CN108892788B - Hydrogel capable of keeping high strength in physiological environment and preparation method thereof - Google Patents
Hydrogel capable of keeping high strength in physiological environment and preparation method thereof Download PDFInfo
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- CN108892788B CN108892788B CN201810618393.0A CN201810618393A CN108892788B CN 108892788 B CN108892788 B CN 108892788B CN 201810618393 A CN201810618393 A CN 201810618393A CN 108892788 B CN108892788 B CN 108892788B
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims abstract description 47
- 239000000378 calcium silicate Substances 0.000 claims abstract description 39
- 229910052918 calcium silicate Inorganic materials 0.000 claims abstract description 39
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims abstract description 39
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 33
- 235000010410 calcium alginate Nutrition 0.000 claims abstract description 33
- 239000000648 calcium alginate Substances 0.000 claims abstract description 33
- 229960002681 calcium alginate Drugs 0.000 claims abstract description 33
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- 229920002401 polyacrylamide Polymers 0.000 claims abstract description 32
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 claims abstract description 24
- 239000007864 aqueous solution Substances 0.000 claims abstract description 21
- 239000002105 nanoparticle Substances 0.000 claims abstract description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000004115 Sodium Silicate Substances 0.000 claims abstract description 20
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052911 sodium silicate Inorganic materials 0.000 claims abstract description 20
- -1 hydrogen ions Chemical class 0.000 claims abstract description 18
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 15
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 15
- 239000000661 sodium alginate Substances 0.000 claims abstract description 15
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 15
- 239000000741 silica gel Substances 0.000 claims abstract description 12
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims abstract description 9
- 238000011065 in-situ storage Methods 0.000 claims abstract description 9
- 239000012528 membrane Substances 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 27
- 238000002791 soaking Methods 0.000 claims description 25
- 239000001110 calcium chloride Substances 0.000 claims description 24
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 24
- 239000000499 gel Substances 0.000 claims description 21
- 238000005266 casting Methods 0.000 claims description 18
- 239000011521 glass Substances 0.000 claims description 18
- 238000007790 scraping Methods 0.000 claims description 13
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 12
- 108010025899 gelatin film Proteins 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 12
- 230000008961 swelling Effects 0.000 claims description 9
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 8
- 230000003993 interaction Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 238000010382 chemical cross-linking Methods 0.000 claims description 7
- 239000003431 cross linking reagent Substances 0.000 claims description 7
- 230000003301 hydrolyzing effect Effects 0.000 claims description 7
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 6
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000005303 weighing Methods 0.000 claims description 6
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 5
- 150000002500 ions Chemical class 0.000 claims description 5
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 5
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims description 4
- 238000005191 phase separation Methods 0.000 claims description 4
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 claims description 3
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 230000004962 physiological condition Effects 0.000 claims 1
- 210000000845 cartilage Anatomy 0.000 abstract description 8
- 238000004132 cross linking Methods 0.000 abstract description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 239000012890 simulated body fluid Substances 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 239000000463 material Substances 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 4
- 229920001661 Chitosan Polymers 0.000 description 3
- 239000012620 biological material Substances 0.000 description 2
- 125000005442 diisocyanate group Chemical group 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000008204 material by function Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000010146 3D printing Methods 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- KIQKWYUGPPFMBV-UHFFFAOYSA-N diisocyanatomethane Chemical compound O=C=NCN=C=O KIQKWYUGPPFMBV-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 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 1
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- 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
- C08J3/075—Macromolecular gels
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F251/00—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
- C08J5/18—Manufacture of films or sheets
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- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
- C08J7/14—Chemical modification with acids, their salts or anhydrides
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2351/00—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers
- C08J2351/02—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers grafted on to polysaccharides
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/34—Silicon-containing compounds
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Abstract
The invention provides a hydrogel keeping high strength in a physiological environment and a preparation method thereof. Firstly, sodium silicate, acrylamide and sodium alginate are dissolved in water together, acrylamide polymerization is initiated by ultraviolet, calcium silicate nano particles are generated in situ in hydrogel through calcium chloride solution cross-linking with gradient concentration, then the hydrogel is soaked in gluconic acid-lactone aqueous solution, the gluconic acid-lactone is hydrolyzed to release hydrogen ions, and the hydrogen ions react with calcium silicate to generate calcium silicate with mesoporous silica gel on the surface. The mesoporous silica gel has hydrogen bond effect with calcium alginate and polyacrylamide, thereby improving the strength and stability of the hydrogel in physiological environment. The hydrogel can maintain over 70% of the initial value after being soaked in normal saline and simulated body fluid for 45 days, and the fracture energy is higher than that of the natural cartilage. The preparation method is simple and quick, does not introduce any toxic reagent, has good biocompatibility, and can be used as a cartilage substitute.
