hydrogel which is a porous three-network structure filled with water molecules, wherein a first network is a cross-linking network between modified gelatins, a second network is a cross-linking network between polyethylene glycol diacrylate, and a third network is a cross-linking network between the modified gelatins and the polyethylene glycol diacrylate. The invention also discloses a preparation method of the gelatin hydrogel, which is characterized in that the gelatin hydrogel is prepared by crosslinking the modified gelatin and the polyethylene glycol diacrylate by utilizing an ultraviolet light catalytic crosslinking technology. The gelatin hydrogel can regulate and control the elastic modulus and the degradation performance of the scaffold by changing the modification degree of the modified gelatin and the addition amount of the polyethylene glycol diacrylate, can better adjust the structure according to the requirements of different tissue engineering scaffolds, provides proper space and strength for the growth of cells, and forms an ordered spatial structure.
Description
Technical field
The present invention relates to tissue engineering technique field.More particularly, to a kind of gelatin hydrogel and preparation method thereof and
Using.
Background technology
Gelatin is that a kind of collagen passes through the natural macromolecular that hydrolysis is obtained, and its protein structure determines that it has good life
Thing compatibility and biodegradability, no immunogenicity compared with collagen, machinability are strong, and remain what collagen had
Cellular adhesion peptide and Proteinase cleavage site.Therefore gelatin hydrogel and gelatin-based composite aquogel are widely used in group
Weaver's journey.
Gelatin hydrogel for organizational project can be injected into body in the form of cell/carrier complexes, and
In-situ solidifying reaches the purpose of repair deficiency, can also in vitro solidify and be implanted directly into vivo, and can add in hydrogel
Plus different medicines, reach specific slow release effect.
Generally there is two ways to prepare gelatin hydrogel, a kind of is the characteristic of the collosol and gel conversion using gelatin in itself,
Gelatin solution forms physical cross-linking hydrogel by hydrogen bond action at low temperature；Another is method of the gelatin by chemical crosslinking
Form the hydrogel of covalent cross-linking.All there is respective shortcoming in both approaches：First, pure gelatin hydrogel poor mechanical property,
It is soluble in water under body temperature to maintain its gel state, limit its application；Secondly, the hydrogel of chemical crosslinking is often adopted
Crosslinking agent has formaldehyde, glutaraldehyde, EDC and Geniposide etc., and aldehydes has stronger toxicity, and EDC and Geniposide are expensive all
Limit its application.
Accordingly, it is desirable to provide a kind of safe, mechanical strength and the gelatin that degradation property is controllable and production cost is low
Hydrogel.
The content of the invention
It is an object of the present invention to provide a kind of gelatin hydrogel.
It is another object of the present invention to provide a kind of preparation method of gelatin hydrogel.
It is another object of the present invention to provide a kind of application of gelatin hydrogel.
To reach above-mentioned first purpose, the present invention uses following technical proposals：
A kind of gelatin hydrogel, be hydrone filling porous three network structure, wherein first network be modified gelatin it
Between cross-linked network, the second network be polyethyleneglycol diacrylate between cross-linked network, the 3rd network be modified gelatin with
Cross-linked network between polyethyleneglycol diacrylate.The gelatin hydrogel of the present invention is constituted by these three networks are interspersed mutually,
The stability of hydrogel is improved, and the degradation speed of heterogeneous networks is different, it is to avoid the fast degradation of single network, to maintaining
Hydrogel physical aspect is advantageously.
Modified gelatin and polyethyleneglycol diacrylate cooperate in the gelatin hydrogel of the present invention, synergy, no
The problem of traditional chemical crosslinking crosslinking agent toxicity used is larger is only overcome, product is safer, and adds gelatin water-setting
The amount of unsaturated double-bond in glue, makes in gelatin hydrogel crosslinking points increase, improves the crosslinking degree of hydrogel, and can be with
By adjusting the degree of modification of modified gelatin and the amount of polyethyleneglycol diacrylate, that realizes mechanical strength and degradation property can
Control regulation.
Preferably, count by weight, the gelatin hydrogel includes：1~30 part of modified gelatin, the double propylene of polyethylene glycol
1~40 part of acid esters, 20~80 parts of water.
Preferably, the modified gelatin is the gelatin that unsaturated double-bond is carried after side-chain amino group is modified.The present invention is used
Modified gelatin with unsaturated double-bond, can be by ultraviolet light-initiated cross-linking reaction.
