CN116693931B - Super-structure porous wet adhesive hydrogel and preparation method and application thereof - Google Patents
Super-structure porous wet adhesive hydrogel and preparation method and application thereof Download PDFInfo
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- CN116693931B CN116693931B CN202310913469.3A CN202310913469A CN116693931B CN 116693931 B CN116693931 B CN 116693931B CN 202310913469 A CN202310913469 A CN 202310913469A CN 116693931 B CN116693931 B CN 116693931B
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 128
- 230000001070 adhesive effect Effects 0.000 title claims abstract description 60
- 239000000853 adhesive Substances 0.000 title claims abstract description 59
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 33
- 238000000016 photochemical curing Methods 0.000 claims abstract description 24
- 210000004872 soft tissue Anatomy 0.000 claims abstract description 7
- 238000011065 in-situ storage Methods 0.000 claims abstract description 6
- -1 quaternary ammonium cations Chemical class 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 48
- 239000000499 gel Substances 0.000 claims description 41
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 21
- 239000000178 monomer Substances 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 14
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 13
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 13
- 239000008367 deionised water Substances 0.000 claims description 13
- 229910021641 deionized water Inorganic materials 0.000 claims description 13
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 10
- 239000012711 adhesive precursor Substances 0.000 claims description 9
- 239000003431 cross linking reagent Substances 0.000 claims description 9
- VXSASNNBOYCZMY-UHFFFAOYSA-M ethenyl-dimethyl-(2-phenylethyl)azanium;chloride Chemical compound [Cl-].C=C[N+](C)(C)CCC1=CC=CC=C1 VXSASNNBOYCZMY-UHFFFAOYSA-M 0.000 claims description 9
- 230000007547 defect Effects 0.000 claims description 7
- 238000007605 air drying Methods 0.000 claims description 6
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- 238000006136 alcoholysis reaction Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 230000008439 repair process Effects 0.000 claims description 5
- 238000011068 loading method Methods 0.000 claims description 4
- YXMISKNUHHOXFT-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) prop-2-enoate Chemical compound C=CC(=O)ON1C(=O)CCC1=O YXMISKNUHHOXFT-UHFFFAOYSA-N 0.000 claims description 3
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 229960002317 succinimide Drugs 0.000 claims description 3
- RAWPGIYPSZIIIU-UHFFFAOYSA-N [benzoyl(phenyl)phosphoryl]-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)P(=O)(C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 RAWPGIYPSZIIIU-UHFFFAOYSA-N 0.000 claims description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- RRHXZLALVWBDKH-UHFFFAOYSA-M trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CC(=C)C(=O)OCC[N+](C)(C)C RRHXZLALVWBDKH-UHFFFAOYSA-M 0.000 claims description 2
- FXIVKZGDYRLHKF-UHFFFAOYSA-N C(C)OP(OC(C1=C(C=C(C=C1C)C)C)=O)(=O)C1=CC=CC=C1 Chemical compound C(C)OP(OC(C1=C(C=C(C=C1C)C)C)=O)(=O)C1=CC=CC=C1 FXIVKZGDYRLHKF-UHFFFAOYSA-N 0.000 claims 1
- 239000012710 curable adhesive precursor Substances 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract description 151
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract description 151
- 230000008961 swelling Effects 0.000 abstract description 19
- 208000031737 Tissue Adhesions Diseases 0.000 abstract description 17
- 239000010410 layer Substances 0.000 abstract description 14
- 239000012790 adhesive layer Substances 0.000 abstract description 9
- 238000005191 phase separation Methods 0.000 abstract description 9
- 238000005516 engineering process Methods 0.000 abstract description 8
- 230000017423 tissue regeneration Effects 0.000 abstract description 3
- 238000004132 cross linking Methods 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 10
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 9
- 229920002125 Sokalan® Polymers 0.000 description 8
- 230000002265 prevention Effects 0.000 description 8
- 238000002791 soaking Methods 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 7
- ATXASKQIXAJYLM-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;prop-2-enoic acid Chemical compound OC(=O)C=C.ON1C(=O)CCC1=O ATXASKQIXAJYLM-UHFFFAOYSA-N 0.000 description 6
- 238000003848 UV Light-Curing Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000001723 curing Methods 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 239000010453 quartz Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 238000010998 test method Methods 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 3
- 206010000050 Abdominal adhesions Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 210000003815 abdominal wall Anatomy 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000009172 bursting Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000009864 tensile test Methods 0.000 description 2
- XMLYCEVDHLAQEL-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-phenylpropan-1-one Chemical group CC(C)(O)C(=O)C1=CC=CC=C1 XMLYCEVDHLAQEL-UHFFFAOYSA-N 0.000 description 1
- 206010058039 Cardiac perforation Diseases 0.000 description 1
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000002579 anti-swelling effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- NCCDSMDQQJKEBP-UHFFFAOYSA-N prop-2-enoic acid;pyrrolidine-2,5-dione Chemical compound OC(=O)C=C.O=C1CCC(=O)N1 NCCDSMDQQJKEBP-UHFFFAOYSA-N 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000007655 standard test method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003894 surgical glue Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/36—After-treatment
- C08J9/40—Impregnation
- C08J9/405—Impregnation with polymerisable compounds
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0036—Porous materials, e.g. foams or sponges
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- 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
- 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
-
- 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
- C08J2433/00—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 only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2433/04—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 only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
- C08J2433/14—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 only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
Abstract
The application relates to a super-structure porous wet adhesive hydrogel, a preparation method and application thereof, wherein asymmetric porous polyvinyl alcohol (PVA) hydrogel is obtained by moisture-induced phase separation and solvent replacement as a mechanical dissipation layer and an anti-adhesion layer, and then PAAc-N is subjected to in-situ photo-curing technology + The wet adhesive layer is compounded with the loose porous surface of the PVA dissipation layer to obtain the super-structure wet adhesive hydrogel. PAAc-N + The ionic crosslinking between quaternary ammonium cations and carboxylate anions in the wet bond layer and the high crystallinity of the PVA dissipative layer, give PVA/PAAc-N + The hydrogel realizes high-strength wet adhesion and ultra-low swelling rate at the same time; the compact surface of the PVA dissipation layer can effectively prevent tissue adhesion, and the porous surface can promote PAAc-N + Mechanical interlocking of wet bond layer with tough PVA dissipative layer interface, PVA/PAAc-N + The hydrogel has an ultra-high average burst pressure of up to 493 mm Hg; thereby making PVA/PAAc-N + The hydrogel has an attractive application prospect in the aspect of soft tissue repair.