Description
Technical Field
The invention relates to a hydrogel keeping high strength in a physiological environment and a preparation method thereof, belonging to the field of functional materials and biological materials.
Background
The polymer hydrogel is a multi-element system consisting of a polymer three-dimensional network and water, and can generate huge changes on macroscopic (volume) shapes under the stimulation of environment. Hydrogels are widely used in industrial, agricultural, biological and materials fields. The hydrogel is a high molecular material similar to living tissues, has good biocompatibility, does not influence the metabolic process of a living body, and can be used as a tissue filler because metabolites can be discharged through the hydrogel. The polymer hydrogel can also be made into microcapsules to be used as a carrier of the drug. However, the strength of the conventional hydrogel is low, which limits further practical application.
The study of high strength hydrogels has made significant progress in recent years. Gong Jian Nu et al proposed the idea of "double-layer network" hydrogel, which on the basis of gel forming a rigid first-layer network with high degree of crosslinking, internally synthesized a flexible second-layer network with a lower degree of crosslinking [ Advanced materials.2014, 26: 436, 442 ]. Such hydrogels also have high strength while maintaining high water content. However, the double chemical network cross-linked hydrogel needs two-step polymerization, and the preparation process is relatively complicated. High-elasticity and high-toughness polyacrylamide/calcium alginate (PAM/CaAlg) double-network hydrogel is prepared by latcheng et al in one step [ Nature, 2012, 489 (7414): 133-136. the hydrogel has good biocompatibility, excellent lubricity and wear resistance, and can meet the requirements of cartilage tissue replacement [ Biomaterials, 2013, 34 (33): 8042 to 8048). Bakarich et al prepared fiber-reinforced PAM/CaAlg hydrogel artificial articular cartilage substitutes using 3D printing techniques [ ACS Applied Materials & Interfaces, 2014, 6 (18): 15998-. However, under physiological environment, the cross-linking ions in the double-network hydrogel are released, so that the mechanical property of the gel is rapidly reduced.
At present, there are still great challenges in constructing hydrogels with high strength, high toughness and low swelling in physiological environments. If non-covalent interaction with self-repairing function, such as hydrogen bond, electrostatic force, hydrophobic effect and nano effect, is introduced into the double-network hydrogel, the preparation of stable high-strength hydrogel is facilitated. Sheiko et al reported chemically crosslinked hydrogels with weak hydrogen bond enhancement [ Advanced Materials, 2015, 27: 6899 the tensile strength of the hydrogel can reach 2MPa, and the fracture energy can reach 9300J/m2. But the formation of hydrogen bonds in the network requires acidic conditions of pH 3, limiting its practical application. The present invention discloses a supramolecular hydrogel with the strength 4 times of human cartilage is prepared by the professor Liuwen, etc. by using hydrogen bond self-recognition mechanism, the hydrogel can keep better mechanical property in acid-base solution with different pH values [ Advanced Materials, 2015, 27 (23): 3566-35-7 ]. The incorporation of silica into PAM/CaAlg hydrogels by pearl willow et al increases the breaking stress and young's modulus of the double-network gel [ Chemical Engineering Journal, 2014, 240 (6): 331-337 ]. Kim et al obtained PAM/CaAlg hybrid hydrogels that could maintain mechanical properties in physiological solution for a long time using van der waals force and hydrogen bonding between mesoporous molecular sieves and polymers [ Advanced Functional Materials, 2017, DOI: 10.1002/adfm.201703826 ]. Wudecheng et al first incorporated short chain Chitosan (CS) into the polyacrylamide network by hydrogen bonding, allowing it to form CS crystallites and an entangled network, resulting in a double-network hydrogel with high mechanical properties [ Advanced Materials, 2016, 28(33), 7178-. Nature journal in 2017 reports that Tiller and the like form uniformly dispersed nano calcium phosphate in double-network hydrogel through enzyme initiation, so that the elastic modulus of the hydrogel reaches 440MPa, which is far higher than that of cartilage [ Nature, 2017, 543 (7645): 407- & ltwbr- & gt 410 ].
