A hydrogel and its preparation method and application

Abstract

The present invention provides a hydrogel and a preparation method and application thereof. The hydrogel is a hydrogel based on cross-linking of alginate and gelatin molecules, and has good biocompatibility; after further modifying alginate by maleimidation, the cross-linking of alginate and gelatin molecules can be made tighter and more stable, thereby further effectively improving the mechanical properties of the hydrogel under the premise of ensuring the biocompatibility of the hydrogel, so that the hydrogel of the present invention has both excellent biocompatibility and mechanical properties. The hydrogel has good application effects in wound dressings and coatings of implantable medical devices, and the preparation method of the hydrogel has simple operation procedures, high repeatability, and is easy to realize industrialization, so that the hydrogel has strong practicality and is conducive to the large-scale application of the hydrogel.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a hydrogel and a preparation method and application thereof. Background Art

[0002] Biomedical materials are materials used to diagnose, treat, repair, or replace damaged tissues and organs of organisms. Their history can be traced back to around 3500 BC when the ancient Egyptians used cotton fibers and horsehair to suture wounds. In the following five thousand years, limited by the low productivity and scientific level of ancient civilizations, the development of biomedical materials was extremely slow, and humans could only use some easily accessible natural materials to carry out a small number of simple medical applications. For example, the Aztecs in ancient Mexico used wood chips to repair damaged skulls; while the Itrascans in ancient Rome carved animal bones into dentures and used gold to make dental bridges and dental trays. During the two world wars in modern times, various new technologies and new materials emerged, which had a profound impact on human civilization. The emergence of synthetic polymer materials has not only greatly promoted the progress of human society, but also prompted the development of biomedical materials to enter a new stage. After entering modern society, driven by various advanced science and technology and the impact of the world's population growth and aging, the discipline of biomedical engineering began to rise, and its development is inseparable from a variety of biomedical materials. Current biomedical materials are not only used to repair damaged tissues, but also to construct artificial tissues and organs with complex structures and functions. In addition, biomedical materials are also widely used to prepare drug carriers, biosensors, coatings for implantable medical devices, and so on.

[0003] As an emerging material, hydrogel is undoubtedly one of the hot spots in the current research and development and application of biomedical materials. Hydrogel is a colloidal material with a three-dimensional cross-linked network structure and water as the dispersion medium, and the three-dimensional network structure is usually constructed by chemical cross-linking of polymers. Due to the characteristics of containing a large amount of water in its composition, hydrogel has been widely used in the field of biomedical engineering, including the preparation of tissue engineering scaffolds, drug carriers, biosensors, wound dressings, coatings for implantable medical devices, etc. For example, Australian and American scientists have jointly developed a highly elastic protein hydrogel and used it to construct artificial heart tissue. Because parallel microgrooves are introduced on the surface of this hydrogel, the implanted cardiomyocytes can be induced to arrange and grow in a specific orientation. The obtained artificial heart tissue has the physiological structure and function of the natural myocardium and is expected to be used to treat myocardial infarction. For another example, Professor Takeuchi's research group at the University of Tokyo in Japan used microfluidics technology to prepare a fibrous hydrogel material with a core-shell structure, and confirmed that it can be used to load a variety of cell types including fibroblasts, muscle cells, endothelial cells, nerve cells, epidermal cells, pancreatic islet cells, etc. In particular, hydrogel fibers loaded with pancreatic B cells can respond to glucose and release insulin like normal pancreatic islets, so they have the potential to be used to treat diabetes. For another example, American scholars Braun and others have developed a hydrogel-based biosensor for detecting glucose. The molecular chain of the hydrogel contains phenylboronic acid, which is firmly bound to the polyvinyl alcohol in the component through hydrogen bonding, which can keep the hydrogel in a contracted state in an aqueous solution. Once glucose is added to the aqueous solution, the above hydrogen bonding will be broken, causing the hydrogel to swell, and the degree of swelling can be accurately measured by reflectance spectroscopy. The hydrogel biosensor has high detection sensitivity and accuracy, and is expected to be used for blood sugar detection.

