CN114395147A

CN114395147A - Hydrogel and preparation method and application thereof

Info

Publication number: CN114395147A
Application number: CN202210110027.0A
Authority: CN
Inventors: 黄骏; 于珊; 国翠平
Original assignee: Institute of Biological and Medical Engineering of Guangdong Academy of Sciences
Current assignee: Institute of Biological and Medical Engineering of Guangdong Academy of Sciences
Priority date: 2022-01-29
Filing date: 2022-01-29
Publication date: 2022-04-26
Anticipated expiration: 2042-01-29
Also published as: CN114395147B

Abstract

The invention relates to the technical field of medical biomaterials, and particularly discloses a hydrogel and a preparation method and application thereof. The hydrogel comprises a first network structure and a second network structure which are mutually interwoven, wherein the first network structure is formed by interweaving main chains of different chitosans through hydrogen bonds, and the second network structure is formed by interweaving the main chains of the chitosans and the main chain of the sodium alginate oxide through C-N bonds. In the hydrogel system prepared by the invention, a large number of hydrogen bonds exist among chitosan main chains, so that the bonding strength among the chitosan main chains can be effectively enhanced, and a stable first network structure is formed. Meanwhile, the primary amine group on the chitosan main chain and the carbonyl group in the oxidized sodium alginate are subjected to Schiff base reaction to obtain a C-N bond to form a second network structure, so that the acting force between the chitosan main chain and the oxidized sodium alginate is increased.

Description

Hydrogel and preparation method and application thereof

Technical Field

The invention relates to the technical field of medical biomaterials, in particular to hydrogel and a preparation method and application thereof.

Background

Hydrogels are a class of very hydrophilic three-dimensional network-structured gels that swell rapidly in water and can hold large volumes of water without dissolving in this swollen state. The hydrogel can provide a wet environment for skin wounds, is beneficial to wound healing and can be applied to tissue adhesives; but the hydrogel has poor adhesion with wound tissues and is easy to fall off in the using process. The tissue adhesive is used as an effective supplement and auxiliary mode for traditional wound treatment, and can realize the performances of effectively inhibiting bacteria, resisting inflammation, promoting the growth of local defective tissues and the recovery of functions, and the like, and simultaneously considers the material cost and the safety. Aiming at the performance requirements of the tissue adhesive, designing related materials is an important component of the current medical material research. At present, the mainstream tissue adhesive in the market is mainly based on cyanoacrylate chemical components, has the characteristics of high curing speed, strong viscosity and the like, but is easy to release heat during curing, causes secondary damage to wounds, and has poor elasticity and ductility of the wounds. The chitosan is a natural alkaline aminopolysaccharide which has rich source, good biocompatibility and both antibacterial property and biodegradability, can be used for medical biomaterials, but has poor solubility, and limits further development and application of the chitosan. Therefore, how to prepare a tissue adhesive with good biocompatibility, good tissue adhesion and high mechanical strength is a technical problem which needs to be solved urgently at present.

Disclosure of Invention

The present invention is directed to solving at least one of the problems of the prior art described above. Therefore, the invention provides the hydrogel which has good tissue adhesiveness and mechanical property.

The invention also provides a preparation method and application of the hydrogel.

According to the first aspect of the invention, the hydrogel is provided, and the hydrogel comprises a first network structure and a second network structure which are interwoven with each other, wherein the first network structure is formed by interweaving main chains of different chitosans through hydrogen bonds, and the second network structure is formed by interweaving the main chains of the chitosans and the main chain of the sodium alginate oxide through C-N bonds.

According to the first aspect of the present invention, at least the following advantages are provided:

the chitosan has good biocompatibility, antibacterial property and biodegradability. In the hydrogel system prepared by the invention, a large number of hydrogen bonds exist among chitosan main chains, so that the bonding strength among the chitosan main chains can be effectively enhanced, and a stable first network structure is formed. Meanwhile, the primary amine group on the chitosan main chain and the carbonyl group on the oxidized sodium alginate main chain are subjected to Schiff base reaction to obtain a C-N bond to form a second network structure, so that the acting force between the chitosan main chain and the oxidized sodium alginate is increased. Therefore, the hydrogel prepared by the invention has a double-network structure, good mechanical property, adhesion property, biocompatibility and biodegradability, and has wide application prospects in the aspects of biological adhesives, hemostats and the like.

Preferably, the hydrogen bonds in the first network structure are formed by base complementary pairing.

