CN112521633A - Preparation method and application of biomineral composite hydrogel - Google Patents
Preparation method and application of biomineral composite hydrogel Download PDFInfo
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- CN112521633A CN112521633A CN202011404703.2A CN202011404703A CN112521633A CN 112521633 A CN112521633 A CN 112521633A CN 202011404703 A CN202011404703 A CN 202011404703A CN 112521633 A CN112521633 A CN 112521633A
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 62
- 239000002131 composite material Substances 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000000243 solution Substances 0.000 claims abstract description 23
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 17
- 239000010452 phosphate Substances 0.000 claims abstract description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 17
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 16
- 239000011259 mixed solution Substances 0.000 claims abstract description 16
- 229920000867 polyelectrolyte Polymers 0.000 claims abstract description 16
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910001424 calcium ion Inorganic materials 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000012377 drug delivery Methods 0.000 claims abstract description 6
- 230000004044 response Effects 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 4
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 4
- 238000004140 cleaning Methods 0.000 claims abstract description 4
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- 239000004584 polyacrylic acid Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 9
- 239000001506 calcium phosphate Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 229920002401 polyacrylamide Polymers 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 229920002845 Poly(methacrylic acid) Polymers 0.000 claims description 2
- 229920002873 Polyethylenimine Polymers 0.000 claims description 2
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 235000019691 monocalcium phosphate Nutrition 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 2
- 229920000172 poly(styrenesulfonic acid) Polymers 0.000 claims description 2
- 229940005642 polystyrene sulfonic acid Drugs 0.000 claims description 2
- 229920002717 polyvinylpyridine Polymers 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 229910000150 monocalcium phosphate Inorganic materials 0.000 claims 1
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- 239000000047 product Substances 0.000 description 7
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- 229910000389 calcium phosphate Inorganic materials 0.000 description 5
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- 238000006731 degradation reaction Methods 0.000 description 5
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- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 4
- 229960001714 calcium phosphate Drugs 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 230000033558 biomineral tissue development Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002114 nanocomposite Substances 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000004434 Calcinosis Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 229940062672 calcium dihydrogen phosphate Drugs 0.000 description 1
- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
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- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000002407 tissue scaffold Substances 0.000 description 1
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- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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Abstract
The invention provides a preparation method of biomineral composite hydrogel, which comprises the following steps: dissolving polyelectrolyte and soluble calcium salt in water to obtain mixed solution, wherein the weight average molecular weight of the polyelectrolyte is 800-600000, and the mass ratio of the polyelectrolyte to the soluble calcium salt is (5-0.5): 1, the concentration of the soluble calcium salt is 1-50 g/L; according to the molar concentration ratio of calcium ions to phosphate being 1-2: 1, dripping a soluble phosphate solution into the mixed solution at the speed of 0.01-5 mL/min to obtain a reaction solution, wherein the concentration of the soluble phosphate solution is 0.05-2M; and stirring the reaction liquid for 15-60 min, and cleaning a product to obtain the biomineral composite hydrogel. And provides the application of the biomineral composite hydrogel obtained by the preparation method of the biomineral composite hydrogel in the fields of drug delivery, tissue engineering or stimulus response devices.
Description
Technical Field
The invention belongs to the technical field of biomedical engineering, and particularly relates to a preparation method and application of biomineral composite hydrogel.
Background
Hydrogels are three-dimensionally interconnected network-structured materials that have received much attention due to their high moisture content, hydrophilic, flexible, and biocompatible properties.
Incorporation of mineral particles into hydrogel matrices or crystalline minerals growing in situ in hydrogels can produce nanocomposite hydrogels with good mechanical properties or novel structures, but their gelling properties are largely dependent on the polymer matrix itself. For example, Schmidt et al prepared highly extensible elastic nanocomposite hydrogels by mixing polyethylene glycol and hydroxyapatite nanoparticles; however, hydrogels are not moldable and do not heal spontaneously due to chemical crosslinking of the polyethylene glycol network. Sun et al mix CaCl in water2，Na2CO3And polyacrylic acid (PAA), which produces a deformable and stretchable hydrogel that has self-healing and shear-thinning properties and can be recovered by swelling a dried transparent film. However, compared with amorphous calcium phosphate, amorphous calcium phosphate has better application prospect in the field of biomaterials.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects of the prior art and provide a preparation method and application of biomineral composite hydrogel.
