CN110643056A - High-strength polyvinyl alcohol gel and preparation method and application thereof - Google Patents
High-strength polyvinyl alcohol gel and preparation method and application thereof Download PDFInfo
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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
- C08J3/075—Macromolecular gels
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- C—CHEMISTRY; METALLURGY
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- 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
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/34—Materials or treatment for tissue regeneration for soft tissue reconstruction
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- C08J2329/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal, or ketal radical; Hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Derivatives of such polymer
- C08J2329/02—Homopolymers or copolymers of unsaturated alcohols
- C08J2329/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
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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
- C08K5/00—Use of organic ingredients
- C08K5/04—Oxygen-containing compounds
- C08K5/15—Heterocyclic compounds having oxygen in the ring
- C08K5/151—Heterocyclic compounds having oxygen in the ring having one oxygen atom in the ring
- C08K5/1515—Three-membered rings
Abstract
The invention relates to a high-strength polyvinyl alcohol gel and a preparation method and application thereof. The method for preparing the high-strength polyvinyl alcohol gel comprises the following steps: a) carrying out crosslinking reaction on a polyvinyl alcohol aqueous solution in the presence of a crosslinking agent and a catalyst to obtain polyvinyl alcohol primary gel; b) repeatedly freezing and melting the polyvinyl alcohol primary gel to obtain polyvinyl alcohol gel; the cross-linking agent is selected from multi-epoxy compounds; the mass ratio of the cross-linking agent to the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 0.001-5: 1. The chemical crosslinking of the multi-element epoxy compound not only ensures the biological safety of the polyvinyl alcohol gel, but also provides powerful guarantee for the flexibility and the stability of the polyvinyl alcohol gel; the chemical crosslinking is combined with the physical crosslinking of freeze-thaw cycle, so that the obtained polyvinyl alcohol gel has more excellent mechanical property, better strength, flexibility and stability, and is more favorable for meeting the application requirements of the polyvinyl alcohol gel in the aspect of artificial cartilage or soft tissue.
Description
Technical Field
The invention relates to the field of materials and biological materials, in particular to high-strength polyvinyl alcohol gel and a preparation method and application thereof.
Background
The injury and lesion of the articular cartilage are common diseases in clinical orthopedics department, and the articular cartilage has extremely limited self-repairing capability, so that once the injury or lesion occurs, the articular cartilage is difficult to self-heal, and cartilage replacement is necessary. Clinically, the artificial total joint replacement is widely applied, and the clinical achievement of the artificial total joint replacement enables osteoarthropathy patients to benefit seriously, but various surgical complications also exist. At present, commonly used metal and ultrahigh molecular weight polyethylene counter-grinding joint prosthesis, silicon rubber and polyurethane joint cushion materials have the defects of easy abrasion and loosening, poor interface lubricity, easy aging and the like.
In recent years, polyvinyl alcohol (PVA) hydrogel with good biocompatibility and mechanical properties is considered as a more ideal artificial cartilage implant material, and the greatest defect of common PVA hydrogel in cartilage replacement is insufficient mechanical properties, and the mechanical strength of the gel is generally enhanced by crosslinking.
