CN117659447A - Preparation method and application of anti-fatigue hydrogel - Google Patents
Preparation method and application of anti-fatigue hydrogel Download PDFInfo
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Abstract
The invention provides a preparation method of an anti-fatigue hydrogel, which comprises the steps of respectively carrying out radiation grafting modification on an anionic compound and a cationic compound through polyvinylpyrrolidone, respectively adding the modified compounds into polyvinyl alcohol, and finally carrying out radiation-freezing crosslinking to obtain the anti-fatigue hydrogel. The preparation method of the hydrogel provided by the application introduces dynamic non-covalent bonds (ionic bonds and intermolecular hydrogen bonds) into a cross-linked network of radiation covalent bonds, and forms the hydrogel with a three-dimensional network structure with multiple bonding effects, so that the hydrogel has excellent toughness and fatigue resistance, good biological safety, cytotoxicity less than or equal to 1 level and is very suitable for the aspects of artificial cartilage, artificial achilles tendon and the like.
Description
Technical Field
The invention belongs to the technical field of medical materials, and particularly relates to a preparation method and application of an anti-fatigue hydrogel.
Background
With aging and the influence of various diseases, the joint is easy to degenerate, and the use of human joint replacement materials is now the mainstream method for treating joint injury by experts. The artificial articular cartilage substitute needs to have the following advantages: 1) Good mechanical properties to bear the pressure of the human body and support daily exercise; 2) Good biocompatibility; 3) Low friction and reduced damage to surrounding tissue.
The hydrogel is a material having good biocompatibility and good physicochemical properties, has a smooth surface, and has a multi-network structure similar to that of human articular cartilage, and thus, the hydrogel can be applied to artificial articular cartilage.
Polyvinyl alcohol (PVA) has been a popular industry consensus and research hotspot because of its versatility and biocompatibility, which is often used to construct artificial cartilage hydrogels. PVA hydrogel prepared by the traditional freezing method has limited application in artificial cartilage replacement materials due to the problems of uneven network structure, lack of energy dissipation mechanism, irreversibility after polymer network damage and the like. Therefore, there is an urgent need in the market to develop a hydrogel with high biocompatibility, high toughness, and fatigue resistance, and to be applied to cartilage materials.
Disclosure of Invention
The technical problem solved by the invention is to provide a preparation method of the anti-fatigue hydrogel, and the preparation method provided by the application can prepare the hydrogel with biocompatibility, high toughness and fatigue resistance.
In view of this, the present application provides a method for preparing an anti-fatigue hydrogel, comprising the following steps:
a) Mixing polyvinylpyrrolidone, an anionic compound and water, and radiating to obtain a polymer solution with anionic characteristics;
mixing polyvinylpyrrolidone, a cationic compound and water, and radiating to obtain a polymer solution with cationic property;
b) Mixing polyvinyl alcohol and the polymer solution with the anionic property, and heating to obtain a first solution;
mixing polyvinyl alcohol and the polymer solution with cationic property, and heating to obtain a second solution;
c) Mixing the first solution and the second solution to obtain a pre-crosslinked body;
radiating the pre-crosslinked body to obtain radiation crosslinked hydrogel;
d) Repeatedly freezing and thawing the radiation crosslinked hydrogel to obtain the anti-fatigue hydrogel.
Preferably, the anionic compound is selected from one or more of sodium carboxymethyl cellulose, sodium alginate and sodium polyacrylate, and the cationic compound is selected from chitosan.
Preferably, the polymer solution with anionic property is obtained, the content of polyvinylpyrrolidone is 0.3-1.2 wt%, the content of anionic compound is 2-4 wt%, the radiation is electron accelerator radiation or high-energy ray radiation, and the dose of the radiation is 5-10 kGy.
Preferably, the polymer solution with cationic property is obtained, the content of polyvinylpyrrolidone is 2-4wt%, the content of cationic compound is 2-4wt%, the radiation is electron accelerator radiation or high-energy ray radiation, and the dose of the radiation is 5-10 kGy.