The invention provides a hydrogel keeping high strength in a physiological environment and a preparation method thereof. Firstly, sodium silicate, acrylamide and sodium alginate are dissolved in water together, acrylamide polymerization is initiated by ultraviolet, calcium silicate nano particles are generated in situ in hydrogel through calcium chloride solution cross-linking with gradient concentration, then the hydrogel is soaked in gluconic acid-lactone aqueous solution, the gluconic acid-lactone is hydrolyzed to release hydrogen ions, and the hydrogen ions react with calcium silicate to generate calcium silicate with mesoporous silica gel on the surface. The mesoporous silica gel has hydrogen bond effect with calcium alginate and polyacrylamide, thereby improving the strength and stability of the hydrogel in physiological environment. The hydrogel can maintain over 70% of the initial value after being soaked in normal saline and simulated body fluid for 45 days, and the fracture energy is higher than that of the natural cartilage. The preparation method is simple and quick, does not introduce any toxic reagent, has good biocompatibility, and can be used as a cartilage substitute.
Disclosure of Invention
Aiming at the defects of the prior art, the technical problems to be solved by the invention are that the conventional hydrogel has poor mechanical properties, and the polyacrylamide/calcium alginate double-network hydrogel is difficult to have high strength, high toughness and low swelling in a physiological environment.
The invention solves the problems that the conventional hydrogel has poor mechanical properties, and the polyacrylamide/calcium alginate double-network hydrogel is difficult to have high strength, high toughness and low swelling in a physiological environment.
A hydrogel that retains high strength in a physiological environment, comprising: the preparation method comprises the steps of dissolving sodium silicate, acrylamide, a chemical cross-linking agent and sodium alginate in water, initiating acrylamide polymerization by ultraviolet rays, carrying out cross-linking by a calcium chloride solution with gradient concentration, generating calcium silicate nano particles in situ in a polyacrylamide/calcium alginate hydrogel, then soaking the hydrogel in a gluconic acid-lactone aqueous solution, hydrolyzing the gluconic acid-lactone to release hydrogen ions, reacting the hydrogen ions with calcium silicate to generate calcium silicate with mesoporous silica gel on the surface, and carrying out hydrogen bond interaction on the mesoporous silica gel, the calcium alginate and the polyacrylamide so as to improve the strength of the polyacrylamide/calcium alginate hydrogel and the stability of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
The invention provides a preparation method of hydrogel keeping high strength in physiological environment, which is characterized by comprising the following steps:
a) weighing 0.005-2g of sodium silicate, 5-15g of acrylamide, 0.5-2g of sodium alginate and 0.03-0.30% of chemical cross-linking agent in mass percent of acrylamide, dissolving the sodium silicate, the acrylamide and the chemical cross-linking agent in 50-100ml of deionized water, standing and defoaming to obtain a membrane casting solution, and placing the membrane casting solution in an aseptic container for later use; preparing calcium chloride aqueous solution with gradient concentration for later use, wherein the mass percentage concentration of the calcium chloride is respectively 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2.5% and 5.0% from low to high;
b) adding ammonium persulfate with the mass percent of acrylamide of 0.1-5 percent and bisulfite with the mass percent of acrylamide of 0.1-5 percent into the casting solution prepared in the step a)Tetramethyl ethylenediamine with the mass percent of sodium and acrylamide of 0.01-2%, stirring and dispersing evenly, pouring the solution onto a dry and clean glass plate immediately, scraping into a liquid film with the thickness of 10-3000 mu m by a film scraping rod, and then adding N2Under protection, ultraviolet irradiation is carried out for 1-30min to initiate acrylamide polymerization, and a chemically crosslinked gel film is obtained;
c) soaking the chemically crosslinked gel membrane obtained in the step b) and the glass plate into the calcium chloride solution with gradient concentration obtained in the step a), soaking for 0.1-2h under each gradient concentration, removing the gel membrane from the glass plate in the soaking process, fully and uniformly reacting calcium chloride and sodium alginate to form calcium alginate hydrogel with an ion crosslinked network structure, and reacting the calcium chloride and sodium silicate to generate calcium silicate nano particles in situ in the polyacrylamide/calcium alginate hydrogel to obtain a calcium silicate-containing gel membrane;
d) preparing a gluconic acid-lactone aqueous solution with the mass percentage concentration of 0.1-10%, soaking the calcium silicate-containing gel film obtained in the step c) in the gluconic acid-lactone aqueous solution for 0.1-24h, hydrolyzing the gluconic acid-lactone to release hydrogen ions, and reacting the hydrogen ions with calcium silicate to form a mesoporous silica gel structure on the surface of calcium silicate nanoparticles to obtain a hydrogel keeping high strength in a physiological environment; the mesoporous silica gel, calcium alginate and polyacrylamide have hydrogen bond interaction, and the enhancement effect of the nano particles improves the mechanical stability and the swelling resistance of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
The chemical cross-linking agent is any one or a mixture of more than two of ethylene glycol dimethacrylate, divinyl benzene, N' -methylene bisacrylamide and diisocyanate.
