CN112940180A - PHEAA-based high-toughness hydrogel and preparation method and application thereof - Google Patents
PHEAA-based high-toughness hydrogel and preparation method and application thereof Download PDFInfo
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Images
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—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 a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/58—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing oxygen in addition to the carbonamido oxygen, e.g. N-methylolacrylamide, N-(meth)acryloylmorpholine
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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
- 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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- 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
- 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
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—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 a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/04—Anhydrides, e.g. cyclic anhydrides
- C08F222/06—Maleic anhydride
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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
- A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments
Abstract
The invention provides a high-toughness hydrogel based on PHEAA, a preparation method and application thereof, belonging to the technical field of high polymer materials. The structure of the hydrogel is shown as a formula I, wherein x is 100-300; y is 20 to 50; z is 50-300. According to the invention, N- (2-hydroxyethyl) acrylamide (HEAA) and maleic anhydride are copolymerized to obtain the hydrogel with a uniform network structure, and the hydrogel has high fracture toughness and good biocompatibility. The hydrogel of the invention can overcome the defects of the existing tissue repair materials such as cartilage, achilles tendon and the like by virtue of excellent mechanical property and biocompatibility, and the hydrogel is preparedThe tissue repair material with more excellent performance is expected to be widely applied to the aspects of artificial cartilage, artificial achilles tendon and the like, and has good application prospect.
Description
Technical Field
The invention belongs to the technical field of high polymer materials, and particularly relates to a high-toughness hydrogel based on PHEAA, and a preparation method and application thereof.
Background
Articular cartilage defect is caused by diseases such as trauma, inflammation, tumor and the like, and is a common pathological change in clinic. The cartilage defect repair liquid has the advantages that the blood supply in cartilage is limited, so that the self-repair capacity of cartilage tissues is poor, and large-area cartilage damage (>4mm) cannot be repaired by self, because the cartilage defect becomes one of the most concerned problems in the medical field. For cartilage tissue repair, currently, cartilage inhibition, chondrocyte transplantation or periosteum transplantation and other methods are mainly used, and although a certain curative effect is obtained, the graft and the cartilage tissue of the patient cannot be well integrated in the clinical repair process, so that the curative effect is poor. In recent years, the application of artificial cartilage scaffold materials in repairing cartilage defects in orthopedics is more and more extensive. The gel material which is similar to the articular cartilage in structure and function is considered as an articular cartilage repair material with development prospect.
The hydrogel material has the potential advantages as a cartilage tissue engineering scaffold material: high water content, low friction coefficient, etc. However, most hydrogel materials contain more than 80% moisture, and have poor mechanical properties such as low fracture toughness, low fracture strain, and low strength, although they have high flexibility. In addition, since the hydrogel tends to have crosslinking points randomly introduced into the network structure during gelation, the network structure of the gel is not uniform. When the gel with the uneven network bears deformation, the gel starts to break from the weakest link, so that the overall mechanical property of the gel is reduced. The weaker mechanical properties make it difficult for the hydrogel to withstand large mechanical loads and to accommodate large deformations. At present, the material mainly used for cartilage repair is polyvinyl alcohol (PVA), the mechanical property of the PVA is very similar to that of articular cartilage, the PVA has good biocompatibility, and the PVA can partially replace the articular cartilage after being implanted into a human body.
In order to improve the mechanical properties of the hydrogel, various chemical additives are often required to be added, and most of the additives are harmful to the human body, so that the biocompatibility of the hydrogel is reduced. Therefore, the mechanical properties and biocompatibility of the hydrogel are difficult to be simultaneously considered, and the application of the hydrogel material in the fields of artificial cartilage, artificial achilles tendon and the like is further hindered. Therefore, it is necessary to provide a new design principle based on the network structure design of hydrogel, and select non-toxic raw materials to prepare hydrogel materials with high toughness and biocompatibility, so as to be suitable for artificial cartilage, artificial achilles tendon and other aspects.
Poly N- (2-hydroxyethyl) acrylamide (PHEAA) is an electrically neutral polymer with good biocompatibility and thermal stability, and researches show that PHEAA has the function of resisting nonspecific protein adsorption. ZHAO et al (C.ZHAO et al, Dual functional of Antimicrobial and inhibiting of Poly (N-hydroxyacrylamide)/Salicolate Hydrogels [ J ]. Langmuir,2013,29(5):1517-1524.) synthesized PHEAA/salicylic acid hydrogel which was both stain-resistant and antibacterial, and found that the hydrogel had the ability to resist protein adsorption, bacteria and cell adhesion with high efficiency.