Preferably, the polyvinyl alcohol content in the first solution and the second solution is the same, and the range is 10 to 20wt%.
Preferably, the step of obtaining the pre-crosslinked body comprises:
dropwise adding the second solution into the first solution while stirring to obtain a pre-crosslinked body;
the stirring speed is 1500-3000 r/min, and stirring is carried out for 10-20 min.
Preferably, in the step C), the radiation is high-energy ray radiation or electron accelerator radiation, and the dose of the radiation is 5-10 kGy.
Preferably, in the repeated freezing-thawing, the freezing temperature is-10 ℃ to-20 ℃ for 5-15 hours, the thawing temperature is 25-35 ℃ for 2-5 hours, and the repeated freezing-thawing times are repeated for 3-5 times.
The application also provides the application of the hydrogel prepared by the preparation method in medical materials.
Preferably, the medical material is artificial cartilage or artificial achilles tendon.
The invention provides a preparation method of an anti-fatigue hydrogel, which comprises the steps of firstly radiating an anionic compound and a cationic compound respectively, degrading the anionic compound and the cationic compound into small molecular states respectively, simultaneously radiating to enable polyvinylpyrrolidone to generate free radicals, grafting and crosslinking the free radicals with the anionic compound and the cationic compound respectively to obtain polyvinylpyrrolidone crosslinked polymers with anions and cations respectively, introducing the polyvinylpyrrolidone crosslinked polymers into a polyvinyl alcohol system, finally conducting radiation-freezing crosslinking, and introducing dynamic non-covalent bonds (ionic bonds and hydrogen bonds) into a crosslinking network of radiation covalent bonds to obtain the hydrogel with multiple bonding effects. Therefore, the anti-fatigue hydrogel prepared by the application takes the polyvinyl alcohol crosslinked network as the skeleton structure of the hydrogel, improves the good biocompatibility of the hydrogel, introduces dynamic non-covalent bonds (hydrogen bonds and ionic bonds) as an energy dissipation mechanism in a system through a radiation grafting mode, provides excellent toughness and self-healing capacity for materials due to the dynamic characteristics (repairability) of the non-covalent bonds, can improve the toughness and fatigue resistance of the hydrogel, and finally obtains the biocompatible, high-toughness and fatigue-resistant hydrogel.
Drawings
FIG. 1 is a graph showing the tensile properties of experiment 4 in example 1 of the present invention for 5 consecutive times;
FIG. 2 is a bar graph of cell compatibility of experimental groups 1-4 and comparative samples in example 1 of the present invention;
FIG. 3 is a bar graph of the cell compatibility of experimental groups 5-6 and comparative samples in example 2 of the present invention.
Detailed Description
For a further understanding of the present invention, preferred embodiments of the invention are described below in conjunction with the examples, but it should be understood that these descriptions are merely intended to illustrate further features and advantages of the invention, and are not limiting of the claims of the invention.
In view of the requirements of medical materials in the prior art on the biocompatibility, high toughness and fatigue resistance of the hydrogel, the application provides a preparation method of the fatigue-resistant hydrogel, which takes a crosslinked network formed by polyvinyl alcohol as a skeleton structure of the hydrogel, and introduces non-covalent bonds in a radiation grafting mode to finally obtain the hydrogel material with a network structure with multiple bonding effects, so that the hydrogel material has the biocompatibility, high toughness and fatigue resistance. Specifically, the embodiment of the invention discloses a preparation method of an anti-fatigue hydrogel, which comprises the following steps:
a) Mixing polyvinylpyrrolidone, an anionic compound and water, and radiating to obtain a polymer solution with anionic characteristics;
mixing polyvinylpyrrolidone, a cationic compound and water, and radiating to obtain a polymer solution with cationic property;
b) Mixing polyvinyl alcohol and the polymer solution with the anionic property, and heating to obtain a first solution;
mixing polyvinyl alcohol and the polymer solution with cationic property, and heating to obtain a second solution;
c) Mixing the first solution and the second solution to obtain a pre-crosslinked body;
radiating the pre-crosslinked body to obtain radiation crosslinked hydrogel;
d) Repeatedly freezing and thawing the radiation crosslinked hydrogel to obtain the anti-fatigue hydrogel.