Description
Technical Field
The application relates to the technical field of surgical biomedical materials, in particular to a super-structure porous wet adhesive hydrogel and a preparation method and application thereof.
Background
At present, various soft tissue defects are commonly connected with each other in a stable mode through surgical suturing. However, surgical suturing has drawbacks such as stress concentration at the site of suturing, excessive surgical time, infection, and scar tissue formation. In recent years, wet adhesive hydrogels have been widely used as a potential suture substitute on various wet tissues in the body (heart, stomach, intestinal tract, liver, kidney, abdominal wall, etc.). They are generally used in the form of xerogels, which, while in contact with wet tissue, rapidly absorb the moisture from the tissue surface to form a large number of hydrogen bonds and gradually form covalent bonds to crosslink, thus achieving strong adhesive properties.
At present, various wet adhesive hydrogels have been developed which enable rapid adhesion. However, these efforts have not met the complex clinical application needs. Firstly, the wet adhesive hydrogels often have the problems of high swelling and obviously reduced mechanical strength in the in-vivo wet environment, so that the conditions of high burst pressure requirement of tissues, even adhesive failure and the like cannot be met; second, the double-sided tackiness of wet adhesive hydrogels can also cause severe tissue adhesions (e.g., between the heart and the inner wall of the chest, the intestines and the abdominal wall, etc.). At present, no ideal material is available to deal with both soft tissue attachment and tissue adhesion problems. Therefore, the development of the wet adhesive hydrogel with the characteristics of ultra-low swelling rate, ultra-high burst pressure and tissue adhesion prevention has important significance in expanding the wet adhesive hydrogel in biomedical applications.
Disclosure of Invention
The application aims to overcome the defects in the prior art and provides a super-structure porous wet adhesive hydrogel with the characteristics of ultralow swelling rate, ultrahigh burst pressure and tissue adhesion resistance, and a preparation method and application thereof.
In order to achieve the above purpose, the technical scheme adopted by the application is as follows: provides a super-structure porous moisture adhesive hydrogel which is constructed based on moisture-induced phase separation, solvent replacement and in-situ photo-curing technology and is bio-friendly, and the preparation method comprises the following steps:
(1) Dissolving PVA in an organic solvent to form a PVA solution, and standing in an environment with constant temperature and humidity to obtain PVA organogel;
(2) Immersing the PVA organic gel obtained in the step (1) into an aqueous solution for solvent replacement to obtain PVA hydrogel; the PVA hydrogel has a double-sided asymmetric structure and comprises a loose porous surface and a uniform dense porous surface;
(3) Dissolving acrylic acid, succinimidyl acrylate, a cross-linking agent, a quaternary ammonium salt monomer and a photoinitiator into deionized water according to a proportion, and uniformly mixing to obtain a photo-curing adhesive precursor solution;
(4) And dripping the photo-curing adhesive precursor solution on the loose porous surface of the PVA hydrogel, placing the porous surface of the PVA hydrogel in an oxygen-free environment, performing in-situ photo-curing, immersing the porous surface of the PVA hydrogel in an aqueous solution to wash out unreacted monomers, and then performing partial air drying to obtain the super-structure porous wet adhesive hydrogel with the characteristics of ultralow swelling rate, ultrahigh bursting pressure and tissue adhesion resistance.
Further, the organic solvent is dimethyl sulfoxide DMSO, and the specific operation of the step (1) is as follows: PVA and DMSO were added to a round bottom flask followed by stirring in an oil bath at 70℃for 2 h to complete dissolution, as was done in the examples of the application.
Further, in the PVA solution, the concentration of PVA is 5% -40%, the polymerization degree of PVA is 100% -4500, and the alcoholysis degree is 88% -99%; preferably, the PVA has a polymerization degree of 1700-4500 and an alcoholysis degree of 97-99%, and the asymmetric porous hydrogel with better mechanical strength can be obtained in the range.
