CN114656595B - Anti-swelling composite double-network hydrogel and preparation method thereof - Google Patents
Anti-swelling composite double-network hydrogel and preparation method thereof Download PDFInfo
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Images
Classifications
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- 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
- C08F251/00—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
-
- 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
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2351/00—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers
- C08J2351/02—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers grafted on to polysaccharides
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/01—Use of inorganic substances as compounding ingredients characterized by their specific function
- C08K3/011—Crosslinking or vulcanising agents, e.g. accelerators
Abstract
The invention relates to the field of biomedical materials, and particularly provides an anti-swelling composite double-network hydrogel and a preparation method thereof, wherein the components for preparing the composite double-network hydrogel comprise: the polymer comprises a monomer, chitosan, a cross-linking agent, a photoinitiator and an inorganic salt, wherein the monomer is used for preparing a polymer containing a carboxylated tail end; by mass, monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6-8): (0.001-1): (0.1-20). The hydrogel has excellent mechanical property, shape recovery capability and swelling resistance.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to an anti-swelling composite double-network hydrogel and a preparation method thereof.
Background
Hydrogels are generally formed by chemically or physically crosslinking polymer chains to form a three-dimensionally crosslinked network structure. The polymer used for preparing the hydrogel has very good hydrophilic performance and can absorb water and swell under the action of water, so that the hydrogel material generally has the characteristics of high water content, large porosity and the like, and is a synthetic material which is very similar to human tissues. Has very wide application in the biomedical field including wound dressing, drug carrier, tissue engineering and the like. However, the traditional hydrogel material has poor mechanical properties and large difference with the mechanical strength of natural tissues, so that the requirements of the fields of biomedicine, complex devices and the like on high-strength hydrogel cannot be met, and the improvement of the mechanical properties of the hydrogel has important significance for expanding the application range of the hydrogel. In addition, when the hydrogel is applied in vivo, too high swelling rate thereof may cause compression of nerves and blood vessels around the tissue, seriously impair the normal physiological function of the tissue and cause complications. For example, after the tissue adhesive absorbs water and swells, the tissue adhesion performance of the tissue adhesive is greatly reduced.
Disclosure of Invention
The invention mainly solves the technical problem of how to improve the swelling resistance of the hydrogel.
According to a first aspect, in one embodiment, there is provided a composite double-network hydrogel resistant to swelling, the components used to prepare the composite double-network hydrogel comprising: the polymer comprises a monomer, chitosan, a cross-linking agent, a photoinitiator and an inorganic salt, wherein the monomer is used for preparing a polymer containing a carboxylated tail end; by mass, monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6-8): (0.001-1): (0.1-20).
According to the second aspect, in an embodiment, there is provided a method for preparing the composite double-network hydrogel according to the first aspect, including:
the preparation step of the precursor liquid comprises the steps of dissolving a monomer, chitosan, a cross-linking agent and a photoinitiator in a solvent according to the formula amount to prepare the precursor liquid;
an illumination step, comprising illuminating the precursor fluid to obtain a crosslinked hydrogel;
and a soaking step, which comprises soaking the crosslinked hydrogel in an aqueous solution containing inorganic salt to prepare the composite double-network hydrogel.
According to a third aspect, in an embodiment, there is provided a dressing comprising the composite double-network hydrogel of the first aspect.
According to a fourth aspect, in an embodiment, there is provided a scaffold or carrier material comprising the composite double-network hydrogel of the first aspect.
According to a fifth aspect, in an embodiment, there is provided an artificial organ comprising the composite double-network hydrogel of the first aspect.
According to the anti-swelling composite double-network hydrogel and the preparation method thereof, the hydrogel system is prepared from olefin monomers with carboxyl at the tail end and chitosan. The hydrogel resists swelling and has higher mechanical strength.
In one embodiment, the preparation method of the hydrogel is simple, and the prepared hydrogel has excellent mechanical property, shape recovery capability and swelling resistance, and has wide biomedical prospects in the aspects of medical dressings, tissue adhesives, cartilage repair and replacement and the like.
Drawings
FIG. 1 is a photograph of the dual network gel prepared in example 1 before swelling and at equilibrium swelling.
FIG. 2 is a photograph of the dual network gel prepared in example 2 before swelling and at equilibrium swelling.
FIG. 3 is a photograph of the dual network gel obtained in example 3 before swelling and at equilibrium swelling.
FIG. 4 is a photograph of the dual network gel prepared in example 4 before swelling and at equilibrium swelling.
FIG. 5 is a photograph of the dual network gel prepared in comparative example 1 before swelling and at equilibrium swelling.
FIG. 6 is a photograph of the dual network gel prepared in comparative example 2 before swelling and at equilibrium swelling.
FIG. 7 is a photograph of the dual network gel prepared in comparative example 3 before swelling and at equilibrium swelling.
FIG. 8 is a photograph of the dual network gel prepared in comparative example 4 before swelling and at equilibrium swelling.
Detailed Description
The present invention will be described in further detail with reference to the following detailed description and accompanying drawings. Wherein like elements in different embodiments have been given like element numbers associated therewith. In the following description, numerous specific details are set forth in order to provide a better understanding of the present application. However, those skilled in the art will readily recognize that some of the features may be omitted or replaced with other elements, materials, methods in different instances. In some instances, certain operations related to the present application have not been shown or described in this specification in order not to obscure the core of the present application with unnecessary detail, and it is not necessary for those skilled in the art to describe these operations in detail, so that they may be fully understood from the description in the specification and the general knowledge in the art.
Furthermore, the described features, operations, or characteristics may be combined in any suitable manner to form various embodiments. Also, the various steps or actions in the description of the methods may be transposed or transposed in order, as will be apparent to a person skilled in the art. Thus, the various sequences in the specification and drawings are for the purpose of describing certain embodiments only and are not intended to imply a required sequence unless otherwise indicated where such sequence must be followed.