In the preparation process of the anti-fatigue hydrogel, polyvinylpyrrolidone, an anionic compound and water are mixed and then irradiated to obtain a polymer solution with anionic characteristics; in the process, the radiation is used for carrying out radiation degradation on the anionic compound to degrade the anionic compound into a small molecular state, and simultaneously, the radiation is used for enabling polyvinylpyrrolidone to generate free radicals, and the free radicals are grafted and crosslinked with the anionic compound to obtain the polyvinylpyrrolidone crosslinked polymer with anions. In the present application, the anionic polymer is selected from one or more of sodium carboxymethyl cellulose, sodium alginate and sodium polyacrylate; in a specific embodiment, the anionic polymer is selected from sodium carboxymethyl cellulose. In the polymer solution with the anionic property, the content of the anionic compound is 2-4wt% and the content of the polyvinylpyrrolidone is 0.3-1.2wt%; specifically, the content of the anionic compound is 2.5-3.5 wt%, and the content of the polyvinylpyrrolidone is 0.4-1.0 wt%. The anionic compound and polyvinylpyrrolidone are modified by radiation crosslinking, and the anionic compound can be crosslinked and modified by the polyvinylpyrrolidone with a lower concentration. The radiation may be high energy radiation or electron accelerator radiation, the dose of which is 5-10 kGy, specifically, the dose of which is 6-8 kGy.
According to the invention, polyvinylpyrrolidone, a cationic compound and water are mixed and irradiated to obtain a polymer solution with cationic characteristics; in the process, the radiation is used for carrying out radiation degradation on the cationic compound to degrade the cationic compound into a small molecular state, and simultaneously, the radiation is used for enabling polyvinylpyrrolidone to generate free radicals, and the free radicals are grafted and crosslinked with the cationic compound to obtain the polyvinylpyrrolidone crosslinked polymer with cations. In the present application, the cationic compound is selected from chitosan. The content of the cationic compound is 2-4wt% and the content of the polyvinylpyrrolidone is 2-4wt%; specifically, the content of the cationic compound is 2.5-3.5 wt%, and the content of the polyvinylpyrrolidone is 2.5-3.5 wt%. The cationic compound is a positively charged solution that requires a higher concentration of polyvinylpyrrolidone to effect crosslinking radiation modification. The radiation may be high energy radiation or electron accelerator radiation, the dose of which is 5-10 kGy, specifically, the dose of which is 6-8 kGy.
Mixing polyvinyl alcohol and the polymer solution with the anionic characteristic, heating to obtain a first solution, mixing the polyvinyl alcohol and the polymer solution with the cationic characteristic, and heating to obtain a second solution; the polyvinyl alcohol content in the first solution and the polyvinyl alcohol content in the second solution are the same, the range is 10-20wt%, and specifically, the polyvinyl alcohol content is 12-18wt%.
According to the invention, the first solution and the second solution are mixed to obtain a pre-crosslinked body, and the first solution can be added into the second solution while stirring in order to realize uniform mixing of the two solutions, wherein the stirring is performed at a high speed, and the stirring speed is 1500-3000 r/min and the stirring is performed for 10-20 min.