However, no hydrogel with good biocompatibility and high toughness obtained by copolymerization of PHEAA and Maleic Anhydride (MA) is known at present.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a hydrogel which is prepared by copolymerizing N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA), has high toughness and excellent biocompatibility, and can be used as a repair material for tissues such as cartilage, achilles tendon and the like.
The invention provides a high-toughness hydrogel based on PHEAA, which has a structure shown in a formula I:
wherein the content of the first and second substances,
x is 100-300; y is 20 to 50; z is 50-300.
Furthermore, the hydrogel is prepared from N- (2-hydroxyethyl) acrylamide and acid or acid anhydride containing C ═ C unsaturated bonds as raw materials; wherein the molar ratio of the N- (2-hydroxyethyl) acrylamide to the acid or the acid anhydride containing the C ═ C unsaturated bond is 8: (1-8).
Further, the molar ratio of the N- (2-hydroxyethyl) acrylamide to the acid or acid anhydride containing a C ═ C unsaturated bond is 8: (2-3).
Further, the acid or anhydride containing a C ═ C unsaturated bond is maleic anhydride.
Furthermore, the fracture toughness of the hydrogel is not lower than 1MJ/m3。
The hydrogel is obtained by copolymerizing N- (2-hydroxyethyl) acrylamide and an acid or an acid anhydride containing a C ═ C unsaturated bond.
Preferably, the hydrogel is obtained by copolymerizing N- (2-hydroxyethyl) acrylamide and an acid or an acid anhydride containing a C ═ C unsaturated bond after ultraviolet irradiation in the presence of a photoinitiator.
The invention also provides a method for preparing the high-toughness hydrogel, which comprises the following steps:
a. dissolving N- (2-hydroxyethyl) acrylamide and an acid or anhydride containing a C ═ C unsaturated bond in water;
b. adding a photoinitiator;
c. irradiating with ultraviolet light.
Further, before the photoinitiator is added in the step b, oxygen in the system is removed.
Preferably, the oxygen in the removal system is removed by introducing an inert gas.
More preferably, the inert gas is nitrogen, and the time for introducing the nitrogen is 1-60 min.
Further, the molar ratio of the photoinitiator in the step b to the N- (2-hydroxyethyl) acrylamide is (0.0001-0.024): 8; preferably, the molar ratio of the photoinitiator to the N- (2-hydroxyethyl) acrylamide is (0.001-0.003): 8; the photoinitiator is 2-hydroxy-2-methyl propiophenone or benzoin dimethyl ether.
Further, the ultraviolet irradiation conditions in step c are as follows: the wavelength of the ultraviolet light is 10-400 nm; and/or the irradiation power of the ultraviolet light is 10-400W; and/or the ultraviolet light irradiation time is 10-120 min.
Preferably, the wavelength of the ultraviolet light is 300-380 nm; and/or the irradiation power of the ultraviolet light is 300-360W.
More preferably, the ultraviolet light wavelength is 365 nm; and/or the irradiation power of the ultraviolet light is 330W; and/or the ultraviolet light irradiation time is 40-120 min.
The invention also provides application of the high-toughness hydrogel in preparation of a tissue repair material.
Preferably, the high-toughness hydrogel is used for preparing cartilage repair materials and achilles tendon repair materials.
More preferably, the use of said high-toughness hydrogel in the preparation of artificial cartilage, artificial achilles tendon.
The mechanical properties and biocompatibility of the hydrogel are difficult to be simultaneously considered, so that the application of the hydrogel in the aspects of artificial cartilage, artificial achilles tendon and the like is limited. It is necessary to improve the toughness of PHEAA and ensure good biocompatibility so as to prepare hydrogel with high toughness and good biocompatibility. The invention provides a technical scheme for preparing a PHEAA-based hydrogel with high toughness and good biocompatibility.
The hydrogel is prepared by reacting HEAA and maleic anhydride for 10-120 min under the action of light initiation. Wherein the photoinitiator is benzoin dimethyl ether (Irgacure-651) or 2-hydroxy-2-methyl propiophenone (1173), and the light source is ultraviolet light with the wavelength of 10-400 nm, preferably 300-380 nm, and the power of 10-400W, preferably 300-360W. The irradiation power of the ultraviolet light is not high enough, otherwise, the heat is too high, and the heat can cause the thermal initiation of free radical polymerization, thereby affecting the performance of the hydrogel.