Further preferably, the PVA has a degree of polymerization of 1700 and an alcoholysis degree of 99%.
Preferably, the PVA model is PVA-1799.
In a certain range, as the polymerization degree and alcoholysis degree of PVA are increased, the viscosity of PVA/DMSO solution is increased, meanwhile, the solubility of PVA is reduced, and the mechanical strength and uniformity of the finally obtained PVA hydrogel are influenced. In combination, PVA-1799 is preferably used in the present application.
Further, the specific operation of step (1) further includes: an appropriate amount of PVA/DMSO solution was poured into a container and allowed to stand horizontally in an environment of constant temperature and humidity for a period of time.
Further, the side length of the inner bottom surface of the container is 1-15 cm, and the height of the solution is 0.2-5 mm.
Preferably, the side length of the inner bottom surface of the container is 10 cm, and the height of the solution is about 1 mm.
Further, the ambient temperature is 4-40 ℃, and the air humidity is 0-100%.
Preferably, the ambient temperature is 25 ℃ and the air humidity is 70%.
Further, the PVA solution is placed for a time of not less than 2 h; preferably, the time of placement is 12 h.
In a certain range, as the ambient humidity increases, the aggregation of liquid on the surface of the solution is accelerated, and the gel forming speed is also increased; as the temperature increases, the gel becomes more and more porous and the mechanical properties decrease. Considering the cost and the operation difficulty comprehensively, the application preferably has the environment temperature of 25 ℃, the air humidity of 70 percent and the time for placing the adhesive into glue of 12 h.
Further, the specific operation of the step (2) is as follows: the PVA organogel is removed from the container and immersed in a large amount of aqueous solution for solvent replacement.
Further, the aqueous solution used in the step (2) is one of deionized water, physiological saline or PBS buffer solution.
Further, the water temperature of the aqueous solution for solvent replacement is 4-40 ℃, the aqueous solution is replaced every 6-24 hours, and the total time is not less than 48 and h.
Preferably, the water temperature of the aqueous solution used for solvent replacement is 25 ℃, and the total time is 48 h for each 12 h replacement of the aqueous solution.
Within a certain range, the solvent displacement rate increases with increasing solvent temperature, but the mechanical properties of the gel decrease. Meanwhile, the number of solvent exchanges or the total time of solvent exchanges increases, and the organic solvent in the PVA gel is smaller but the solvent consumption increases. In combination, the aqueous solution of the present application preferably used for solvent replacement is replaced every 12, 12 h, the water temperature is 25 ℃, and the total solvent replacement time is 48, 48 h.
Further, the specific operation of the step (3) is as follows: sequentially adding acrylic acid, succinimide acrylic ester, a cross-linking agent, a quaternary ammonium salt monomer and a photoinitiator into deionized water, and uniformly mixing to obtain a photo-curing adhesive precursor solution.
Further, each unit of the photo-curing adhesive precursor solution comprises 1-5 mL of acrylic acid, 50-500 mg of succinimide acrylic ester, 2.5-50 mg of cross-linking agent, 50-1000 mg of quaternary ammonium salt monomer and 50-400 mu L of photoinitiator.
Preferably, each unit of the photo-curing adhesive precursor solution contains 2.85 to mL acrylic acid, 300 to mg succinimide acrylate, 5 to mg cross-linking agent mass, 200 to mg quaternary ammonium salt monomer and 200 mu L photoinitiator.
Further, the cross-linking agent is one or more of Gelma, N-methylene bisacrylamide.
Preferably, the cross-linking agent is N, N-methylenebisacrylamide.
Further, the quaternary ammonium salt is one or more of methacryloxyethyl trimethyl ammonium chloride and benzyl vinyl trimethyl ammonium chloride.
Preferably, the quaternary ammonium salt is benzyl vinyl trimethyl ammonium chloride.
Further, the photoinitiator is one or more of dibenzoyl phenyl phosphine oxide, ethyl 2,4, 6-trimethyl benzoyl phenyl phosphonate and 2-hydroxy-2-methyl-1-phenyl-1-acetone.
Preferably, the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.
Further, the specific operation of the step (4) is as follows: dropping the photo-curing adhesive precursor solution in the step (3) on the loose porous surface of the PVA hydrogel, performing in-situ photo-initiated polymerization in an oxygen-free environment, immersing the composite gel in a large amount of aqueous solution to absorb unreacted monomers, and placing the composite gel in an oven for partial air drying.
Further, the area loading capacity of the precursor solution is 10-100 mu L cm -2 The photo-curing time is 1-120 min.
Preferably, the area loading of the precursor solution is 50. Mu.L cm -2 The photo-curing time was 15 min.
Further, in the step (4), the solvent replacement temperature is 4-40 ℃ and the solvent replacement time is not less than 2 h in the monomer removal process; and the aqueous solution is one of deionized water, physiological saline or PBS buffer solution.
Preferably, the solvent replacement temperature during monomer removal is 25 ℃, the solvent replacement time is 12 h, and the aqueous solution is deionized water.
Further, the oxygen-free environment is specifically any one of an atmosphere of nitrogen, argon, helium, and the like, or a vacuum environment.
