CN111909396B

CN111909396B - Natural polymer-based supramolecular self-healing hydrogel and preparation method and application thereof

Info

Publication number: CN111909396B
Application number: CN202010702427.1A
Authority: CN
Inventors: 蒋刚彪; 胡甜; 刘金文; 朱水容; 蓝玲敏
Original assignee: South China Agricultural University
Current assignee: South China Agricultural University
Priority date: 2020-07-21
Filing date: 2020-07-21
Publication date: 2021-05-28
Anticipated expiration: 2040-07-21
Also published as: CN111909396A

Abstract

The invention discloses a natural polymer-based supramolecular self-healing hydrogel and a preparation method and application thereof. The method comprises the following steps: (1) reacting chitosan with p-aldehyde benzoic acid, 4-dimethylamino pyridine and dicyclohexyl carbodiimide to obtain aldehyde chitosan; (2) mixing carboxymethyl chitosan or sodium alginate with aldehyde chitosan to prepare aldehyde chitosan mixed solution; (3) and adding the nano and/or micron copper suspension or chloroauric acid solution into the aldehyde chitosan mixed solution, stirring, and standing to obtain the supermolecule self-healing hydrogel. The natural polymer-based supramolecular self-healing hydrogel disclosed by the invention has the advantages of quick self-healing, antibacterial property and biocompatibility, metal ions are slowly released, the fixing time of the hydrogel is prolonged, the defects that natural polymers and metal ions are easy to quickly chelate and are difficult to use due to local gelling are overcome, and the natural polymer-based supramolecular self-healing hydrogel can be used as an antibacterial material for healing wound surfaces.

Description

Natural polymer-based supramolecular self-healing hydrogel and preparation method and application thereof

Technical Field

The invention belongs to the technical field of hydrogel, and particularly relates to natural polymer-based supramolecular self-healing hydrogel and a preparation method and application thereof.

Background

In recent years, self-healing materials are concerned by people because the materials can self-heal and repair after being damaged, so that the service life of the materials can be greatly prolonged, and the use cost is reduced. In particular to a self-healing hydrogel material which is more and more widely applied in the fields of artificial intelligence, biosensing, tissue engineering, wound dressing and the like. Most of the existing self-healing hydrogel materials realize the self-healing performance thereof by introducing dynamic bonds, including dynamic covalent bonds (acylhydrazone bonds, disulfide bonds, Schiff bond bonds and the like) and dynamic non-covalent bonds (metal coordination bonds, hydrogen bonds, host-guest actions and the like). The introduction of dynamic covalent bonds generally requires complex synthetic steps, the preparation conditions are harsh, and the introduction of light stimulation, high temperature or an initiator is required; self-healing hydrogels prepared with dynamic non-covalent bonds generally suffer from poor mechanical properties, which greatly hinder the application of self-healing hydrogels.

Metal complexation is widely introduced into the preparation of supramolecular hydrogels because it has mechanical properties comparable to covalent bonds on the one hand, and on the other hand, most of the metal chelation is dynamically reversible. At present, most of supramolecular hydrogels are mainly prepared by taking synthetic polymer materials as a framework, and pure natural polymer-based hydrogels are less researched. The main reason is that natural polymer materials generally have more hydrophilic groups, such as amino groups, carboxyl groups, hydroxyl groups, and the like, which can be chelated with metal ions faster, so that the problems of local rapid gelling, long time, rapid gelling, and non-uniform dispersion of pure natural polymer based supramolecular hydrogels can be formed between pure natural polymers and metal ions, and the pure natural polymer based supramolecular hydrogels are stopped at the initial stage of research.

Therefore, it is significant to develop a simple method for preparing supramolecular self-healing hydrogels.

Disclosure of Invention

In order to overcome the defects and shortcomings in the prior art, the invention aims to provide a preparation method of natural polymer-based supramolecular self-healing hydrogel. The invention adopts green, safe, abundant and cheap chitosan and derivatives thereof as the hydrogel framework and the metal nanoparticles as the chelating agent to prepare the natural polymer-based self-healing hydrogel simultaneously containing Schiff bond function and metal chelating function. The supermolecule hydrogel prepared by the method has the rapid healing capability without any external stimulation and the excellent bacteriostatic capability. Has good application prospect in the fields of tissue engineering repair, wound repair, drug controlled release, drug preparation, biosensing and the like.