The present application then irradiates the pre-crosslinked body obtained as described above, with high-energy radiation or electron beam accelerator radiation, the dose of which is 5 to 10kGy, more specifically, the dose of which is 6 to 8kGy. Finally, repeatedly freezing and thawing the obtained radiation crosslinked hydrogel to obtain the anti-fatigue hydrogel; the freezing temperature is-10 ℃ to 20 ℃ and the time is 5 to 15 hours, the thawing temperature is 25 ℃ to 35 ℃ and the time is 2 to 5 hours, and the repeated freezing-thawing times are repeated for 3 to 5 times; specifically, the freezing temperature is-12-17 ℃, the time is 6-12 h, the thawing temperature is 28-32 ℃, the time is 3-4 h, and the repeated freezing-thawing times are repeated for 3 times. According to the method, the pre-crosslinked body is irradiated, so that the polyvinyl alcohol in the pre-crosslinked body forms a crosslinked network structure, and dynamic non-covalent bonds and hydrogen bonds are introduced into a crosslinked network of irradiated covalent bonds through the irradiation-freezing crosslinking, so that the hydrogel with multiple bonding effects is obtained.
According to the invention, through radiation degradation effects of radiation on high molecular polymers such as anionic compound sodium carboxymethyl cellulose (CMC) and cationic compound Chitosan (CS), the high molecular polymers are degraded into a small molecular state, simultaneously, polyvinylpyrrolidone generates free radicals, and then the free radicals are introduced into grafting crosslinking of the small molecular chitosan and sodium carboxymethyl cellulose to obtain PVP crosslinked polymers (CMC-PVP and CS-PVP) with anions and cations; and then CMC-PVP and CS-PVP are respectively added into a PVA system, and dynamic non-covalent bonds (ionic bonds and hydrogen bonds) are introduced into a radiation covalent bond crosslinking network through radiation-freezing crosslinking, so that the hydrogel with multiple bonding effects is obtained.
The application also provides application of the hydrogel prepared by the preparation method in medical materials.
In this application, the medical material is an artificial cartilage material, such as artificial cartilage or artificial achilles tendon.
Compared with the traditional frozen PVA hydrogel, the hydrogel material with dynamic non-covalent bonds prepared by the radiation freezing method has a uniform covalent bond network structure, dynamic cationic and anionic polymers are introduced by radiation grafting, so that a dynamic ionic bond effect is formed, a self-repairable energy dissipation mechanism is provided, and the strength, toughness and fatigue resistance of the hydrogel are improved.
Therefore, in the initial stage of the forced deformation of the hydrogel, the deformation is prevented by a uniform covalent bond network, so that the breakage caused by stress concentration is avoided; with further increase of deformation, when external force is stretching, the ionic bond is broken by the external force, energy is dissipated, and when the external force is removed, the ionic bond is under the action of attractive force, and is linked again to restore to the original state. When the external force is acted by pressure, the repulsive force is larger as the distance between the ionic bonds is smaller, so that energy can be dissipated, and when the pressure is removed, the ionic bonds are subjected to the repulsive force, and are restored to the initial state, so that the remarkable improvement of the toughness of the hydrogel is finally realized.
The hydrogel is prepared from medical-grade synthetic polymers and natural polymers by a radiation method, and has good biological safety and cytotoxicity less than or equal to grade 1; is harmless to human body, has water content close to that of cartilage tissue of human body, and is suitable for application in artificial cartilage, artificial achilles tendon, etc.
In order to further understand the present invention, the following examples are provided to illustrate the preparation method of the anti-fatigue hydrogel and the application thereof in detail, and the scope of the present invention is not limited by the following examples.
Example 1
The specific synthesis steps of the hydrogel are as follows:
1) Heating polyvinylpyrrolidone (PVP), sodium carboxymethylcellulose (CMC) and water in proportion, mixing, discharging bubbles, packaging into a mould, and radiating with electron accelerator at a dose of 5kGy;
2) Heating polyvinylpyrrolidone, chitosan (CS) and water in proportion, mixing, discharging bubbles, packaging into a mold, and radiating with electron accelerator with a dose of 5kGy;
3) Weighing a certain amount of polyvinyl alcohol (PVA), taking 50ml of the solution obtained in the step 1) as a solvent, and heating and stirring to obtain a solution 1;
4) Weighing polyvinyl alcohol with the same mass as that of the step 3), taking 50ml of the solution of the step 2) as a solvent, and heating and stirring to obtain a solution 2;
5) Dropwise adding the solution 2 into the solution 1 while stirring at a stirring speed of 2000r/min, stirring for 10min, and vacuum defoaming to obtain a uniformly mixed pre-crosslinked body;
6) Sub-packaging the pre-crosslinked body into a mould, and crosslinking by using high-energy ray radiation with the dosage of 15kGy;
7) And (3) crosslinking the irradiated hydrogel by adopting a repeated freezing-thawing process, wherein the freezing time is 10 hours, the thawing time is 2 hours, and repeating for 3 times to obtain the target gel.