Preferably, the anaerobic environment employs a vacuum environment.
Further, in the step (4), the temperature of the environment for air drying of the gel part is 20-80 ℃ and the time is 1-120 min.
Preferably, the air drying environment for the gel part is a forced air oven, the temperature is 60 ℃, and the time is 15 min.
In a certain range, the moisture adhesion performance and the swelling ratio of the adhesive layer are obviously different along with the change of the components of the precursor solution of the photo-curing adhesive and the photo-curing conditions, and the condition that the solution oozes out of the surface of PVA gel or the surface of the PVA gel is not provided with an adhesive layer along with the increase or decrease of the surface loading of the precursor solution. In comprehensive consideration, the application preferably uses precursor solution with the components of acrylic acid, succinimidyl acrylate, N-methylene bisacrylamide, quaternary ammonium salt monomer and photoinitiator of 2.85 mL,300 mg,5 mg,200 mg,200 mu L respectively according to 50 mu L cm -2 Is added dropwise to the rough surface of the PVA gel and is subjected to photocuring under vacuum for 15 minutes.
It is still another object of the present application to provide a super-structured porous wet adhesive hydrogel obtained by the above-mentioned preparation method.
It is a further object of the present application to provide the use of the above-described super-structured porous wet adhesive hydrogels for repair of soft tissue defects including heart, intestine, artery, lung, stomach, peritoneum, liver and kidney, etc.
It is a further object of the present application to provide a wet adhesive for soft tissue defect repair. The super-structure porous wet adhesive hydrogel for tissue repair provided by the application has excellent ultra-low swelling rate, ultra-high burst pressure and tissue adhesion prevention characteristics, and can bear average burst pressure of up to 493 mm Hg.
Compared with the prior art, the application has the beneficial effects that:
(1) The application provides a preparation method of a super-structure porous wet adhesive hydrogel, which adopts the technologies of phase separation based on moisture induction, solvent replacement and in-situ photo-crosslinking to obtain the super-structure porous wet adhesive hydrogel with the characteristics of ultralow swelling rate, ultrahigh bursting pressure and tissue adhesion prevention, and the synthesis method is simple, convenient and efficient.
(2) The super-structure porous wet adhesive hydrogel prepared by the application has excellent anti-swelling performance, has a swelling rate as low as 0.29 under a wet environment, and can maintain stable mechanical properties and adhesive strength in a long-term in-vivo use process.
(3) The super-structure porous wet adhesive hydrogel prepared by the application has single-sided strong adhesiveness and higher pressure-resistant capability, can realize high-strength connection of defect parts, effectively seals high-pressure wound tissues, and simultaneously has the other side of a PVA compact surface, and can effectively prevent tissue adhesion, so that the super-structure porous wet adhesive hydrogel has attractive application prospects in the aspect of tissue repair.
Drawings
FIG. 1 shows a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) according to the present application + ) Is a schematic structural diagram of the (c).
FIG. 2 shows a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) according to the present application + ) Is a schematic diagram of the manufacturing flow.
FIG. 3 is a plot of tensile stress versus strain for PVA hydrogels of example 1 and their cyclic tensile curves at 40% strain.
FIG. 4 is PVA/PAAc-N of example 1 + Wet bond strength histogram of hydrogels.
FIG. 5 shows PAAc hydrogel and PVA/PAAc-N of example 1 + Swelling ratio histogram of hydrogels.
Fig. 6 is a graph of burst pressure test model of hydrogels.
FIG. 7 is a PAAc hydrogel and PVA/PAAc-N of example 1 + Average burst pressure column contrast plot for hydrogels.
FIG. 8 is PVA/PAAc-N of example 1 + CCK-8 assay for hydrogels.
FIG. 9 is a schematic representation of PAAc hydrogel, PVA/PAAc hydrogel, and PVA/PAAc-N of example 1 + Hydrogel was adhered to the liver surface of the rat on day 14 post-operative photograph.
FIG. 10 is a PVA/PAAc-N of example 1 showing PAAc hydrogel + And (3) quantitatively analyzing the abdominal cavity adhesion score of the hydrogel on the surface of the liver of the rat on the 14 th day after operation.
FIG. 11 is PVA/PAAc-N of example 1 + The hydrogel has the effect of repairing pig heart defects.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present application. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
The application will now be further illustrated with reference to specific examples, which are given solely for the purpose of illustration and are not to be construed as limiting the application. The test specimens and test procedures used in the following examples include those (if the specific conditions of the experiment are not specified in the examples, generally according to conventional conditions or according to the recommended conditions of the reagent company; the reagents, consumables, etc. used in the examples described below are commercially available unless otherwise specified).