The invention also aims to provide the natural polymer-based supramolecular self-healing hydrogel prepared by the method.

The invention further aims to provide application of the natural polymer-based supramolecular self-healing hydrogel in the fields of medicine preparation and biosensing.

The purpose of the invention is realized by the following technical scheme:

a preparation method of natural polymer-based supramolecular self-healing hydrogel comprises the following steps:

(1) sequentially adding p-aldehyde benzoic acid, 4-Dimethylaminopyridine (DMAP) and Dicyclohexylcarbodiimide (DCC) into a chitosan solution at room temperature under the protection of nitrogen or inert gas, reacting, purifying, drying and dialyzing to obtain aldehyde chitosan;

(2) dispersing the aldehyde chitosan into water, then adding the water into a carboxymethyl chitosan or sodium alginate solution, and uniformly mixing to obtain an aldehyde chitosan mixed solution;

(3) adding the nano and/or micron copper suspension or chloroauric acid solution into the aldehyde chitosan mixed solution under stirring, continuously stirring, standing to form a gel state, and solidifying to obtain the natural polymer-based supramolecular self-healing hydrogel;

in the step (3), the mass ratio of the carboxymethyl chitosan, the aldehyde chitosan and the nano and/or micro copper or chloroauric acid is (5-200) to (1-30): (2-16).

Preferably, the mass ratio of the p-aldehyde benzoic acid, the 4-Dimethylaminopyridine (DMAP), the Dicyclohexylcarbodiimide (DCC) and the chitosan in the step (1) is (450.39-900.75): (1.22-12.2): (0.21-20.6): 1000, parts by weight; more preferably 600: 4: 2: 1000.

preferably, the molecular weight of the chitosan in the step (1) is 1000-5000; more preferably 5000.

Preferably, in the chitosan solution in the step (1), the ratio of chitosan to solvent is (0.6-4.8) g: (5-40) ml; more preferably 2.5g/40 ml.

Preferably, the solvent of the chitosan solution in step (1) is at least one of dichloromethane, pyridine, dimethyl sulfoxide, tetrahydrofuran and dimethylformamide.

Preferably, the reaction time in the step (1) is 12-36 h.

Preferably, the purification method in step (1) is: adding water to the reaction product of step (1) to precipitate the product, filtering, and then washing with water several times.

Preferably, the drying in step (1) is a drying operation conventional in the art.

Preferably, the dialysis method in step (1) is: dialyzing the reaction product in water for 3 days by using a dialysis bag with the molecular weight of 1000 to obtain the aldehyde chitosan.

Preferably, the aldehyde chitosan in the step (2) is dispersed in water by ultrasonic, and the ultrasonic time is 10-30 min; more preferably 15 min.

Preferably, the ratio of the aldehyde chitosan in the step (2) to water is 0.06 g: (1-10) ml; more preferably 0.06 g: 4 ml.

Preferably, the solvent of the carboxymethyl chitosan or sodium alginate solution in the step (2) is water, and the ratio of the carboxymethyl chitosan or sodium alginate to the water is (0.1-1) g: (10-40) ml; more preferably 0.4 g: 10 ml.

Preferably, the mass ratio of the aldehyde chitosan to the carboxymethyl chitosan or sodium alginate in the step (2) is (0.2-1.5): (1-10), more preferably 1.5: 10.

preferably, in the aldehyde chitosan mixed solution in the step (2), the ratio of the carboxymethyl chitosan or sodium alginate to the solvent is (0.1-1.2) g (1-20) ml; the ratio of the aldehyde chitosan to the solvent is (0.006-0.3) g, (1-4) ml.

Preferably, the rotation speed for stirring and mixing uniformly in the step (2) is 800-1200 rpm, and the time is 1-3 h.