The invention provides a preparation method of biomineral composite hydrogel, which comprises the following steps:
dissolving polyelectrolyte and soluble calcium salt in water to obtain mixed solution, wherein the weight average molecular weight of the polyelectrolyte is 800-600000, and the mass ratio of the polyelectrolyte to the soluble calcium salt is (5-0.5): 1, the concentration of the soluble calcium salt is 1-50 g/L;
according to the molar concentration ratio of calcium ions to phosphate being 1-2: 1, dripping a soluble phosphate solution into the mixed solution at the speed of 0.01-5 mL/min to obtain a reaction solution, wherein the concentration of the soluble phosphate solution is 0.05-2M;
and stirring the reaction liquid for 15-60 min, and cleaning a product to obtain the biomineral composite hydrogel.
And provides the application of the biomineral composite hydrogel obtained by the preparation method of the biomineral composite hydrogel in the fields of drug delivery, tissue engineering or stimulus response devices.
According to the preparation method of the biomineral composite hydrogel provided by the invention, the calcium phosphate is a main inorganic component existing in a human body, and the biomineralization of the calcium phosphate is very important for the formation of bones, teeth and other pathological calcifications. In the biomineralization process, Amorphous Calcium Phosphate (ACP) is an important precursor for hydroxyapatite production, has the lowest surface energy and the least stable thermodynamic stability, and is rapidly hydrolyzed when dispersed in an aqueous solution and then converted into a more stable crystalline phase. ACP continues to stabilize in the presence of stabilizers in solution. The preparation method comprises mixing CaCl in water at a specific ratio2，PAA，K2HPO4The biomineral composite hydrogel with special properties of deformability, stretchability, rapid degradation under specific environment, drying and transparence is prepared.
Drawings
FIG. 1 is a schematic diagram of the preparation of the biomineral composite hydrogel of the present invention.
FIG. 2 is an infrared spectrum of the biomineral composite hydrogel obtained in the example of the present invention.
FIG. 3 shows the degradation behavior of the biomineral composite hydrogel obtained in the example of the present invention.
FIG. 4 shows the mass change of the biomineral composite hydrogel obtained in the example of the present invention when stored in the original solution, PBS and not in the liquid.
Fig. 5 is the rheological behavior of the biomineral composite hydrogel obtained in the example of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The embodiment of the invention provides a preparation method of biomineral composite hydrogel, which comprises the following steps:
s01: dissolving polyelectrolyte and soluble calcium salt in water to obtain mixed solution, wherein the weight average molecular weight of the polyelectrolyte is 800-600000, and the mass ratio of the polyelectrolyte to the soluble calcium salt is (5-0.5): 1, the concentration of the soluble calcium salt is 1-50 g/L;
s02: according to the molar concentration ratio of calcium ions to phosphate being 1-2: 1, dripping a soluble phosphate solution into the mixed solution at the speed of 0.01-5 mL/min to obtain a reaction solution, wherein the concentration of the soluble phosphate solution is 0.05-2M;
s03: and stirring the reaction liquid for 15-60 min, and cleaning a product to obtain the biomineral composite hydrogel.
In step S01, the polyelectrolyte is at least one selected from polyacrylic acid (PAA), polymethacrylic acid, polystyrenesulfonic acid, polyvinylsulfonic acid, polyvinylphosphoric acid, polyethyleneimine, polyvinylamine, polyvinylpyridine, and polyacrylamide salt. Preferably, the polyelectrolyte is polyacrylic acid. More preferably, the polyacrylic acid has a weight average molecular weight of 400000 to 500000. The ratio of the molar concentration of the repeating unit of the polyacrylic acid to the molar concentration of the calcium ions is 1-3: 1.
in step S02, the soluble calcium salt is at least one of calcium chloride, calcium dihydrogen phosphate and calcium nitrate, preferably, the soluble calcium salt is calcium chloride. The soluble phosphate is at least one of dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen phosphate and sodium phosphate. Preferably, the soluble phosphate is dipotassium hydrogen phosphate, and the molar concentration ratio of calcium ions to phosphate is 1-1.5: 1. the concentration of the soluble calcium salt is preferably 5-30 g/L.