Preferably, the modified gelatin can be methacryl amido gelatin.Methacryl amido is bright in the present invention
Self space steric hindrance is smaller while xanthan molecule chain introduces unsaturated double-bond, beneficial to the photo-crosslinking between molecule.
Preferably, the methacryl amido degree of modification of the modified gelatin is 50~100%.In some tools of the present invention
In body embodiment, the methacryl amido degree of modification of the modified gelatin can be, for example：50~75%, 50~88%, 75
~100%, 75~88%, 88~100% etc..The degree of modification of modified gelatin is in the scope in the present invention, obtained gelatin
Hydrogel crosslinking degree is higher, three-dimensional structure more consolidation.More preferably 75~88%, in the range of more preferably, obtained result
It is more excellent.
Preferably, the modified gelatin is prepared using conventional method, it is highly preferred that preparation method is as follows：First by gelatin
Put and be swelled in cold water 30 minutes, then in 50 DEG C of stirring and dissolvings, obtain the gelatin solution that mass volume ratio is 5%-30%.Then
Methacrylic anhydride is added in gelatin solution, in 50 DEG C of stirring reactions 3 hours, by controlling addition and reaction time to adjust
The degree of modification of gelatin.Liquid is fitted into 8-14kD bag filter after reaction, is placed in 50 DEG C of deionized waters and stirs 5 days, every 4 is small
Deionized water of Shi Genghuan, obtains methacryl amido gelatin after finally liquid freezing is dried.
Preferably, the molecular weight of the polyethyleneglycol diacrylate is less than 2000；In some specific implementations of the present invention
In mode, the molecular weight of the polyethyleneglycol diacrylate can be, for example：Molecular weight≤575,575≤molecular weight<2000、
575≤molecular weight≤1800,575≤molecular weight≤700, molecular weight≤700,700≤molecular weight<2000th, 700≤molecular weight≤
1800th, molecular weight≤1800,1800≤molecular weight<2000 etc..The present invention introduces the poly- second two of low molecule amount in reaction system
Alcohol double methacrylate, it has the higher free degree in system, and is bi-functional monomer, and the unsaturation added in system is double
The amount of key, makes crosslinking points increase in system, and the crosslinking degree of the hydrogel of raising realizes the degree of cross linking, mechanical property and degraded
The controllable adjustment of performance.
To reach above-mentioned second purpose, the present invention uses following technical proposals：
A kind of preparation method of above-mentioned gelatin hydrogel, comprises the following steps：
The gelatin hydrogel is by the way that modified gelatin and polyethyleneglycol diacrylate are prepared through ultraviolet photo-initiated crosslinking.
The present invention prepares gelatin hydrogel using ultraviolet light-initiated cross-linking reaction, overcome traditional chemical crosslinking crosslinking agent toxicity used compared with
Big the problem of, product safety environmental protection, simultaneously because injection aquagel can be prepared into the characteristics of ultraviolet light cross-linking, it is former in vivo
Position polymerization.
Preferably, the ultraviolet wavelength can be 254nm or 365nm.
Preferably, the temperature of the cross-linking reaction is 25~50 DEG C；It is described in some embodiments of the present invention
The temperature of cross-linking reaction can be, for example：25~45 DEG C, 25~40 DEG C, 25~35 DEG C, 25~30 DEG C, 30~50 DEG C, 30~45
DEG C, 30~40 DEG C, 30~35 DEG C, 35~50 DEG C, 35~45 DEG C, 35~40 DEG C, 40~50 DEG C, 40~45 DEG C, 45~50 DEG C etc..
Preferably, the time of the cross-linking reaction is 5~20 minutes.In some embodiments of the present invention, institute
Stating the time of cross-linking reaction can be, for example：5~15 minutes, 5~12 minutes, 5~10 minutes, 5~8 minutes, 8~20 minutes, 8
~15 minutes, 8~12 minutes, 8~10 minutes, 10~20 minutes, 10~15 minutes, 10~12 minutes, 12~20 minutes, 12~
15 minutes, 15~20 minutes etc., more preferably 10~20 in more preferably scheme, and obtained result is more excellent.
Preferably, the light trigger of the cross-linking reaction is BASF light trigger Irgacure 2959.
