CN117402378A - Preparation method of high-strength double-network hydrogel - Google Patents
Preparation method of high-strength double-network hydrogel Download PDFInfo
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Classifications
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- 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
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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
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/56—Acrylamide; Methacrylamide
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- 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
- C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2333/24—Homopolymers or copolymers of amides or imides
- C08J2333/26—Homopolymers or copolymers of acrylamide or methacrylamide
-
- 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
- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/04—Alginic acid; Derivatives thereof
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- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention discloses a preparation method of high-strength double-network hydrogel, which is improved in process on the basis of interpenetrating network alginate hydrogel by controlling Ca 2+ EDTA complex liberates Ca in aqueous gluconolactone solution 2+ The dispersion of the polymer in the gel network is more uniform, the stress concentration is reduced, and the effect of enhancing the mechanical property of the hydrogel is achieved. The high-strength double-network hydrogel can perfectly fit with the cartilage end plate of the intervertebral discAnd the nucleus pulposus residual cavity left by the operation is closed and broken fibrous ring is filled, so that the nucleus pulposus residual cavity has high strength and toughness mechanical property and good tissue compatibility. The high-strength and high-toughness hydrogel is applied to repairing the defect of the intervertebral disc, and has important scientific and clinical significance.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to a preparation method of high-strength double-network hydrogel.
Background
Disc Herniation (DH) is a clinical and more common orthopedic disease, and is caused by rupture of the outer annulus fibrosus of an intervertebral disc due to various reasons, and as local pressure increases, the nucleus pulposus inside the intervertebral disc protrudes from the rupture of the annulus fibrosus, so that adjacent nerve roots and intraductal nerves are stressed, and pain in waist and legs is the main symptom. Studies show that the incidence rate of intervertebral disc protrusion of the common people is about 2%, symptoms are expressed as pain, living capacity is lost, most people select conservative treatment to relieve the pain, and 10% -18% of patients still need surgical treatment.
Intervertebral discs are complex structures composed of different but interrelated tissues: as shown in FIG. 1, the center is a highly hydrated gel-like Nucleus Pulposus (Nucleus Pulpos), the outer layer is a ring of elastic fibers (Annulus fibriosus) that are cross-aligned, and the cartilage endplates that attach these tissues to the vertebral bodies (Layer of hyaline cartilage). Related studies have shown that the annulus is a layered bundle of fibers arranged in concentric circles around the nucleus pulposus tissue, consisting essentially of type I and type II collagen fibers. Degenerated discs are often accompanied by a decrease in cell density and a decrease in extracellular matrix synthesis, particularly proteoglycans and collagen fibers. This will alter the structural and mechanical properties of the disc, ultimately leading to annulus rupture, herniation of the nucleus pulposus, etc. and a series of clinical symptoms.
With the development of minimally invasive spine surgery, minimally invasive surgery for removing the protruding nucleus pulposus under an endoscope has the advantages of small surgical incision, less damage to human body than conventional spine surgery, definite curative effect, higher safety and the like, so that the minimally invasive surgery is widely applied to clinic. Numerous clinical observations at home and abroad indicate that the corresponding pain symptom can be relieved by simple nuclectomy, but after the herniated nucleuses are removed, the external annulus fibrosus needs 6 months or even longer, the defect of the annulus fibrosus is repaired by local scar hyperplasia, but the defect of the internal annulus fibrosus is difficult to repair completely. Clinical observations show that the recurrence risk of the herniated disk of the patient is always present within 1 year after the operation. The reason for this is that disc degeneration is an irreversible process, which is aggravated continuously, and the ability of the annulus to self-repair is limited because it lacks blood supply and the ability of the annulus cells to regenerate is poor. The annulus fibrosus is not completely repaired within 6 months after operation, and the nucleus pulposus protrudes from the annulus fibrosus again due to improper activities, so that pain symptoms are caused, and unnecessary social and economic burden is brought. It follows that if a method were available to form a barrier at the annulus rupture early in the operation, preventing herniation of the nucleus pulposus, and promoting repair of the damaged annulus fibrosus for a long period of time, this would greatly reduce the risk of recurrence of herniated disc, benefiting the patient.