Preparing target gel of four experimental groups by adopting different raw material ratios according to the method, wherein the raw material ratios are shown in table 1;
TABLE 1 data sheet for the amounts of the components added in example 1
The performance test of the hydrogel of the invention is carried out according to the following method:
1) The tensile properties were tested as follows: a single-column desktop computer peeling tester (CREE-8007B) is adopted to carry out tensile test on the sample, the tensile rate is 200mm/min, and the test temperature is room temperature; the test sample is dumbbell-shaped, the total length is 75mm, the width of the end is 12.5mm, the length of the narrow parallel part is 33mm, and the width of the narrow parallel part is 4mm; 3 groups of parallel samples are tested, the average value of the tensile strength and the elongation at break is calculated, and the toughness is calculated through a stress-strain curve theory;
2) The compression performance test method is as follows: carrying out compression test on the sample by adopting a single-column desktop computer type peeling tester (CREE-8007B), manufacturing the hydrogel sample into a cylinder shape by a die, measuring the height of the cylindrical hydrogel by utilizing a vernier caliper at room temperature, setting the compression deformation to be 80% of the height of the cylindrical hydrogel sample, setting the compression rate to be 20mm/min, testing 3 groups of parallel samples, and recording the compression strength;
3) The fatigue resistance testing method comprises the following steps: according to the tensile test method, continuously and repeatedly carrying out 5 times of tensile performance tests on a single sample, recording a stress-strain curve, observing curve change of the stress-strain curve, calculating toughness change, and monitoring fatigue resistance;
4) Cytotoxicity test: section 5 according to GB/T16886.5-2003 medical device biology evaluation: in vitro cytotoxicity assay "assay.
The hydrogel samples of experiments 1-4 were subjected to the above test, with the following test results:
table 2 table of tensile and compressive properties of hydrogels prepared in examples 1 and 1 at laboratories 1 to 4
As can be seen from Table 2, the hydrogels of experiments 1 to 4 have excellent pulling-up and compression properties, and the tensile and compression properties of the gel are obviously improved along with the increase of the ionic bond proportion and the increase of the radiation cross-linked skeleton PVA, so that the hydrogel can meet the mechanical requirements of the cartilage material.
Experiment 4 was selected as a fatigue resistance test object, tensile properties were tested 5 times in succession, the test results are shown in fig. 1 and table 2,
fig. 2 is a comparative cytocompatible bar graph of example 1 and comparative sample PEI25K, in which each group of bar data is the survival content of cells of experiment 1, experiment 2, experiment 3, experiment 4 and PEI25K at different concentrations from left to right, and it can be seen from the graph that the cytotoxicity of hydrogels of experiment 1 to experiment 4 is less than grade 1, and the hydrogel has excellent biocompatibility, and is suitable for the field of medical biomimetic materials.