Example 1
As shown in FIGS. 1-2, the present embodiment provides a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) + ) Is made of (1)As a method, this embodiment is a preferred embodiment. Firstly, constructing PVA hydrogel with double-sided asymmetric structure based on a method of moisture-induced phase separation and solvent replacement, wherein the PVA hydrogel comprises a loose porous surface and a uniform porous surface, and PAAc-N is prepared by a surface photocuring technology + The wet adhesive layer and the loose porous surface of the PVA dissipation layer are compounded together to obtain the super-structure porous wet adhesive hydrogel (PVA/PAAc-N) with the characteristics of super-low swelling rate, super-high burst pressure and excellent tissue adhesion prevention + ) Specifically, the method comprises the following steps:
(1) 1.8. 1.8 g polyvinyl alcohol (PVA-1799) was dissolved in 10 mL dimethyl sulfoxide; pouring the mixed solution into a surface dish (the thickness of the solution is about 1 mm), and placing the solution in moist air (the humidity is 70 percent and the temperature is 25 ℃) to slowly gel 12 h to obtain PVA organogel;
(2) Soaking PVA organic gel in a large amount of deionized water to replace solvent by 48 h, and replacing water every 12 h to obtain PVA hydrogel;
(3) Sequentially adding 300 mg of N-hydroxysuccinimide acrylate, 2.85 mL of acrylic acid, 5 mg of N, N' -methylenebisacrylamide and 5.70 mL of water into a 10 mL test tube, adding 200 mu L of photoinitiator and 200 mg of benzyl vinyl trimethyl ammonium chloride after complete dissolution, shaking uniformly, and marking as a solution A;
(4) PVA hydrogel was placed in a vacuum quartz vessel and solution A was taken at 50. Mu.L cm -2 Is added dropwise to the loose porous face of the PVA gel. After the internal pressure of the vessel was reduced to about 5 kPa using a circulating water vacuum pump (SHZ-D (iii)) and the vessel was sealed, light curing was then performed with a UV curing lamp (48W) for 15 min. The gel was then soaked in a large amount of water to wash out unreacted monomers (co-soak 12 h, water change every 2 h), and baked in a 60℃air oven for 15 min to give PVA/PAAc-N + A hydrogel.
Example 2
As shown in FIGS. 1-2, the present embodiment provides a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) + ) First, a method based on moisture-induced phase separation and solvent replacementPVA hydrogel with double-sided asymmetric structure is constructed by the method, the PVA hydrogel comprises a loose porous surface and a uniform dense porous surface, and PAAc-N is prepared by a surface photocuring technology + The wet adhesive layer and the loose porous surface of the PVA dissipation layer are compounded together to obtain the wet adhesive hydrogel (PVA/PAAc-N) with ultralow swelling rate, ultrahigh burst pressure and excellent tissue adhesion prevention property + ) The method specifically comprises the following steps:
(1) 1.8. 1.8 g polyvinyl alcohol (PVA-1799) was dissolved in 10 mL dimethyl sulfoxide; pouring the mixed solution into a surface dish (the thickness of the solution is about 1 mm), and placing the solution in moist air (the humidity is 100 percent and the temperature is 40 ℃) to slowly gel 12 h to obtain PVA organogel;
(2) Soaking PVA organic gel in a large amount of deionized water to replace solvent by 48 h, and replacing water every 12 h to obtain PVA hydrogel;
(3) Sequentially adding 300 mg of N-hydroxysuccinimide acrylate, 2.85 mL of acrylic acid, 5 mg of N, N' -methylenebisacrylamide and 5.70 mL of water into a 10 mL test tube, adding 200 mu L of photoinitiator and 200 mg of benzyl vinyl trimethyl ammonium chloride after complete dissolution, shaking uniformly, and marking as a solution A;
(4) PVA hydrogel was placed in a vacuum quartz vessel and solution A was taken at 50. Mu.L cm -2 Is added dropwise to the loose porous face of the PVA gel. After the internal pressure of the vessel was reduced to about 5 kPa using a circulating water vacuum pump (SHZ-D (iii)) and the vessel was sealed, light curing was then performed with a UV curing lamp (48W) for 15 min. The gel was then soaked in a large amount of water to wash out unreacted monomers (co-soak 12 h, water change every 2 h), and baked in a 60℃air oven for 15 min to give PVA/PAAc-N + A hydrogel.
Example 3
As shown in FIGS. 1-2, the present embodiment provides a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) + ) Firstly, constructing PVA hydrogel with double-sided asymmetric structure based on a method of moisture-induced phase separation and solvent replacement, wherein the PVA hydrogel comprises a loose porous surface and a uniform dense porous surface, andPAAc-N is cured by surface light + The wet adhesive layer and the loose porous surface of the PVA dissipation layer are compounded together to obtain the wet adhesive hydrogel (PVA/PAAc-N) with ultralow swelling rate, ultrahigh burst pressure and excellent tissue adhesion prevention property + ) The method specifically comprises the following steps:
(1) 1.8. 1.8 g polyvinyl alcohol (PVA-1799) was dissolved in 10 mL dimethyl sulfoxide; pouring the mixed solution into a surface dish (the thickness of the solution is about 1 mm), and placing the solution in moist air (the humidity is 40 percent and the temperature is 10 ℃) to slowly gel 12 h to obtain PVA organogel;
(2) Soaking PVA organic gel in a large amount of deionized water to replace solvent by 48 h, and replacing water every 12 h to obtain PVA hydrogel;
(3) Sequentially adding 300 mg of N-hydroxysuccinimide acrylate, 2.85 mL of acrylic acid, 5 mg of N, N' -methylenebisacrylamide and 5.70 mL of water into a 10 mL test tube, adding 200 mu L of photoinitiator and 200 mg of benzyl vinyl trimethyl ammonium chloride after complete dissolution, shaking uniformly, and marking as a solution A;
(4) PVA hydrogel was placed in a vacuum quartz vessel and solution A was taken at 50. Mu.L cm -2 Is added dropwise to the loose porous face of the PVA gel. After the internal pressure of the vessel was reduced to about 5 kPa using a circulating water vacuum pump (SHZ-D (iii)) and the vessel was sealed, light curing was then performed with a UV curing lamp (48W) for 15 min. The gel was then soaked in a large amount of water to wash out unreacted monomers (co-soak 12 h, water change every 2 h), and baked in a 60℃air oven for 15 min to give PVA/PAAc-N + A hydrogel.