[0004] Although hydrogels have great application value in the field of biomedical engineering, ordinary hydrogels have poor mechanical properties and are prone to brittle fracture, which restricts their application in situations where they need to withstand large stresses and strains (such as wound dressings at joints and coatings of implantable medical devices). In order to overcome the problem of insufficient mechanical properties of ordinary hydrogels, many new hydrogels with excellent mechanical properties have been developed, such as interpenetrating network hydrogels and composite hydrogels composed of polymers and nanoparticles. However, related research work often one-sidedly pursues the mechanical strength of hydrogels (such as high elongation at break and fracture strength), but ignores the biocompatibility of the material, or the preparation process of the material itself is complicated and cumbersome, making it difficult to be practical. Summary of the invention

[0005] The purpose of the present invention is to provide a hydrogel in view of the deficiencies in the prior art. The hydrogel has excellent mechanical properties and biocompatibility and has extremely high medical value.

[0006] The present invention also aims to provide a method for preparing the hydrogel described above. The method for preparing the hydrogel has simple operation procedures and high repeatability, which makes the hydrogel highly practical.

[0007] Another object of the present invention is to provide applications of the hydrogel described above.

[0008] The purpose of the present invention is achieved through the following technical solutions.

[0009] A method for preparing a hydrogel comprises the following steps:

[0010] (1) dissolving maleimidized alginate in a phosphate buffer and adjusting the pH value to 7.0-8.0 to obtain a maleimidized alginate solution;

[0011] (2) dissolving gelatin in hot phosphate buffer and adjusting the pH value to 7.0-8.0 to obtain a gelatin solution;

[0012] (3) Mixing the maleimidized alginate solution with the gelatin solution to form a hydrogel mixed solution, and solidifying the solution to obtain the hydrogel (AM / G hydrogel).

[0013] Preferably, the maleimidized alginate is maleimidized modified alginate, and the modification rate is 5-15%.

[0014] Preferably, in step (1), the maleimidized alginate is prepared by the following method:

[0015] (1-1) Dissolve alginate in phosphate buffer, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) and N-hydroxysulfosuccinimide (Sulfo-NHS) for activation;

[0016] (1-2) adding N-(2-aminoethyl)maleimide trifluoroacetate salt (AEM.TFA) to the solution activated in step (1-1) to carry out a coupling reaction;

[0017] (1-3) After the reaction is completed, the pH value is adjusted to 4.0-6.0; dialysis is performed, the dialysate is collected, and freeze-dried to obtain the maleimidized alginate.

[0018] More preferably, the mass ratio of alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysulfosuccinimide and N-(2-aminoethyl)maleimide trifluoroacetate is 4.2:1.38-4.14:0.52-1.56:0.51-1.53.

[0019] More preferably, in step (1-1), the activation is carried out at 20 to 40° C. for 0 to 4 hours.

[0020] More preferably, in step (1-1), the activation is carried out at 25° C. for 1 hour.

[0021] More preferably, in step (1-2), the coupling reaction is carried out at 20 to 40° C. with stirring for 6 to 10 hours.

[0022] More preferably, in step (1-3), a hydrochloric acid solution is used to adjust the pH value.

[0023] More preferably, in step (1-3), the dialysis is to transfer the solution after adjusting the pH value to a dialysis bag, dialyze it for 2 to 5 days using a dilute hydrochloric acid solution with a pH value of 4.0 to 6.0, and collect the solution in the dialysis bag after the dialysis is completed.

[0024] Preferably, in steps (1) and (2), sodium hydroxide (NaOH) solution is used to adjust the pH value.

[0025] Preferably, the concentration of the maleimidized alginate solution is 100-150 mg / mL; the concentration of the gelatin solution is 100-150 mg / mL; the maleimidized alginate solution and the gelatin solution are mixed in a volume ratio of 1:4 to 3:2.

