CN114984326B - Multi-crosslinked injectable bone repair hydrogel preparation material and preparation method thereof - Google Patents
Multi-crosslinked injectable bone repair hydrogel preparation material and preparation method thereof Download PDFInfo
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- CN114984326B CN114984326B CN202210624664.XA CN202210624664A CN114984326B CN 114984326 B CN114984326 B CN 114984326B CN 202210624664 A CN202210624664 A CN 202210624664A CN 114984326 B CN114984326 B CN 114984326B
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- hydrogel
- corilagin
- carboxymethyl chitosan
- bone repair
- magnesium alginate
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Abstract
The invention discloses a multi-crosslinked injectable bone repair hydrogel preparation material and a preparation method thereof, and belongs to the technical field of biomedical engineering. The hydrogel takes carboxymethyl chitosan and oxidized magnesium alginate as matrixes, meets the clinical injection requirement, and is modified by adding silk fibroin and dopamine-coated nano hydroxyapatite on the basis, so that the hydrogel has good mechanical property, biocompatibility and biodegradability. The hydrogel has strong photo-thermal conversion efficiency and obvious promotion effect on osteoblast proliferation and osteoblast induced ossification.
Description
Technical Field
The invention belongs to the technical field of biomedical engineering, and particularly relates to a multi-crosslinked injectable bone repair hydrogel preparation material and a preparation method thereof.
Background
In clinic, for repairing bone defects caused by various reasons such as wounds, tumors, infection and the like, strategies of mainly using autologous bones and secondarily using artificial bones are adopted. The existing artificial bone products are mostly inorganic ceramics, are mostly implanted by adopting local filling of instruments, are easy to collapse under the condition of blood flushing, have weak in-situ bone repair capability, and are easy to form ectopic ossification. In addition to inorganic ceramics, bone repair materials such as metals and organic polymers have been developed, but any existing bone repair materials have the risk of losing bone mass at the defect part. The existing bone repair materials mostly adopt bionic designs, and a repair platform is constructed by combining organic and inorganic materials. Calcium Phosphate Cement (CPC) and alpha-Calcium Sulfate Hemihydrate (CSH) have been clinically used, but CPC has poor injectability, is prone to collapse, and CSH has poor osteoinductive capacity. Injectable hydrogels have inherent biocompatibility, biodegradability and injectability and find application in a variety of biological fields. But as a bone repair material, its mechanical properties have limited its application.
Disclosure of Invention
The invention aims to provide a multi-crosslinked injectable bone repair hydrogel preparation material and a preparation method thereof, wherein the injectable bone repair hydrogel has the advantages of remarkably improved mechanical properties, high biocompatibility, strong injectability, good bone induction capability and high photo-thermal conversion efficiency in function design.
The technical scheme adopted by the invention for achieving the purpose is as follows:
an injectable bone repair hydrogel material comprises a hydrogel matrix and a multiple crosslinking modifier; the hydrogel matrix at least comprises carboxymethyl chitosan and oxidized magnesium alginate, and the multiple crosslinking modifier comprises silk fibroin and dopamine coated nano hydroxyapatite.
The invention constructs an injectable hydrogel system for repairing bone defects, which takes carboxymethyl chitosan and magnesium alginate oxide as matrixes, can form gel in a short time at normal temperature, and meets the clinical injection requirement. The inorganic component nano hydroxyapatite in the system is not purely physically combined, but is coated by organic molecules, so that chemical crosslinking is further realized, and the gel performance of the system is more stable. In addition, the body system hydrogel is also added with silk fibroin, and the mechanical property of the hydrogel is further improved by utilizing the mechanical property and double chemical crosslinking of the silk fibroin. Thus, the injectable hydrogel with injectability, mechanical property and biological property meeting the requirement of repairing clinical bone defect is obtained. The hydrogel has strong photo-thermal conversion efficiency and obvious promotion effect on osteoblast proliferation.