Example 4
As shown in FIGS. 1-2, the present embodiment provides a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) + ) Firstly, constructing PVA hydrogel with double-sided asymmetric structure based on a method of moisture-induced phase separation and solvent replacement, wherein the PVA hydrogel comprises a loose porous surface and a uniform dense porous surface, and PAAc-N is prepared by a surface photocuring technology + The wet adhesive layer and the loose porous surface of the PVA dissipation layer are compounded together to obtainA wet adhesive hydrogel (PVA/PAAc-N) with ultra-low swelling ratio, ultra-high burst pressure and excellent tissue adhesion resistance + ) The method specifically comprises the following steps:
(1) 1.8. 1.8 g polyvinyl alcohol (PVA-1799) was dissolved in 10 mL dimethyl sulfoxide; pouring the mixed solution into a surface dish (the thickness of the solution is about 1 mm), and placing the solution in moist air (the humidity is 70 percent and the temperature is 25 ℃) to slowly gel 12 h to obtain PVA organogel;
(2) Soaking PVA organic gel in a large amount of deionized water to replace solvent by 48 h, and replacing water every 12 h to obtain PVA hydrogel;
(3) Sequentially adding 300 mg of N-hydroxysuccinimide acrylate, 2.85 mL of acrylic acid, 5 mg of N, N' -methylenebisacrylamide and 5.70 mL of water into a 10 mL test tube, adding 200 mu L of photoinitiator and 400 mg of benzyl vinyl trimethyl ammonium chloride after complete dissolution, shaking uniformly, and marking as a solution A;
(4) PVA hydrogel was placed in a vacuum quartz vessel and solution A was taken at 30. Mu.L cm -2 Is added dropwise to the loose porous face of the PVA gel. After the internal pressure of the vessel was reduced to about 5 kPa using a circulating water vacuum pump (SHZ-D (iii)) and the vessel was sealed, light curing was then performed with a UV curing lamp (48W) for 15 min. The gel was then soaked in a large amount of water to wash out unreacted monomers (co-soak 12 h, water change every 2 h), and baked in a 60℃air oven for 15 min to give PVA/PAAc-N + A hydrogel.
Example 5
As shown in FIGS. 1-2, the present embodiment provides a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) + ) Firstly, constructing PVA hydrogel with double-sided asymmetric structure based on a method of moisture-induced phase separation and solvent replacement, wherein the PVA hydrogel comprises a loose porous surface and a uniform dense porous surface, and PAAc-N is prepared by a surface photocuring technology + The wet adhesive layer and the loose porous surface of the PVA dissipation layer are compounded together to obtain the wet adhesive hydrogel (PVA/PAAc-N) with ultralow swelling rate, ultrahigh burst pressure and excellent tissue adhesion prevention property + ) The method specifically comprises the following steps:
(1) 0.9. 0.9 g polyvinyl alcohol (PVA-2099) was dissolved in 10 mL dimethyl sulfoxide; pouring the mixed solution into a surface dish (the thickness of the solution is about 0.5 and mm), and placing the solution in moist air (the humidity is 70 percent and the temperature is 25 ℃) to slowly gel 12 h to obtain PVA organogel;
(2) Soaking PVA organic gel in a large amount of deionized water to replace solvent by 48 h, and replacing water every 12 h to obtain PVA hydrogel;
(3) Sequentially adding 300 mg of N-hydroxysuccinimide acrylate, 2.85 mL of acrylic acid, 5 mg of N, N' -methylenebisacrylamide and 5.70 mL of water into a 10 mL test tube, adding 200 mu L of photoinitiator and 200 mg of benzyl vinyl trimethyl ammonium chloride after complete dissolution, shaking uniformly, and marking as a solution A;
(4) PVA hydrogel was placed in a vacuum quartz vessel and solution A was taken at 50. Mu.L cm -2 Is added dropwise to the loose porous face of the PVA gel. After the internal pressure of the vessel was reduced to about 5 kPa using a circulating water vacuum pump (SHZ-D (iii)) and the vessel was sealed, light curing was then performed with a UV curing lamp (48W) for 15 min. The gel was then soaked in a large amount of water to wash out unreacted monomers (co-soak 12 h, water change every 2 h), and baked in a 60℃air oven for 15 min to give PVA/PAAc-N + A hydrogel.