The numbering of the components as such, e.g., "first", "second", etc., is used herein only to distinguish the objects as described, and does not have any sequential or technical meaning.
As used herein, "room temperature" means 23 ℃. + -. 2 ℃.
Herein, "aqueous solution containing inorganic salt" and "salt solution" are used interchangeably.
In view of the defects of the prior art, there is a need to develop a hydrogel with higher mechanical strength and resistance to water absorption swelling.
According to a first aspect, in one embodiment, there is provided a composite double-network hydrogel resistant to swelling, the components used to prepare the composite double-network hydrogel comprising: the polymer comprises a monomer, chitosan, a cross-linking agent, a photoinitiator and an inorganic salt, wherein the monomer is used for preparing a polymer containing a carboxylated tail end; by mass, monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6-8): (0.001-1): (0.1-20).
In one embodiment, the monomer comprises an olefinic monomer having a carboxyl group at a terminal.
In one embodiment, the monomer includes, but is not limited to, at least one of the compounds of formulas I-IV:
in the formulae I to IV, R 1 Is hydrogen or methyl, and n is an integer of 1 to 12.
In one embodiment, the monomer includes, but is not limited to, at least one of N-acryloyl glycine, N-acryloyl glutamic acid, N-acryloyl alanine, N-acryloyl aminocaproic acid, acrylic acid.
In one embodiment, the mass parts of the monomer include, but are not limited to, 60 parts, 70 parts, 80 parts, 90 parts, 100 parts, 110 parts, 120 parts, 130 parts, 140 parts, 150 parts.
In one embodiment, the mass parts of chitosan include, but are not limited to, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts.
In one embodiment, the mass parts of the crosslinking agent include, but are not limited to, 0.001 parts, 0.002 parts, 0.003 parts, 0.004 parts, 0.005 parts, 0.006 parts, 0.007 parts, 0.008 parts, 0.009 parts, 0.01 parts, 0.02 parts, 0.03 parts, 0.04 parts, 0.05 parts, 0.06 parts, 0.07 parts, 0.08 parts, 0.09 parts, 0.1 parts, 0.2 parts, 0.3 parts, 0.4 parts, 0.5 parts, 0.6 parts, 0.7 parts, 0.8 parts, 0.9 parts, 1 part.
In one embodiment, the mass portion of the photoinitiator includes, but is not limited to, 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts.
In one embodiment, the monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6-8): (0.1-1): (0.1-10).
In one embodiment, the monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6-8): 0.2: (0.1-10).
In one embodiment, the chitosan comprises a water-soluble chitosan.
In one embodiment, the cross-linking agent includes, but is not limited to, at least one of N, N-methylenebisacrylamide (MBA for short), pentaerythritol tetraacrylate, ethylene glycol diacrylate, diallyl ether, divinylbenzene, and allyl sucrose ether.
In one embodiment, the photoinitiator includes, but is not limited to, at least one of 651 photoinitiator (also known as benzil bismethyl ether, a-dimethoxy-a-phenylacetophenone, DMPA for short, CAS number: 24650-42-8), 1173 photoinitiator (2-hydroxy-2-methyl-1-phenyl-1-propanone for short, HMPP for short, CAS number 7473-98-5), 2959 photoinitiator (2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone, CAS number: 106797-53-9), 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide (TPO, CAS number: 75980-60-8), alpha-ketoglutaric acid (2-oxoglutaric acid, CAS number: 328-50-7), phenyl-2, 4, 6-trimethylbenzoyllithium phosphite (LAP, CAS number: 85073-19-4), and the like).
In one embodiment, 2959 photoinitiator is also known as Irgacure 2959, the manufacturer being basf, germany.
In one embodiment, the components used to prepare the composite double-network hydrogel comprise an aqueous solution containing the inorganic salt (referred to as a salt solution).
In one embodiment, the aqueous solution containing the inorganic salt is a saturated aqueous solution.
In one embodiment, the concentration of the inorganic salt in the aqueous solution may be 0.1 to 10mol/L.
In one embodiment, the valence of the cation in the inorganic salt is ≧ 3.
In one embodiment, the inorganic salt includes, but is not limited to FeCl 3 、Fe 2 (SO 4 ) 3 、Fe(NO 3 ) 3 、AlCl 3 、Al 2 (SO 4 ) 3 、Al(NO 3 ) 3 、CrCl 3 、Cr 2 (SO 4 ) 3 And Cr (NO) 3 ) 3 At least one of (a).
In one embodiment, the monomer includes, but is not limited to, a monomer prepared by reacting a small molecule having a carboxyl group at one end and an amino or hydroxyl group at the other end with acryloyl chloride or methacryloyl chloride.
In one embodiment, the method of preparing the monomer comprises:
(1) According to the mass, 500-1000 parts of deionized water, 1.0-10 parts of micromolecule with one end being carboxyl and the other end being amino or hydroxyl and 1-30 parts of NaOH are added into a two-mouth reaction bottle.
(2) Adding 50-100 parts of tetrahydrofuran into the dropping funnel, and dissolving 1-30 parts of acryloyl chloride or methacryloyl chloride.
(3) The reaction bottle is placed in ice-water bath at 0-5 ℃, nitrogen is introduced for 5-30 min, and then methylene dichloride dissolved with acryloyl chloride or/and methacryloyl chloride is dripped.
(4) After the dropwise adding is finished for 10-30 min, the reaction is carried out for 10-50 h at room temperature in a dark place.
(5) And adopting NaOH aqueous solution with the concentration of 5M to stabilize the pH value of a reaction system to be 7.5-7.8, and preparing the monomer.