For the purposes of the present invention, the use of a corilagin/carboxymethyl chitosan complex in the hydrogel matrix is an alternative to carboxymethyl chitosan. According to the preparation method, the corilagin/carboxymethyl chitosan compound is obtained by grinding and compounding corilagin and carboxymethyl chitosan, and then the corilagin/carboxymethyl chitosan compound and magnesium alginate oxide are used for constructing a hydrogel network system, so that the network structure of the hydrogel network system is beneficially influenced, the hydrogel has better mechanical properties, and the elastic modulus and the compression strength of the hydrogel are remarkably improved; the prepared hydrogel has good biocompatibility and degradability, can promote the proliferation of hydrogel cells and the ossification induction capability of osteoblasts to a certain extent, and improves the photo-thermal conversion performance of the hydrogel.
For the present invention, the preparation method of the corilagin/carboxymethyl chitosan complex comprises the following steps: adding deionized water into corilagin and carboxymethyl chitosan, wetting, mixing, and grinding to dry and fluffy state to obtain corilagin/carboxymethyl chitosan compound.
For the invention, the mass ratio of the corilagin to the carboxymethyl chitosan is 1:5-7.
In the present invention, the magnesium alginate oxide is obtained by oxidizing magnesium alginate with sodium periodate.
Specifically, the preparation method of the magnesium alginate oxide comprises the following steps: dissolving magnesium alginate MA in deionized water, and stirring thoroughly to obtain MA solution with concentration of 0.015-0.025 g/mL; adding sodium periodate, stirring at room temperature under dark condition for reaction for 12-15h, adding ethylene glycol for continuous reaction for 2-3h to terminate oxidation reaction; dialyzing with deionized water for 72-84 hr, freezing the dialyzed solution at-80- -85deg.C, and drying to obtain magnesium alginate oxide OMA.
For the invention, the mass ratio of MA to sodium periodate is 1:1-1.5; the mass volume ratio of MA to glycol is 1g:4-6mL.
Specifically, the preparation method of the dopamine-coated nano hydroxyapatite comprises the following steps: dissolving nano hydroxyapatite in a Trils buffer solution with the pH of 8-9, sufficiently stirring, and performing ultrasonic treatment for 20-30min to obtain a solution A with the concentration of 0.1-0.3 wt%; dissolving dopamine hydrochloride in deionized water, and fully stirring and mixing to obtain a solution B with the concentration of 0.1-0.3 wt%; dropwise adding the solution A into the solution B at a constant speed, stirring and mixing at a stirring speed of 500-1000r/min, continuously stirring for 12-24h, and freeze-drying to obtain the dopamine-coated nano hydroxyapatite PHA.
For the invention, the mass ratio of the nano hydroxyapatite to the dopamine hydrochloride is 1:1-1.3.
The invention also provides a preparation method of the injectable bone repair hydrogel, which comprises the following steps: dissolving carboxymethyl chitosan and magnesium alginate oxide in deionized water, adding modifier silk fibroin and dopamine-coated nano hydroxyapatite, stirring for 5-10min, and standing to obtain modified carboxymethyl chitosan-magnesium alginate oxide hydrogel;
or alternatively, the first and second heat exchangers may be,
dissolving the corilagin/carboxymethyl chitosan compound and magnesium alginate oxide in deionized water, then adding modifier silk fibroin and dopamine to wrap nano hydroxyapatite, stirring for 5-10min, and standing to obtain the modified corilagin/carboxymethyl chitosan compound-magnesium alginate oxide hydrogel.
For the invention, the percentage of carboxymethyl chitosan or corilagin/carboxymethyl chitosan compound in deionized water is 4-6%; the mass ratio of the carboxymethyl chitosan or the corilagin/carboxymethyl chitosan compound to the magnesium alginate oxide is 1:0.7-1; the mass ratio of the carboxymethyl chitosan or the corilagin/carboxymethyl chitosan compound to the silk fibroin and the dopamine coated nano hydroxyapatite is 5:2-3:1.5-2.5.