Preferably, the first network structure comprises a first base modified chitosan and a second base modified chitosan, wherein a first base in the first base modified chitosan and a second base in the second base modified chitosan are paired with each other to form a hydrogen bond, so that the main chains of different chitosans are interwoven through the hydrogen bond to form the first network structure. Compared with unmodified chitosan, the solubility of the chitosan modified by the basic group is greatly improved, the formation of a first network structure is facilitated, and the mechanical property of the hydrogel is enhanced.

Preferably, the first base-modified chitosan comprises at least one of thymine-modified chitosan, cytosine-modified chitosan, and uracil-modified chitosan; more preferably, the first base-modified chitosan is thymine-modified chitosan.

Preferably, the grafting ratio of the first base-modified chitosan is 20 to 44%, preferably 30 to 40%, and more preferably about 33.3%.

Preferably, the second base-modified chitosan comprises at least one of adenine-modified chitosan and guanine-modified chitosan; more preferably, the second base-modified chitosan is adenine-modified chitosan.

Preferably, the grafting ratio of the second alkali-modified chitosan is 20 to 44%, preferably 30 to 40%, and more preferably about 33.3%.

Preferably, the mass ratio of the first base-modified chitosan to the second base-modified chitosan is 1:1 to 1.2, more preferably 1:1 to 1.1, and more preferably 1: about 1.

Preferably, the second network structure comprises a first base modified chitosan, a second base modified chitosan and a derivative of sodium alginate oxide and/or sodium alginate oxide, wherein a primary amine group in the first base modified chitosan forms a C ═ N bond with a carbonyl group in the derivative of sodium alginate oxide and/or sodium alginate oxide, and a primary amine group in the second base modified chitosan forms a C ═ N bond with a carbonyl group in the derivative of sodium alginate oxide and/or sodium alginate oxide, so that the main chain of chitosan and the main chain of sodium alginate oxide are interwoven through the C ═ N bond to form the second network structure.

Preferably, the oxidized sodium alginate derivative comprises dopamine modified oxidized sodium alginate. The molecular structure of the dopamine modified sodium alginate oxide contains a catechol structure, so that the dopamine modified sodium alginate has excellent adhesion performance, and can effectively improve the mechanical property and tissue adhesion performance of hydrogel.

Preferably, the oxidation degree of the dopamine modified oxidized sodium alginate is 10-20%, more preferably 12-16%, and even more preferably about 14.8%.

Preferably, the mass ratio of the first base modified chitosan, the second base modified chitosan and the oxidized sodium alginate and/or the derivative of the oxidized sodium alginate is 1: 1-1.2: 1 to 3, more preferably 1: 1-1.1: 1-2, such as 1:1: 1. 1:1: about 2.

In a second aspect of the present invention, a method for preparing a hydrogel is provided, which comprises the following steps: and reacting the main chains of the different chitosans to generate hydrogen bonds and interweaving the hydrogen bonds to form the first network structure, and reacting the main chains of the chitosans with the main chain of the sodium alginate oxide to generate C-N bonds to form a second network structure interweaving with the first network structure, so as to obtain the hydrogel.

Preferably, the main chains of the different chitosans react with hydrogen bonds and interweave to form the first network structure, and the method comprises the following steps: and the first base modified chitosan and the second base modified chitosan are subjected to blending reaction to generate hydrogen bonds and are interwoven to form a first network structure.

Preferably, the reaction of the chitosan backbone with the sodium alginate oxide backbone generates a C ═ N bond to form a second network structure interwoven with the first network structure, comprising the steps of: and (3) blending and reacting the first base modified chitosan, the second base chitosan and oxidized sodium alginate and/or derivatives of oxidized sodium alginate to generate a second network structure with C ═ N bonds interwoven with the first network structure.

Preferably, the preparation method of the hydrogel specifically comprises the following steps: and mixing the first base modified chitosan solution, the second base modified chitosan solution and the oxidized sodium alginate and/or the oxidized sodium alginate derivative solution to obtain the hydrogel.

Preferably, the preparation method of the first base modified chitosan comprises the following steps: reacting the first base with chitosan to obtain the first base modified chitosan.

Preferably, the preparation method of the first base modified chitosan specifically comprises the following steps:

step S11, reacting the first base with bromoacetic acid to obtain a carboxyl modified first base;

step S12, reacting the carboxyl-modified first base with the chitosan to obtain a first base-modified chitosan.