In one embodiment, the chitosan may have a molecular weight of 1kDa to 30kDa, including but not limited to 1kDa, 2kDa, 3kDa, 4kDa, 5kDa, 6kDa, 7kDa, 8kDa, 9kDa, 10kDa, 11kDa, 12kDa, 13kDa, 14kDa, 15kDa, 16kDa, 17kDa, 18kDa, 19kDa, 20 kDa, 21kDa, 22kDa, 23kDa, 24kDa, 25kDa, 26kDa, 27kDa, 28kDa, 29kDa, 30kDa.
According to a second aspect, in an embodiment, there is provided a method for preparing the composite double-network hydrogel according to the first aspect, comprising:
the preparation step of the precursor liquid comprises the steps of dissolving a monomer, chitosan, a cross-linking agent and a photoinitiator in a solvent according to the formula amount to prepare the precursor liquid;
an illumination step, comprising illuminating the precursor fluid to obtain a crosslinked hydrogel;
and a soaking step, which comprises soaking the crosslinked hydrogel in an aqueous solution containing inorganic salt to prepare the composite double-network hydrogel.
In one embodiment, in the precursor liquid preparation step, the solvent is water.
In one embodiment, in the precursor liquid preparation step, the monomer, the chitosan, the cross-linking agent aqueous solution and the photoinitiator are dissolved in the solvent according to the formula amount. Because the dosage of the cross-linking agent is small, the cross-linking agent cannot be directly weighed, and the cross-linking agent is prepared into an aqueous solution for use.
In one embodiment, the concentration of the cross-linking agent in the aqueous cross-linking agent solution is 10mg/mL.
In one embodiment, in the precursor liquid preparation step, the mass of the solvent is 5 to 20 times that of the monomer compound, and the mass of the solvent is 50 to 100 times that of the chitosan. Too much solvent reduces the mechanical strength of the gel, and too little solvent makes it difficult to form a uniform transparent solution, resulting in non-uniform gel and low transparency.
The solvent may be 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 11 times, 12 times, 13 times, 14 times, 15 times, 16 times, 17 times, 18 times, 19 times, 20 times, or the like the mass of the monomer compound.
The solvent mass may be 50 times, 60 times, 70 times, 80 times, 90 times, 100 times, etc. the mass of chitosan.
In one embodiment, there is no specific requirement for the amount of photoinitiator used.
In one embodiment, in the step of irradiating, the light used for irradiating is ultraviolet light.
In one embodiment, in the step of irradiating, the wavelength of light used for irradiating is 200-450 nm. Wavelengths of light include, but are not limited to, 200nm, 250nm, 300nm, 350nm, 400nm, 450nm, and the like.
In one embodiment, the illumination time in the illumination step is 1 to 100min, preferably 1 to 30min. The illumination time includes, but is not limited to, 1min, 2min, 3min, 4min, 5min, 6min, 7min, 8min, 9min, 10min, 11min, 12min, 13min, 14min, 15min, 16min, 17min, 18min, 19min, 20min, 30min, 40min, 50min, 60min, 70min, 80min, 90min, 100min.
In one embodiment, in the soaking step, the aqueous solution containing the inorganic salt is a saturated aqueous solution.
In one embodiment, in the soaking step, the concentration of the inorganic salt in the aqueous solution may be 0.1 to 10mol/L.
In one embodiment, the soaking time in the soaking step is 1-500 min. The soaking time includes, but is not limited to, 1min, 2min, 3min, 4min, 5min, 6min, 7min, 8min, 9min, 10min, 20min, 30min, 40min, 50min, 60min, 70min, 80min, 90min, 100min, 200min, 300min, 400min, 500min.
In one embodiment, in the soaking step, after the soaking step is finished, the hydrogel is taken out of the aqueous solution containing the inorganic salt and then stands to prepare the composite double-network hydrogel.
In one embodiment, the standing time in the soaking step is 1-100 h. The function of standing is to allow the salt solution to further penetrate in the air environment (not in the soaking solution) and form stable cross-linked network gel, and the gel property is more stable. The standing time includes but is not limited to 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 20h, 30h, 40h, 50h, 60h, 70h, 80h, 90h, 100h. And in the standing process, naturally draining the salt solution on the surface of the hydrogel.
According to a third aspect, in an embodiment, there is provided a dressing comprising the composite double-network hydrogel of the first aspect.
In an embodiment, the dressing comprises a wound dressing.
According to a fourth aspect, in an embodiment, there is provided a scaffold or carrier material comprising the composite double-network hydrogel of the first aspect.
In one embodiment, the carrier comprises a drug carrier.
According to a fifth aspect, in an embodiment, there is provided an artificial organ comprising the composite double-network hydrogel of the first aspect.
In one embodiment, the invention provides an anti-swelling high-strength composite double-network hydrogel and a preparation method thereof. The hydrogel system is prepared from an olefin monomer with carboxyl at the tail end and chitosan. Adding the monomer, the chitosan solution and the cross-linking agent into a mould, uniformly mixing, adding a photocross-linking agent, photocrosslinking under illumination (such as ultraviolet illumination) to prepare the semi-interpenetrating network hydrogel, and further performing secondary cross-linking on carboxylate radicals and the chitosan network in a gel system by adopting a salt solution soaking method to obtain the swelling-resistant composite hydrogel with higher mechanical strength. The hydrogel has simple preparation method, excellent mechanical property, shape recovery capability and swelling resistance, and wide biomedical prospect in the aspects of medical dressing, tissue adhesive, cartilage repair and substitution and the like.
In one embodiment, the invention aims to provide an anti-swelling high-strength composite double-network hydrogel and a preparation method thereof.