Preferably, the particle size of copper in the nano and/or micro copper suspension in the step (3) is 1 nm-500 um, and more preferably 1-500 um/nm.

Preferably, the copper in the nano-copper suspension liquid in the step (3) is derived from at least one of carbon-supported copper and nano-copper; the copper in the micron copper suspension is derived from at least one of carbon-supported copper and micron copper.

Preferably, the ratio of copper to water in the nano and/or micro copper suspension in the step (3) is 2-8 mg/ml, and more preferably 2 mg/ml; the ratio of the chloroauric acid to the water in the chloroauric acid solution is 0.17-7 mg/ml.

Preferably, the volume ratio of the nano and/or micro copper suspension or the chloroauric acid solution to the aldehyde chitosan mixed solution in the step (3) is 2: (5-20); more preferably 2: 14.

preferably, the rotating speed of the stirring in the step (3) is 500-1200 rpm, and the time for continuing stirring is 5-24 hours; more preferably 6 to 24 hours.

Preferably, the standing time in the step (3) is 6-36 h; more preferably 6 to 12 hours.

The natural polymer-based supramolecular self-healing hydrogel prepared by the method.

The natural polymer-based supramolecular self-healing hydrogel is applied to the fields of medicine preparation and biosensing.

Compared with the prior art, the invention has the following advantages and beneficial effects:

the natural polymer-based supramolecular self-healing hydrogel has good biocompatibility, can be quickly self-healed without external condition stimulation, has excellent antibacterial performance, and has good application prospect in the fields of tissue engineering repair, wound repair, drug controlled release, biosensing and the like.

Drawings

FIG. 1 shows a schematic view of aFor the mechanism diagram of the copper ion release in example 1 and comparative examples 1-2, the samples in FIGS. 1(a) to (d) are labeled (1), (2), and (3), respectively, from left to right; in FIG. 1(a), (1) is CuSO in comparative example 1₄Solution, (2) Cu (NO) in comparative example 2₄)₂Solution, (3) is the nano-copper solution in example 1; FIGS. 1(b) (1) to (3) are mixed solutions of CMC and aldehyde-based chitosan in comparative examples 1 and 2 and step (3) of example 1, respectively; FIGS. 1(c), (1) to (3) are views showing the states of the metal ions just after mixing with the CMCs and the aldehyde-modified chitosan mixed solution in comparative examples 1 and 2 and example 1, respectively; in FIG. 1(d), (1) to (3) are the states after the metal ions were mixed with the CMCs and the aldehyde-based chitosan mixed solution and stirred for 6 hours in comparative examples 1 and 2 and example 1, respectively.

FIG. 2 is the self-healing monitoring of the natural polymer-based supramolecular self-healing hydrogel obtained in example 1 under a fluorescence microscope.

FIG. 3 shows the bio-safety of the natural polymer-based supramolecular self-healing hydrogel gel obtained in example 1.

Detailed Description

The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.

Those who do not specify specific conditions in the examples of the present invention follow conventional conditions or conditions recommended by the manufacturer. The raw materials, reagents and the like which are not indicated for manufacturers are all conventional products which can be obtained by commercial purchase.

Example 1

(1) Dissolving 2.5g of chitosan (with the molecular weight of 5000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexyl carbodiimide under the protection of nitrogen, reacting at room temperature of 25 ℃ for 24h, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with the molecular weight of 1000 to obtain the graft-modified aldehyde chitosan.

(2) 0.4g carboxymethyl chitosan powder is dissolved in 10ml deionized water and stirred for 3h to be completely dissolved to form a light yellow solution.

(3) Dispersing 0.06g of graft modified aldehyde chitosan into 4ml of deionized water, performing ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into the carboxymethyl chitosan solution, and stirring at 1200rpm for 3h to obtain a uniform solution, thereby obtaining the carboxymethyl chitosan-graft modified aldehyde chitosan solution.

(4) Dissolving 4mg of nano copper powder (with particle size of 1-500nm) in 2ml of water, and performing ultrasonic treatment for 15min to uniformly disperse the nano copper powder to form a suspension.