Preferably, the preparation of the gelatin hydrogel specifically includes following steps：
Modified gelatin, light trigger and water are mixed to get mixed liquor A, by polyethyleneglycol diacrylate and mixed liquor A
Mixed liquid B is mixed to obtain, mixed liquid B is placed in into cross-linking reaction under ultraviolet light obtains gelatin hydrogel.
Preferably, the mass ratio of the modified gelatin and light trigger is 1~300:1.In some specific realities of the present invention
Apply in mode, the mass ratio of the modified gelatin and light trigger can be, for example：1~200:1st, 1~100:1st, 1~50:1、1
~40:1st, 1~30:1st, 1~25:1st, 1~20:1st, 1~10:1st, 1~5:1st, 1~2.5:1st, 2.5~300：1st, 2.5~200:1、
2.5~100:1st, 2.5~50:1st, 2.5~40:1st, 2.5~30:1st, 2.5~25:1st, 2.5~20:1st, 2.5~10:1st, 2.5~
5:1st, 5~300：1st, 5~200:1st, 5~100:1st, 5~50:1st, 5~40:1st, 5~30:1st, 5~25:1st, 5~20:1st, 5~10:
1st, 10~300：1st, 10~200:1st, 10~100:1st, 10~50:1st, 10~40:1st, 10~30:1st, 10~25:1st, 10~20:1、
20~300：1st, 20~200:1st, 20~100:1st, 20~50:1st, 20~40:1st, 20~30:1st, 20~25:1st, 25~300:1、
25~200:1st, 25~100:1st, 25~50:1st, 25~40:1st, 25~30:1st, 30~300:1st, 30~200:1st, 30~100:1、
30~50:1st, 30~40:1st, 40~300:1st, 40~200:1st, 40~100:1st, 40~50:1st, 50~300:1st, 50~200:1、
50~100:1st, 100~300:1st, 100~200:1st, 200~300:1 etc., more preferably 20~40:1, in the range of more preferably,
Obtained result is more excellent.
Preferably, the mixed method of the mixed liquor A is：Modified gelatin is added in the solution containing light trigger and mixed
It is even.
Preferably, the mixed method of the mixed liquid B is：Polyethyleneglycol diacrylate is added in mixed liquor A and mixed.
To reach above-mentioned 3rd purpose, the present invention uses following technical proposals：
A kind of above-mentioned gelatin hydrogel is in biological support, the thin application for running the fields such as culture, medicine controlled releasing and organizational project.
In addition, unless otherwise specified, it is raw materials used in the present invention can be by commercially available commercially available, described in the present invention
What any number that any scope includes between any numerical value and end value or end value between end value and end value was constituted
Any subrange.
Beneficial effects of the present invention are as follows：
(1) the problem of crosslinking agent toxicity used is larger is crosslinked instant invention overcomes traditional chemical, product is safer.
(2) instant invention overcomes conventional physical crosslinking mechanics intensity difference and the too fast shortcoming of degradation rate in water, lead to
The degree of modification of modified gelatin and the amount of polyethyleneglycol diacrylate are overregulated, realize mechanical strength and degradation property can
Control regulation.
(3) instant invention overcomes the low shortcoming of single modified gelatin ultraviolet catalytic crosslinking degree, carried out by gelatin itself
Acrylated avtive spot is less, so carrying out for having after the simple progress graft modification to gelatin is ultraviolet light-initiated
Activated centre is also less, while gelatine molecular weight is big, with larger space hyte, also limit the crosslinking effect of modified gelatin
Rate.The polyethyleneglycol diacrylate of low molecule amount is introduced in reaction system, it has the higher free degree in system, and
For bi-functional monomer, the amount of the unsaturated double-bond in system is added, makes crosslinking points increase, the friendship of the hydrogel of raising in system
Connection degree, realizes the controllable adjustment of the degree of cross linking, mechanical property and degradation property.
(4) method that the present invention prepares hydrogel by the way of ultraviolet photo-initiated crosslinking, i.e., can realize hydrogel
External preparation, can be prepared into injection aquagel and solidify in vivo again.
(5) hydrogel prepared by the present invention is three network aqueous gels, and first network is cross-linked network between modified gelatin,
Second network is cross-linked network between polyethyleneglycol diacrylate, and the 3rd network is modified gelatin and the double acrylic acid of polyethylene glycol
Ester cross-linked network, prepared hydrogel is constituted by these three networks are interspersed mutually, improves the stability of hydrogel, and not
It is different with the degradation speed of network, it is to avoid the fast degradation of single network, to maintaining hydrogel physical aspect advantageously.