Example 6
As shown in FIGS. 1-2, the present embodiment provides a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) + ) Firstly, constructing PVA hydrogel with double-sided asymmetric structure based on a method of moisture-induced phase separation and solvent replacement, wherein the PVA hydrogel comprises a loose porous surface and a uniform dense porous surface, and PAAc-N is prepared by a surface photocuring technology + The wet adhesive layer and the loose porous surface of the PVA dissipation layer are compounded together to obtain the wet adhesive hydrogel (PVA/PAAc-N) with ultralow swelling rate, ultrahigh burst pressure and excellent tissue adhesion prevention property + ) The method specifically comprises the following steps:
(1) 1.8. 1.8 g polyvinyl alcohol (PVA-1799) was dissolved in 10 mL dimethyl sulfoxide; pouring the mixed solution into a surface dish (the thickness of the solution is about 1 mm), and placing the solution in moist air (the humidity is 70 percent and the temperature is 25 ℃) to slowly gel 12 h to obtain PVA organogel;
(2) Soaking PVA organic gel in a large amount of deionized water to replace 72 h by solvent, and replacing water every 12 h to obtain PVA hydrogel;
(3) Sequentially adding 300 mg of N-hydroxysuccinimide acrylate, 2.85 mL of acrylic acid, 5 mg of N, N' -methylenebisacrylamide and 5.70 mL of water into a 10 mL test tube, adding 200 mu L of photoinitiator and 200 mg of benzyl vinyl trimethyl ammonium chloride after complete dissolution, shaking uniformly, and marking as a solution A;
(4) PVA hydrogel was placed in a vacuum quartz vessel and solution A was taken at 50. Mu.L cm -2 Is added dropwise to the loose porous face of the PVA gel. After the internal pressure of the vessel was reduced to about 5 kPa using a circulating water vacuum pump (SHZ-D (iii)) and the vessel was sealed, light curing was then performed with a UV curing lamp (48W) for 15 min. The gel was then soaked in a large amount of water to wash out unreacted monomers (24: 24 h total soaking, every 4: 4 h water exchange), and baked in a 80℃air oven for 10 min to give PVA/PAAc-N + A hydrogel.
Effect example 1
This effect example uses a universal mechanical tester (WD-5A, guangzhou laboratory instruments, china) to conduct tensile tests to characterize the mechanical properties of PVA hydrogels prepared by the preparation method provided in example 1. The specific test method comprises the following steps: PVA hydrogel samples were cut into dumbbell shapes (4 mm wide) and set at a draw speed of 30 mm min -1 . The results are shown in FIG. 3: the elastic modulus of PVA hydrogel is 170.2 kPa, the elongation at break is 232%, and the PVA hydrogel has better mechanical stability in a cyclic tensile test, which indicates that the gel can maintain stable mechanical properties in an in-vivo environment.
Effect example 2
The effect example uses a universal mechanical tester (WD-5A, guangzhou laboratory instruments, china) at 30 mm min -1 To characterize the preparation provided in example 1The super-structure porous wet adhesive hydrogel (PVA/PAAc-N) prepared by the method + ) Is used for the adhesive strength of the adhesive tape. The specific test method comprises the following steps: a superstructural porous wet adhesive hydrogel (PVA/PAAc-N) of about 1.5. 1.5 cm width and 3.0. 3.0 cm length was applied + ) The adhesive side of the sample was adhered to fresh pigskin (adhesion area about 1.5 cm 2 ) To test the wet adhesive shear strength of the gel. Samples (approximately 1.5. 1.5 cm width) were adhered to pigskin and tested for interfacial toughness using a 180 degree peel test. The results are shown in FIG. 4: superstructural porous wet adhesive hydrogel (PVA/PAAc-N) + ) The wet bond shear strength between the sample and the pigskin was 63.1 kPa and the interfacial toughness was 303J m -2 The gel was demonstrated to have very strong wet adhesion properties.
Effect example 3
Effect example the superstructural porous wet adhesive hydrogel (PVA/PAAc-N) prepared by the preparation method provided in example 1 was subjected to a weighing method + ) Is measured. The specific test method comprises the following steps: PVA/PAAc-N is weighed + The initial mass of the hydrogel sample wasw 0 It was immersed in deionized water at 37℃and oscillated at 120 rpm. After a predetermined time, PVA/PAAc-N is weighed + Hydrogel sample weight wasw t . Swelling ratioΔwCalculated according to the following equation:
the results are shown in FIG. 5: PAAc hydrogel provided by control group and PVA/PAAc-N provided in example 1 + Swelling ratios of the hydrogels after 3 days of soaking in water were 10.39 and 0.29, respectively, PVA/PAAc-N + Hydrogels have ultra-low swelling ratios.
Effect example 4
Example of the effect according to the Standard test method for burst Strength of surgical sealants (ASTM F2392-04), the super-structured porous Wet adhesive hydrogel (PVA/PAAc-N) prepared by the preparation method provided in example 1 + ) The gel adhesion effect of (2) was characterized. The specific test method comprises the following steps: using customizationsExperimental facility (FIG. 6), a hole of 3 mm was punched in the center of a pig skin of about 40. 40 mm diameter by a punch, and after the pig skin was fixed to the facility, a super-structured porous wet adhesive hydrogel (PVA/PAAc-N) of 15. 15 mm diameter was applied + ) The sample was adhered to the center of the pigskin and closed for 15 min. With a syringe pump at 2 mL min -1 The system is filled with water to pressurize, the pressure inside the system is recorded by a digital pressure gauge through a branch pipe, and the maximum pressure is taken as the burst pressure. The results are shown in FIG. 7: PVA/PAAc-N compared to the PAAc hydrogel of the control group + The hydrogel had an ultra-high average burst pressure of 493 mm Hg.