In one embodiment, the composite double-network hydrogel system provided by the invention is mainly prepared from an olefin monomer with a carboxyl group at the terminal and Chitosan (CS). Olefin monomers (including but not limited to monomers shown in formulas I-IV) with carboxyl at the tail end, chitosan, a crosslinking agent N, N-methylene bisacrylamide and a photoinitiator are dissolved in water and then placed in a mould, and polymerizable monomers with double bonds initiate polymerization under the action of illumination and are crosslinked to form a first layer of network; then the hydrogel is soaked in salt solution containing high-valence metal cations, and chitosan in the gel system can form chitosan carbohydrate chain entanglement network under the action of anions; the carboxyl group can form strong ionic complexation with the high valence metal cation. The gel structure after the salt solution is soaked is more stable, the mechanical strength is higher, and the swelling resistance is good.
In one embodiment, the olefin monomer compound having carboxyl groups at the terminal used in the present invention may be any one of the following formulas I, II, III, and IV:
in the formulae I to IV, R 1 Is hydrogen or methyl, and n is an integer of 1 to 12.
In one embodiment, it may be acrylic acid, methacrylic acid, acrylate, methacrylate or acrylamide compounds with 1 or 2 carboxyl groups at the end and different alkyl chain lengths.
In one embodiment, the compound I used in the present invention is commercially available. The compounds II, III and IV are prepared by a chemical synthesis modification method, and the reaction formulas for synthesizing the compounds II, III and IV are as follows:
the compounds II, III and IV are very few and difficult to purchase, so that the compounds can be prepared by themselves.
Specifically, according to the mass, adding 1-10 parts of micromolecule with one end being carboxyl and the other end being amino or hydroxyl into a double-mouth bottle, adding 500-1000 parts of deionized water for dissolving, placing in an ice bath, and adding 1-30 parts of sodium hydroxide. And dissolving acryloyl chloride or methacryloyl chloride (1-30 parts) by using 50-100 parts of tetrahydrofuran, adding the solution into a constant-pressure dropping funnel, slowly dropping the solution into a double-mouth bottle, stabilizing the pH value of a reaction system to 7.5-7.8 by using a sodium hydroxide aqueous solution with the concentration of 5M, and reacting at room temperature for 10-50 hours. After the reaction, ethyl acetate was added to extract the reaction solution, and the aqueous phase was retained. The aqueous solution was adjusted to pH 2 with 5M aqueous HCl and extracted with copious amounts of ethyl acetate, the organic phases were combined and dried over anhydrous magnesium sulfate overnight. Filtering, concentrating, and precipitating in petroleum ether to obtain the product.
In one embodiment, the preparation method of the anti-swelling double-network hydrogel provided by the invention comprises the following steps: 60-150 parts by mass of olefin monomers (including but not limited to monomers shown in formulas I, II, III and IV) with carboxyl at the tail end, 6-8 parts of chitosan, 0.001-1 part of cross-linking agent N, N-methylene bisacrylamide and 0.1-20 parts of photoinitiator are dissolved in 400-800 parts of water and placed in a mold, and the mold is irradiated by light with the wavelength of 200-450 nm and the time of 1-100 min to obtain the interpenetrating network hydrogel of the first network. Taking out the sample, and soaking the sample in FeCl with different concentrations 3 、Fe 2 (SO 4 ) 3 ，Fe(NO 3 ) 3 、AlCl 3 ，Al 2 (SO 4 ) 3 、Al(NO 3 ) 3 、CrCl 3 、Cr 2 (SO 4 ) 3 And Cr (NO) 3 ) 3 And the like in inorganic salt water solution for 1 to 500min to obtain salt ionsA crosslinked double-network hydrogel.
In one embodiment, the composite double-network hydrogel finally obtained by the invention has excellent mechanical property, shape recovery property and swelling resistance.
Compared with the prior art, the invention has the beneficial effects of at least one of the following effects:
(1) The preparation method of the anti-swelling high-strength composite double-network hydrogel provided by the invention is simple and short in preparation period.
(2) The swelling-resistant high-strength composite double-network hydrogel provided by the invention has excellent and adjustable mechanical properties.
(3) The multiple physical actions in the anti-swelling high-strength composite double-network hydrogel system provided by the invention enable the gel to have a stronger energy dissipation mechanism and show excellent self-recovery performance.
(4) The high-strength composite double-network hydrogel provided by the invention is soaked in an aqueous solution for about 1 month, the volume of the hydrogel is not obviously changed, and the hydrogel has excellent swelling resistance. And the mechanical properties after swelling tend to be enhanced.
In the following examples and comparative examples, chitosan having a molecular weight of 10kDa was used.
In the following examples and comparative examples, the crosslinker MBA (N, N-methylenebisacrylamide) was purchased from Shanghai Aladdin Biotech, inc. under the product number M274298. Pentaerythritol tetraacrylate was purchased from Shanghai Allantin Biotech Co., ltd, cat # P160170. Ethylene glycol diacrylate was purchased from Shanghai Michelin Biochemical technology, inc. under item number E808703.
In the following examples and comparative examples, the photoinitiator Irgacure 2959 was purchased from Pasteur, germany. Photoinitiator 1173 was purchased from Shanghai Michelin Biotechnology, inc., under the designation H811172. Photoinitiator 1173 was purchased from Shanghai Allantin Biotech, inc. under the designation K105570. Example 1
The synthesis of N-Acryloyl Glycine (AG) is as follows:
45g of glycine was dissolved in 480mL of deionized water, and the reaction flask was placed in an ice bath, 26g of NaOH was added, and nitrogen was purged for 30min. Then 54mL of acryloyl chloride was dissolved in 200mL of tetrahydrofuran and slowly added dropwise to the glycine solution. The pH value of the reaction system is adjusted by 5M NaOH aqueous solution and maintained at 7.5-7.8, and the reaction is carried out for 24 hours at room temperature. After the reaction, the aqueous phase was extracted three times with ethyl acetate. The aqueous phase was further adjusted to a pH below 2 using 5M aqueous hydrochloric acid. After that, the acidified aqueous phase was extracted three more times with ethyl acetate, and the ethyl acetate organic phases were combined and dried over anhydrous magnesium sulfate overnight. Filtering, concentrating, adding a proper amount of petroleum ether for precipitation, collecting a product and drying in vacuum to obtain the N-Acryloyl Glycine (AG).