[0026] Preferably, in step (3), the curing is carried out at 20 to 80° C. for 12 to 72 hours.

[0027] More preferably, in step (3), the curing is carried out at 25° C. for 72 hours.

[0028] A hydrogel is prepared by any of the methods described above.

[0029] The application of the hydrogel described above in making a wound dressing specifically comprises the following steps:

[0030] The hydrogel mixed solution is dripped onto the wound of the skin and solidified in moist air at room temperature to obtain a hydrogel dressing tightly connected to the wound tissue.

[0031] The application of the hydrogel described above in preparing a coating for an implantable medical device specifically comprises the following steps:

[0032] (1) maintaining the hydrogel mixed solution at above 35° C. in a water bath;

[0033] (2) Immersing the implantable medical device in a hydrogel mixed solution maintained at a constant temperature in a water bath, taking it out, removing excess solution from the gap, and solidifying it in a sealed container to obtain a hydrogel coating tightly connected to the implantable medical device.

[0034] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0035] (1) The hydrogel of the present invention is a hydrogel based on cross-linking of gelatin and alginate molecules, and has good biocompatibility. After further modification of alginate by maleimidation, the cross-linking of alginate and gelatin molecules can be made tighter and more stable, thereby further effectively improving the mechanical properties of the hydrogel while ensuring the biocompatibility of the hydrogel, so that the hydrogel of the present invention has both excellent biocompatibility and mechanical properties.

[0036] (2) The preparation method of the present invention has simple operation procedures, high repeatability, and is easy to industrialize, which makes the hydrogel highly practical and is conducive to the large-scale application of the hydrogel.

[0037] (3) The hydrogel of the present invention has excellent biocompatibility and mechanical properties, and has good application effects in wound dressings and coatings of implantable medical devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Schematic diagram of the synthesis principle of the AM / G hydrogel of the present invention in a specific embodiment;

[0039] Figure 2 is the hydrogen nuclear magnetic resonance spectrum of the maleimidized alginate synthesized in specific examples 1 to 3;

[0040] Figure 3 This is a dynamic mechanical test curve of the AM / G hydrogel prepared in Example 1;

[0041] Figure 4a This is a tensile test curve of the AM / G hydrogel prepared in Example 2;

[0042] Figure 4b This is a graph showing the Young's modulus of the AM / G hydrogel prepared in Example 2;

[0043] Figure 4c This is a graph showing the fracture strength results of the AM / G hydrogel prepared in Example 2;

[0044] Figure 4d This is a graph showing the elongation at break of the AM / G hydrogel prepared in Example 2;

[0045] Figure 4e This is a graph showing the toughness of the AM / G hydrogel prepared in Example 2;

[0046] Figure 5 This is a tensile test curve of the AM / G hydrogel prepared in Example 3;

[0047] Figure 6 This is a microscopic observation image of a tissue section of a wound dressing of a pig skin wound model prepared using the AM / G hydrogel of Example 2 in Example 4;

[0048] Figure 7a This is a morphology diagram of a vascular stent coating made using the AM / G hydrogel of Example 2 in Example 5;

[0049] Figure 7b This is a morphology diagram of the vascular stent coating made of the AM / G hydrogel in Example 2 after balloon expansion in Example 5. DETAILED DESCRIPTION

[0050] The protection scope and implementation modes of the present invention are further described in detail below in conjunction with specific examples, but the protection scope and implementation modes of the present invention are not limited thereto. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific implementation modes and are not intended to limit the present invention.

[0051] In a specific embodiment, the method for preparing the hydrogel of the present invention comprises the following steps:

[0052] (1) dissolving maleimidized alginate in a phosphate buffer and adjusting the pH value to 7.0 to 8.0 to obtain a maleimidized alginate solution; wherein the maleimidized alginate is maleimidized alginate modified with a modification rate of 5 to 15%;

[0053] (2) dissolving gelatin in hot phosphate buffer and adjusting the pH value to 7.0-8.0 to obtain a gelatin solution;

[0054] (3) mixing the maleimidized alginate solution with the gelatin solution to form a hydrogel mixed solution, and solidifying the solution to obtain the hydrogel.