For the invention, the elastic modulus of the hydrogel is more than or equal to 0.16MPa, and the compressive strength is more than or equal to 0.19MPa; more preferably, the elastic modulus of the hydrogel is more than or equal to 0.18MPa, and the compressive strength is more than 0.25MPa.
The invention also discloses application of the hydrogel prepared by the preparation method in preparation of bone repair materials, adsorption materials and carrier materials.
The invention also discloses a composition, which comprises the hydrogel prepared by the preparation method, and has the following effects: hemostatic activity, promoting bone cell proliferation activity, and osteoblast induced ossification activity.
More preferably, the above composition further comprises theaflavin, wherein the amount of theaflavin is 5-10% of the mass of the hydrogel. The hydrogel prepared by the invention has good biological activity, is matched with tea Huang Sufu for use in health products and medicaments, and has good biocompatibility and degradability and higher hemostatic performance; and under the condition that theaflavin and corilagin/carboxymethyl chitosan compound exist simultaneously, the cell proliferation promoting capability, the osteoblast ossification inducing capability and the hemostatic capability of the hydrogel are further improved.
The invention has the beneficial effects that:
the invention provides a preparation method of injectable bone repair hydrogel. The hydrogel is prepared by adopting a semi-wet grinding method, then the corilagin/carboxymethyl chitosan compound or carboxymethyl chitosan and oxidized magnesium alginate are taken as matrixes, the clinical injection requirement is met, and on the basis, silk fibroin and dopamine coated nano hydroxyapatite are added to modify the hydrogel, so that the hydrogel has stronger photo-thermal conversion efficiency and better mechanical property, and the cell proliferation promotion and osteoblast induced ossification capability are effectively improved. In addition, when the hydrogel is matched with tea Huang Sufu, the prepared hydrogel has good biocompatibility and degradability, and simultaneously has further improved osteoblast proliferation, ossification induction capability and hemostatic activity.
Therefore, the invention provides a multi-crosslinked injectable bone repair hydrogel preparation material and a preparation method thereof, the mechanical property of the injectable bone repair hydrogel is obviously improved, and in the aspect of functional design, the injectable bone repair hydrogel meets the requirements of high biocompatibility, strong injectability, good bone induction capability and high photo-thermal conversion efficiency.
Drawings
FIG. 1 is a diagram showing the magnesium alginate oxide prepared in example 1;
FIG. 2 is a scanning electron microscope image of the dopamine-coated nano-hydroxyapatite prepared in example 1;
FIG. 3 is a graph showing the results of the compressive strength test of hydrogels;
FIG. 4 is a graph showing the elastic modulus test results of hydrogels;
FIG. 5 is a scanning electron microscope image of the hydrogel prepared in example 1;
FIG. 6 is a graph showing the results of the swelling ratio test of hydrogels;
FIG. 7 is an in vitro degradation of hydrogels;
FIG. 8 is a photo-thermal conversion property test result of hydrogel;
FIG. 9 is a graph showing the effect of hydrogels on cell proliferation;
FIG. 10 is the effect of hydrogels on osteoblast induced ossification;
FIG. 11 is a blood compatibility test result of hydrogels;
fig. 12 is a hemostatic test result of the hydrogel.
Detailed Description
The technical scheme of the invention is further described in detail below with reference to the specific embodiments and the attached drawings:
the preparation method of the silk fibroin used in the embodiment of the invention comprises the following steps:
taking dry silkworm cocoons according to the mass-volume ratio of 1g to 30mL, and putting the dry silkworm cocoons into Na with the concentration of 5g/L 2 CO 3 Boiling for 30min to degumm, washing with deionized water, and drying in a drying oven for 2 times; dissolving degummed silk in a ternary system CaCl according to the mass-volume ratio of 1g to 10mL 2 ·CH 3 CH 2 OH·H 2 O, heating for 2h at 80 ℃ in an aqueous solution with a molar ratio of 1:2:8; centrifuging at 2000r/min for 15min, filtering, dialyzing with deionized water, and freeze-drying to obtain silk fibroin.