(5) Adding 2ml of the nano-copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution under the stirring state of 1200rpm, stirring for 12h at 800rpm, standing for 6h, observing by adopting an inversion method, forming uniform gel in a beaker marked by a mark (3) in figure 1, tracking the self-healing behavior under a fluorescence microscope, and spontaneously completing the self-healing within 90s under the conditions of no addition of other substances and external induction as shown in figure 2; meanwhile, the safety of the material is researched, and the hydrogel is prepared into a 24-well plate with the area of one well and is placed in the 24-well plate. 2X 10 in a volume of 50. mu.L⁵UC-MSC cells were seeded onto the hydrogel. UC-MSC cells (obtained by stem cell differentiation), and cells on the hydrogel are subjected to CCK-8 detection and dead-live staining. (1) And (2) dead and live cell staining pictures of 1 day, 3 days and 5 days after cell inoculation are shown, live cells are stained to be green, dead cells are stained to be red, and obviously more live cells are obtained, and the result shows that the hydrogel has low cytotoxicity and high biological safety, and (4) the CCK-8 detection result shows that cells planted on the surface of the material can effectively proliferate. The hydrogel is observed on the inhibition zone of a culture medium of escherichia coli (ATCC 2592) and staphylococcus aureus (8325-4), and is found to have the inhibition capacity.

Comparative example 1

(1) Dissolving 2.5g of chitosan (with the molecular weight of 5000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexyl carbodiimide under the protection of nitrogen, reacting at room temperature of 25 ℃ for 24h, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing in water by using a dialysis bag with the molecular weight of 1000 for 3 days to obtain the grafted and modified aldehyde chitosan.

(3) Dispersing 0.06g of graft-modified aldehyde chitosan into 4ml of deionized water, performing ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a carboxymethyl cellulose solution, and stirring at 1200rpm for 3h to obtain a uniform solution, thereby obtaining the carboxymethyl chitosan-graft-modified aldehyde chitosan solution.

(4) 0.39g of CuSO₄·5H₂Dissolving O powder in 100ml water, dissolving sufficiently to obtain Cu²⁺A solution with a concentration of 2 mg/ml.

(5) And (3) slowly and dropwise adding 2ml of copper sulfate prepared in the step (4) into 14ml of the carboxymethyl chitosan graft-modified aldehyde chitosan solution at 1200rpm, and immediately forming gel locally in the stirring process, wherein a uniform gel state cannot be formed by an oblique method after stirring at 800rpm for 12 hours and standing for 6 hours as shown in a beaker marked by (1) in the figure 1.

Comparative example 2

(2) 0.4g of carboxymethyl chitosan is dissolved in 10ml of deionized water and stirred for 3 hours to be completely dissolved to form a transparent solution.

(3) Dispersing 0.06g of graft-modified aldehyde chitosan into 4ml of deionized water, performing ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a sodium alginate solution, and stirring at 1200rpm for 3h to obtain a uniform solution, thereby obtaining the carboxymethyl chitosan-graft-modified aldehyde chitosan solution.

(4) 0.29g of Cu (NO)₃)₂Dissolving the powder in 100ml water, and preparing into Cu²⁺A solution with a concentration of 2 mg/ml.

(5) And (3) slowly and dropwise adding 2ml of copper sulfate prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution under the stirring state of 1200rpm, and immediately forming partial gel in the stirring process, wherein the uniform gel state cannot be formed by the oblique method after the stirring is continuously carried out for 12 hours at 800rpm and the standing is carried out for 6 hours as shown in a beaker marked by (2) in the figure 1.

Example 2

(1) Dissolving 2.5g of chitosan (molecular weight is 3000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexyl carbodiimide under the protection of nitrogen, reacting at room temperature and 25 ℃ for 24h, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the graft-modified aldehyde chitosan.

(2) 0.4g of carboxymethyl chitosan is dissolved in 10ml of deionized water and stirred for 3 hours to be completely dissolved to form a light yellow solution.

(3) Dispersing 0.06g of graft modified aldehyde chitosan into 4ml of deionized water, performing ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into the carboxymethyl chitosan solution, and stirring the mixture for 3h at the rotating speed of 1200rpm until the mixture is uniformly dissolved to obtain the carboxymethyl chitosan-graft modified aldehyde chitosan solution.