The conventional crosslinking methods are mainly classified into physical crosslinking and chemical crosslinking. Physical cross-linking is mainly a gel formed by the action of secondary bonds such as intermolecular entanglement, hydrogen bonds, ionic bonds, hydrophobic interactions, and biospecific recognition. Chinese patent CN106552286A discloses a method for preparing HA (nano-hydroxyapatite) -PVA artificial cartilage, which comprises the steps of firstly preparing a three-dimensional network-shaped pore scaffold by using an organic polymer material, then mechanically mixing HA powder and PVA, performing reverse molding on a composite solution in the pore scaffold, then performing freeze-thaw cycle, and selectively dissolving the pore scaffold by using a solvent to obtain the artificial cartilage; chinese patent CN106039418A discloses a preparation method of a gradient HA-PVA artificial cartilage material, which comprises the steps of injecting HA-PVA solution into an artificial cartilage mould I, carrying out freeze-thaw cycle to form primarily crosslinked HA-PVA hydrogel, then placing the HA-PVA hydrogel into a mould II (the size of the mould II is larger than that of the artificial cartilage mould I), injecting hot PLGA (poly (glycolide-lactide) -HA-PVA solution, and carrying out freeze-thaw again to obtain the artificial cartilage. The methods are all physical crosslinking methods, which can effectively improve the mechanical strength of the gel to a certain extent, but the physical crosslinking has the following disadvantages: firstly, physical crosslinking is greatly influenced by concentration, and cannot be formed under the condition of low concentration; secondly, during physical crosslinking, the shrinkage rate before and after molding is large, and the size control of the product during later large-scale production is influenced to a certain extent; thirdly, the mechanical properties of physical cross-linking can reach the cartilage level, but the mechanical properties still need to be enhanced in practical application. Therefore, the polyvinyl alcohol cartilage substitute formed purely by physical crosslinking has failed to meet the current requirements in cartilage implantation, and there is still room for improvement in mechanical properties.
The chemical crosslinking method is mainly to form a three-dimensional network structure through covalent bond crosslinking, and commonly used crosslinking agents include boric acid (or borax), aldehydes, heavy metal salts capable of forming gel through coordination and complexation, and the like. Chinese patent CN105885064A discloses a method for preparing hydrogel by using boride chemical cross-linked polyvinyl alcohol, and chinese patent CN106750396A discloses a method for preparing hydrogel by using glutaraldehyde chemical cross-linked polyvinyl alcohol. The addition of the cross-linking agent greatly improves the mechanical property of the gel, but the disadvantages of chemical cross-linking are not few: firstly, the toughness of gel formed by chemical crosslinking is insufficient, and the gel is easy to break after repeated compression; secondly, when a boron-containing crosslinking agent or a heavy metal crosslinking agent is used, release of boron or heavy metal in a long-term implantation process cannot be avoided, and certain biological toxicity can be caused. Therefore, the polyvinyl alcohol cartilage substitute formed by pure chemical crosslinking cannot meet the requirements of the current cartilage or soft tissue implantation, and has room for improvement in the aspect of mechanical properties.
In order to further improve the mechanical properties, the requirements can only be met by combining chemical crosslinking with physical crosslinking. For the double-crosslinking method, chinese patent CN105327382A discloses a method for preparing medical transparent polyvinyl alcohol hydrogel by using a double-crosslinking method of freezing crosslinking and borax chemical crosslinking, but borax introduced in the patent has certain biotoxicity, so that there is a risk of excessive release of boron in the long-time implantation process, and since borax and polyvinyl alcohol are crosslinked to form a ring structure, the rigidity of the crosslinking site is too large, and the toughness is insufficient, so that the gel cannot meet the requirement of cartilage implantation. Therefore, the polyvinyl alcohol gel prepared by the prior art still has obvious defects in the aspects of effectiveness, safety and quality controllability when being used as an artificial cartilage or soft tissue implant material.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The first purpose of the invention is to provide a method for preparing high-strength polyvinyl alcohol gel, wherein the method adopts a multi-epoxy compound to carry out chemical crosslinking on polyvinyl alcohol, combines physical crosslinking of freeze-thaw cycle, endows the obtained polyvinyl alcohol gel with more excellent mechanical properties, better strength, flexibility and stability, and is more favorable for meeting the application requirements of the polyvinyl alcohol gel in the aspect of artificial cartilage or soft tissue.
It is a second object of the present invention to provide a high strength polyvinyl alcohol gel prepared according to the above method.