Current repair strategies for the annulus fibrosus mainly include: and the modes of stitching, tissue engineering repair, high polymer synthetic material filling, and the like. However, with respect to the long-term effect, simple fiber circumferential stitching does not promote repair of the fiber annulus. Tissue engineering research in the past decade has focused on regeneration repair of the nucleus pulposus, and the lack of an effective annulus repair strategy, without noticing repair of the annulus fibrosis, may result in failure of regeneration repair of the nucleus pulposus. Advantages of polymeric synthetic materials include good mechanical properties, reproducibility, controllability, lack of immunogenicity and ease of processing, disadvantages including lack of bioactivity, poor cell affinity and susceptibility to tissue sterility. It is now common to combine natural biological materials with polymeric synthetic materials to address such drawbacks, including: including collagen/hyaluronic acid, alginate/collagen, poly (DL-lactic acid)/bioglass, silk fibroin/hydroxybutyl chitosan and hyaluronic acid gel/polylactic acid nanofibers.
The following criteria should be met as an artificial composite of the annulus fibrosus: hydrogel materials are nontoxic or low toxic; the hydrogel can completely fill and fill the irregular nucleus pulposus residual cavity; minimally invasive, can be used to inject into the nucleus pulposus residual cavity; has enough mechanical strength and fatigue resistance. In recent years, alginate hydrogels have been used for the study of annulus repair because of their characteristics similar to the structure of biological natural tissues. Alginate hydrogels, which due to their unique high water content can allow for the transport of nutrients or metabolic waste products, similarity to disc tissues, and good biocompatibility, are valued by scientists. At present, alginate hydrogel is commonly used for intervertebral disc tissue engineering scaffolds, not only can maintain biomechanical action, but also can enable cell matrixes to be deposited to enhance loading capacity, but the pure alginate hydrogel is poor in strength and toughness, is easy to swell and crack in aqueous solution, cannot meet clinical requirements, and needs to be improved in performance.
Disclosure of Invention
The present invention is directed to at least partially overcoming the above and/or other potential problems in the art: provides a preparation method of high-strength double-network hydrogel with excellent strength and toughness, which can meet the mechanical property and biocompatibility required by repairing the fibrous annulus of the intervertebral disc.
The technical scheme of the invention is as follows: a preparation method of high-strength double-network hydrogel comprises the following steps:
1) Dispersing ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 3-5h under the heating condition of 60-80 ℃ to obtain Ca 2+ EDTA buffer solution;
2) Adding sodium alginate into Ca prepared in the step 1) 2+ Uniformly stirring in EDTA buffer solution to obtain mixed solution;
3) Adding dimethylaminoethyl methacrylate into hydrochloric acid, uniformly mixing, adding an acrylamide monomer and N, N-methylenebisacrylamide, and uniformly stirring to obtain a mixed solution;
4) Mixing the mixed solution prepared in the step 2) with the mixed solution prepared in the step 3), uniformly stirring, adding ammonium persulfate, uniformly stirring, pouring into a mould, and placing in an environment of 55-65 ℃ for polymerization reaction to obtain hydrogel;
5) And (3) taking the hydrogel obtained in the step (4) out of a die, and placing the die in a gluconolactone aqueous solution for soaking and replacing for 12-18 hours to prepare the high-strength double-network hydrogel.
In step 1), the Ca 2+ The concentration of the EDTA buffer aqueous solution is 0.1-0.3M.
In the step 2), the concentration of the sodium alginate in the mixed solution is 0.02-0.04 g/mL.
In the step 3), the concentration of the dimethylaminoethyl methacrylate in the mixed solution is 0.07-0.09 g/mL, the concentration of the hydrochloric acid is 0.4-0.6M, and the mass ratio of the acrylamide monomer to the N, N-methylenebisacrylamide is (30-150):1.
In the step 4), the volume ratio of the mixed solution obtained in the step 2) to the mixed solution obtained in the step (3) is (2-4):1. The addition amount of ammonium persulfate is 0.001-0.003 g/mL, the polymerization reaction time is 7-9h, and the polymerization temperature is 60-80 ℃;
in the step 5), the concentration of gluconolactone in the aqueous solution of gluconolactone is 0.01-g/mL, and the soaking replacement time is 3-5h.
The invention also provides application of the high-strength double-network hydrogel to preparation of an artificial intervertebral disc annulus fibrosus prosthesis.