Preparing the double-network composite hydrogel: weighing 0.6g of monomer N-Acryloyl Glycine (AG), 0.07g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959, adding into 4mL of deionized water, fully stirring and dissolving to obtain a uniform transparent solution, pouring into a mold, and irradiating by adopting ultraviolet light for 30min to obtain the poly (N-acryloyl glycine)/chitosan first cross-linked network hydrogel (PAG/CS). Further soaking hydrogel PAG/CS in 0.1mol/L FeCl 3 Keeping in inorganic salt water solution for 30min, taking out hydrogel from the inorganic salt water solution, standing for 1h to obtain high-strength composite double-network hydrogel PAG/CS-FeCl 3 。
And (3) testing tensile property: the gel was cut into a dumbbell-shaped bar having a thickness of 1mm, an effective middle length of 30mm and a width of 4mm, and then a sample was broken at a tensile rate of 50mm/min using a universal tester.
PAG/CS-FeCl measured according to the above method 3 The gel fracture strength was 2.92MPa.
And (3) testing the compression performance: the gel was cut to a ratio of diameter to height of 1: (0.33-0.67) samples, compressed at a constant rate of 5mm/min while setting the compression strain to 97% and the maximum load to 4000N.
And cutting the gel to obtain a compressed sample, taking an average value by 5 groups each time, and calculating the ratio of the diameter to the height of the gel to be 1: values of compressed samples within the ratio interval of (0.33-0.67) are available.
PAG/CS-FeCl measured according to the above method 3 The gel compressive strength was 80MPa.
Swelling property test: weighing the gel mass (W) 0 ) And then soaked in deionized water at 25 ℃. After a certain time interval, the gel is removed and the gel mass (Ws) is weighed again until there is essentially no change in mass, which is considered to be gel swelling equilibrium. The Swelling Ratio (SR) of the gel is calculated as follows: SR (g/g) = (Ws-W) 0 )/W 0 ×100％。
PAG/CS-FeCl measured according to the above method 3 The equilibrium swelling ratio in the aqueous solution was 0.5%. FIG. 1 is a photograph of the dual network gel before swelling and when equilibrium swelling occurs.
The subsequent examples and comparative breaking strength, compressive strength, equilibrium swell ratio tests were conducted with reference to this example.
Example 2
The synthesis of N-acryloylglutamic acid (AGlu) was as follows:
44g glutamic acid was dissolved in 500mL deionized water, and the reaction flask was placed in an ice bath, 15g NaOH was added, and nitrogen was purged for 30min. Then, 30mL of acryloyl chloride was dissolved in 200mL of tetrahydrofuran and slowly added dropwise to the glutamic acid solution. The pH value of the reaction system is adjusted by 5M NaOH aqueous solution and maintained at 7.5-7.8, and the reaction is carried out for 24 hours at room temperature. After the reaction, the aqueous phase was extracted three times with ethyl acetate. The aqueous phase was further adjusted to a pH below 2 using 5M aqueous hydrochloric acid. After that, the acidified aqueous phase was extracted three more times with ethyl acetate, and the ethyl acetate organic phases were combined and dried over anhydrous magnesium sulfate overnight. After filtration, concentration, precipitation with the appropriate amount of petroleum ether, collection of the product and vacuum drying, N-acryloyl glutamic acid (AGlu) is obtained.
Preparing the double-network composite hydrogel: at room temperature, weighing1.5g of monomer N-acryloyl glutamic acid (AGlu), 0.08g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959 are added into 8mL of deionized water, and the mixture is fully stirred to obtain a uniform transparent solution, poured into a mold and irradiated by ultraviolet light for 30min to obtain poly (N-acryloyl glutamic acid)/chitosan hydrogel (PAGlu/CS). Further soaking hydrogel PAGlu/CS in 0.1mol/L Fe 2 (SO 4 ) 3 Keeping the temperature in the aqueous solution for 30min, then taking out the hydrogel from the inorganic salt aqueous solution, and standing for 1h to obtain the high-strength composite double-network hydrogel PAGlu/CS-Fe 2 (SO 4 ) 3 。
PAGlu/CS-Fe obtained by tensile, compression and swelling ratio tests 2 (SO 4 ) 3 The gel fracture strength and the compression strength are respectively 2.28MPa and 82MPa; PAGLu/CS-Fe 2 (SO 4 ) 3 The gel had an equilibrium swelling ratio of 1.6% in deionized water. FIG. 2 is a photograph of the dual network gel before swelling and at equilibrium swelling.
Example 3
The synthesis of N-acryloylalanine (AAla) is as follows:
dissolving 35g of alanine in 500mL of deionized water, placing the reaction bottle in an ice bath, adding 25g of NaOH, and introducing nitrogen for 30min. Then 50mL of acryloyl chloride was dissolved in 200mL of tetrahydrofuran and slowly added dropwise to the alanine solution. The pH value of the reaction system is adjusted by 5M NaOH aqueous solution and maintained at 7.5-7.8, and the reaction is carried out for 24 hours at room temperature. After the reaction, the aqueous phase was extracted three times with ethyl acetate. The aqueous phase was further adjusted to a pH below 2 using 5M aqueous hydrochloric acid. After that, the acidified aqueous phase was extracted three more times with ethyl acetate, and the ethyl acetate organic phases were combined and dried over night with anhydrous magnesium sulfate. After filtration, concentration, precipitation with the appropriate amount of petroleum ether, collection of the product and vacuum drying, N-acryloyl alanine (AAla) obtained.