Preferably, the mass ratio of the first base to the bromoacetic acid in the step S11 is 1: 1.5 to 3, more preferably 1: 1.5 to 2.0.

Preferably, the reaction temperature of the step S11 is 50-70 ℃, such as 60 ℃. The reaction time is 0.5-3 h, such as 1 h.

Preferably, the step S11 further adds a base. The base is not limited, and examples thereof include potassium hydroxide, sodium hydroxide, solutions thereof, and the like. The mass ratio of the first base to the base is 1: 1.5 to 3, more preferably 1: 1.5 to 2.0.

Preferably, the step S11 further includes the steps of precipitating, filtering, washing, drying, and the like after the reaction is completed, specifically, the pH of the reaction system is adjusted to 2 to 3, and the carboxyl modified first base is obtained by precipitating, filtering, washing, and drying. Wherein, the reagent used for washing comprises at least one of water, ethanol, propanol, butanol, ethyl acetate and butyl acetate, more preferably a composition of water, ethanol and ethyl acetate, and specifically washing with water, ethanol and ethyl acetate sequentially.

Preferably, in the step S12, the carboxyl-modified first base and the imine compound are added to a chitosan solution, and the first base-modified chitosan is obtained by reaction.

Preferably, the solvent of the chitosan solution is a buffer, in particular a 0.1M solution of 2- (N-morpholine) ethanesulfonic acid (MES). The mass-volume ratio of the chitosan to the buffer solution is 1: 80-120 g/mL, more preferably 1: about 100 g/mL.

Preferably, the mass ratio of the carboxyl modified first base to the chitosan is 0.7-0.9: 1, more preferably 0.8 to 0.9: 1, such as 0.847: about 1.

Preferably, the imine compound includes at least one of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxythiosuccinimide (NHS), more preferably a combination of EDC and NHS.

Preferably, the mass ratio of the imine compound to the chitosan is 2-4: 1, more preferably 3 to 4: 1, as 3.524: 1.

preferably, the mass ratio of EDC to NHS is 1.2-1.8: 1, more preferably 1.5 to 1.7: 1, as 1.66: 1.

preferably, the reaction temperature of the step S22 is 20-50 ℃, more preferably 20-40 ℃, such as room temperature. The reaction time is 24-72 h, preferably 36-60 h, such as 48 h.

Preferably, the step S12 further comprises dialysis and lyophilization treatment steps after the reaction, wherein the first base modified chitosan is obtained by dialysis for 5-9 days with 7000-9000 molecular weight dialysis bags and lyophilization.

Preferably, the method for preparing the second base-modified chitosan comprises the step of reacting a second base with chitosan to obtain the second base-modified chitosan.

Preferably, the preparation method of the second base modified chitosan comprises the following steps,

step S21, reacting the second base with ethyl acrylate to obtain a carboxyl-modified second base;

step S22, reacting the carboxyl modified second base with chitosan to obtain second base modified chitosan.

Preferably, the step S21 is to drop the ethyl acrylate into the second base solution to obtain the intermediate product, where the solvent in the second base solution includes at least one of sodium ethoxide, absolute ethyl alcohol, and propyl alcohol. The mass-to-volume ratio of the second base to the solvent in the second base solution is 1: 20-30 g/mL, such as 1: 25 g/mL.

Preferably, the reaction temperature of step S21 is 70-90 ℃, such as 80 ℃. The reaction time is 6-12 h, and more preferably 8-10 h.

Preferably, the step S21 further includes the steps of removing the solvent under reduced pressure, washing, filtering, drying, etc. Specifically, the mixed solvent after the reaction is decompressed, the solvent is removed, and the intermediate product is obtained after multiple times of washing and drying; and adding the intermediate product into an acidic solution for reaction, adjusting the pH value to 3, washing and drying to obtain second base modified chitosan.

Preferably, the washing reagent comprises at least one of glacial ethanol and glacial water.

Preferably, the acidic solution comprises at least one of a hydrochloric acid solution, a sulfuric acid solution and a nitric acid solution, and the concentration of the acidic solution is 1-5M, such as about 3M.

Preferably, in step S22, the carboxyl-modified second base and the imine compound are added to a chitosan solution, and reacted to obtain the second base-modified chitosan.