The third purpose of the invention is to provide the application of the high-strength polyvinyl alcohol gel in the aspect of biological materials.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
a method of making a high strength polyvinyl alcohol gel comprising the steps of:
a) carrying out crosslinking reaction on a polyvinyl alcohol aqueous solution in the presence of a crosslinking agent and a catalyst to obtain polyvinyl alcohol primary gel;
b) repeatedly freezing and melting the polyvinyl alcohol primary gel to obtain polyvinyl alcohol gel;
the cross-linking agent is selected from multi-epoxy compounds;
the mass ratio of the cross-linking agent to the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 0.001-5: 1.
In the prior art, cross-linking site positions formed when a multi-aldehyde cross-linking agent or boric acid (or borax) is used for cross-linking have rigid five-membered ring or six-membered ring structures, so that the toughness of polyvinyl alcohol gel is insufficient. In the technical scheme of the invention, the polyepoxy compound is adopted to chemically crosslink the polyvinyl alcohol, and the advantages are as follows: (1) the poly-epoxy compound is used as a cross-linking agent, so that the application of toxic elements such as boron, heavy metal and the like in the prior art is avoided, and the biological safety of the polyvinyl alcohol gel is ensured; (2) an ether bond structure formed after the addition reaction of epoxy and hydroxyl in the multi-epoxy compound is a single bond and is not easy to break, and powerful guarantee is provided for the flexibility and the stability of the polyvinyl alcohol gel.
In the present invention, after crosslinking with a polyepoxy compound, physical crosslinking of a freeze-thaw cycle is performed. Due to the rotatability (single bond can rotate) and flexibility of the ether bond, the existence of the crosslinking site does not influence the winding process of a polyvinyl alcohol molecular chain in a freeze-thaw cycle, and under the combined action of molecular winding and chemical crosslinking, the mechanical property of the polyvinyl alcohol gel can be further enhanced, and the polyvinyl alcohol gel has the advantages of wear resistance, pressure resistance and strong toughness, and is more favorable for meeting the application requirements of the polyvinyl alcohol gel in the aspect of artificial cartilage or soft tissue.
Optionally, the multi-epoxy compound is selected from at least one of 1, 4-butanediol diglycidyl ether (BDDE), 1,2,3, 4-diepoxybutane, 1,2,7, 8-Diepoxyoctane (DEO), trimethylolpropane triglycidyl ether and pentaerythritol tetraglycidyl ether.
Optionally, the concentration of the aqueous polyvinyl alcohol solution is 1 wt.% to 60 wt.%.
In the present invention, the method for preparing the aqueous solution of polyvinyl alcohol comprises: dissolving polyvinyl alcohol in water at 80-95 deg.c while stirring to obtain water solution of polyvinyl alcohol.
Optionally, the weight average molecular weight of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 10-2000 kDa, the molecular weight distribution is 1.0-3.0, and the alcoholysis degree is 80.0-99.9%.
Optionally, the catalyst is selected from basic compounds.
Optionally, the basic compound is selected from the group consisting of hydroxides and/or carbonates of alkali metals.
Optionally, the alkaline compound is selected from at least one of sodium hydroxide or potassium hydroxide.
Optionally, the mass ratio of the catalyst to the cross-linking agent is 0.01-10: 1.
Optionally, the temperature of the crosslinking reaction is 0-90 ℃ and the time is 6-72 h.
Optionally, the repeated freeze-thaw process comprises:
freezing the polyvinyl alcohol initial gel at-70 to-5 ℃ for 4 to 20 hours, taking out the polyvinyl alcohol initial gel, and unfreezing the polyvinyl alcohol initial gel at 1 to 50 ℃ for 20min to 4 hours; repeating the above operation 3-10 times.
Optionally, the repeated freeze-thaw process comprises:
placing the polyvinyl alcohol primary gel in liquid nitrogen for quick freezing for 1 min-5 min, then transferring to-70 ℃ to-5 ℃ for continuous freezing for 4 h-20 h, taking out and unfreezing for 20 min-4 h at 1 ℃ to 50 ℃; repeating the above operation 3-10 times.