Table 3 example 1 experiment 4 continuous 5 tensile property test table
| No. | Tensile Strength (MPa) | Elongation at break (%) | Toughness (MPa) |
| 1 time | 1.565 | 181.290 | 1.418 |
| 2 times | 1.486 | 183.070 | 1.360 |
| 3 times | 1.524 | 177.624 | 1.353 |
| 4 times | 1.427 | 174.572 | 1.246 |
| 5 times | 1.433 | 175.610 | 1.258 |
The graph shows that the gel has a recovery function after the gel is subjected to repeated tensile test for 5 times continuously, the tensile strength of the first tensile test is 1.565MPa, the tensile strength of the fifth tensile test is 1.433MPa, and the difference between the tensile strength and the tensile strength is very small, because when the external strain is applied, the crosslinked network which is broken first is a recovered ionic bond, and after the external force disappears, the gel can be quickly repaired through the ionic bond, and the gel has good fatigue resistance after repeated tensile for many times.
Example 2
The mechanical properties of the hydrogels were tested by controlling the dose of radiation grafting and the dose of radiation crosslinking, and the experimental procedure was as follows:
1) Heating and blending 0.5% polyvinylpyrrolidone (PVP), 4% sodium carboxymethylcellulose (CMC) and water according to a proportion, discharging bubbles, and then subpackaging into a mould, wherein the dose is 10kGy by using electron accelerator radiation;
2) Heating and blending 4% polyvinylpyrrolidone, 4% Chitosan (CS) and water according to a proportion, discharging bubbles, and then sub-packaging into a mould, wherein the dose is 10kGy by using electron accelerator radiation;
3) Weighing 20% polyvinyl alcohol (PVA), taking 50ml of the solution obtained in the step 1) as a solvent, and heating and stirring to obtain a solution 1;
4) Weighing 20% polyvinyl alcohol, taking 50ml of the solution obtained in the step 2) as a solvent, and heating and stirring to obtain a solution 2;
5) Dropwise adding the solution 2 into the solution 1 while stirring at a stirring speed of 2000r/min, stirring for 10min, and vacuum defoaming to obtain a uniformly mixed pre-crosslinked body;
6) The pre-crosslinked body is subpackaged in a mold, and is crosslinked by high-energy ray radiation, the radiation doses are respectively 10kGy and 30kGy, and experiment 5 and experiment 6 are marked;
7) And (3) crosslinking the irradiated hydrogel by adopting a repeated freezing and thawing process, wherein the freezing time is 10 hours, the thawing time is 2 hours, and repeating for 3 times to obtain the target gel.
The gel was tested for tensile, compressive and cytotoxicity according to the test method of example 1, and the test results are shown in table 4 and fig. 3;
table 4 tensile and compressive properties tables for experiments 5 and 6 in example 2
| Experimental group | Tensile Strength (MPa) | Toughness (MJ/m) 3 ) | Compressive Strength (MPa) |
| Experiment 5 | 1.325 | 1.125 | 1.685 |
| Experiment 6 | 1.685 | 1.463 | 1.875 |
As can be seen from Table 4, the gel still has good tensile and compressive properties by changing the dose of the radiation medium and the dose of the radiation crosslinking;
in the bar graph in fig. 3, the survival contents of cells under different concentrations of experiment 5, experiment 6 and PEI25K are sequentially shown from left to right, and the cell compatibility bar graphs of experiment 5 and experiment 6 in fig. 3 can show that cytotoxicity of the hydrogel prepared in example 2 is 0 level, which indicates that the prepared hydrogel material has good biological safety and meets the requirements of high-strength and high-biocompatibility medical materials.
Comparative example 1
The comparative example is to directly mix sodium carboxymethyl cellulose and chitosan with polyvinylpyrrolidone, without adopting radiation grafting, then blend with PVA solution to obtain radiation precursor polymer, carry out radiation crosslinking, test the mechanical and biological characteristics of the radiation precursor polymer, and the specific process is as follows:
1) Heating and blending 0.5% polyvinylpyrrolidone (PVP), 4% sodium carboxymethylcellulose (CMC) and water according to a proportion, discharging bubbles, and standing;
2) Heating and blending 4% polyvinylpyrrolidone, 4% Chitosan (CS) and water according to a proportion, and standing after foam removal;
3) Weighing 20% polyvinyl alcohol (PVA), taking 50ml of the solution obtained in the step 1) as a solvent, and heating and stirring to obtain a solution 1;
4) Weighing 20% polyvinyl alcohol, taking 50ml of the solution obtained in the step 2) as a solvent, and heating and stirring to obtain a solution 2;
5) Dropwise adding the solution 2) into the solution 1) while stirring at a stirring speed of 2000r/min, stirring for 10min, and performing vacuum bubble removal to obtain a uniformly mixed radiation precursor polymer solution;
6) Sub-packaging the irradiated prepolymer into a mould, and using high-energy rays to carry out radiation crosslinking, wherein the radiation dose is 30kGy;
7) The irradiated hydrogel was crosslinked by repeated freeze-thaw process for 10 hours and 2 hours for 3 times to obtain a target gel as comparative example 1.