The preparation method is simple, and no organic solvent is used, so that the obtained material has good biocompatibility and can be used as a cartilage substitute and artificial skin.
Detailed Description
Specific examples of the present invention will be described below, but the present invention is not limited to the examples.
Example 1.
a) Weighing 0.005g of sodium silicate, 5g of acrylamide, 0.5g of sodium alginate and 0.03% of ethylene glycol dimethacrylate by mass of the acrylamide, dissolving the components in 50ml of deionized water, standing and defoaming to obtain a casting solution, and placing the casting solution in an aseptic container for later use; preparing calcium chloride aqueous solution with gradient concentration for later use, wherein the mass percentage concentration of the calcium chloride is respectively 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2.5% and 5.0% from low to high;
b) adding ammonium persulfate with the mass percent of acrylamide of 0.1 percent, sodium bisulfite with the mass percent of acrylamide of 0.1 percent and tetramethylethylenediamine with the mass percent of acrylamide of 0.01 percent into the casting solution prepared in the step a), stirring and dispersing uniformly, pouring the solution onto a dry and clean glass plate immediately, scraping into a liquid film with uniform thickness by using a film scraping rod with the thickness of 10 mu m, and performing N-phase separation on the liquid film2Carrying out ultraviolet irradiation for 1min under protection to initiate acrylamide polymerization to obtain a chemically crosslinked gel film;
c) soaking the chemically crosslinked gel membrane obtained in the step b) and the glass plate into the calcium chloride solution with gradient concentration obtained in the step a), soaking for 0.1h under each gradient concentration, removing the gel membrane from the glass plate in the soaking process, fully and uniformly reacting calcium chloride and sodium alginate to form calcium alginate hydrogel with an ion crosslinked network structure, and reacting calcium chloride and sodium silicate to generate calcium silicate nano particles in situ in the polyacrylamide/calcium alginate hydrogel to obtain a calcium silicate-containing gel membrane;
d) preparing a gluconic acid-lactone aqueous solution with the mass percentage concentration of 0.1%, soaking the calcium silicate-containing gel film obtained in the step c) in the gluconic acid-lactone aqueous solution for 0.1h, hydrolyzing the gluconic acid-lactone to release hydrogen ions, and reacting the hydrogen ions with calcium silicate to form a mesoporous silica gel structure on the surface of calcium silicate nanoparticles to obtain the hydrogel keeping high strength in a physiological environment; the mesoporous silica gel, calcium alginate and polyacrylamide have hydrogen bond interaction, and the enhancement effect of the nano particles improves the mechanical stability and the swelling resistance of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
Example 2.
a) Weighing 2g of sodium silicate, 15g of acrylamide, 2g of sodium alginate and divinylbenzene with the mass percent of the acrylamide being 0.30%, dissolving the sodium silicate, the acrylamide and the divinylbenzene in 100ml of deionized water, standing and defoaming to obtain a membrane casting solution, and placing the membrane casting solution in a sterile container for later use; preparing calcium chloride aqueous solution with gradient concentration for later use, wherein the mass percentage concentration of the calcium chloride is respectively 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2.5% and 5.0% from low to high;
b) adding ammonium persulfate with 5 percent of acrylamide by mass, sodium bisulfite with 5 percent of acrylamide by mass and tetramethylethylenediamine with 2 percent of acrylamide by mass into the casting solution prepared in the step a), stirring and dispersing uniformly, pouring the solution onto a dry and clean glass plate immediately, scraping into a liquid film with uniform thickness by using a film scraping rod with the thickness of 3000 mu m, and carrying out N-phase separation on the liquid film2Carrying out ultraviolet irradiation for 30min under protection to initiate acrylamide polymerization to obtain a chemically crosslinked gel film;
c) soaking the chemically crosslinked gel membrane obtained in the step b) and the glass plate into the calcium chloride solution with gradient concentration obtained in the step a), soaking for 2h under each gradient concentration, removing the gel membrane from the glass plate in the soaking process, fully and uniformly reacting calcium chloride and sodium alginate to form calcium alginate hydrogel with an ionic crosslinking network structure, and reacting calcium chloride and sodium silicate to generate calcium silicate nano particles in situ in the polyacrylamide/calcium alginate hydrogel to obtain a calcium silicate-containing gel membrane;
d) preparing a gluconic acid-lactone aqueous solution with the mass percentage concentration of 10%, soaking the calcium silicate-containing gel film obtained in the step c) in the gluconic acid-lactone aqueous solution for 24 hours, hydrolyzing the gluconic acid-lactone to release hydrogen ions, and reacting the hydrogen ions with calcium silicate to form a mesoporous silica gel structure on the surface of calcium silicate nano particles to obtain the hydrogel keeping high strength in a physiological environment; the mesoporous silica gel, calcium alginate and polyacrylamide have hydrogen bond interaction, and the enhancement effect of the nano particles improves the mechanical stability and the swelling resistance of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
Example 3.