[0055] Gelatin is made from the partial degradation of collagen in connective tissues such as animal skin, bone, and fascia. There are a large number of hydroxyl groups, as well as many carboxyl and amino groups in the molecular structure of gelatin, which makes gelatin extremely hydrophilic and water-binding, and can absorb 5 to 10 times its own weight of water. As one of the most important natural biopolymer materials, gelatin has been widely used in food, medicine and chemical industries.

[0056] Alginate, as a salt of alginic acid, is easily soluble in water. One alginate molecule often has three regions, namely the M region (rich in mannuronic acid), the G region (rich in guluronic acid) and the MG region (containing both uronic acids).

[0057] Alginate and gelatin both have good biocompatibility, but the mechanical properties of hydrogels obtained by simply physically blending alginate and gelatin are weak. After alginate is modified with maleimide, the maleimide modification is connected to the M unit and G unit of alginate; in the hybrid hydrogel of maleimide alginate and gelatin, the maleimide group on the maleimide alginate can further chemically cross-link with the amino group of gelatin (see Figure 1 As shown in the figure, the mechanical properties of the hybrid hydrogel are effectively improved while ensuring the biocompatibility of the hydrogel. Compared with the hydrogel formed by the simple physical blending of alginate and gelatin, the breaking strength, elongation at break and toughness of the hydrogel obtained by chemical crosslinking of maleimidized alginate and gelatin are improved by one to two orders of magnitude.

[0058] Specifically, the maleimidized alginate is prepared by the following method:

[0059] (1-1) Dissolve alginate in phosphate buffer, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) and N-hydroxysulfosuccinimide (Sulfo-NHS) for activation;

[0060] (1-2) adding N-(2-aminoethyl)maleimide trifluoroacetate (AEM-TFA) to the solution activated in step (1-1) to carry out a coupling reaction;

[0061] (1-3) After the reaction is completed, the pH value is adjusted to 4.0-6.0; dialysis is performed, the dialysate is collected, and freeze-dried to obtain the maleimidized alginate.

[0062] The specific synthesis principle of maleimidized alginate is shown in Formula I. EDC and Sulfo-NHS are used to activate the carboxyl group in the alginate structural unit, and then an amide coupling reaction is carried out with the amino group in the AEM-TFA molecule, thereby introducing the maleimide group into the alginate. The maleimide group in maleimidized alginate can undergo a Michael addition reaction with the amino group in gelatin, thereby forming a chemical crosslink.

[0063]

[0064] Example 1

[0065] The preparation of maleimidized alginate comprises the following steps:

[0066] (1) 4.2 g of alginate was dissolved in 100 mL of phosphate buffer, and then 1.38 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.52 g of N-hydroxysulfosuccinimide were added, and activated at 25°C for 1 hour;

[0067] (2) adding 0.51 g of N-(2-aminoethyl)maleimide trifluoroacetate to the solution activated in step (1), and carrying out coupling reaction under magnetic stirring at room temperature for 6 h;

[0068] (3) After the reaction is completed, the pH value of the solution is adjusted to 6.0 with hydrochloric acid; the solution is transferred to a dialysis bag and dialyzed in a dilute hydrochloric acid solution with a pH of 5.0 for 3 days. After the dialysis is completed, the dialysate in the dialysis bag is collected and freeze-dried to obtain a purified maleimidized alginate white solid.

[0069] The prepared maleimidized alginate has a maleimidization modification rate of 5%. The H NMR spectrum of the prepared maleimidized alginate is shown in FIG. Figure 2 As shown. Figure 2 It can be seen that the modified alginate has new proton peak signals near the chemical shifts of 2.8 and 6.8, corresponding to the methylene hydrogen and unsaturated hydrogen on the maleimide group, confirming the successful synthesis of maleimidized alginate (AM(5)).