Preparing the double-network composite hydrogel: at room temperatureUnder the environment, 0.8g of monomer N-acryloyl alanine (AAla), 0.06g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959 are weighed and added into 5mL of deionized water, the mixture is fully stirred to obtain a uniform transparent solution, the uniform transparent solution is poured into a mold, and the mold is irradiated by ultraviolet light for 30min to obtain poly (N-acryloyl alanine)/chitosan hydrogel (PAAla/CS). Further soaking the hydrogel PAAla/CS in 0.1mol/L AlCl 3 Keeping the temperature in the aqueous solution for 30min, then taking out the hydrogel from the inorganic salt aqueous solution, and standing for 1h to obtain the high-strength composite double-network hydrogel PAAla/CS-AlCl 3 。
PAAla/CS-AlCl obtained by tensile, compression and swelling ratio test 3 The gel fracture strength and the compression strength are respectively 1.21MPa and 62MPa; PAAla/CS-AlCl 3 The gel had an equilibrium swell ratio of-3.2% in deionized water. Negative values indicate shrinkage of the gel. FIG. 3 is a photograph of the dual network gel before swelling and at equilibrium swelling.
Example 4
The synthesis of N-acryloyl amino caproic acid (AAca) is as follows:
30g of aminocaproic acid is dissolved in 500mL of deionized water, and the reaction flask is placed in an ice bath, 30g of NaOH is added, and nitrogen is introduced for 30min. Then 50mL of acryloyl chloride was dissolved in 200mL of tetrahydrofuran and slowly added dropwise to the aminocaproic acid solution. The pH value of the reaction system is adjusted by 5M NaOH aqueous solution and maintained at 7.5-7.8, and the reaction is carried out for 24h at room temperature. After the reaction, the aqueous phase was extracted three times with ethyl acetate. The aqueous phase was further adjusted to a pH below 2 using 5M aqueous hydrochloric acid. After that, the acidified aqueous phase was extracted three more times with ethyl acetate, and the ethyl acetate organic phases were combined and dried over anhydrous magnesium sulfate overnight. After filtration, concentration, precipitation with the appropriate amount of petroleum ether, collection of the product and vacuum drying, N-acryloyl amino caproic acid (AAca) is obtained.
Preparing the double-network composite hydrogel: 0.6g of monomeric N-acryloyl amino caproic acid is weighed out at room temperature(AAca), 0.06g of Chitosan (CS), 10mg/mL of crosslinker MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959 are added into 6mL of deionized water, and the mixture is fully stirred to obtain a uniform transparent solution, poured into a mold, and irradiated by ultraviolet light for 30min to obtain the poly (N-acryloyl aminocaproic acid)/chitosan hydrogel (PAAca/CS). Further soaking the hydrogel PAAca/CS in 0.1mol/L Al 2 (SO 4 ) 3 Keeping the inorganic salt water solution for 30min, then taking out the hydrogel from the inorganic salt water solution, and standing for 1h to obtain the high-strength composite double-network hydrogel PAAca/CS-Al 2 (SO 4 ) 3 。
PAAca/CS-Al obtained by tensile, compression and swelling ratio tests 2 (SO 4 ) 3 The gel fracture strength and the compression strength are respectively 1.13MPa and 66MPa; PAAca/CS-Al 2 (SO 4 ) 3 The gel had an equilibrium swell ratio of-2.9% in deionized water. Negative values indicate shrinkage of the gel. Figure 4 is a photograph of the dual network gel before swelling and at equilibrium swelling.
Example 5
Weighing 0.7g of monomer Acrylic Acid (AA), 0.06g of Chitosan (CS), 10mg/mL of crosslinking agent ethylene glycol diacrylate aqueous solution (20 mu L) and 0.01g of photoinitiator 1173 into 4mL of deionized water at room temperature, fully stirring to obtain a uniform transparent solution, pouring the uniform transparent solution into a mold, and performing ultraviolet irradiation for 30min to obtain polyacrylic acid/chitosan hydrogel (PAA/CS). Further soaking the hydrogel PAA/CS in 0.1mol/L CrCl 3 Keeping in water solution for 30min, taking out hydrogel from inorganic salt water solution, standing for 1h to obtain polyacrylic acid/chitosan high-strength composite double-network hydrogel PAA/CS-CrCl 3 。
PAA/CS-CrCl obtained by tensile, compression and swelling ratio tests 3 The gel fracture strength and the compression strength are respectively 1.86MPa and 72MPa; PAA/CS-CrCl 3 The gel had an equilibrium swell ratio of 1.8% in deionized water.
Example 6
Weighing 0.7g of monomer Acrylic Acid (AA), 0.06g of Chitosan (CS), 10mg/mL of cross-linking agent pentaerythritol tetraacrylate aqueous solution (20 mu.L) and 0.01g of light under room temperature environmentAdding an initiator alpha-ketoglutaric acid into 4mL of deionized water, fully stirring to obtain a uniform and transparent solution, pouring the uniform and transparent solution into a mould, and irradiating for 30min by adopting ultraviolet light to obtain polyacrylic acid/chitosan hydrogel (PAA/CS). Further soaking the hydrogel PAA/CS in 0.1mol/L Al 2 (SO 4 ) 3 Keeping the temperature in the aqueous solution for 30min, then taking out the hydrogel from the inorganic salt aqueous solution, and standing for 1h to obtain the polyacrylic acid/chitosan high-strength composite double-network hydrogel PAA/CS-Al 2 (SO 4 ) 3 。
PAA/CS-Al obtained by tensile, compression and swelling ratio tests 2 (SO 4 ) 3 The gel fracture strength and the compression strength are respectively 1.37MPa and 61MPa; PAA/CS-Al 2 (SO 4 ) 3 The gel had an equilibrium swell ratio of-1.3% in deionized water.