a) Weighing 1g of sodium silicate, 1g of acrylamide, 1g of sodium alginate and N, N '-methylene bisacrylamide with the mass percent of the acrylamide being 0.10%, dissolving the sodium silicate, the acrylamide and the N, N' -methylene bisacrylamide in 60ml of deionized water, standing and defoaming to obtain a membrane casting solution, and placing the membrane casting solution in an aseptic container for later use; preparing calcium chloride aqueous solution with gradient concentration for later use, wherein the mass percentage concentration of the calcium chloride is respectively 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2.5% and 5.0% from low to high;
b) adding ammonium persulfate with the mass percent of acrylamide of 1 percent, sodium bisulfite with the mass percent of acrylamide of 1 percent and tetramethylethylenediamine with the mass percent of acrylamide of 1 percent into the casting solution prepared in the step a), stirring and dispersing uniformly, pouring the solution onto a dry and clean glass plate immediately, scraping the solution into a liquid film with uniform thickness by using a film scraping rod with the thickness of 100 mu m, and scraping the liquid film into a liquid film with uniform thickness by using N2Carrying out ultraviolet irradiation for 10min under protection to initiate acrylamide polymerization to obtain a chemically crosslinked gel film;
c) soaking the chemically crosslinked gel membrane obtained in the step b) and the glass plate into the calcium chloride solution with gradient concentration obtained in the step a), soaking for 1h under each gradient concentration, removing the gel membrane from the glass plate in the soaking process, fully and uniformly reacting calcium chloride and sodium alginate to form calcium alginate hydrogel with an ionic crosslinking network structure, and reacting calcium chloride and sodium silicate to generate calcium silicate nano particles in situ in the polyacrylamide/calcium alginate hydrogel to obtain a calcium silicate-containing gel membrane;
d) preparing 1% by mass of a gluconic acid-lactone aqueous solution, soaking the calcium silicate-containing gel film obtained in the step c) in the gluconic acid-lactone aqueous solution for 1h, hydrolyzing the gluconic acid-lactone to release hydrogen ions, and reacting the hydrogen ions with calcium silicate to form a mesoporous silica gel structure on the surface of calcium silicate nanoparticles to obtain the hydrogel keeping high strength in a physiological environment; the mesoporous silica gel, calcium alginate and polyacrylamide have hydrogen bond interaction, and the enhancement effect of the nano particles improves the mechanical stability and the swelling resistance of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
Example 4.