Compared with the prior art, the invention has the following outstanding advantages and technical effects:
the PHEAA-based hydrogel prepared by the invention has a uniform network structure, and is different from the traditional PHEAA hydrogel in that the breakage of short chains is easy to occur due to the fact that the molecular chain length is different; and, the carboxyl of maleic anhydride forms strong hydrogen bond with hydroxyl and amino in HEAA; the interior of the HEAA structural unit can also form hydrogen bonds among amino-amino, amino-hydroxyl and hydroxyl-hydroxyl. Therefore, the hydrogel disclosed by the invention can generate affine deformation through the uniform network in the initial deformation stage, so that the phenomenon that the hydrogel is broken due to the existence of stress concentration is avoided; with further increase of deformation, the fracture of hydrogen bond action can effectively dissipate energy, and the remarkable improvement of the toughness of the hydrogel is realized. Therefore, the PHEAA-based hydrogel prepared by photo-initiated free radical copolymerization of HEAA and maleic anhydride has the advantage of high toughness, is harmless to human bodies, has good biocompatibility, and is expected to be widely applied to aspects such as artificial cartilage, artificial achilles tendon and the like.
In conclusion, the N- (2-hydroxyethyl) acrylamide (HEAA) and maleic anhydride are copolymerized to obtain the hydrogel with a uniform network structure, and the hydrogel has high fracture toughness and good biocompatibility. The hydrogel disclosed by the invention can overcome the defects of the existing tissue repair materials such as cartilage and achilles tendon due to excellent mechanical properties and biocompatibility, can be used for preparing the tissue repair materials with more excellent properties, is expected to be widely applied to the aspects of artificial cartilage, artificial achilles tendon and the like, and has a good application prospect.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 is a graph of time-averaged scattering intensity for different hydrogel samples<I>TAmplitude of fluctuation as a function of sample position.
Detailed Description
The raw materials and equipment used in the embodiment of the present invention are known products and obtained by purchasing commercially available products.
The synthesis route of the hydrogel of the invention is as follows:
wherein the content of the first and second substances,
x is 100-300; y is 20 to 50; z is 50-300.
Example 1 preparation of hydrogel of the invention
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 8:1, namely dissolving 8mol of HEAA and 1mol of MA in 50mL of water, introducing nitrogen into the solution for 10min under stirring to remove oxygen in the solution, adding 0.003mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and carrying out a light irradiation reaction for 40min under an ultraviolet lamp with the wavelength of 365nm and the power of 330W to obtain the P (HEAA-co-MA) hydrogel A.
Example 2 preparation of hydrogel of the invention
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 8:2, namely dissolving 8mol of HEAA and 2mol of MA in 50mL of water, introducing nitrogen into the solution for 20min under stirring to remove oxygen in the solution, adding 0.003mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and carrying out illumination reaction for 40min under an ultraviolet lamp with the wavelength of 365nm and the power of 330W to obtain the P (HEAA-co-MA) hydrogel B.
Example 3 preparation of hydrogel of the invention
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 12:5, namely dissolving 12mol of HEAA and 5mol of MA in 50mL of water, introducing nitrogen into the solution for 60min under stirring to remove oxygen in the solution, adding 0.003mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and carrying out a light irradiation reaction for 40min under an ultraviolet lamp with the wavelength of 365nm and the power of 330W to obtain the P (HEAA-co-MA) hydrogel C.
Example 4 preparation of the hydrogel of the invention
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 8:3, namely dissolving 8mol of HEAA and 3mol of MA in 50mL of water, introducing nitrogen into the solution for 1min under stirring to remove oxygen in the solution, adding 0.001mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and performing light reaction for 120min under an ultraviolet lamp with the wavelength of 10nm and the power of 10W to obtain P (HEAA-co-MA) hydrogel D.
Example 5 preparation of hydrogel of the invention
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 1:1, namely dissolving 1mol of HEAA and 1mol of MA in 50mL of water, introducing nitrogen into the solution for 10min under stirring to remove oxygen in the solution, adding 0.003mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and performing light reaction for 10min under an ultraviolet lamp with the wavelength of 365nm and the power of 330W to obtain the P (HEAA-co-MA) hydrogel E.