Optionally, after performing the repeated freeze-thaw treatment, the method further comprises a washing step;
the washing step comprises: soaking the polyvinyl alcohol gel subjected to repeated freezing and thawing treatment in water for 12-36 h, preferably 24 h; and then soaking in a phosphate buffer solution with the pH value of 1.0-7.0 for 12-36 h, preferably 24 h.
Optionally, the method further comprises a pre-treatment step prior to performing the crosslinking reaction;
the pretreatment step comprises: and uniformly stirring the mixture of the cross-linking agent, the catalyst and the polyvinyl alcohol aqueous solution, centrifuging to remove bubbles, and then placing in a mold for sealing.
As an embodiment, a method of preparing a high strength polyvinyl alcohol gel includes the steps of:
a) adding polyvinyl alcohol particles into water, heating, stirring and dissolving to prepare a polyvinyl alcohol aqueous solution with a certain concentration;
b) adding a cross-linking agent and a catalyst into a polyvinyl alcohol aqueous solution, uniformly stirring, centrifuging at a high speed to remove bubbles, filling into a fixed mold, and carrying out chemical cross-linking reaction after sealing;
c) after the chemical crosslinking reaction is finished, taking out the polyvinyl alcohol gel, and carrying out physical crosslinking by a repeated freezing and thawing method;
d) and washing the frozen and unfrozen polyvinyl alcohol sample to remove the catalyst and the residual cross-linking agent, thereby obtaining the high-strength polyvinyl alcohol gel.
As a specific embodiment, the method for preparing a high strength polyvinyl alcohol gel comprises the steps of:
a) dissolving polyvinyl alcohol in water at 80-95 ℃ to prepare a polyvinyl alcohol solution with the concentration of 1-60 wt.%;
b) adding a cross-linking agent and a catalyst into a polyvinyl alcohol aqueous solution; wherein the mass ratio of the crosslinking agent to the solid content of polyvinyl alcohol in the solution is 0.001-5: 1, the mass ratio of the catalyst to the crosslinking agent is 0.01-10: 1, the mixture is uniformly stirred, centrifuged at high speed to remove bubbles, filled into a fixed mold, sealed and placed into a temperature of 0-90 ℃ for reaction for 6-72 hours;
c) after the chemical crosslinking reaction is finished, taking out the polyvinyl alcohol gel, and freezing by adopting two different modes: one is that the gel is directly put into an environment with the temperature of minus 70 ℃ to minus 5 ℃ for freezing for 4h to 20h, then the gel is taken out and unfrozen for 20min to 4h at the temperature of 1 ℃ to 50 ℃, and freeze thawing is carried out for 3 to 10 times repeatedly; the other is that the gel is quickly frozen for 1min to 5min by liquid nitrogen, then is continuously frozen for 4h to 20h in an environment with the temperature of minus 70 ℃ to minus 5 ℃, is taken out and is unfrozen for 20min to 4h at the temperature of 1 ℃ to 50 ℃, and is repeatedly frozen and thawed for 3 to 10 times;
d) and washing the frozen and unfrozen polyvinyl alcohol gel sample by using a phosphoric acid buffer solution with the pH value of 1.0-7.0 to remove the catalyst and the residual cross-linking agent, thereby obtaining the double-cross-linked polyvinyl alcohol gel.
According to another object of the present invention, there is also provided a high-strength polyvinyl alcohol gel prepared according to any one of the above-mentioned methods.
According to another object of the present invention, there is also provided the use of any one of the high strength polyvinyl alcohol gels described above in biomaterials.
Optionally, the biomaterial is selected from an artificial soft tissue material and/or an artificial cartilage material.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the method for preparing the high-strength polyvinyl alcohol gel, provided by the invention, the polyvinyl alcohol is subjected to chemical crosslinking by adopting the multi-epoxy compound, and the physical crosslinking of freeze-thaw cycle is combined, so that the obtained polyvinyl alcohol gel has more excellent mechanical property, better strength, flexibility and stability, and is more favorable for meeting the application requirements of the polyvinyl alcohol gel in the aspect of artificial cartilage or soft tissue.