Comparative example 1
Weighing 0.6g of monomer N-Acryloyl Glycine (AG), 0.07g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959, adding into 4mL of deionized water, fully stirring to obtain a uniform transparent solution, pouring into a mold, and irradiating by ultraviolet light for 30min to obtain the poly (N-acryloyl glycine)/chitosan crosslinking network hydrogel (PAG/CS). Further, the hydrogel PAA/CS was immersed in pure water for 30min, and then the hydrogel was taken out from the pure water and left to stand for 1h. The difference from example 1 is that the hydrogel PAG/CS was not soaked in any aqueous inorganic salt solution. PAG/CS gel fracture strength and compression strength obtained by tensile and compression tests are 0.56MPa and 34MPa respectively, and the mechanical strength is far lower than that of soaked FeCl 3 Post PAG/CS-FeCl 3 And (4) gelling. In addition, the equilibrium swelling ratio of PAG/CS gel in deionized water reaches 450 percent, which is higher than that of PAG/CS-FeCl gel soaked in salt solution 3 And (4) gelling. FIG. 5 is a photograph of the gel before swelling and at equilibrium swelling.
Comparative example 2
Weighing 0.6g of monomer N-Acryloyl Glycine (AG), 0.07g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959 at room temperature, adding into 4mL of deionized water, and fully stirring to obtain the productAnd pouring the uniform transparent solution into a mould, and irradiating for 30min by adopting ultraviolet light to obtain the poly (N-acryloyl glycine)/chitosan first cross-linked network hydrogel (PAG/CS). Further soaking hydrogel PAG/CS in 0.1mol/L NaCl inorganic salt aqueous solution, keeping for 30min, taking out hydrogel from the inorganic salt aqueous solution, standing for 1h to obtain hydrogel PAG/CS-NaCl 3 . The difference from example 1 is that hydrogel PAG/CS is soaked in NaCl solution with low cation valence. Due to the lower valence of Na + The carboxylate in the gel can not be further subjected to coordination crosslinking to form a more compact and stable structure, hydrogen bonds among molecular chains are destroyed, and the breaking strength, the compressive strength and the swelling resistance of the gel are obviously reduced. The breaking strength and the compressive strength of PAG/CS-NaCl gel are respectively 0.8MPa and 65MPa and are lower than that of soaking FeCl 3 Post PAG/CS-FeCl 3 And (4) gelling. In addition, the equilibrium swelling ratio of PAG/CS-NaCl gel in deionized water is as high as 32000 percent and is far higher than that in FeCl 3 PAG/CS-FeCl worthy of being obtained in solution 3 And (4) gelling. FIG. 6 is a photograph of the gel before swelling and when equilibrium swelling occurs.
Comparative example 3
Weighing 0.6g of monomer N-Acryloyl Glycine (AG), 0.07g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959, adding into 4mL of deionized water, fully stirring to obtain a uniform transparent solution, pouring into a mold, and irradiating by adopting ultraviolet light for 30min to obtain the poly (N-acryloyl glycine)/chitosan first crosslinking network hydrogel (PAG/CS). Further soaking hydrogel PAG/CS in 0.1mol/L CaCl 2 Keeping in inorganic salt water solution for 30min, taking out hydrogel from the inorganic salt water solution, and standing for 1h to obtain hydrogel PAG/CS-CaCl 2 . The difference from the example 1 is that the hydrogel PAG/CS is soaked in CaCl 2 In solution. Fe having higher valence and ionic radius 3+ Specific ratio of Ca 2+ The formed gel network is more compact, PAG/CS-CaCl 2 The gel fracture strength and the compression strength are respectively 1.2MPa and 73MPa and are lower than PAG/CS-FeCl 3 And (4) gelling. Further, PAG/CS-CaCl 2 The equilibrium swelling ratio of the gel in deionized water is as high as44000% far higher than that in FeCl 3 PAG/CS-FeCl worthy of being obtained in solution 3 And (4) gelling. FIG. 7 is a photograph of the gel before swelling and when equilibrium swelling occurs.
Comparative example 4
Under the room temperature environment, 1.5g of monomer N-acryloyl glutamic acid (AGlu), 0.08g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959 are weighed, added into 8mL of deionized water, fully stirred to obtain a uniform transparent solution, poured into a mold and irradiated by ultraviolet light for 30min to obtain poly (N-acryloyl glutamic acid)/chitosan hydrogel (PAGlu/CS). Further, the hydrogel PAGLu/CS was immersed in purified water for 30min, and then the hydrogel was taken out from the purified water and left to stand for 1h. The difference from example 2 is that hydrogel PAGlu/CS was not soaked in an inorganic saline solution. The breaking strength and the compressive strength of PAGLu/CS gel obtained by tensile and compressive tests are respectively 0.56MPa and 46MPa, and the mechanical strength is lower than that of soaking Fe 2 (SO 4 ) 3 Post PAGlu/CS-Fe 2 (SO 4 ) 3 Double-network composite hydrogel. In addition, the equilibrium swelling ratio of PAGLu/CS gel in deionized water is up to 360 percent, which is higher than that in Fe 2 (SO 4 ) 3 PAGlu/CS-Fe soaked in solution 2 (SO 4 ) 3 . FIG. 8 is a photograph of the gel before swelling and when equilibrium swelling occurs.