The tensile and compressive properties of the gel of comparative example 1 were measured according to the test method of example 1, and the test results are shown in table 5 below:
table 5 tensile, compressive and biosafety test table of comparative example 1
As is clear from Table 5, the gel of comparative example 1 has relatively low tensile strength, toughness and compression properties, and cannot meet the requirements of high-strength high-toughness hydrogels, as compared with examples.
Comparative example 2
In the comparative example, the mass fraction of polyvinylpyrrolidone is changed in the chitosan radiation modification step, other preparation processes are unchanged, and the mechanical properties of the chitosan are tested, wherein the specific process is as follows:
1) Heating and blending 0.5% polyvinylpyrrolidone (PVP), 4% sodium carboxymethylcellulose (CMC) and water according to a proportion, discharging bubbles, and then subpackaging into a mould, wherein the dose is 10kGy by using electron accelerator radiation;
2) Heating and blending 0.5% polyvinylpyrrolidone, 4% Chitosan (CS) and water according to a proportion, discharging bubbles, and then sub-packaging into a mould, wherein the dose is 10kGy by using electron accelerator radiation;
3) Weighing 20% polyvinyl alcohol (PVA), taking 50ml of the solution obtained in the step 1) as a solvent, and heating and stirring to obtain a solution 1;
4) Weighing 20% polyvinyl alcohol, taking 50ml of the solution obtained in the step 2) as a solvent, and heating and stirring to obtain a solution 2;
5) Dropping the solution 2 into the solution 1 while stirring at the stirring speed of 2000r/min, stirring for 10min, and performing vacuum foam removal to obtain a pre-cross connection body which is uniformly mixed;
6) The pre-crosslinked split charging mold was crosslinked by irradiation with high-energy rays at a radiation dose of 30kGy, respectively, to obtain a target gel as comparative example 2.
The gel of comparative example 2 was tested for tensile, compressive properties and was tested according to the test method of example 1, with the test results shown in table 6 below:
table 6 tensile and compressive test sheets of comparative example 2
As is clear from Table 6, the gel of comparative example 2 has relatively low tensile strength, toughness and compression properties, and cannot meet the requirements of high-strength high-toughness hydrogels, as compared with examples. Compared with comparative example 1, the tensile strength, toughness and compression performance are slightly improved, and the comprehensive description shows that the polyvinylpyrrolidone can radiate to modify chitosan, and the grafting rate of radiation modification can be improved along with the improvement of the proportion of the polyvinylpyrrolidone, so that the gel network can form a dynamic ionic bond effect, and the anti-fatigue hydrogel material can be prepared.