Example 1:
preparation of a multiple crosslinked injectable bone repair hydrogel:
adding deionized water into corilagin and carboxymethyl chitosan, wetting and mixing, and grinding to dry and fluffy state to obtain corilagin/carboxymethyl chitosan compound; wherein the mass ratio of the corilagin to the carboxymethyl chitosan is 1:5;
dissolving magnesium alginate MA in deionized water, and fully stirring to obtain MA solution with the concentration of 0.02 g/mL; adding sodium periodate, and stirring and reacting for 12 hours at room temperature under the dark condition; adding ethylene glycol to continue the reaction for 2 hours to terminate the oxidation reaction; dialyzing with deionized water for 72 hr (dialysis bag molecular weight: 3500 Da), freezing and drying the dialyzed solution at-80deg.C to obtain magnesium alginate oxide OMA (its actual product is shown in figure 1); wherein the mass ratio of MA to sodium periodate is 1:1; the mass volume ratio of MA to glycol is 1g to 5mL;
dissolving nano hydroxyapatite in a Trils buffer solution with the pH of 8.5, sufficiently stirring, and performing ultrasonic treatment for 20min to obtain a solution A with the concentration of 0.2 wt%; dissolving dopamine hydrochloride in deionized water, and fully stirring and mixing to obtain a solution B with the concentration of 0.2 wt%; then dropwise adding the solution A into the solution B at a constant speed according to the mass ratio of the nano-hydroxyapatite to the dopamine hydrochloride of 1:1, stirring and mixing at a stirring speed of 1000r/min, continuously stirring for 12h, and freeze-drying to obtain the dopamine-coated nano-hydroxyapatite PHA, wherein the scanning observation knot of an electron microscope is shown in the figure 2, and the successful synthesis of the nano-particles is proved;
dissolving the corilagin/carboxymethyl chitosan compound and magnesium alginate oxide in deionized water to prepare a mixture, wherein the percentage content of the corilagin/carboxymethyl chitosan compound is 5%; then adding modifier silk fibroin and dopamine-coated nano hydroxyapatite, stirring for 10min, and standing to obtain modified corilagin/carboxymethyl chitosan compound-magnesium alginate oxide hydrogel; wherein the mass ratio of the corilagin/carboxymethyl chitosan compound to the magnesium alginate oxide is 1:1; the mass ratio of the corilagin/carboxymethyl chitosan complex to the silk fibroin and the dopamine-coated nano hydroxyapatite is 5:2.5:2.
Example 2:
the method for preparing a multi-crosslinked injectable bone repair hydrogel differs from example 1:
the mass ratio of the corilagin/carboxymethyl chitosan compound to the magnesium alginate oxide is 1:0.8; the mass ratio of the corilagin/carboxymethyl chitosan complex to the silk fibroin and the dopamine-coated nano hydroxyapatite is 5:2:1.5.
Example 3:
the method for preparing a multi-crosslinked injectable bone repair hydrogel differs from example 1:
the mass ratio of the corilagin/carboxymethyl chitosan complex to the magnesium alginate oxide is 1:0.7; the mass ratio of the corilagin/carboxymethyl chitosan complex to the silk fibroin and the dopamine-coated nano hydroxyapatite is 5:3:2.5.
Example 4:
the method for preparing a multi-crosslinked injectable bone repair hydrogel differs from example 1: in the preparation process of the hydrogel, theaflavin, modifier silk fibroin and dopamine-coated nano hydroxyapatite are added simultaneously, and the mixture is stirred for 10 minutes and then is left to stand, so that the hydrogel added with the theaflavin is prepared, wherein the amount of the theaflavin is 5% of the mass of the hydrogel.