Preferably, the solvent of the chitosan solution is a buffer, in particular a 0.1M MES solution. The mass-volume ratio of the chitosan to the buffer solution is 1: 80-120 g/mL, more preferably 1: about 100 g/mL.

Preferably, the mass ratio of the carboxyl modified second base to the chitosan is 0.8-1: 1, more preferably 0.9 to 1:1, such as 0.945: about 1.

Preferably, the step S22 further includes dialysis, lyophilization, and the like, wherein the second base-modified chitosan is obtained by dialysis for 5-9 days with 7000-9000 molecular weight dialysis bags and lyophilization.

Preferably, the oxidized sodium alginate derivative comprises dopamine modified oxidized sodium alginate, and the preparation method of the dopamine oxidized sodium alginate comprises the following steps of reacting the oxidized sodium alginate with dopamine hydrochloride to obtain the dopamine oxidized sodium alginate.

Preferably, the preparation method of the dopamine oxidized sodium alginate specifically comprises the following steps of adding an imine compound and dopamine hydrochloride into an oxidized sodium alginate solution, and reacting to obtain the dopamine modified oxidized sodium alginate. Preferably, the reaction time is 8-14 h, such as 12 h. The reaction is carried out under a protective atmosphere, more preferably under an inert gas atmosphere, such as nitrogen or argon.

Preferably, the solvent in the oxidized sodium alginate solution is a buffer solution, specifically a PBS buffer solution, and the pH of the PBS buffer solution is 4-6, more preferably 5-6, such as 5.7.

Preferably, the mass-volume ratio of the oxidized sodium alginate to the solvent in the oxidized sodium alginate solution is 1: 80-120 g/mL, such as 1: 100 g/mL.

Preferably, the mass ratio of the oxidized sodium alginate to the dopamine hydrochloride is 1: 1.5-3, such as 1: 2.

preferably, the imine compound includes at least one of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC), N-hydroxythiosuccinimide (NHS). More preferably, 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxythiosuccinimide (NHS).

Preferably, the mass ratio of the imine compound to sodium alginate oxide is 1.4-1.6: 1; wherein the mass ratio of the 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) to the N-hydroxythiosuccinimide (NHS) is 1.5-1.8: 1, more preferably 1.6 to 1.7: 1.

preferably, the preparation process of the oxidized sodium alginate comprises the following steps of adding an aqueous solution into a sodium alginate ethanol solution, and reacting in the dark to obtain the oxidized sodium alginate. The reaction time is 4-8 h, and preferably 4-6 h.

Preferably, the mass-volume ratio of the sodium alginate to the ethanol in the sodium alginate ethanol solution is 1: 30-60 g/mL, such as 1: 50 g/mL.

Preferably, the preparation method of the oxidized sodium alginate further comprises the processing steps of precipitation, dialysis and freeze-drying, and specifically comprises the steps of adding ethylene glycol after the reaction is finished, continuing stirring, adding ethanol to precipitate, dialyzing and freeze-drying to obtain the oxidized sodium alginate.

Preferably, the addition amount of the ethylene glycol is 5-20 mL, such as 10 mL.

In a third aspect of the invention, the use of a hydrogel for the preparation of medical materials (e.g. bioadhesives, haemostatic agents) is proposed.

Compared with the prior art, the invention has at least the following beneficial effects:

in the hydrogel system prepared by the invention, a large number of hydrogen bonds exist among chitosan main chains, so that the bonding strength among the chitosan main chains can be effectively enhanced, and a stable first network structure is formed. Meanwhile, the primary amine group on the chitosan main chain and the carbonyl group on the oxidized sodium alginate main chain are subjected to Schiff base reaction to obtain a C-N bond to form a second network structure, so that the acting force between the chitosan main chain and the oxidized sodium alginate is increased.

The chitosan has good biocompatibility, antibacterial property and biodegradability. A large number of active groups such as hydroxyl, amino and the like are distributed on a chitosan molecular chain, and after the chitosan is modified by the basic groups, the chitosan modified by the basic groups has good biocompatibility, antibacterial property and biodegradability, and meanwhile, the solubility of the chitosan is greatly improved, and the application prospect of the chitosan is widened. The primary amine group in the first base modified chitosan and the carbonyl group in the dopamine modified sodium alginate oxide form a C ═ N bond, and the primary amine group in the second base modified chitosan and the carbonyl group in the dopamine modified sodium alginate oxide form a C ═ N bond, so that the main chain of the chitosan and the dopamine modified sodium alginate oxide are interwoven through the C ═ N bond to form a second network structure. Meanwhile, the molecular structure of the dopamine modified sodium alginate oxide contains a catechol structure, so that the dopamine modified sodium alginate oxide has excellent adhesion performance.