a) Weighing 0.5g of sodium silicate, 8g of acrylamide, 1.5g of sodium alginate and diisocyanate with the mass percent of the acrylamide being 0.15%, dissolving the sodium silicate, the acrylamide and the diisocyanate in 90ml of deionized water, standing and defoaming to obtain a membrane casting solution, and placing the membrane casting solution in an aseptic container for later use; preparing calcium chloride aqueous solution with gradient concentration for later use, wherein the mass percentage concentration of the calcium chloride is respectively 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2.5% and 5.0% from low to high;
b) adding ammonium persulfate with the mass percent of acrylamide of 0.5 percent, sodium bisulfite with the mass percent of acrylamide of 0.5 percent and tetramethylethylenediamine with the mass percent of acrylamide of 0.02 percent into the casting solution prepared in the step a), stirring and dispersing uniformly, pouring the solution onto a dry and clean glass plate immediately, scraping into a liquid film with uniform thickness by using a film scraping rod with the thickness of 500 mu m, and performing N-phase separation on the liquid film2Carrying out ultraviolet irradiation for 5min under protection to initiate acrylamide polymerization to obtain a chemically crosslinked gel film;
c) soaking the chemically crosslinked gel membrane obtained in the step b) and the glass plate into the calcium chloride solution with gradient concentration obtained in the step a), soaking for 0.5h under each gradient concentration, removing the gel membrane from the glass plate in the soaking process, fully and uniformly reacting calcium chloride and sodium alginate to form calcium alginate hydrogel with an ion crosslinked network structure, and reacting calcium chloride and sodium silicate to generate calcium silicate nano particles in situ in the polyacrylamide/calcium alginate hydrogel to obtain a calcium silicate-containing gel membrane;
d) preparing a gluconic acid-lactone aqueous solution with the mass percentage concentration of 0.5%, soaking the calcium silicate-containing gel film obtained in the step c) in the gluconic acid-lactone aqueous solution for 5 hours, hydrolyzing the gluconic acid-lactone to release hydrogen ions, and reacting the hydrogen ions with calcium silicate to form a mesoporous silica gel structure on the surface of calcium silicate nano particles to obtain the hydrogel keeping high strength in a physiological environment; the mesoporous silica gel, calcium alginate and polyacrylamide have hydrogen bond interaction, and the enhancement effect of the nano particles improves the mechanical stability and the swelling resistance of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
Claims (2)
1. A preparation method of hydrogel keeping high strength in physiological environment is characterized by comprising the following steps:
a) weighing 0.005-2g of sodium silicate, 5-15g of acrylamide, 0.5-2g of sodium alginate and 0.03-0.30% of chemical cross-linking agent in mass percent of acrylamide, dissolving the sodium silicate, the acrylamide and the chemical cross-linking agent in 50-100ml of deionized water, standing and defoaming to obtain a membrane casting solution, and placing the membrane casting solution in an aseptic container for later use; preparing calcium chloride aqueous solution with gradient concentration for later use, wherein the mass percentage concentration of the calcium chloride is respectively 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2.5% and 5.0% from low to high;
b) adding ammonium persulfate with the mass percent of acrylamide of 0.1-5%, sodium bisulfite with the mass percent of acrylamide of 0.1-5% and tetramethylethylenediamine with the mass percent of acrylamide of 0.01-2% into the casting solution prepared in the step a), stirring and dispersing uniformly, pouring the solution onto a dry and clean glass plate immediately, scraping into a liquid film with uniform thickness by using a film scraping rod with the thickness of 10-3000 mu m, and performing N-phase separation on the liquid film2Under protection, ultraviolet irradiation is carried out for 1-30min to initiate acrylamide polymerization, and a chemically crosslinked gel film is obtained;
c) soaking the chemically crosslinked gel membrane obtained in the step b) and the glass plate into the calcium chloride solution with gradient concentration obtained in the step a), soaking for 0.1-2h under each gradient concentration, removing the gel membrane from the glass plate in the soaking process, fully and uniformly reacting calcium chloride and sodium alginate to form calcium alginate hydrogel with an ion crosslinked network structure, and reacting the calcium chloride and sodium silicate to generate calcium silicate nano particles in situ in the polyacrylamide/calcium alginate hydrogel to obtain a calcium silicate-containing gel membrane;
d) preparing a gluconic acid-lactone aqueous solution with the mass percentage concentration of 0.1-10%, soaking the calcium silicate-containing gel film obtained in the step c) in the gluconic acid-lactone aqueous solution for 0.1-24h, hydrolyzing the gluconic acid-lactone to release hydrogen ions, and reacting the hydrogen ions with calcium silicate to form a mesoporous silica gel structure on the surface of calcium silicate nanoparticles to obtain a hydrogel keeping high strength in a physiological environment; the mesoporous silica gel, calcium alginate and polyacrylamide have hydrogen bond interaction, and the enhancement effect of the nano particles improves the mechanical stability and the swelling resistance of the polyacrylamide/calcium alginate hydrogel in a physiological environment.
2. The method for preparing a hydrogel that maintains high strength under physiological conditions according to claim 1, wherein the chemical crosslinking agent is any one or a mixture of two or more of ethylene glycol dimethacrylate, divinylbenzene and N, N' -methylenebisacrylamide.
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