Example 5:
the method for preparing a multi-crosslinked injectable bone repair hydrogel differs from example 1: theaflavin is added into the hydrogel, wherein the amount of theaflavin is 8% of the mass of the hydrogel.
Example 6:
the method for preparing a multi-crosslinked injectable bone repair hydrogel differs from example 1: carboxymethyl chitosan is used to replace the corilagin/carboxymethyl chitosan complex.
Example 7:
the method for preparing a multi-crosslinked injectable bone repair hydrogel differs from example 6: theaflavin is added into the hydrogel, wherein the amount of theaflavin is 5% of the mass of the hydrogel.
Test example 1:
properties of hydrogels
1. Testing of hydrogel compressive Strength and elastic modulus
The gel sample was placed in a 10mL centrifuge tube, and a cylindrical hydrogel with a diameter of 10mm and a thickness of 8mm was prepared at room temperature, and then subjected to compression test at a rate of 1mm/min using a tester MX-0580. The elastic modulus E of the hydrogel is calculated as follows:
E=NH/A△H
wherein N is stress and Pa; h is the thickness of the gel before deformation, m; a is the area of the compressed sample, m 2 The method comprises the steps of carrying out a first treatment on the surface of the Δh is the thickness of the sample deformed under pressure, m.
The above tests were performed on examples 1 to 7, and the results are shown in fig. 3 and 4. As can be seen from fig. 3 and 4, the compressive strength and elastic modulus of example 4 and example 1 are not greatly different, and the effect of example 7 is equivalent to that of example 6, which shows that the addition of theaflavin has no negative effect on the compressive strength and elastic modulus of the hydrogel. Example 1 has improved elastic modulus and compressive strength compared to example 6, indicating that the presence of corilagin/carboxymethyl chitosan complex significantly improves its compression properties; and the elastic modulus of the obtained hydrogel is similar to that of cancellous bone, so that the repair requirement of cancellous bone defect in large-section defect is met.
2. Scanning electron microscope topography observation (SEM)
To observe the internal microstructure of the hydrogel, the hydrogel was lyophilized on a lyophilizer. The lyophilized sample was cut to expose its cross section and fixed to an electron microscope stage with a conductive paste, and subjected to metal spraying for 90 seconds, and observed using a cold field emission scanning tunneling microscope (S-4800 of Hitachi Co.) with an acceleration voltage of 15KV.
The hydrogel prepared in example 1 was subjected to the above test, and the results are shown in fig. 5. Analysis of fig. 5 shows that the micro structure of the freeze-dried hydrogel is observed by a scanning electron microscope, the hydrogel has a porous structure, pores are connected with each other, the intercommunicating porous structure is beneficial to the transportation of nutrients and oxygen and the removal of metabolites, and the pore size of the hydrogel is suitable for bone ingrowth.
3. Swelling test
The membranes were used to prepare uniformly sized hydrogels, and each set of hydrogels was immersed in excess PBS. The hydrogel sets were weighed at 15min, 30min, 1h, 2h, 3h, 5h, 9h, 24h, 48h, respectively, until the swelling equilibrium was reached. The swelling ratio formula is as follows:
SR=（Ws-Wd）/Wd×100%
where Ws and Wd are the weight of the swollen hydrogel and the unswollen hydrogel, respectively.
The results of the above tests performed in example 1, example 4 and example 6 are shown in fig. 6, and it is evident from the analysis in fig. 6 that the swelling ratio of the hydrogel gradually increases with time and eventually becomes gentle. The modified hydrogel has reduced swelling performance compared with the hydrogel before modification, but still has better swelling performance, which can ensure the nutrition components of the defect part in vivo, thereby promoting the aggregation growth of surrounding tissues to the middle.