Comparative example 3
The comparative example is carried out without repeated freezing-thawing, other preparation processes are unchanged, and the mechanical properties are tested, wherein the specific process is as follows:
1) Heating and blending 0.5% polyvinylpyrrolidone (PVP), 4% sodium carboxymethylcellulose (CMC) and water according to a proportion, discharging bubbles, and then subpackaging into a mould, wherein the dose is 10kGy by using electron accelerator radiation;
2) Heating and blending 4% polyvinylpyrrolidone, 4% Chitosan (CS) and water according to a proportion, discharging bubbles, and then sub-packaging into a mould, wherein the dose is 10kGy by using electron accelerator radiation;
3) Weighing 20% polyvinyl alcohol (PVA), taking 50ml of the solution obtained in the step 1) as a solvent, and heating and stirring to obtain a solution 1;
4) Weighing 20% polyvinyl alcohol, taking 50ml of the solution obtained in the step 2) as a solvent, and heating and stirring to obtain a solution 2;
5) Dropping the solution 2 into the solution 1 while stirring at the stirring speed of 2000r/min, stirring for 10min, and performing vacuum foam removal to obtain a pre-cross connection body which is uniformly mixed;
6) The pre-crosslinked split charging mold was crosslinked by irradiation with high-energy rays at a radiation dose of 30kGy, respectively, to obtain a target gel as comparative example 2.
The gel of comparative example 3 was tested for tensile, compressive properties and was tested according to the test method of example 1, and the test results are shown in table 7 below:
table 7 tensile and compressive test sheets of comparative example 3
As is clear from Table 7, the gel of comparative example 2 has relatively low tensile strength, toughness and compression properties, and cannot meet the requirements of high-strength high-toughness hydrogels, as compared with examples.
The above description of the embodiments is only for aiding in the understanding of the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. The preparation method of the anti-fatigue hydrogel comprises the following steps:
a) Mixing polyvinylpyrrolidone, an anionic compound and water, and radiating to obtain a polymer solution with anionic characteristics;
mixing polyvinylpyrrolidone, a cationic compound and water, and radiating to obtain a polymer solution with cationic property;
b) Mixing polyvinyl alcohol and the polymer solution with the anionic property, and heating to obtain a first solution;
mixing polyvinyl alcohol and the polymer solution with cationic property, and heating to obtain a second solution;
c) Mixing the first solution and the second solution to obtain a pre-crosslinked body;
radiating the pre-crosslinked body to obtain radiation crosslinked hydrogel;
d) Repeatedly freezing and thawing the radiation crosslinked hydrogel to obtain the anti-fatigue hydrogel.
2. The preparation method according to claim 1, wherein the anionic compound is selected from one or more of sodium carboxymethyl cellulose, sodium alginate and sodium polyacrylate, and the cationic compound is selected from chitosan.
3. The preparation method according to claim 2, wherein the content of polyvinylpyrrolidone in the polymer solution having anionic characteristics is 0.3 to 1.2wt%, the content of the anionic compound is 2 to 4wt%, the irradiation is electron accelerator irradiation or high energy ray irradiation, and the dose of the irradiation is 5 to 10kGy.
4. The preparation method according to claim 2, wherein the polymer solution having cationic property is obtained, the polyvinylpyrrolidone is 2 to 4wt%, the cationic compound is 2 to 4wt%, the radiation is electron accelerator radiation or high energy ray radiation, and the dose of the radiation is 5 to 10kGy.
5. The method according to claim 3 or 4, wherein the polyvinyl alcohol content in the first solution and the second solution is the same in the range of 10 to 20wt%.
6. The method according to claim 1, wherein the step of obtaining a pre-crosslinked body comprises:
dropwise adding the second solution into the first solution while stirring to obtain a pre-crosslinked body;
the stirring speed is 1500-3000 r/min, and stirring is carried out for 10-20 min.
7. The method according to claim 1, wherein in the step C), the radiation is high-energy ray radiation or electron accelerator radiation, and the dose of the radiation is 5 to 10kGy.
8. The method according to claim 1, wherein in the repeated freezing-thawing, the freezing temperature is-10 ℃ to-20 ℃, the time is 5 to 15 hours, the thawing temperature is 25 to 35 ℃, the time is 2 to 5 hours, and the number of repeated freezing-thawing is 3 to 5 times.
9. Use of the hydrogel prepared by the preparation method of any one of claims 1 to 8 in medical materials.
10. The use according to claim 9, wherein the medical material is artificial cartilage or artificial achilles tendon.
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