In step S03, the stirring speed is 500-1500 rpm.
The embodiment of the invention also provides application of the biomineral composite hydrogel obtained by the preparation method of the biomineral composite hydrogel in the fields of drug delivery, tissue engineering or stimulus response devices. In drug delivery, the biomineral composite hydrogel has the characteristic of degradation under a specific environment, can serve as an excellent environment-responsive drug delivery system, and simultaneously provides conditions for drug loading due to the internal structure and the crosslinking mode.
In tissue engineering, the biomineral composite hydrogel has strong elasticity and toughness, can be converted into a transparent high-strength tissue scaffold after being dried, has excellent mechanical properties and a network structure, provides space for cell growth and differentiation, and provides an excellent platform for tissue repair.
In the bone tissue repair, the main component of the biomineral composite hydrogel is ACP, so that the biomineral composite hydrogel can provide a raw material for bone tissue regeneration, and the strength of the material can also provide an environment for bone tissue regeneration.
In the field of stimulus response devices, electrochemical performance data show that the capacitance of the biomineral composite hydrogel can change along with deformation, and the biomineral composite hydrogel has the potential capability of developing into a biosensor.
Specific implementations of the present invention are described in detail below with reference to specific embodiments.
Example 1:
2.88g of PAA (Mw: 450000) and 2.22g of CaCl are weighed out2200mL of the mixed solution was prepared. Taking 30mL of the mixed solution in a beaker at the speed of 900rpm/minStirring is carried out according to the calcium ion concentration: hydrogen phosphate concentration ═ 1: 1, slowly dropped into 0.1M K at a rate of 1mL/min2HPO4The solution was stirred for 30min until the system stabilized. And washing the product with deionized water to obtain the biomineral composite hydrogel.
Example 2:
2.96g of polyacrylamide salt (Mw 450000) and 2.22g of CaCl are weighed out2200mL of the mixed solution was prepared. 30mL of the mixed solution was put in a beaker and stirred at 900rpm/min, according to the calcium ion concentration: hydrogen phosphate concentration ═ 3: 2, slowly dropped at a rate of 1mL/min to 0.1M K2HPO4The solution was stirred for 30min until the system stabilized. And washing the product with deionized water to obtain the biomineral composite hydrogel.
Example 3:
3.2g of PAA (Mw: 450000) and 2.22g of CaCl are weighed out2200mL of the mixed solution was prepared. 30mL of the mixed solution was put in a beaker and stirred at 900rpm/min, according to the calcium ion concentration: hydrogen phosphate concentration ═ 1: 1, slowly dropped into 0.1M K at a rate of 1mL/min2HPO4The solution was stirred for 30min until the system stabilized. And washing the product with deionized water to obtain the biomineral composite hydrogel.
Example 4:
3.2g of PAA (Mw: 450000) and 2.22g of CaCl are weighed out2200mL of the mixed solution was prepared. 30mL of the mixed solution was put in a beaker and stirred at 900rpm/min, according to the calcium ion concentration: hydrogen phosphate concentration ═ 3: 2, slowly dropped at a rate of 1mL/min to 0.1M K2HPO4The solution was stirred for 30min until the system stabilized. And washing the product with deionized water to obtain the biomineral composite hydrogel.
The invention controls the molecular weight of PAA, the concentration ratio of PAA to calcium ion, the stirring speed, K2HPO4The dropping rate and the subsequent treatment of the stable solution, and the prepared product has the advantages of deformability, stretchability, rapid degradation under specific environment, dryness and transparencyBiological mineral inorganic/organic composite hydrogel with special performances. As shown in the infrared spectrogram of biomineral composite hydrogel (figure 2), 1714 and 1249cm-1Tensile peaks for C ═ O and C-O as carboxylate groups, 2935cm-1Characteristic peaks of C-H on PAA main chain, 3468 and 2532cm-1Is the vibration peak and stretching peak of hydroxyl, 1419cm-1The oscillation peak is O-H, and the data indicate the existence of PAA in the hydrogel; 1249cm-1Is the stretching peak of C-O, 1168cm-1Is a characteristic peak of P ═ O, 1049cm-1Characteristic peaks for P-O-C, 610 and 550cm-1These data demonstrate the presence of ACP in the gel as a characteristic peak for ACP.