[0070] The preparation method of the hydrogel comprises the following steps:

[0071] (1) dissolving maleimidized alginate in phosphate buffer to prepare a solution with a concentration of 150 mg / mL, and adjusting the pH value to 7.0 with a NaOH solution to obtain a maleimidized alginate solution;

[0072] (2) dissolving gelatin in hot phosphate buffer to prepare a solution with a concentration of 150 mg / mL, and adjusting the pH value to 8.0 with NaOH solution to obtain a gelatin solution;

[0073] (3) The maleimidized alginate solution and the gelatin solution are mixed in a volume ratio of 3:2 to form a hydrogel mixed solution, and the solution is cured at 25° C. for 72 h to obtain the hydrogel (i.e., AM(5) / G_3 / 2 hydrogel).

[0074] The dynamic mechanical properties of the prepared AM(5) / G_3 / 2 hydrogel were tested at 37°C. The test results are shown in Figure 3 As shown. Figure 3 It can be seen that the prepared AM(5) / G_3 / 2 hydrogel has elasticity.

[0075] Example 2

[0076] The preparation of maleimidized alginate comprises the following steps:

[0077] (1) 4.2 g of alginate was dissolved in 100 mL of phosphate buffer, and then 2.76 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1.04 g of N-hydroxysulfosuccinimide were added, and activated at 25°C for 1 hour;

[0078] (2) adding 1.02 g of N-(2-aminoethyl)maleimide trifluoroacetate to the solution activated in step (1), and carrying out coupling reaction under magnetic stirring at room temperature for 8 h;

[0079] (3) After the reaction is completed, the pH value of the solution is adjusted to 5.0 with hydrochloric acid; the solution is transferred to a dialysis bag and dialyzed in a dilute hydrochloric acid solution with a pH of 5.0 for 4 days. After the dialysis is completed, the dialysate in the dialysis bag is collected and freeze-dried to obtain a purified maleimidized alginate white solid.

[0080] The prepared maleimidized alginate has a maleimidization modification rate of 10%. The H NMR spectrum of the prepared maleimidized alginate is shown in FIG. Figure 2 As shown. Figure 2 It can be seen that the modified alginate has new proton peak signals near the chemical shifts of 2.8 and 6.8, corresponding to the methylene hydrogen and unsaturated hydrogen on the maleimide group, confirming the successful synthesis of maleimidized alginate (AM(10)).

[0081] The preparation method of the hydrogel comprises the following steps:

[0082] (1) dissolving maleimidized alginate in phosphate buffer to prepare a solution with a concentration of 150 mg / mL, and adjusting the pH value to 7.5 with a NaOH solution to obtain a maleimidized alginate solution;

[0083] (2) dissolving gelatin in hot phosphate buffer to prepare a solution with a concentration of 150 mg / mL, and adjusting the pH value to 7.5 with NaOH solution to obtain a gelatin solution;

[0084] (3) The maleimidized alginate solution and the gelatin solution are mixed in a volume ratio of 2:3 to form a hydrogel mixed solution, and the solution is cured at 25°C for 72 hours to obtain the hydrogel (i.e., AM(10) / G_2 / 3 hydrogel).

[0085] The tensile test curve, Young's modulus, breaking strength, breaking elongation and toughness test results of the prepared AM(10) / G_2 / 3 hydrogel are shown in Figure 2. Figure 4a , Figure 4b , Figure 4c , Figure 4d as well as Figure 4e As shown. Figure 4a to Figure 4e It can be seen that compared with the hydrogel formed by simple physical blending of alginate and gelatin (A / G_2 / 3 hydrogel), the hydrogel obtained by chemical crosslinking of maleimidized alginate and gelatin (AM(10) / G_2 / 3 hydrogel) has an improvement of one to two orders of magnitude in breaking strength, elongation at break and toughness.