(6) preparation method process of the present invention is simple, and production cost is low, easily large-scale production.
Brief description of the drawings
The embodiment to the present invention is described in further detail below in conjunction with the accompanying drawings.
Fig. 1 shows that the weight-loss ratio of product and the schematic diagram of time relationship is made in the embodiment of the present invention 2 and comparative example 1.
Fig. 2 shows the ESEM (SEM) of methacryl amido gelatin cross-linked hydrogel made from comparative example 1 of the present invention
Figure.
Fig. 3 shows methacryl amido gelatin made from the embodiment of the present invention 2-polyethyleneglycol diacrylate crosslinking
ESEM (SEM) figure of hydrogel.
Embodiment
In order to illustrate more clearly of the present invention, the present invention is done further with reference to preferred embodiments and drawings
It is bright.It will be appreciated by those skilled in the art that specifically described content is illustrative and be not restrictive below, should not be with this
Limit the scope of the invention.
Embodiment 1
A kind of preparation of gelatin hydrogel, comprises the following steps：
(1) weigh 10g gelatin to be added in 100mL deionized water, room temperature is swelled 1h, stirred in 60 DEG C of waters bath with thermostatic control
To being completely dissolved.16mL methacrylic anhydrides are added drop-wise in gelatin solution with 1mL/min speed, in 50 DEG C of constant-temperature table
Middle concussion reaction 4h, then adds 50 DEG C of 400mL deionized water dilute reaction solution, and the solution after dilution is loaded into 8-14kDa
Bag filter in, in 50 DEG C of deionized water dialyse 1 week, every 4 hours replacing deionized water, dialyzate is existed after terminating
3000rpm centrifugation 10min, takes supernatant, is placed in -80 DEG C of refrigerator overnights, carries out freeze-drying and obtains methacryl in 3 days
Amido gelatin, degree of modification 88%.
(2) configuration Irgacure 2959 mass concentration 0.25wt% aqueous solution 50mL, is placed in 40 DEG C of waters bath with thermostatic control and stirs
Dissolving is mixed, the methacryl amido gelatin 2.5g stirring and dissolvings after freezing are taken, polyethyleneglycol diacrylate is then added and (divides
Son measures 575) 2.5g stirring and dissolvings, and solution is placed in into power for 10mW/cm2365nm uviol lamps under react 10min, obtain this
The gelatin hydrogel of invention is the hydrogel of methacryl amido gelatin-polyethyleneglycol diacrylate crosslinking.
Embodiment 2
A kind of preparation of gelatin hydrogel, comprises the following steps：
(1) weigh 10g gelatin to be added in 100mL deionized water, room temperature is swelled 1h, stirred in 60 DEG C of waters bath with thermostatic control
To being completely dissolved.16mL methacrylic anhydrides are added drop-wise in gelatin solution with 1mL/min speed, in 50 DEG C of constant-temperature table
Middle concussion reaction 4h, then adds 50 DEG C of 400mL deionized water dilute reaction solution, and the solution after dilution is loaded into 8-14kDa
Bag filter in, in 50 DEG C of deionized water dialyse 1 week, every 4 hours replacing deionized water, dialyzate is existed after terminating
3000rpm centrifugation 10min, takes supernatant, is placed in -80 DEG C of refrigerator overnights, carries out freeze-drying and obtains methacryl in 3 days
Amido gelatin, degree of modification 88%.
(2) configuration Irgacure 2959 mass concentration 0.5wt% aqueous solution 50mL, is placed in 40 DEG C of waters bath with thermostatic control and stirs
Dissolving is mixed, the methacryl amido gelatin 5g stirring and dissolvings after freezing are taken, polyethyleneglycol diacrylate (molecule is then added
700) 2.5g stirring and dissolvings are measured, solution is placed in power for 10mW/cm2365nm uviol lamps under react 15min, obtain this hair
Bright gelatin hydrogel is the hydrogel of methacryl amido gelatin-polyethyleneglycol diacrylate crosslinking.