(2) According to the method for preparing the high-strength polyvinyl alcohol gel, the multi-epoxy compound is used as the cross-linking agent, so that the application of toxic elements such as boron, heavy metal and the like in the prior art is avoided, and the biological safety of the polyvinyl alcohol gel is guaranteed; an ether bond structure formed after the addition reaction of epoxy and hydroxyl in the multi-epoxy compound is a single bond and is not easy to break, and powerful guarantee is provided for the flexibility and the stability of the polyvinyl alcohol gel.
(3) According to the method for preparing the high-strength polyvinyl alcohol gel, after the polyepoxy compound is adopted for crosslinking, the physical crosslinking of freeze-thaw cycle is carried out, and under the combined action of the winding process and the chemical crosslinking of a polyvinyl alcohol molecular chain in the freeze-thaw cycle, the mechanical property of the polyvinyl alcohol gel is further enhanced, and the polyvinyl alcohol gel is wear-resistant, pressure-resistant and high in toughness.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a graph of polyvinyl alcohol gel stress versus compression displacement in accordance with one embodiment of the present invention;
FIG. 2 is a graph of polyvinyl alcohol gel stress versus compression displacement according to another embodiment of the present invention;
FIG. 3 is a graph of gel stress versus compression displacement for physically crosslinked polyvinyl alcohol in a comparative example of the present invention;
FIG. 4 is a graph showing the relationship between gel stress and compression displacement of chemically crosslinked polyvinyl alcohol in a comparative example of the present invention.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
EXAMPLE 1 preparation of polyvinyl alcohol gel
The polyvinyl alcohol (PVA) used in this example was obtained from Aladdin and had a weight average molecular weight of 120kDa, a molecular weight distribution of 1.5 and a degree of alcoholysis of 99.4%.
1#Polyvinyl alcohol gel
1) Preparation of aqueous PVA solution: weighing 25g of PVA into a 250mL three-neck flask, adding 100mL of purified water, placing the flask into a water bath kettle at 95 ℃, heating and stirring until the PVA is completely dissolved to obtain a PVA aqueous solution for later use;
2) chemical crosslinking: weighing 15g of PVA aqueous solution in a 100mL beaker, adding 1.5mL of NaOH solution (15.0 wt.%) into the PVA aqueous solution, stirring uniformly, adding 60mg of BDDE, continuously stirring uniformly, filling into a mold, sealing, and placing a PVA sample in a 25 ℃ water bath kettle for chemical crosslinking for 24 hours;
3) physical crosslinking: chemically crosslinking in a water bath for 24h, taking out, rapidly freezing in liquid nitrogen (-196 deg.C) for 1min, freezing in a refrigerator at-20 deg.C for 4h, thawing at 25 deg.C for 2h, and repeatedly freezing and thawing for 6 times to complete physical crosslinking;
4) washing: putting the PVA sample subjected to freezing-unfreezing circulation into purified water, and soaking for 24 hours; then the sample is soaked in phosphate buffer solution with pH 6.5 for 24h, and finally the sample is taken out and recorded as 1#Polyvinyl alcohol gel.
2#Polyvinyl alcohol gel
2#Process for preparing polyvinyl alcohol gel and 1#Polyvinyl alcohol gels are approximately the same except that:
the physical crosslinking method comprises the following steps: and chemically crosslinking in a water bath for 24h, taking out, freezing in a refrigerator at-20 ℃ for 12h, taking out from the refrigerator, unfreezing at 25 ℃ for 2h, putting in the refrigerator again, and repeatedly performing 6 times of cyclic freezing-unfreezing to complete physical crosslinking.