[0086] Example 3

[0087] The preparation of maleimidized alginate comprises the following steps:

[0088] (1) 4.2 g of alginate was dissolved in 100 mL of phosphate buffer, and then 4.14 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1.56 g of N-hydroxysulfosuccinimide were added, and activated at 20°C for 3 hours;

[0089] (2) adding 1.53 g of N-(2-aminoethyl)maleimide trifluoroacetate to the solution activated in step (1), and carrying out coupling reaction under magnetic stirring at room temperature for 10 h;

[0090] (3) After the reaction is completed, the pH value of the solution is adjusted to 4.0 with hydrochloric acid; the solution is transferred to a dialysis bag and dialyzed in a dilute hydrochloric acid solution with a pH of 5.0 for 5 days. After the dialysis is completed, the dialysate in the dialysis bag is collected and freeze-dried to obtain a purified maleimidized alginate white solid.

[0091] The prepared maleimidized alginate has a maleimidization modification rate of 15%. The H NMR spectrum of the prepared maleimidized alginate is shown in FIG. Figure 2 As shown. Figure 2It can be seen that the modified alginate has new proton peak signals near the chemical shifts of 2.8 and 6.8, corresponding to the methylene hydrogen and unsaturated hydrogen on the maleimide group, confirming the successful synthesis of maleimidized alginate (AM(15)).

[0092] The preparation method of the hydrogel comprises the following steps:

[0093] (1) dissolving maleimidized alginate in phosphate buffer to prepare a solution with a concentration of 150 mg / mL, and adjusting the pH value to 8.0 with a NaOH solution to obtain a maleimidized alginate solution;

[0094] (2) dissolving gelatin in hot phosphate buffer to prepare a solution with a concentration of 150 mg / mL, and adjusting the pH value to 7.0 with NaOH solution to obtain a gelatin solution;

[0095] (3) The maleimidized alginate solution and the gelatin solution are mixed in a volume ratio of 1:4 to form a hydrogel mixed solution, and the solution is cured at 25°C for 72 hours to obtain the hydrogel (i.e., AM(15) / G_1 / 4 hydrogel).

[0096] The tensile mechanical properties of the prepared AM(15) / G_1 / 4 hydrogel were tested. The test results are shown in Figure 5 As shown. Figure 5 It can be seen that the prepared AM(15) / G_1 / 4 hydrogel has good tensile properties, high elongation at break and excellent mechanical properties.

[0097] Example 4

[0098] Application of hydrogels in wound dressings.

[0099] In the examples, a pig skin wound model was used as the test model.

[0100] Specifically, under 45° C. water bath conditions, ① 80 μL of oxidized sodium alginate solution with a modification degree of 10% (AM(10), 150 mg / mL) and 120 μL of gelatin solution (150 mg / mL) were fully mixed to obtain a mixed solution I;

[0101] ② Thoroughly mix 120 μL of oxidized sodium alginate solution (AM(5), 150 mg / mL) with 80 μL of gelatin solution (150 mg / mL) to obtain mixed solution II;

[0102] ③ Thoroughly mix 40 μL of oxidized sodium alginate solution with a modification degree of 15% (AM(15), 150 mg / mL) and 160 μL of gelatin solution (150 mg / mL) to obtain a mixed solution III.

[0103] Then, use a pipette to respectively absorb mixed solution I, mixed solution II and mixed solution III, and drop them onto three pig skin wounds (10 mm in diameter, 1 mm in depth) until the wounds are filled (approximately 80 μL of mixed solution is used), and solidify them under room temperature and moist conditions for 1 day.

[0104] The test results can be found in Figure 6 As shown in the tissue sections, the hydrogel dressing (white transparent area) is tightly connected to the tissue surrounding the skin wound, and the mixed solution forms a hydrogel dressing that is tightly connected to the tissue surrounding the skin wound and has excellent mechanical properties.

[0105] Example 5

[0106] The use of hydrogels in the preparation of coatings for implantable medical devices.