The hydrogel prepared by using the base modified chitosan and the dopamine modified alginic acid oxide has hydrogen bond acting force of base complementary pairing, C-N bond acting force generated by Schiff base reaction and electrostatic action in the hydrogel, so that the cohesive force of a hydrogel system is improved; and the system also has a catechol structure, so that the adhesion property of the system to tissues is improved. Therefore, the hydrogel with double networks prepared by the invention has good biocompatibility, antibacterial property, biodegradability, tissue adhesiveness and mechanical property, and has wide application prospect in the aspects of biological adhesive, hemostatic and the like.

Drawings

The invention is further described with reference to the following figures and examples, in which:

FIG. 1 is a schematic representation of the forces within a hydrogel system of example 1 of the present invention;

FIG. 2 is a schematic diagram of hydrogels prepared in example 1 and comparative examples 1 to 2 of the present invention;

FIG. 3 is a graph showing the results of lap shear performance tests of hydrogels prepared in example 1 of the present invention and comparative examples 1-2 on gelatin-coated glass slides;

FIG. 4 is a graph showing the results of lap shear performance tests on pigskin using hydrogels prepared in example 1 of the present invention and hydrogels prepared in comparative examples 1 to 2.

Detailed Description

The concept and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and those skilled in the art can obtain other embodiments without inventive effort based on the embodiments of the present invention, and all embodiments are within the protection scope of the present invention.

Example 1

This example prepared a hydrogel comprising the steps of:

1. weighing 1.5g of thymine modified chitosan with the grafting rate of 33.3 percent, dissolving in 10.0mL of deionized water, and fully dissolving to obtain a precursor solution CS-T;

2. weighing 1.5g of adenine modified chitosan with the grafting rate of 33.3 percent, dissolving in 10.0mL of deionized water, and fully dissolving to obtain A precursor solution CS-A;

3. weighing 1.5g of dopamine modified sodium alginate with a grafting rate of 14.8 percent, dissolving the dopamine modified sodium alginate in 10.0mL of deionized water, and fully dissolving to obtain a precursor liquid OSA-C₆-2OH；

4. Taking CS-A, CS-T, OSA-C with the volume ratio of 1:1:1₆Mixing-2 OH uniformly to obtain CS-A/CS-T/OSA-C₆-2OH hydrogel.

The preparation method of the thymine modified chitosan specifically comprises the following steps:

1. dissolving 2.5g of thymine, 5g of potassium hydroxide and 5g of bromoacetic acid in 50mL of water, heating to 60 ℃, refluxing for 1h, and cooling to room temperature;

2. adjusting pH to 2 with 1M hydrochloric acid, precipitating, filtering, washing with water, ethanol and ethyl acetate in sequence, and drying to obtain carboxyl modified thymine (T-COOH);

adding 3.2 g of chitosan into 200mL of MES solution with the concentration of 0.1M for dissolution;

4. 1.694g T-COOH, 4.4g EDC and 2.648g NHS were added to the MES system solution, stirred at room temperature for 48 hours, and the product was transferred to 8000 molecular weight dialysis bag for dialysis for 7 days, and lyophilized to obtain thymine modified chitosan.

The preparation method of the adenine modified chitosan specifically comprises the following steps:

dissolving 1.2 g of adenine in 50ml of sodium ethoxide solution, adding ethyl acrylate, heating to 80 ℃, refluxing for 10 hours, cooling to room temperature, removing the solvent under reduced pressure, washing with glacial ethanol, washing out the precipitate, filtering to obtain the precipitate, washing with the glacial ethanol for multiple times, and performing vacuum drying to obtain a product A;

2. adding 1g of the product A into 3M hydrochloric acid for refluxing for 3 hours, cooling to room temperature, adjusting the pH value to 3 with sodium hydroxide solid, filtering, washing with ice water, and performing vacuum drying to obtain a product B (carboxyl modified adenine, A-COOH);

adding 3.2 g of chitosan into 200mL of MES solution with the concentration of 0.1M for dissolving, adding 1.89g A-COOH, 4.38g of EDC and 2.63g of NHS into the MES solution, stirring at room temperature for 48 hours, transferring the product into a 8000 molecular weight dialysis bag for dialysis for 7 days, and freeze-drying to obtain the product, namely, adenine modified chitosan.