3#Polyvinyl alcohol gel
3#Process for preparing polyvinyl alcohol gel and 1#Polyvinyl alcohol gels are approximately the same except that:
the addition amount of the NaOH solution is 2.5 mL; the dosage of the BDDE is 150 mg;
the physical crosslinking method comprises the following steps: and chemically crosslinking in a water bath for 24h, taking out, freezing in a refrigerator at-20 ℃ for 8h, taking out from the refrigerator, unfreezing at 25 ℃ for 2h, putting in the refrigerator again, and repeatedly performing 6 times of cyclic freezing-unfreezing to complete physical crosslinking.
4#Polyvinyl alcohol gel
4#Process for preparing polyvinyl alcohol gel and 1#Polyvinyl alcohol gels are approximately the same except that:
the chemical cross-linking agent is 1,2,3, 4-diepoxybutane; the catalyst is KOH;
the temperature of chemical crosslinking is 90 ℃, and the time is 6 h;
in the washing step, the pH of the phosphate buffer solution was 1.0.
Comparative example 1
C1#Polyvinyl alcohol gel
C1#Process for the preparation of polyvinyl alcohol gel and the invention of example 1#Polyvinyl alcohol gels are approximately the same except that:
the chemical crosslinking of step 2) is not carried out; the washing step is not soaked in phosphate buffer solution.
C2#Polyvinyl alcohol gelGlue
C2#Process for the preparation of polyvinyl alcohol gel and the invention of example 1#Polyvinyl alcohol gels are approximately the same except that: the physical crosslinking of step 3) is not performed.
C3#Polyvinyl alcohol gel
1) Preparation of aqueous PVA solution: weighing 25g of PVA into a 250mL three-neck flask, adding 100mL of purified water, placing the flask into a water bath kettle at 95 ℃, heating and stirring until the PVA is completely dissolved to obtain a PVA aqueous solution for later use;
2) preparing a borax water solution: dissolving 1g of borax in 100mL of purified water, and stirring to completely dissolve the borax to obtain a borax water solution for later use;
3) chemical crosslinking: placing 15g of PVA aqueous solution in a beaker, adding 15g of borax aqueous solution, slowly stirring to fully crosslink the PVA aqueous solution with the borax aqueous solution, filling the mixture into a mold, sealing, and placing a PVA sample in a 25 ℃ water bath kettle for chemical crosslinking for 24 hours;
4) physical crosslinking: chemically crosslinking in a water bath for 24h, taking out, rapidly freezing in liquid nitrogen (-196 deg.C) for 1min, freezing in a refrigerator at-20 deg.C for 4h, thawing at 25 deg.C for 2h, and repeatedly freezing and thawing for 6 times to complete physical crosslinking;
5) washing: putting the PVA sample subjected to freezing-unfreezing circulation into purified water, and soaking for 24 hours; then the sample is soaked in phosphate buffer solution with pH value of 6.5 for 24h, and finally the sample is taken out and is marked as C3#Polyvinyl alcohol gel.
Experimental example 1 unconfined compression modulus of polyvinyl alcohol gel
With 1 prepared in inventive example 1#Polyvinyl alcohol gel, 2#Polyvinyl alcohol gel, C1 prepared in comparative example#Polyvinyl alcohol gel and C2#Polyvinyl alcohol gel is typical, and unconfined compressive modulus is detected by an electronic universal tensile machine device of UTM6202 type. The method comprises the following specific steps:
making the above sample into cylindrical polyethylene with diameter of 0.85cm and height of 1cmEnol gel, detecting unconfined compression modulus; detection conditions are as follows: the compression speed is 50mm/min, and the maximum deformation is 60%. 1 prepared in example 1#Polyvinyl alcohol gel, 2#Polyvinyl alcohol gel, C1 prepared in comparative example#Polyvinyl alcohol gel and C2#The graphs of the relationship between the stress and the compressive displacement of the three polyvinyl alcohol gels are shown in fig. 1, fig. 2, fig. 3 and fig. 4.