[0107] In the embodiment, a vascular stent is used as a representative for verification, which specifically includes the following steps:

[0108] (1) In a 45°C water bath, ① thoroughly mix 200 μL of 10% modified sodium alginate solution (AM(10), 150 mg / mL) and 300 μL of gelatin solution (150 mg / mL) to obtain a mixed solution I;

[0109] ② Thoroughly mix 300 μL of oxidized sodium alginate solution (AM(5), 150 mg / mL) with 200 μL of gelatin solution (150 mg / mL) with a modification degree of 5% to obtain a mixed solution II;

[0110] ③ Thoroughly mix 100 μL of oxidized sodium alginate solution with a modification degree of 15% (AM(15), 150 mg / mL) and 400 μL of gelatin solution (150 mg / mL) to obtain a mixed solution III.

[0111] (2) Three vascular stents are immersed in solution I, mixed solution II, and mixed solution III, respectively, and then taken out and excess solution in the gaps is removed to obtain vascular stents covered with the mixed solutions.

[0112] (3) The vascular stent covered with the mixed solution is placed in a centrifuge tube and cured in humidified air at 37° C. for 48 hours to obtain a hydrogel coating that is tightly connected to the vascular stent and has excellent mechanical properties.

[0113] The vascular stent covered with the hydrogel coating obtained in this embodiment is shown in Figure 7a As shown, the morphology after balloon dilation is shown in Figure 7b Comparing the two figures, it can be seen that the hydrogel coating did not fall off or break after being stretched, fully demonstrating its strong adhesion and excellent mechanical properties.

[0114] The above embodiments are only preferred embodiments of the present invention and are only intended to further describe the technical solutions of the present invention in detail. However, the protection scope and implementation methods of the present invention are not limited thereto. Any changes, combinations, deletions, replacements or modifications made without departing from the spirit and principles of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a hydrogel, It is characterized in that The steps include: (1) dissolving maleimidized alginate in phosphate buffer and adjusting the pH value to 7.0-8.0 to obtain a maleimidized alginate solution; (2) Dissolving gelatin in hot phosphate buffer and adjusting the pH value to 7.0-8.0 to obtain a gelatin solution; (3) mixing the maleimidized alginate solution with the gelatin solution and solidifying the mixture to obtain the hydrogel; In step (1), the maleimidized alginate is prepared by the following method: (1-1) Dissolve alginate in phosphate buffer, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysulfosuccinimide for activation; (1-2) adding N-(2-aminoethyl)maleimide trifluoroacetate to the solution activated in step (1-1) to carry out a coupling reaction; (1-3) After the reaction is completed, the pH value is adjusted to 4.0-6.0; dialysis is performed, the dialysate is collected, and freeze-dried to obtain the maleimidized alginate.

2. A method for preparing a hydrogel according to claim 1, It is characterized in that The maleimidized alginate is maleimidized alginate with a modification rate of 5-15%.

3. The method for preparing a hydrogel according to claim 1, It is characterized in that The mass ratio of the alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysulfosuccinimide and N-(2-aminoethyl)maleimide trifluoroacetate is 4.2:1.38-4.14:0.52-1.56:0.51-1.

53.

4. The method for preparing a hydrogel according to claim 1, It is characterized in that In step (1-1), the activation is carried out at 20-40° C. for 1-4 hours.

5. The method for preparing a hydrogel according to claim 1, It is characterized in that In step (1-2), the coupling reaction is carried out by stirring at 20-40° C. for 6-10 hours.

6. The method for preparing a hydrogel according to claim 1, It is characterized in that The concentration of the maleimidized alginate solution is 100-150 mg / mL; the concentration of the gelatin solution is 100-150 mg / mL; the maleimidized alginate solution and the gelatin solution are mixed in a volume ratio of 1:4-3:

2.

7. The method for preparing a hydrogel according to claim 1, It is characterized in that In step (3), the curing is carried out at 20-80°C for 12-72 hours.

8. A hydrogel, It is characterized in that It is prepared by the method according to any one of claims 1 to 7.

9. Use of the hydrogel according to claim 8 in making wound dressings or in making coatings for implantable medical devices.

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