The preparation method of the dopamine modified oxidized sodium alginate specifically comprises the following steps:

1.20 g of sodium alginate is dissolved in 100ml of ethanol and then added to 100ml of aqueous solution (containing 20g of sodium alginate); after 6 hours of reaction in dark place, 10ml of ethylene glycol is added to terminate the reaction;

2. continuing magnetically stirring for 2h, adding 1L of alcohol to precipitate, filtering, collecting precipitate, dialyzing for three days, and lyophilizing to obtain oxidized sodium alginate;

dissolving 3.2 g of sodium alginate oxide in 200mL of PBS (pH5.7), adding 1.94g of EDC and 1.165g of NHS1.165g, magnetically stirring for 30min, adding 4g of dopamine hydrochloride, and reacting the whole system for 12 hours under the protection of nitrogen;

4. and adding 1L of ethanol to terminate the reaction after the reaction is finished, filtering, collecting the precipitate, dialyzing with deionized water for three days, and freeze-drying to obtain the product dopamine modified sodium alginate oxide.

Example 2

4. Taking CS-A, CS-T, OSA-C with the volume ratio of 1:1:2₆Mixing-2 OH uniformly to obtain CS-A/CS-T/OSA-C₆-2OH hydrogel.

Comparative example 1

This comparative example prepared a hydrogel, differing from example 1 in that the chitosan used was unmodified, comprising the following steps:

1. weighing 0.2g of chitosan, dissolving in 10.0mL of 1% acetic acid solution, and fully dissolving to obtain a precursor solution CS;

2. weighing 1.5g of dopamine modified sodium alginate with a grafting rate of 14.8 percent, dissolving the dopamine modified sodium alginate in 10.0mL of deionized water, and fully dissolving to obtain a precursor liquid OSA-C₆-2OH；

3. Taking 2 volumes of CS solution and 1 volume of OSA-C with the same volume₆Mixing with-2 OH to obtain CS/OSA-C₆-2OH hydrogel.

Comparative example 2

This comparative example prepared a hydrogel, which differs from example 1 in that both the chitosan and the oxidized sodium alginate used were unmodified, comprising the following steps:

2. weighing 1.5g of sodium alginate oxide, dissolving in 10.0mL of deionized water, and fully dissolving to obtain a precursor liquid OSA;

3. and mixing 2 volumes of CS solution and 1 volume of OSA with the same volume to obtain the CS/OSA hydrogel.

Test examples

After a proper amount of the hydrogel prepared in example 1 and comparative examples 1-2 was applied to a gelatin smear slide or a pigskin, the lap shear strength was tested by using a material testing machine, and the experimental results are shown in fig. 3-4.

FIG. 2 is A diagram of A hydrogel prepared in example 1 and comparative examples 1-2, in which example 1 of the present invention employs adenine-modified chitosan, thymine-modified chitosan, and dopamine-modified sodium alginate oxide to prepare A hydrogel CS-A/CS-T/OSA-C₆The-2 OH had a pale yellow color, darker than the hydrogels prepared in comparative examples 1 and 2. The chitosan used in comparative examples 1 and 2 was not modified, had very low solubility in aqueous solution, and could be dissolved only in a weak acid environment, the saturated solubility was low, the amount involved in the reaction was small, and the hydrogel obtained was lighter in color. The solubility of the chitosan modified by the basic groups (adenine and thymine) is greatly increased, the chitosan is soluble in water and can fully react, and the obtained hydrogel is darker in color.

The lap shear properties of the hydrogels prepared in example 1 of the present invention and comparative examples 1-2 on gelatin-coated glass slides are shown in FIG. 3, and the hydrogel prepared in example 1 of the present invention is CS-A/CS-T/OSA-C₆The shearing force of-2 OH on the gelatin coating glass slide is up to 17.4N, and the shearing strength is up to 35.03 kPa; comparative example 1 hydrogel CS/OSA-C prepared using unmodified chitosan₆The shear force of-2 OH is only 3.4N, and the shear strength is only 6.756kPa, and the hydrogel CS/OSA prepared by using unmodified chitosan and unmodified sodium alginate in the comparative example 2 has extremely poor mechanical property, the shear force is only 1.2N, and the shear strength is 2.638 kPa. By comparison, CS-A/CS-T/OSA-C prepared in example 1 of the present invention₆The shear strength of the-2 OH on the gelatin coating glass slide is far greater than that of the comparative example and is 5.18-13.27 times that of the comparative example.