Weight-loss ratio is tested：
The hydrogel of the methacryl amido gelatin of the present invention-polyethyleneglycol diacrylate crosslinking is taken into 1cm respectively
× 1cm × 0.5cm water-setting blob, weighs and is denoted as W0, in the deionized water for being placed in 37 DEG C, washed off per 24h taking-ups with blotting paper
Surface moisture, weighs and is denoted as W, calculates weight-loss ratio, continuous 7 days, sets 3 groups of parallel laboratory tests, average；Wherein weight-loss ratio=1-
W/W0。
Test result is as shown in figure 1, compared with initial mass, the double acrylic acid of methacryl amido gelatin-polyethylene glycol
Ester crosslinking hydrogel first day weight-loss ratio be 5.1%, the 5th day be 9.1%, the 7th day be 9.7%, weight-loss ratio with when
Between gradually tend towards stability, and the methacryl amido gelatin cross-linked hydrogel weight-loss ratio in comparative example 1 is generally higher than methyl-prop
The hydrogel of acrylamide base gelatin-polyethyleneglycol diacrylate crosslinking, and do not show within the testing time of 7 days
In stable trend.It can be seen that water of the hydrogel of methacryl amido gelatin-polyethyleneglycol diacrylate crosslinking at 37 DEG C
More preferably, the quality of the hydrogel after 7 days is still more than the 90% of initial mass for middle stability.This is due to the double propylene of polyethylene glycol
The addition of acid esters causes the amount increase of unsaturated double-bond in system, and system crosslinking degree rise, heat endurance is more preferable.
Fig. 3 is methacryl amido gelatin-polyethyleneglycol diacrylate cross-linked hydrogel made from the present embodiment
In ESEM (SEM) figure, Fig. 3, because the addition of polyethyleneglycol diacrylate causes methacryl amido gelatin molecule
There is the structure of rib strip shaped in crosslink density increase between chain, surface, and hole wall is thickening.Due to can ultraviolet light in the presence of two kinds in system
Trigger the monomer of crosslinking, so forming porous three network structure, wherein first network is the cross-linked network between modified gelatin, the
Two networks are the cross-linked network between polyethyleneglycol diacrylate, and the 3rd network is modified gelatin and the double acrylic acid of polyethylene glycol
Cross-linked network between ester, preparation-obtained hydrogel is that three kinds of networks intert mutually composition.So methacryl amido
The crosslinking degree of gelatin-polyethyleneglycol diacrylate cross-linked hydrogel is higher, and structure is more stablized.
Comparative example 1
A kind of methacryl amido gelatin cross-linked hydrogel, method and step be the same as Example 2 the difference is that only：Step
It is rapid 2) in be added without polyethyleneglycol diacrylate.
Methacryl amido gelatin cross-linked hydrogel is made, weight-loss ratio test, method of testing be the same as Example are carried out to it
2, as a result as shown in Figure 1.Methacryl amido gelatin cross-linked hydrogel weight-loss ratio in comparative example 1 is generally higher than embodiment 2
The hydrogel of middle methacryl amido gelatin-polyethyleneglycol diacrylate crosslinking, and do not have within the testing time of 7 days
Show the trend tended towards stability.
Fig. 2 shows ESEM (SEM) figure of methacryl amido gelatin cross-linked hydrogel, as shown in Fig. 2 can see
Go out that simple methacryl amido gelatin cross-linked hydrogel internal structure is more regular, aperture is basically identical, is single network
Structure.
Embodiment 3
A kind of preparation of gelatin hydrogel, comprises the following steps：
(1) weigh 1000g gelatin to be added in 10L deionized water, room temperature is swelled 1h, stirred in 60 DEG C of waters bath with thermostatic control
To being completely dissolved.800mL methacrylic anhydrides are added drop-wise in gelatin solution with 50mL/min speed, in 50 DEG C of reactor
Middle stirring reaction 4h, then adds 50 DEG C of 40L deionized water dilute reaction solution, and it is small that the solution after dilution is carried out into ultrafiltration 8
When, using filter membrane 8kDa, filtrate is placed in -80 DEG C of refrigerator overnights, it is bright that progress freeze-drying obtains methacryl amido in 3 days
Glue, degree of modification 75%.