Example 6 preparation of hydrogel of the invention
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 8:3, namely dissolving 8mol of HEAA and 3mol of MA in 50mL of water, introducing nitrogen into the solution for 10min under stirring to remove oxygen in the solution, adding 0.003mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and carrying out illumination reaction for 60min under an ultraviolet lamp with the wavelength of 365nm and the power of 330W to obtain the P (HEAA-co-MA) hydrogel F.
Comparative example 1 preparation of PHEAA hydrogel
Dissolving N- (2-hydroxyethyl) acrylamide (HEAA) and Maleic Anhydride (MA) in water at a molar ratio of 8:0, namely dissolving 8mol of HEAA in 50mL of water, introducing nitrogen into the solution for 10min under stirring to remove oxygen in the solution, adding 0.003mol of photoinitiator benzoin dimethyl ether (Irgacure-651), and carrying out a light irradiation reaction for 40min under an ultraviolet lamp with the wavelength of 365nm and the power of 330W to obtain the PHEAA hydrogel.
The advantageous effects of the present invention are demonstrated by specific test examples below.
Test example 1 Performance test of hydrogel of the present invention
(1) And (3) testing mechanical properties: the tensile stress-strain behavior of each set of hydrogels (examples 1 to 6 and comparative example 1) was evaluated separately with a universal tensile tester Instron 3367, with a tensile rate of 100mm/min, the samples were stretched until breaking and the stress-strain curves were recorded. Where fracture toughness is determined by the integrated area under the corresponding stress-strain curve at the time of fracture of the sample. The hydrogel sample is dumbbell-shaped, and the gauge length, the width and the thickness of the hydrogel sample are respectively 10mm, 4mm and 1 mm.
(2) Cell compatibility testing: the hydrogels prepared in examples 1 to 6 and comparative example 1 were cut into a disc shape having a diameter of 2.5mm and a thickness of 1mm, and mesenchymal stem cells were seeded on the surface at the same density at 37 ℃ for 24 hours, and then the cell activity was evaluated using CCK-8 analysis.
(3) Homogeneity test (dynamic light scattering test): characterization of the time-averaged scattering intensity at different sample positions for each set of hydrogels (examples 1-6 and comparative example 1) using a BI-200SM measurement System<I>TThe amplitude of the fluctuation of (a). The time-averaged scattered intensity refers to the average scattered light intensity over a certain time.
The mechanical properties and cell compatibility test results of the hydrogel of the present invention are shown in table 1.
TABLE 1 mechanical Properties and cell compatibility test results of the hydrogels of the present invention
As can be seen from Table 1: compared with the PHEAA hydrogel, the fracture toughness of the hydrogel copolymerized with MA is obviously improved and is increased by 0.12MJ/m3The temperature is increased to 1.36-2.36 MJ/m3The mechanical property of the material is improved by more than 10 times, and the material can meet the mechanical requirements of tissue repair materials such as cartilage, achilles tendon and the like. Meanwhile, from the cell culture experiment, after the mesenchymal stem cells are cultured on each group of hydrogel for 24 hours, the cell survival rate is as high as 85-95%, which indicates that the hydrogel has excellent biocompatibility. Taken together, hydrogel B, C, D performed best.
The change of the hydrogel network heterogeneity and the time average scattering intensity can be analyzed by a dynamic light scattering test<I>TThe more pronounced the fluctuation of (a) indicates the more heterogeneous the hydrogel structure. Time-averaged scattering intensity of hydrogels from each group<I>TThe fluctuation amplitude of (a) is as shown in fig. 1. The results show that: time-averaged scattering intensity of PHEAA hydrogel<I>TTo the time-average scattering intensity of the hydrogels A-F<I>The fluctuations in T were more pronounced and dramatic, indicating that the structure of hydrogels A-F was more uniform than that of the PHEAA hydrogel. The more uniform network structure allows the hydrogel to withstand greater mechanical loads and accommodate greater deformation, thereby enhancing the hydrogel propertiesThe whole mechanical property is more suitable for being used as a repairing material of cartilage, achilles tendon and the like.
In conclusion, the N- (2-hydroxyethyl) acrylamide (HEAA) and maleic anhydride are copolymerized to obtain the hydrogel with a uniform network structure, and the hydrogel has high fracture toughness and good biocompatibility. The hydrogel disclosed by the invention can overcome the defects of the existing tissue repair materials such as cartilage and achilles tendon due to excellent mechanical properties and biocompatibility, can be used for preparing the tissue repair materials with more excellent properties, is expected to be widely applied to the aspects of artificial cartilage, artificial achilles tendon and the like, and has a good application prospect.