4. In vitro degradation test
The hydrogel with the size of 2X 1cm was prepared by using the membrane, immersed in PBS, placed in a 37℃incubator, changed at 5-day intervals, and the weight of the dried hydrogel was measured at 15 days, 30 days, and 60 days, respectively. The calculation formula of the residual weight percentage is as follows:
residual weight (%) = (Wt/W) 0 ）×100%
Wherein W is 0 And Wt is the initial weight of the hydrogel and the weight of the hydrogel at each time, respectively.
The above test was performed on examples 1, 4 and 6, and the test results are shown in fig. 7. As can be seen from fig. 7, the degradation amount of the hydrogel gradually increased with the increase of the degradation time. And the hydrogel is degraded by 35-50% in 1 month in vitro, and is basically degraded by 55-70% in two months, which shows that the prepared hydrogel has good biodegradability.
5. Photothermal performance test
The hydrogel was irradiated with near infrared light at 808nm, and the photo-thermal properties of the hydrogel were tested (1000 w current, 734mw output power, 1.1304mm area 2 ）。
The above tests were performed on examples 1, 4, 6 and 7, and the results are shown in fig. 8. As can be seen from fig. 8, as the irradiation time increases, the temperature of the hydrogel increases, which indicates that the hydrogel has a strong photo-thermal conversion efficiency. Considering the intolerance of cells and tissues to temperature, only 2 minutes of irradiation was performed. Moreover, example 4 was not much different from example 1, and example 7 was equivalent to example 6 in effect, demonstrating that the addition of theaflavin had no negative effect on the photothermal conversion of the hydrogel; the hydrogel prepared in example 1 had higher temperature values at various time points than those of example 6, indicating that the addition of the corilagin/carboxymethyl chitosan complex to the hydrogel can further enhance the photo-thermal conversion properties of the hydrogel.
6. Hydrogel detection of osteoblast proliferation and osteogenesis
After irradiating the hydrogel with near infrared light of 808nm for 1min, MC3T3 cells were cultured in the irradiated hydrogel for 1, 3, 5, and 7 days, respectively, and cell proliferation was detected using CCK-8 reagent. The alkaline phosphatase ALP quantitative determination kit is used for detecting ALP expression amounts of hydrogels with different concentrations on days 3 and 7.
The above tests were performed on examples 1, 4, 6 and 7, and the results are shown in fig. 9 and 10. As can be seen from fig. 9 and 10, the absorbance value and the cell proliferation rate of the hydrogel prepared in example 1 at each time point are better than those of example 6, and the ALP expression amount on days 3 and 7 is also higher than that of example 6, which indicates that the addition of corilagin/carboxymethyl chitosan complex has a certain promoting effect on cell proliferation and osteoblast induced ossification; example 4 is better than examples 1, 6 and 7, and the addition of theaflavin in the hydrogel can enhance the effect of theaflavin on cell proliferation and osteoblast induced ossification, and the effect of enhancing the cell proliferation and osteoblast induced ossification of the hydrogel is better under the condition that the corilagin/carboxymethyl chitosan complex exists simultaneously.
7. Hydrogel blood compatibility test
To the EDTA anticoagulation tube, 3mL of fresh mouse blood was added, and the supernatant was centrifuged off. Equal amount of 0.9% physiological saline was added for centrifugation and repeated three times. Red blood cells were resuspended in 0.1M PBS (10 x PBS) and diluted 50-fold to obtain a red blood cell suspension. 900. Mu.L of the red blood cell suspension was added to 100. Mu.L of 25mg/mL of the hydrogel prepared in advance. 100. Mu.L of physiological saline was added to the control group. After 60min at 37℃the supernatant was centrifuged and 100. Mu.L was applied to a 96-well plate and absorbance at 541nm was measured.
Hemolysis ratio= (sample absorbance-physiological saline absorbance)/absorbance of Triton-X100
The above tests were performed on examples 1 to 7 and the control group, and the results are shown in fig. 11. As shown in fig. 11, the hydrogel hemolysis rates of the modified silk fibroin and dopamine-coated nano hydroxyapatite and theaflavin are not different from those of the control group, which indicates that the hydrogels prepared in examples 1-7 have good biocompatibility with blood, and meet the requirement of in vivo implantation.