(4) Dissolving 4mg of nano copper powder (with particle size of 1-200nm) in 2ml of water, and performing ultrasonic treatment for 10min to uniformly disperse the nano copper powder to form a suspension.

(5) And (3) adding 2ml of the nano-copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution under the stirring state of 1200rpm, stirring for 6h at 800rpm, and standing for 6h to form a gel state.

Example 3

(3) Dispersing 0.06g of graft modified aldehyde chitosan into 4ml of deionized water, carrying out ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into the carboxymethyl chitosan solution, and stirring the mixture for 3h at the rotating speed of 1200rpm to obtain the uniform solution, thereby obtaining the carboxymethyl chitosan-graft modified aldehyde chitosan solution.

(4) Dissolving 4mg of micron copper powder (with particle size of 1-500um) in 2ml of water, and performing ultrasonic treatment for 10min to uniformly disperse the copper powder to form a suspension.

(5) And (3) adding the 2ml of micron copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution under the stirring state of 1200rpm, stirring for 24h at 800rpm, and standing for 12h to form a gel state.

Example 4

(2) 0.4g of sodium alginate is dissolved in 10ml of deionized water and stirred for 3 hours to be completely dissolved to form a light yellow solution.

(3) Dispersing 0.06g of graft-modified aldehyde chitosan into 4ml of deionized water, performing ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a sodium alginate solution, and stirring at the rotating speed of 1200rpm for 3h to obtain a uniform solution, thereby obtaining the sodium alginate-graft-modified aldehyde chitosan solution.

(4) Dissolving 4mg of nano copper powder (with particle size of 1-500nm) in 2ml of water, and performing ultrasonic treatment for 10min to uniformly disperse the nano copper powder to form a suspension.

(5) And (3) adding 2ml of the nano-copper suspension prepared in the step (4) into 14ml of the sodium alginate-graft modified aldehyde chitosan solution under the stirring state of 1200rpm, stirring for 12h at 800rpm, and standing for 6h to form a gel state.

Example 5

(1) Dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexyl carbodiimide (DCC) under the protection of nitrogen, reacting for 24h at room temperature of 25 ℃, adding water for precipitation, filtering, washing for multiple times, drying, and dialyzing in water by using a dialysis bag with molecular weight of 1000 for 3 days to obtain the grafted and modified aldehyde-based chitosan.

(2) 0.4g carboxymethyl chitosan powder is dissolved in 10ml deionized water and stirred for 3h to be completely dissolved to form a transparent solution.

(4) Preparing a chloroauric acid solution, wherein the ratio of the chloroauric acid to the solvent is 0.68mg to 1 ml.

(5) And (3) adding 2ml of chloroauric acid solution prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution under the stirring state of 800rpm, heating in water bath at 60 ℃ for 30min, then placing at room temperature under 800rpm, stirring for 12h, and standing for 6h to form a gel state.

Example 6

(1) Dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexylcarbodiimide under the protection of nitrogen, reacting at room temperature of 25 ℃ for 24h, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing in water by using a dialysis bag with molecular weight of 1000 for 3 days to obtain the grafted and modified aldehyde chitosan.

(2) 0.4g of sodium alginate powder is dissolved in 10ml of deionized water and stirred for 3 hours to be completely dissolved to form a transparent solution.

(3) Dispersing 0.06g of graft modified aldehyde chitosan into 4ml of deionized water, performing ultrasonic treatment for 15min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a sodium alginate solution, and stirring at 1200rpm for 3h to obtain a uniform solution, thereby obtaining the sodium alginate-graft modified aldehyde chitosan solution.