Claims (10)
1. A high-toughness PHEAA-based hydrogel, characterized by: the structure of the hydrogel is shown as a formula I:
wherein the content of the first and second substances,
x is 100-300; y is 20 to 50; z is 50-300.
2. The high toughness hydrogel of claim 1, wherein: the hydrogel is prepared from N- (2-hydroxyethyl) acrylamide and acid or acid anhydride containing C ═ C unsaturated bonds as raw materials; wherein the molar ratio of the N- (2-hydroxyethyl) acrylamide to the acid or the acid anhydride containing the C ═ C unsaturated bond is 8: (1-8).
3. The high toughness hydrogel of claim 2, wherein: the molar ratio of the N- (2-hydroxyethyl) acrylamide to the acid or the anhydride containing the C ═ C unsaturated bond is 8: (2-3).
4. A high toughness hydrogel according to claim 3 wherein: the acid or anhydride containing a C ═ C unsaturated bond is maleic anhydride.
5. According to the claimsThe high-toughness hydrogel according to any one of claims 1 to 4, which comprises: the fracture toughness of the hydrogel is not lower than 1MJ/m3。
6. A process for producing a high-toughness hydrogel according to any one of claims 1 to 5, wherein: it comprises the following steps:
a. dissolving N- (2-hydroxyethyl) acrylamide and an acid or anhydride containing a C ═ C unsaturated bond in water;
b. adding a photoinitiator;
c. irradiating with ultraviolet light.
7. The method of claim 6, wherein: and (c) removing oxygen in the system before adding the photoinitiator in the step b.
8. The method of claim 6, wherein: the molar ratio of the photoinitiator in the step b to the N- (2-hydroxyethyl) acrylamide is (0.0001-0.024): 8; preferably, the molar ratio of the photoinitiator to the N- (2-hydroxyethyl) acrylamide is (0.001-0.003): 8; the photoinitiator is 2-hydroxy-2-methyl propiophenone or benzoin dimethyl ether.
9. The method of claim 6, wherein: the ultraviolet irradiation conditions in the step c are as follows: the wavelength of the ultraviolet light is 10-400 nm; and/or the irradiation power of the ultraviolet light is 10-400W; and/or the ultraviolet light irradiation time is 10-120 min.
10. Use of the high-toughness hydrogel according to any one of claims 1 to 5 for the preparation of a tissue repair material.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO112883B1 (en) * | 1996-05-15 | 1998-01-30 | Maria Caloianu | Bioartificial hydrogels with advanced hygroscopicity |
| US20060052478A1 (en) * | 2002-10-02 | 2006-03-09 | Flemming Madsen | Hydrogel |
| CN102226007A (en) * | 2011-04-12 | 2011-10-26 | 厦门大学 | Double network polymer hydrogel and preparation method thereof |
| CN109971105A (en) * | 2019-03-15 | 2019-07-05 | 浙江工业大学 | A kind of chitosan/poly- N- hydroxyethyl acrylamide is tough anti-pollution double-network hydrogel and preparation method thereof |
-
2021
- 2021-01-21 CN CN202110084508.4A patent/CN112940180B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO112883B1 (en) * | 1996-05-15 | 1998-01-30 | Maria Caloianu | Bioartificial hydrogels with advanced hygroscopicity |
| US20060052478A1 (en) * | 2002-10-02 | 2006-03-09 | Flemming Madsen | Hydrogel |
| CN102226007A (en) * | 2011-04-12 | 2011-10-26 | 厦门大学 | Double network polymer hydrogel and preparation method thereof |
| CN109971105A (en) * | 2019-03-15 | 2019-07-05 | 浙江工业大学 | A kind of chitosan/poly- N- hydroxyethyl acrylamide is tough anti-pollution double-network hydrogel and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| CHRISTINA MÜLLER等: ""Covalent Binding of Maleic Anhydride Copolymer Monolayers to Polyacrylamide Hydrogels"", 《MACROMOLECULAR CHEMISTRY AND PHYSICS》 * |
| 许一婷: ""mahPEG800mah-AM-DMAEMA 三元共聚复合水凝胶的增韧及智能响应性"", 《高分子材料科学与工程》 * |
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