Fig. 3 is the degradation behavior of the biomineral composite hydrogel: (a) is a picture of the hydrogel just after its preparation; (b) and (c) are pictures of the next and sixth days of gel storage in the stock solution; (d) and (e) are pictures of the next and sixth days of storage in PBS after the gel has washed the surface; (f) and (g) are pictures of gels stored in PBS the next and sixth days. After being prepared, the biomineral composite hydrogel can be kept stable in the original solution, as shown in fig. 3(b) and (c); in the neutral environment of PBS, the gel on the surface washed every day will be rapidly degraded into colorless and transparent colloid in two days (FIG. 3(d) and (e)); if the surface of the gel is not treated, a film is formed on the surface of the gel to protect the surface structure of the gel, and the ACP inside the gel permeates into the contacted external liquid. FIG. 4 shows the mass change of the biomineral composite hydrogel when stored in the original solution, PBS and not in the liquid. In PBS, the gel can be rapidly degraded, and in air, the gel quality can be reduced along with the increase of time, and if the gel is stored in the original solution, the quality can be maintained to be stable for a long time. This unique property shift also provides a number of possibilities for application after gelation.
Fig. 5 is the rheological behavior of the biomineral composite hydrogel, the viscoelasticity of the hydrogel changes significantly with increasing angular frequency, since the main structure of the hydrogel is formed by crosslinking through physical force. The result that G' is much greater than G "also indicates the excellent elasticity of the gel. The ACP has more excellent elasticity and toughness than common hydrogel (< 1000 Pa). The excellent mechanical property can lead the biomineral inorganic/organic composite hydrogel to have potential requirements in the fields of bone tissue repair scaffolds or biosensors and the like which have certain requirements on scaffold strength, and can also provide another scaffold construction platform for the biomedical field.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. The preparation method of the biomineral composite hydrogel is characterized by comprising the following steps:
dissolving polyelectrolyte and soluble calcium salt in water to obtain mixed solution, wherein the weight average molecular weight of the polyelectrolyte is 800-600000, and the mass ratio of the polyelectrolyte to the soluble calcium salt is (5-0.5): 1, the concentration of the soluble calcium salt is 1-50 g/L;
according to the molar concentration ratio of calcium ions to phosphate being 1-2: 1, dripping a soluble phosphate solution into the mixed solution at the speed of 0.01-5 mL/min to obtain a reaction solution, wherein the concentration of the soluble phosphate solution is 0.05-2M;
and stirring the reaction liquid for 15-60 min, and cleaning a product to obtain the biomineral composite hydrogel.
2. The method of claim 1, wherein the polyelectrolyte is at least one selected from the group consisting of polyacrylic acid, polymethacrylic acid, polystyrenesulfonic acid, polyvinylsulfonic acid, polyvinylphosphoric acid, polyethyleneimine, polyvinylamine, polyvinylpyridine, and polyacrylamide salt.
3. The method of claim 2, wherein the polyelectrolyte is polyacrylic acid.
4. The method for preparing biomineral composite hydrogel according to claim 3, wherein the polyacrylic acid has a weight average molecular weight of 400000 to 500000.
5. The method for preparing biomineral composite hydrogel according to claim 1, wherein the ratio of the molar concentration of the repeating unit of polyacrylic acid to the molar concentration of calcium ions is 1-3: 1.
6. the method for preparing biomineral composite hydrogel according to claim 1, wherein the soluble calcium salt is at least one of calcium chloride, monocalcium phosphate and calcium nitrate.
7. The method of preparing a biomineral composite hydrogel according to claim 1, wherein the soluble phosphate is at least one of dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen phosphate and sodium phosphate.
8. The method of preparing a biomineral composite hydrogel according to claim 7, wherein the soluble phosphate is dipotassium hydrogen phosphate.
9. The method for preparing biomineral composite hydrogel according to claim 1, wherein the stirring speed is 500 to 1500 rpm.
10. Use of the biomineral composite hydrogel obtained by the preparation method of the biomineral composite hydrogel according to any one of claims 1 to 9 in the fields of drug delivery, tissue engineering or stimulus response devices.
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