The beneficial effects of the invention are as follows: because the G molecular chain of the sodium alginate can be complexed with metal ions (the valence state of the metal ions is more than or equal to 2), an ion/G complex is formed, and the strength and toughness of the sodium alginate hydrogel complexed by the ions/G are poor. Therefore, in order to improve the performance of alginate hydrogels, the concept of interpenetrating network hydrogels needs to be introduced. Interpenetrating network hydrogels refer to hydrogels having a topology formed by the interpenetrating entanglement of two or more polymer networks. The polymer networks realize physical blending in a chemical mode, and the mechanical properties of the mutual transmission network hydrogel can obviously exceed those of the single-component single-network hydrogel due to the synergistic effect between the networks. The achievements of the lock-up team at the university of harvard, academy of engineering in the united states of america in 2012 were published in Nature and represent a method for preparing interpenetrating network alginate hydrogels (alginate/polyacrylamide gel) using physically cross-linked sodium alginate as the backbone network (fig. 2 a) and loosely cross-linked polyacrylamide gel as the toughening network (fig. 2 b) to realize an interpenetrating network structure (fig. 2 c). Such alginate/polyacrylamide gels exhibit excellent extensibility, with elongation at break up to 23 times the original length. After the gaps are preformed on the gel, the gaps can be rapidly passivated in the stretching process, so that the partially broken gel still has ductility, namely, the gel has high toughness insensitive to the gaps.
The invention improves the process on the basis of interpenetrating network alginate hydrogel by controlling Ca 2+ EDTA complex liberates Ca in aqueous gluconolactone solution 2+ The dispersion of the polymer in the gel network is more uniform, the stress concentration is reduced, and the effect of enhancing the mechanical property of the hydrogel is achieved. The high-strength double-network hydrogel can perfectly fit with the cartilage end plate of the intervertebral disc and fill nucleus pulposus residual cavity left by operation, seals broken fibrous ring, has high strength and toughness mechanical property, and has good tissue compatibility. The high-strength and high-toughness hydrogel is applied to repairing the defect of the intervertebral disc, and has important scientific and clinical significance.
Drawings
Fig. 1 is a schematic view of a normal disc structure.
FIG. 2 is a schematic structural diagram of an interpenetrating network alginate hydrogel of the prior art.
FIG. 3 is a tensile stress-strain curve of the high strength dual network hydrogel prepared in example 1.
FIG. 4 is a graph showing the compression curve of the high strength dual network hydrogel prepared in example 1.
FIG. 5 is a graph showing various performance tests of the high strength dual network hydrogel prepared in example 1.
FIG. 6 is a graph of various experimental tests using the high strength dual network hydrogels prepared in example 1.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, but the present invention is not limited to the following specific examples.
For the hydrogels obtained in the examples, a sheet-like "sandwich" mold was used consisting of two glass plates with a square ring of silica gel sandwiched between them, the thickness of the square ring of silica gel being 1mm, and the prepolymer liquid polymerized in the intermediate cavity to form the sheet-like hydrogel.
Example 1
(1) Dispersing water-soluble ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 4h under the heating condition of 70 ℃ to obtain transparent Ca with the concentration of 0.2M 2+ EDTA buffer solution;
(2) Adding 0.3 g sodium alginate into Ca prepared in the step (1) 2+ Stirring and mixing in EDTA buffer solution until the mixture is uniform; the concentration of the sodium alginate in the mixed solution is 0.03g/mL;
(3) The dimethylaminoethyl methacrylate 0.842. 0.842 g is added into 10ml of the prepared 0.5. 0.5M hydrochloric acid solution and mixed uniformly. Then adding 1.5 g acrylamide monomer and 0.01 g N, N-methylene bisacrylamide into the mixed solution, and slightly stirring to obtain a clear mixed solution;
(4) Mixing and stirring the mixed solution prepared in the step (2) and the solution prepared in the step (3) at a volume ratio of 2:1, adding ammonium persulfate for mild mixing after uniformly stirring and mixing, pouring the mixture into a self-made sandwich mold with the ammonium persulfate addition of 0.002g/mL, and then placing the mold in a high-temperature environment at 70 ℃ for reaction for 8 hours;
(5) Taking the hydrogel obtained in the step (4) out of the die, and placing the hydrogel in 0.01 g/mL of gluconolactone aqueous solution for soaking and replacing 4 h; the high-strength double-network hydrogel is obtained.
Example 2
(1) Dispersing water-soluble ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 4h under the heating condition of 60 ℃ to obtain transparent Ca with the concentration of 0.2M 2+ EDTA buffer solution;
(2) Adding 0.3 g sodium alginate into Ca prepared in the step (1) 2+ Stirring and mixing in EDTA buffer solution until the mixture is uniform; the concentration of the sodium alginate in the mixed solution is 0.03g/mL;
(3) The dimethylaminoethyl methacrylate 0.842, g is added into the hydrochloric acid solution 0.5, M prepared from 10, mL and mixed uniformly. Then adding 1.5 g acrylamide monomer and 0.01 g N, N-methylene bisacrylamide into the mixed solution, and slightly stirring to obtain a clear mixed solution;
(4) Mixing and stirring the mixed solution prepared in the step (2) and the solution prepared in the step (3) at a volume ratio of 3:1, adding ammonium persulfate for mild mixing after uniformly stirring and mixing, pouring the mixture into a self-made sandwich mold, and then placing the mold in a high-temperature environment at 70 ℃ for reaction 8h;
(5) Taking the hydrogel obtained in the step (4) out of the die, and placing the hydrogel in 0.01 g/mL of gluconolactone aqueous solution for soaking and replacing 5 h; the high-strength double-network hydrogel is obtained.