Effect example 5
Example of the effect the super-structured porous wet adhesive hydrogel (PVA/PAAc-N) prepared by the preparation method provided in example 1 was tested by using CCK 8 kit + ) Is a cell cytotoxicity of (a). The results are shown in FIG. 8: PVA/PAAc-N compared to the control group + No significant difference in proliferation of L929 fibroblasts in the hydrogel group on days 1, 2 and 3 demonstrated PVA/PAAc-N + The hydrogel has good biocompatibility.
Effect example 6
Example of effect the super-structured porous wet adhesive hydrogel (PVA/PAAc-N) prepared by the preparation method provided in example 1 was evaluated by liver adhesion experiments for repairing Sprague-Dawley rats + ) Is effective in stabilizing adhesion and preventing tissue adhesion. PVA/PAAc-N + The hydrogel anti-tissue adhesion effect is shown in fig. 9 and 10: PAAc hydrogel in control group causes severe abdominal adhesion, clinical adhesion score is as high as 8.6 minutes, PVA/PAAc-N + Hydrogels do not cause significant abdominal adhesions to form, and clinical adhesions scores as low as 1.2 points.
Effect example 7
Example of effect the super-structured porous wet adhesive hydrogel (PVA/PAAc-N) prepared by the preparation method provided in example 1 was evaluated by making a pig heart perforation model + ) The repairing effect on the damaged bleeding high-burst pressure tissue. As shown in FIG. 11, PVA/PAAc-N + The hydrogel can realize rapid hemostatic repair of cardiac perforation。
It should be understood that the foregoing examples of the present application are merely illustrative of the present application and are not intended to limit the present application to the specific embodiments thereof. Any modification, equivalent replacement, improvement, etc. that comes within the spirit and principle of the claims of the present application should be included in the protection scope of the claims of the present application.
Claims (6)
1. A method for preparing a super-structure porous wet adhesive hydrogel, which is characterized by comprising the following steps:
(1) Dissolving PVA powder in an organic solvent to form a PVA solution, and standing in an environment with constant temperature and humidity to obtain PVA organogel;
(2) Immersing the PVA organic gel obtained in the step (1) into an aqueous solution for solvent replacement to obtain PVA hydrogel; the PVA hydrogel has a double-sided asymmetric structure and comprises a loose porous surface and a uniform dense porous surface;
(3) Dissolving acrylic acid, succinimidyl acrylate, a cross-linking agent, a quaternary ammonium salt monomer and a photoinitiator into deionized water according to a proportion, and uniformly mixing to obtain a photo-curing adhesive precursor solution;
(4) Dropwise adding the photo-curing adhesive precursor solution on the loose porous surface of the PVA hydrogel, placing the PVA hydrogel in an oxygen-free environment, performing in-situ photo-curing, immersing the PVA hydrogel in an aqueous solution to wash out unreacted monomers, and then partially air-drying to obtain the super-structure porous wet adhesive hydrogel;
in the step (1), the organic solvent is dimethyl sulfoxide (DMSO); in the PVA solution, the PVA concentration is 5% -40%, the PVA polymerization degree range is 100% -4500, and the alcoholysis degree range is 88% -99%; the temperature is 4-40 ℃ and the humidity is 0-100%;
in the step (2), the temperature in the solvent replacement process is 4-40 ℃, and the solvent replacement time is not less than 2 h;
in step (3), each unit of the photo-curable adhesive precursor solution contains: 1-5 mL of acrylic acid, 50-500 mg of succinimide acrylic ester, 2.5-50 mg of cross-linking agent, 50-1000 mg of quaternary ammonium salt monomer and 50-400 mu L of photoinitiator;
in the step (4), the surface loading of the photo-curing adhesive precursor solution is 10-100 mu L cm -2 The photo-curing time is 1-120 min; the anaerobic environment is N 2 One of Ar, he or vacuum environment; the partial air drying temperature is 20-80 ℃ and the time is 1-120 min.
2. The preparation method of claim 1, wherein the cross-linking agent is a combination of more than one of Gelma, N-methylenebisacrylamide; the photoinitiator is a combination of more than one of dibenzoyl phenylphosphine oxide, ethyl 2,4, 6-trimethylbenzoyl phenylphosphonate and 2-hydroxy-2-methyl-1-phenyl-1-acetone.
3. The preparation method according to claim 1, wherein the quaternary ammonium salt is a combination of one or more of methacryloyloxyethyl trimethyl ammonium chloride and benzyl vinyl trimethyl ammonium chloride.
4. A superstructural porous wet adhesive hydrogel obtained by the method according to any one of claims 1 to 3.
5. Use of the super structure porous wet adhesive hydrogel according to claim 4 for soft tissue defect repair.
6. A soft tissue defect repair wet adhesive comprising the super structure porous wet adhesive hydrogel of claim 4.
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