(2) configuration Irgacure 2959 mass concentration 0.5wt% aqueous solution 1L, is placed in 30 DEG C of waters bath with thermostatic control and stirs
Dissolving, takes the methacryl amido gelatin 200g stirring and dissolvings after freezing, and then adds polyethyleneglycol diacrylate (molecule
1800) 150g stirring and dissolvings are measured, solution is placed in two power for 10mW/cm2365nm uviol lamps under react 20min, obtain
The gelatin hydrogel of the present invention is the hydrogel of methacryl amido gelatin-polyethyleneglycol diacrylate crosslinking.
Embodiment 4
Prepare the hydrogel for carrying medicine：
The preparation method of methacryl amido gelatin is in the same manner as in Example 2.
The mass concentration 0.5wt% of Irgacure 2959 aqueous solution 50mL is configured, is placed in 40 DEG C of waters bath with thermostatic control and stirs molten
Solution, takes the methacryl amido gelatin 5g stirring and dissolvings after freezing, and then adds polyethyleneglycol diacrylate (molecular weight
575) 2.5g stirring and dissolvings, add mass fraction 0.1wt% metronidazole stirring and dissolving, and solution is placed in into power for 10mW/cm2
365nm uviol lamps under react 15min, obtain being loaded with the double acrylic acid of methacryl amido gelatin-polyethylene glycol of metronidazole
Ester cross-linked hydrogel so that hydrogel has effects that anti-inflammation.
Embodiment 5
Method and step be the same as Example 4, the difference is that only, be replaced with mass fraction 3wt% nanometer hydroxyapatites
0.1wt% metronidazoles, the hydrogel with Bone Defect Repari effect finally made.
Embodiment 6
Method and step be the same as Example 4, be the difference is that only, before uviol lamp triggers crosslinking, system reaction solution is coated with
It is 10mW/cm on non-woven fabrics, being subsequently placed in power2365nm uviol lamps under react 15min, prepare hydrogel antibacterial
Dressing.
Obviously, the above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and is not pair
The restriction of embodiments of the present invention, for those of ordinary skill in the field, may be used also on the basis of the above description
To make other changes in different forms, all embodiments can not be exhaustive here, it is every to belong to this hair
Row of the obvious changes or variations that bright technical scheme is extended out still in protection scope of the present invention.
Claims (10)
1. a kind of gelatin hydrogel according to claim 1, it is characterised in that the gelatin hydrogel is filled for hydrone
Porous three network structure, wherein first network is the cross-linked network between modified gelatin, and the second network is polyethylene glycol double third
Cross-linked network between olefin(e) acid ester, the 3rd network is the cross-linked network between modified gelatin and polyethyleneglycol diacrylate.
2. a kind of gelatin hydrogel according to claim 1, it is characterised in that count by weight, the gelatin water-setting
Glue includes：
1~30 part of modified gelatin,
1~40 part of polyethyleneglycol diacrylate,
20~80 parts of water.
3. according to a kind of any described gelatin hydrogel of claim 1 or 2, it is characterised in that the modified gelatin is side chain
Amino carries the gelatin of unsaturated double-bond after being modified.
4. according to a kind of any described gelatin hydrogel of claim 1 or 2, it is characterised in that the modified gelatin is methyl
Acrylamido gelatin；Preferably, the methacryl amido degree of modification of the modified gelatin is 50~100%.
5. according to a kind of any described gelatin hydrogel of claim 1 or 2, it is characterised in that the double propylene of the polyethylene glycol
The molecular weight of acid esters is less than 2000.
6. the preparation method of a kind of gelatin hydrogel as described in Claims 1 to 5 is any, it is characterised in that including following step
Suddenly：The gelatin hydrogel is by the way that modified gelatin and polyethyleneglycol diacrylate are prepared through ultraviolet photo-initiated crosslinking.
7. preparation method according to claim 6, it is characterised in that the wavelength of the ultraviolet light is 254nm or 365nm.
8. preparation method according to claim 6, it is characterised in that the temperature of the cross-linking reaction is 25~50 DEG C；It is excellent
Selection of land, the time of the cross-linking reaction is 5~20 minutes.
9. preparation method according to claim 6, it is characterised in that the light trigger of the cross-linking reaction is BASF light
Initiator Irgacure 2959；Preferably, the mass ratio of the modified gelatin and light trigger is 1~300:1.
10. a kind of gelatin hydrogel as described in Claims 1 to 5 is any is in biological support, thin race culture, medicine controlled releasing and group
Knit the application of engineering field.
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