(5) And (3) adding 2ml of chloroauric acid solution prepared in the step (4) into 14ml of sodium alginate-graft modified aldehyde chitosan solution under the stirring state, heating in a water bath at 60 ℃ for 30min, then placing at room temperature, stirring for 12h, and standing for 6h to form a gel state.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims

1. A preparation method of natural polymer-based supramolecular self-healing hydrogel is characterized by comprising the following steps:

(1) adding p-aldehyde benzoic acid, 4-dimethylaminopyridine and dicyclohexylcarbodiimide into a chitosan solution at room temperature under the protection of nitrogen or inert gas, reacting, purifying, drying and dialyzing to obtain aldehyde chitosan;

in the step (3), the mass ratio of the carboxymethyl chitosan, the aldehyde chitosan and the nano and/or micro copper or chloroauric acid is (5-200) to (1-30): (2-16);

the mass ratio of the aldehyde chitosan to the sodium alginate in the step (2) is (0.2-1.5): (1-10).

2. The method for preparing natural polymer-based supramolecular self-healing hydrogel according to claim 1, wherein the p-aldehyde benzoic acid, 4-dimethylaminopyridine and dicyclohexylcarbodiimide of the step (1) are sequentially added into the chitosan solution;

the mass ratio of the p-aldehyde benzoic acid, the 4-dimethylaminopyridine, the dicyclohexylcarbodiimide and the chitosan in the step (1) is (450.39-900.75): (1.22-12.2): (0.21-20.6): 1000, parts by weight; the mass ratio of the aldehyde chitosan to the carboxymethyl chitosan in the step (2) is (0.2-1.5): (1-10).

3. The method for preparing the natural polymer-based supramolecular self-healing hydrogel according to claim 1 or 2, wherein the reaction time in the step (1) is 12-36 h; and (4) standing for 6-36 h.

4. The method for preparing the natural polymer-based supramolecular self-healing hydrogel according to claim 3, wherein the molecular weight of the chitosan in the step (1) is 1000-5000; the particle size of copper in the nano and/or micron copper suspension in the step (3) is 1 nm-500 um; the nano copper in the nano copper suspension liquid in the step (3) is derived from at least one of carbon-supported copper and nano copper powder; the micron copper in the micron copper suspension is derived from at least one of carbon-supported copper and micron copper powder.

5. The method for preparing the natural polymer-based supramolecular self-healing hydrogel according to claim 3, wherein in the chitosan solution in the step (1), the ratio of chitosan to solvent is (0.6-4.8) g: (5-40) ml; the proportion of the aldehyde chitosan and water in the step (2) is 0.06 g: (1-10) ml; the solvent of the carboxymethyl chitosan or sodium alginate solution in the step (2) is water, and the ratio of the carboxymethyl chitosan or sodium alginate to the water is (0.1-1) g: (10-40) ml.

6. The method for preparing natural polymer-based supramolecular self-healing hydrogel according to claim 3, wherein the ratio of copper to water in the nano and/or micro copper suspension in the step (3) is 2-8 mg/ml; the ratio of chloroauric acid to water in the chloroauric acid solution is 0.17-7 mg/ml; the volume ratio of the nano and/or micro copper suspension or the chloroauric acid solution to the aldehyde chitosan mixed solution in the step (3) is 2: (5-20).

7. The method for preparing the natural polymer-based supramolecular self-healing hydrogel according to claim 3, wherein the rotation speed for stirring and mixing uniformly in the step (2) is 800-1200 rpm, and the time is 1-3 hours; and (4) the stirring speed in the step (3) is 500-1200 rpm, and the continuous stirring time is 5-24 h.

8. The method for preparing natural polymer-based supramolecular self-healing hydrogel according to claim 3, wherein the solvent of the chitosan solution in the step (1) is at least one of dichloromethane, pyridine, dimethyl sulfoxide, tetrahydrofuran and dimethylformamide; the purification method in the step (1) comprises the following steps: adding water into the reaction product obtained in the step (1) to precipitate the product, filtering, and then washing with water for multiple times; the dialysis method in the step (1) comprises the following steps: dialyzing the reaction product in water for 3 days by using a dialysis bag with the molecular weight of 1000 to obtain aldehyde chitosan; and (3) dispersing the aldehyde chitosan in water by ultrasonic for 10-30 min.

9. A natural polymer-based supramolecular self-healing hydrogel prepared by the method of any one of claims 1 to 8.