Example 3
(1) Dispersing water-soluble ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 4h under the heating condition of 75 ℃ to obtain transparent Ca with the concentration of 0.2M 2+ EDTA buffer solution;
(2) Adding 0.2. 0.2 g sodium alginate into Ca prepared in the step (1) 2+ Stirring and mixing in EDTA buffer solution until the mixture is uniform; the concentration of the sodium alginate in the mixed solution is 0.02g/mL;
(3) The dimethylaminoethyl methacrylate 0.842, g is added into the hydrochloric acid solution 0.5, M prepared from 10, mL and mixed uniformly. Then adding 1g of acrylamide monomer and 0.01. 0.01 g of N, N-methylene bisacrylamide into the mixed solution, and slightly stirring to obtain a clear mixed solution;
(4) Mixing and stirring the mixed solution prepared in the step (2) and the solution prepared in the step (3) at a volume ratio of 2:1, adding ammonium persulfate for mild mixing after uniformly stirring and mixing, pouring the mixture into a self-made sandwich mold with the addition amount of 0.002g/mL, and then placing the mold in a high-temperature environment at 70 ℃ for reaction 8h;
(5) Taking the hydrogel obtained in the step (4) out of the die, and placing the hydrogel in 0.01 g/mL of gluconolactone aqueous solution for soaking and replacing 4 h; the high-strength double-network hydrogel is obtained.
Example 4
(1) Dispersing water-soluble ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 4h under the heating condition of 70 ℃ to obtain transparent Ca with the concentration of 0.2M 2+ EDTA buffer solution;
(2) Adding 0.4. 0.4 g sodium alginate into the Ca prepared in the step (1) 2+ Stirring and mixing in EDTA buffer solution until the mixture is uniform; the concentration of the sodium alginate in the mixed solution is 0.04g/mL;
(3) The dimethylaminoethyl methacrylate 0.842, g is added into the hydrochloric acid solution 0.5, M prepared from 10, mL and mixed uniformly. Then adding 1g of acrylamide monomer and 0.01. 0.01 g of N, N-methylene bisacrylamide into the mixed solution, and slightly stirring to obtain a clear mixed solution;
(4) Mixing and stirring the mixed solution prepared in the step (2) and the solution prepared in the step (3) at a volume ratio of 3:1, adding ammonium persulfate for mild mixing after uniformly stirring and mixing, pouring the mixture into a self-made sandwich mold with the addition amount of 0.002g/mL, and then placing the mold in a high-temperature environment at 70 ℃ for reaction 8h;
(5) Taking the hydrogel obtained in the step (4) out of the die, and placing the hydrogel in 0.01 g/mL of gluconolactone aqueous solution for soaking and replacing 4 h; the high-strength double-network hydrogel is obtained.
Example 5
(1) Dispersing water-soluble ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 4h under the heating condition of 70 ℃ to obtain transparent Ca with the concentration of 0.2M 2+ EDTA buffer solution;
(2) Adding 0.4. 0.4 g sodium alginate into the Ca prepared in the step (1) 2+ Stirring and mixing in EDTA buffer solution until the mixture is uniform; the concentration of the sodium alginate in the mixed solution is 0.04g/mL;
(3) The dimethylaminoethyl methacrylate 0.842, g is added into the hydrochloric acid solution 0.5, M prepared from 10, mL and mixed uniformly. Then adding 1g of acrylamide monomer and 0.01. 0.01 g of N, N-methylene bisacrylamide into the mixed solution, and slightly stirring to obtain a clear mixed solution;
(4) Mixing and stirring the mixed solution prepared in the step (2) and the solution prepared in the step (3) according to a volume ratio of 4:1, adding ammonium persulfate for mild mixing after uniformly stirring and mixing, pouring the mixture into a self-made sandwich mold, and then placing the mold in a high-temperature environment at 70 ℃ for reaction for 9 hours;
(5) Taking the hydrogel obtained in the step (4) out of the die, and placing the hydrogel in 0.01 g/mL of gluconolactone aqueous solution for soaking and replacing 5 h; the high-strength double-network hydrogel is obtained.