The results of the unconfined compression modulus measurements are listed in table 1.
TABLE 1 unconfined compression modulus test results for polyvinyl alcohol gels
From the above-mentioned unconfined compression modulus test results, it was found that the double crosslinked polyvinyl alcohol gel (1)#) The unconfined compression modulus can reach 3.51MPa, and the single physical crosslinked polyvinyl alcohol gel (C1)#) When the deformation reaches 58.3 percent, the material is crushed, the maximum unconfined compression modulus before crushing is only 0.60MPa, and the single chemically crosslinked polyvinyl alcohol gel (C2)#) The unconfined compression modulus is up to 1.21 MPa. The results show that the pressure resistance of the gel can be effectively improved by the double-crosslinking method provided by the invention.
From 1 to#Polyvinyl alcohol gel and 2#The unconfined compression modulus detection result of the polyvinyl alcohol gel can find that the double-crosslinked polyvinyl alcohol gel (1) is obtained by a physical crosslinking mode of rapidly freezing in liquid nitrogen (-196 ℃) for 1min, continuously freezing in a refrigerator at the temperature of-20 ℃ for 4h, unfreezing at the temperature of 25 ℃ for 2h after being taken out of the refrigerator, putting the refrigerator again, and repeatedly performing 6 times of circulating freezing-unfreezing#) The unconfined compression modulus can reach 3.51MPa, and the double-crosslinked polyvinyl alcohol gel (2) is obtained by a physical crosslinking mode of freezing for 12h in a refrigerator at the temperature of-20 ℃, unfreezing for 2h at the temperature of 25 ℃ after being taken out of the refrigerator, putting the refrigerator again, and repeatedly freezing and unfreezing for 6 times#) The unconfined compressive modulus was 2.99 MPa. The results show that the former physical crosslinking mode results in a double-crosslinked gel compared with the latterThe unconfined compression modulus can be improved by about 17 percent.
Experimental example 2 unconfined cycle compression of polyvinyl alcohol gel
With 1 prepared in inventive example 1#Polyvinyl alcohol gel, C3 prepared in comparative example 2#Polyvinyl alcohol gel is typical, and UTM6202 electronic universal tensile machine equipment is used to detect unconfined cyclic compression. The method comprises the following specific steps:
preparing the sample into cylindrical polyvinyl alcohol gel with the diameter of 0.85cm and the height of 1cm, and detecting the unconfined compression modulus; detection conditions are as follows: the compression speed is 50mm/min, the maximum deformation amount is 60%, the compression is circulated for 10 times, and whether the gel is cracked or not is observed. 1 prepared in example 1#Polyvinyl alcohol gel, C3 prepared in comparative example 1#The results of the unconfined cycle compression test for both polyvinyl alcohol gels are set forth in Table 2.
TABLE 2 unconfined cyclic compression test results for polyvinyl alcohol gels
The result of unconfined cyclic compression detection of the two shows that the BDDE double-crosslinked polyvinyl alcohol gel (1)#) The borax double-crosslinked polyvinyl alcohol gel (C3) can not be cracked after being compressed for 10 times in an unconfined circulation way#) The gel is crushed after being compressed for 4 times, which shows that the brittleness is strong, and the BDDE double-crosslinking method can effectively improve the pressure resistance and the toughness of the gel.
Experimental example 3 shear modulus of polyvinyl alcohol gel
With 1 prepared in inventive example 1#Polyvinyl alcohol gel, C1 prepared in comparative example#Polyvinyl alcohol gel and C2#Polyvinyl alcohol gels are typical and the shear modulus of polyvinyl alcohol gels is measured. The detection method and the preparation method of the sample are carried out according to HG/T3848-2008, measurement of the shear strength of the hard rubber. The results of the tests are shown in Table 3.