8. Hemostatic Properties
The hydrogel samples were weighed 10mg each and placed in a clean beaker and incubated at 37℃for 5min. 20 mu L of CaCl 0.2mol/L 2 The solution was added to 100. Mu.L of anticoagulated rabbit blood, which was then added dropwise to a hydrogel, 25mL of distilled water was added, and after shaking, it was allowed to stand for 10 minutes, and its absorbance value was measured at 545nm with an ultraviolet spectrophotometer.
The above tests were performed on examples 1 to 7, and the results are shown in fig. 12. From fig. 12, the hemostatic effects of example 1 and example 6 are equivalent, and it is shown that the addition of corilagin/carboxymethyl chitosan complex does not negatively affect the hemostatic effect. Example 4 shows a significant decrease in absorbance compared to examples 1 and 7, and example 7 shows a better effect than example 6, demonstrating that the addition of theaflavins can effectively enhance the hemostatic properties of hydrogels; and the presence of the corilagin/carboxymethyl chitosan compound has an effect of promoting the hemostatic performance of theaflavin.
The conventional technology in the above embodiments is known to those skilled in the art, and thus is not described in detail herein.
The foregoing is merely illustrative of the present invention, and the present invention is not limited thereto, and any person skilled in the art will readily recognize that variations or substitutions are within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (7)
1. An injectable bone repair hydrogel material, which is characterized by comprising a hydrogel matrix and a multiple crosslinking modifier; the hydrogel matrix at least comprises a corilagin/carboxymethyl chitosan compound and magnesium alginate oxide, and the multiple crosslinking modifier comprises silk fibroin and dopamine coated nano hydroxyapatite;
in the corilagin/carboxymethyl chitosan compound, the mass ratio of corilagin to carboxymethyl chitosan is 1:5-7;
the preparation method of the corilagin/carboxymethyl chitosan compound comprises the following steps: adding deionized water into corilagin and carboxymethyl chitosan for wetting and mixing, and grinding to dry and fluffy state to obtain corilagin/carboxymethyl chitosan compound;
the preparation method of the magnesium alginate oxide comprises the following steps: the magnesium alginate oxide is prepared by oxidizing magnesium alginate by sodium periodate;
the mass ratio of the magnesium alginate to the sodium periodate is 1:1-1.5.
2. The method for preparing the injectable bone repair hydrogel material according to claim 1, comprising the steps of: dissolving the corilagin/carboxymethyl chitosan compound and magnesium alginate oxide in deionized water, then adding modifier silk fibroin and dopamine to wrap nano hydroxyapatite, stirring for 5-10min, and standing to obtain modified corilagin/carboxymethyl chitosan compound-magnesium alginate oxide hydrogel, namely the injectable bone repair hydrogel material.
3. The method for preparing an injectable bone repair hydrogel material according to claim 2, wherein: the mass ratio of the corilagin/carboxymethyl chitosan compound to the magnesium alginate oxide is 1:0.7-1; the mass ratio of the corilagin/carboxymethyl chitosan complex to the silk fibroin and the dopamine-coated nano hydroxyapatite is 5:2-3:1.5-2.5.
4. The method for preparing the injectable bone repair hydrogel material according to claim 2, wherein: the elastic modulus of the hydrogel material is more than or equal to 0.16MPa, and the compressive strength is more than or equal to 0.19MPa.
5. Use of the hydrogel material prepared by the preparation method of claim 2 for preparing bone repair materials, adsorption materials and carrier materials.
6. A composition comprising the hydrogel material made by the method of manufacture of claim 2, the efficacy of the composition comprising: hemostatic activity, promoting bone cell proliferation activity, and osteoblast induced ossification activity.
7. The composition of claim 6, wherein: theaflavins are also included.
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