The high-strength double-network hydrogel prepared in example 1 was subjected to mechanical property test, and fig. 3 is a tensile stress-strain curve of the double-network hydrogel, and fig. 4 is a compression curve of the double-network hydrogel. It can be seen that it has high strength and toughness mechanical properties, and the morphology of the high strength dual network hydrogel was evaluated using SEM as shown in fig. 5A, and its effect on Nuclear (NP) cell viability and proliferation was evaluated. The results of CCK-8 and EdU experiments showed that high strength double network hydrogels (noted AAm) significantly increased the viability of the nucleus pulposus cells (fig. 5B) and gradually increased their proliferation within 7 days after treatment (fig. 5C).
High strength dual network hydrogel AAm reduces in vivo damage and ECM degradation
Rat disc and adjacent vertebral bodies were separated and paraffin embedded sections were made. HE and safranin O staining measures tissue structure and bone formation. The intervertebral disc structure of the IVDD group is obviously degenerated compared with that of the control group. The nucleus disappeared, disordered fibrous tissue appeared and part of the end plates degenerated (fig. 6A). Red staining and blue staining reduction in IVDD groups indicated impaired bone formation and cartilage formation (fig. 6B). AAm treatment can significantly reduce disc degeneration and promote bone formation. In addition, protein levels of Aggrecan, type I collagen, type II collagen (fig. 6C) and Ki67 were reduced, expression of MMP13 was increased (fig. 6D), and AAm treatment reversed these effects. In addition, the histological score of IVDD group tissue lesions increased significantly (fig. 6E).
In conclusion, the double-network hydrogel is suitable for perfectly fitting with the cartilage end plate of the intervertebral disc and filling the nucleus pulposus residual cavity left by the operation to seal the damaged annulus fibrosus.
The above is merely exemplary embodiments of the present invention, and the scope of the present invention is not limited in any way. All technical schemes formed by adopting equivalent exchange or equivalent substitution fall within the protection scope of the invention.
Claims (6)
1. The preparation method of the high-strength double-network hydrogel is characterized by comprising the following steps of:
1) Dispersing ethylenediamine tetraacetic acid in deionized water to obtain an ethylenediamine tetraacetic acid aqueous solution; then adding calcium carbonate into ethylenediamine tetraacetic acid water solution, stirring and mixing for 3-5h under the heating condition of 60-80 ℃ to obtain Ca 2+ EDTA buffer solution;
2) Adding sodium alginate into Ca prepared in the step 1) 2+ Uniformly stirring in EDTA buffer solution to obtain mixed solution;
3) Adding dimethylaminoethyl methacrylate into hydrochloric acid, uniformly mixing, adding an acrylamide monomer and N, N-methylenebisacrylamide, and uniformly stirring to obtain a mixed solution;
4) Mixing the mixed solution prepared in the step 2) with the mixed solution prepared in the step 3), uniformly stirring, adding ammonium persulfate, uniformly stirring, pouring into a mould, and placing in an environment of 55-65 ℃ for polymerization reaction to obtain hydrogel;
5) And (3) taking the hydrogel obtained in the step (4) out of a die, and placing the die in a gluconolactone aqueous solution for soaking and replacing for 12-18 hours to prepare the high-strength double-network hydrogel.
2. The method for producing a high-strength double-network hydrogel according to claim 1, wherein in step 1), the Ca 2+ The concentration of the EDTA buffer aqueous solution is 0.1-0.3M.
3. The method for preparing a high-strength double-network hydrogel according to claim 1, wherein in step 2), the concentration of sodium alginate in the mixed solution is 0.02-0.04 g/mL.
4. The method for preparing a high-strength dual-network hydrogel according to claim 1, wherein in step 3), the concentration of dimethylaminoethyl methacrylate in the mixed solution is 0.07-0.09 g/mL, the concentration of hydrochloric acid is 0.4-0.6M, and the mass ratio of the acrylamide monomer to N, N-methylenebisacrylamide is (30-150):1.
5. The method for preparing a high-strength dual-network hydrogel according to claim 1, wherein in step 4), the volume ratio of the mixed solution of step 2) to the mixed solution obtained in step (3) is (2-4):1; the addition amount of ammonium persulfate is 0.001-0.003 g/mL, the polymerization reaction time is 7-9h, and the polymerization temperature is 60-80 ℃.
6. The method for producing a high-strength double-network hydrogel according to claim 1, wherein in step 5), the concentration of gluconolactone in the aqueous solution of gluconolactone is 0.01-g/mL and the time for the soaking displacement is 3-5 hours.
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