TABLE 3 shear modulus of polyvinyl alcohol gels
The shear modulus detection results of the three materials show that the double-crosslinked polyvinyl alcohol gel (1)#) Shear modulus of 0.48MPa, while a single physically cross-linked polyvinyl alcohol gel (C1)#) Shear modulus of only 0.11MPa, chemically crosslinked polyvinyl alcohol gel alone (C2)#) The shear modulus was 0.08 MPa. Therefore, the polyvinyl alcohol gel obtained by the double-crosslinking method can obtain more excellent toughness.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. A method of making a high strength polyvinyl alcohol gel, comprising the steps of:
a) carrying out crosslinking reaction on a polyvinyl alcohol aqueous solution in the presence of a crosslinking agent and a catalyst to obtain polyvinyl alcohol primary gel;
b) repeatedly freezing and melting the polyvinyl alcohol primary gel to obtain polyvinyl alcohol gel;
the cross-linking agent is selected from multi-epoxy compounds;
the mass ratio of the cross-linking agent to the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 0.001-5: 1.
2. The method according to claim 1, wherein the poly-epoxy compound is at least one selected from the group consisting of 1, 4-butanediol diglycidyl ether, 1,2,3, 4-diepoxybutane, 1,2,7, 8-diepoxyoctane, trimethylolpropane triglycidyl ether, and pentaerythritol tetraglycidyl ether.
3. The method according to claim 1, wherein the concentration of the aqueous polyvinyl alcohol solution is 1 wt.% to 60 wt.%;
preferably, the weight average molecular weight of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 10 kDa-2000 kDa, the molecular weight distribution is 1.0-3.0, and the alcoholysis degree is 80.0% -99.9%.
4. The process according to claim 1 or 2, characterized in that the catalyst is selected from basic compounds;
preferably, the basic compound is selected from the group consisting of hydroxides and/or carbonates of alkali metals;
further preferably, the alkaline compound is selected from at least one of sodium hydroxide or potassium hydroxide;
preferably, the mass ratio of the catalyst to the cross-linking agent is 0.01-10: 1.
5. The method according to claim 1, wherein the temperature of the crosslinking reaction is 0 ℃ to 90 ℃ and the time is 6h to 72 h.
6. The method of claim 1, wherein the repeated freeze thaw process comprises:
freezing the polyvinyl alcohol initial gel at-70 to-5 ℃ for 4 to 20 hours, taking out the polyvinyl alcohol initial gel, and unfreezing the polyvinyl alcohol initial gel at 1 to 50 ℃ for 20min to 4 hours; repeating the operation for 3-10 times; or
The repeated freezing and thawing method comprises the following steps:
placing the polyvinyl alcohol primary gel in liquid nitrogen for quick freezing for 1 min-5 min, then transferring to-70 ℃ to-5 ℃ for continuous freezing for 4 h-20 h, taking out and unfreezing for 20 min-4 h at 1 ℃ to 50 ℃; repeating the above operation 3-10 times.
7. The method according to claim 1, wherein after the repeated freeze-thaw treatment, the method further comprises a washing step;
the washing step comprises: soaking the polyvinyl alcohol gel subjected to repeated freezing and thawing treatment in water for 12-36 h, preferably 24 h; and then soaking in a phosphate buffer solution with the pH value of 1.0-7.0 for 12-36 h, preferably 24 h.
8. The method according to claim 1, wherein prior to performing the crosslinking reaction, the method further comprises a pretreatment step;
the pretreatment step comprises: and uniformly stirring the mixture of the cross-linking agent, the catalyst and the polyvinyl alcohol aqueous solution, centrifuging to remove bubbles, and then placing in a mold for sealing.
9. The high-strength polyvinyl alcohol gel produced by the method for producing a high-strength polyvinyl alcohol gel according to any one of claims 1 to 8.
10. Use of the high strength polyvinyl alcohol gel of claim 9 in biomaterials;
preferably, the biomaterial is selected from an artificial soft tissue material and/or an artificial cartilage material.
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