As shown in FIG. 4, hydrogel CS-A/CS-T/OSA-C prepared in inventive example 1₆-2OH in pigsThe shear strength on the skins was 3.041kPa, significantly higher than the CS/OSA-C prepared in comparative example 1₆-2OH shear strength on pig skin 2.693kPa and CS/OSA shear strength on pig skin 0.495kPa for the CS/OSA prepared in comparative example 2. Hydrogel CS-A/CS-T/OSA-C prepared in example 1 of the invention₆The shear strength of the-2 OH on the pigskin is also larger than that of the hydrogel prepared in the comparative examples 1-2, and the hydrogel has good tissue adhesiveness and mechanical property.

The test results for the hydrogel prepared in example 2 are similar and will not be described further.

The hydrogel disclosed by the invention has excellent mechanical properties and tissue adhesion properties, and mainly has hydrogen bond acting force generated by complementary pairing of adenine and thymine bases, C-N acting force generated by Schiff base reaction and electrostatic action in the hydrogel prepared from adenine modified chitosan, thymine modified chitosan and dopamine modified sodium alginate oxide, as shown in figure 1, the cohesion of the system is improved; and the system also has a catechol structure, so that the adhesion property of the system to tissues is improved, and the system has wide application prospects in the aspects of biological adhesives, hemostats and the like. When the raw materials of the hydrogel are changed, such as the raw materials of comparative examples 1-2, unmodified chitosan or unmodified chitosan and unmodified sodium alginate oxide are respectively used, the adhesion performance and the mechanical property of the obtained hydrogel are obviously reduced.

Claims

1. The hydrogel is characterized by comprising a first network structure and a second network structure which are interwoven with each other, wherein the first network structure is formed by interweaving main chains of different chitosans through hydrogen bonds, and the second network structure is formed by interweaving the main chains of the chitosans and the main chain of the sodium alginate oxide through C-N bonds.

2. The hydrogel of claim 1, wherein the first network structure comprises a first base-modified chitosan and a second base-modified chitosan, and a first base in the first base-modified chitosan and a second base in the second base-modified chitosan are paired with each other to form a hydrogen bond, such that the backbones of different chitosans are interwoven through the hydrogen bond to form the first network structure.

3. The hydrogel of claim 2, wherein the first base-modified chitosan comprises at least one of thymine-modified chitosan, cytosine-modified chitosan, and uracil-modified chitosan.

4. The hydrogel of claim 2, wherein the second base-modified chitosan comprises at least one of adenine-modified chitosan and guanine-modified chitosan.

5. The hydrogel according to claim 2, wherein the mass ratio of the first base-modified chitosan to the second base-modified chitosan is 1:1 to 1.2.

6. The hydrogel according to any one of claims 2 to 5, wherein the second network structure comprises a first base-modified chitosan, a second base-modified chitosan, sodium alginate oxide and/or a derivative of sodium alginate oxide, a primary amine group in the first base-modified chitosan forms a C ═ N bond with a carbonyl group in the sodium alginate oxide and/or the derivative of sodium alginate oxide, and a primary amine group in the second base-modified chitosan forms a C ═ N bond with a carbonyl group in the sodium alginate oxide and/or the derivative of sodium alginate oxide, so that a main chain of chitosan and a main chain of sodium alginate oxide are interwoven through the C ═ N bond to form the second network structure.

7. The hydrogel according to claim 6, wherein the mass ratio of the first base-modified chitosan, the second base-modified chitosan and sodium alginate oxide and/or a derivative of sodium alginate oxide is 1: 1-1.2: 1 to 3.

8. The hydrogel according to claim 6, wherein said oxidized sodium alginate derivative comprises dopamine modified oxidized sodium alginate.

9. A process for the preparation of a hydrogel according to any of claims 1 to 8 comprising the steps of: and reacting the main chains of the different chitosans to generate hydrogen bonds and interweaving the hydrogen bonds to form the first network structure, and reacting the main chains of the chitosans with the main chain of the sodium alginate oxide to generate C-N bonds to form a second network structure interweaving with the first network structure, so as to obtain the hydrogel.

10. Use of a hydrogel according to any of claims 1 to 8 for the preparation of a medical material.