Comparative example 5
0.6g of monomer N-acryloyl amino caproic acid (AAca), 0.06g of Chitosan (CS), 10mg/mL of crosslinking agent MBA aqueous solution (20 mu L) and 0.01g of photoinitiator Irgacure 2959 are weighed and added into 6mL of deionized water at room temperature, and the mixture is fully stirred to obtain a uniform transparent solution, poured into a mold and irradiated by ultraviolet light for 30min to obtain poly (N-acryloyl amino caproic acid)/chitosan hydrogel (PAAca/CS). Further, the hydrogel PAAca/CS was immersed in pure water for 30min, and then the hydrogel was taken out from the pure water and left to stand for 1h. The difference from example 4 is that hydrogel PAAca/CS was not soaked in an aqueous inorganic salt solution. The PAAca/CS gel fracture strength and the compressive strength obtained by tensile and compressive tests are respectively 0.39MPa and 28MPa, and the mechanical strength is lower than that of soaked Al 2 (SO 4 ) 3 Post PAAca/CS-Al 2 (SO 4 ) 3 And (4) gelling. In addition, the equilibrium swelling ratio of PAG/CS gel in deionized water reaches 240 percent, which is much higher than that of PAAca/CS-Al 2 (SO 4 ) 3 And (4) gelling.
The present invention has been described in terms of specific examples, which are provided to aid understanding of the invention and are not intended to be limiting. For a person skilled in the art to which the invention pertains, several simple deductions, modifications or substitutions may be made according to the idea of the invention.
Claims (15)
1. An anti-swelling composite double-network hydrogel, characterized in that the components for preparing the composite double-network hydrogel comprise: the polymer comprises a monomer, chitosan, a cross-linking agent, a photoinitiator and an inorganic salt, wherein the monomer is used for preparing a polymer containing a carboxylated tail end; by mass, monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6 to 8): (0.001 to 1): (0.1 to 20);
the monomer comprises at least one of compounds shown in formulas I, II and IV:
in the formulae I, II, IV, R 1 Is hydrogen or methyl, n is an integer of 1 to 12;
the crosslinking agent comprisesN, N-at least one of methylenebisacrylamide, pentaerythritol tetraacrylate, ethylene glycol diacrylate, diallyl ether, divinylbenzene, allyl sucrose ether.
2. The complex double network hydrogel of claim 1, wherein said monomer comprises at least one of N-acryloyl glycine, N-acryloyl glutamic acid, N-acryloyl alanine, N-acryloyl amino hexanoic acid, acrylic acid.
3. The composite double-network hydrogel according to claim 1, wherein the ratio of monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6 to 8): (0.1 to 1): (0.1 to 10).
4. The composite double-network hydrogel according to claim 1, wherein the ratio of monomer: and (3) chitosan: a crosslinking agent: photoinitiator = (60 to 150): (6 to 8): 0.2: (0.1 to 10).
5. The composite dual-network hydrogel of claim 1, wherein said chitosan comprises a water-soluble chitosan.
6. The composite double-network hydrogel of claim 1, wherein the photoinitiator comprises at least one of 651 photoinitiator, 1173 photoinitiator, 2959 photoinitiator, 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide, α -ketoglutaric acid, and lithium phenyl-2, 4, 6-trimethylbenzoyl-phosphite.
7. The composite double-network hydrogel according to claim 1, wherein the components for preparing the composite double-network hydrogel comprise an aqueous solution containing the inorganic salt;
the aqueous solution containing the inorganic salt is a saturated aqueous solution;
the concentration of inorganic salt in the aqueous solution is 0.1 to 10mol/L;
the valence of the cation in the inorganic salt is more than or equal to +3.
8. The composite double-network hydrogel of claim 7, wherein the inorganic salt comprises FeCl 3 、Fe 2 (SO 4 ) 3 ，Fe(NO 3 ) 3 、AlCl 3 、Al 2 (SO 4 ) 3 、Al(NO 3 ) 3 、CrCl 3 、Cr 2 (SO 4 ) 3 、Cr(NO 3 ) 3 At least one of (a).
9. The composite double-network hydrogel according to claim 1, wherein the molecular weight of the chitosan is 1kDa to 30kDa.
10. The preparation method of the composite double-network hydrogel according to any one of claims 1 to 9, which comprises the following steps:
the preparation step of the precursor liquid comprises dissolving a monomer, chitosan, a cross-linking agent and a photoinitiator in a solvent according to the formula amount to prepare the precursor liquid;
an illumination step, comprising illuminating the precursor fluid to obtain a crosslinked hydrogel;
and a soaking step, which comprises soaking the crosslinked hydrogel in an aqueous solution containing inorganic salt to prepare the composite double-network hydrogel.
11. The method according to claim 10, wherein in the precursor liquid preparation step, the solvent is water;
in the step of preparing the precursor liquid, the monomer, the chitosan, the cross-linking agent aqueous solution and the photoinitiator are dissolved in the solvent according to the formula amount;
in the precursor liquid preparation step, the mass of the solvent is 50 to 100 times of that of the chitosan;
in the illumination step, the light used for illumination is ultraviolet light;
in the illumination step, the illumination time is 1 to 100 min;
in the soaking step, the aqueous solution containing the inorganic salt is a saturated aqueous solution;
in the soaking step, the concentration of inorganic salt in the aqueous solution is 0.1 to 10mol/L;
in the soaking step, the soaking time is 1 to 500min;
in the soaking step, after soaking is finished, taking out hydrogel from an aqueous solution containing inorganic salt, and then standing to prepare the composite double-network hydrogel;
in the soaking step, the standing time is 1 to 100h.
12. The method according to claim 10, wherein the wavelength of light used in the step of irradiating light is 200 to 450nm.
13. A dressing comprising the composite double-network hydrogel according to any one of claims 1 to 9.
14. A stent or carrier material, comprising the composite double-network hydrogel according to any one of claims 1 to 9.
15. An artificial organ comprising the composite double-network hydrogel according to any one of claims 1 to 9.
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