CN112358572A - Precursor of high-strength hydrogel rapidly constructed in situ by visible light, and preparation method and use method thereof - Google Patents
Precursor of high-strength hydrogel rapidly constructed in situ by visible light, and preparation method and use method thereof Download PDFInfo
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Abstract
The invention discloses a precursor of a high-strength hydrogel quickly constructed in situ by visible light, which comprises 1-500 parts by mass of a high-molecular framework with a double bond grafting rate of 20-80%, 1-1000 parts by mass of a toughening monomer, 0.001-10 parts by mass of an initiator, 0-50 parts by mass of a co-initiator and 1000-10000 parts by mass of an aqueous solution. The hydrogel precursor is dripped on biological tissues and irradiated by a visible light source, so that the hydrogel precursor can be rapidly gelatinized in situ with the biological tissues, and the hydrogel has good rigidity and toughness and high strength and can be widely used for tissue repair.
Description
Technical Field
The invention belongs to the field of biomedical materials, and relates to a precursor of high-strength hydrogel rapidly constructed in situ by visible light, a preparation method and a use method thereof.
Background
The hydrogel is formed by crosslinking hydrophilic reticular polymers which can swell in water, absorb and retain a large amount of water and are insoluble in water. As the hydrogel network is filled with a large amount of water, the hydrogel is similar to the soft tissue organ of the human body and has the characteristic of soft elasticity, so that the hydrogel is a bionic biomaterial with potential medical application. Although the hydrogel has the characteristic similar to soft elasticity of human soft tissues, compared with human tissues, the mechanical strength and tissue adhesion matched with most of hydrogels and tissues can not meet the related medical application requirements, so that the development of the hydrogel with good mechanical properties has important significance for expanding the application of the hydrogel in the biomedical field.
The construction of the hydrogel mainly comprises the selection of hydrogel frameworks and the cross-linking construction among the frameworks. According to the skeleton of the hydrogel, the hydrogel can be divided into natural hydrogel and synthetic hydrogel. The natural hydrogel mainly comprises natural polysaccharide (such as hyaluronic acid, sodium alginate, chitosan, dextran, pullulan, agarose, heparin and the like) and some proteins (such as gelatin, collagen, silk fibroin and the like). Synthetic hydrogels include polyacrylamides, polyacrylic acid, polyvinyl alcohol, poly (2-hydroxyethyl methacrylate), poly (N-hydroxyethyl acrylamide), poly (ethylene glycol) methacrylate), and the like. According to the different cross-linking structure modes between skeletons, the method can be divided into chemical cross-linking and physical cross-linking. The chemical crosslinking is formed by connecting the skeletons of the hydrogel through chemical bonds, and comprises polymerization reaction, click reaction, Schiff base reaction, enzyme crosslinking and the like. Physical cross-linking is cross-linked by non-chemical bonds such as hydrogen bonds, van der waals forces, or entanglement with each other, including hydrogen bonds, coordination bonds, electrostatic interactions, host-guest interactions, hydrophobic interactions, and the like. The hydrogel obtained by chemical crosslinking forms stable chemical bonds, forms a permanent three-dimensional network polymer, provides rigidity for the hydrogel, and maintains the shape of the hydrogel. However, chemical hydrogels lack an effective energy dissipation method to prevent or reduce crack propagation under external force, so chemical hydrogels can well maintain their shape, but cannot withstand large deformation, and are fragile under external force. The hydrogel obtained by physical crosslinking forms a weaker physical bond, can be formed again after being fractured and has self-healing property, and the physical action as a 'sacrificial bond' can effectively improve the energy loss of the hydrogel during loading, so that the toughness of the hydrogel is increased and a certain deformation can be borne. Therefore, chemical crosslinking and physical crosslinking are introduced into the same hydrogel system, the chemical crosslinking is used for maintaining the rigidity of the hydrogel, the physical crosslinking is used for dissipating energy when the hydrogel is damaged by external force, the toughness is improved, and the constructed hydrogel with good mechanical properties can effectively expand the application of the hydrogel as a biomedical material.
As a tissue repair material, a hydrogel is required to have good tissue gap filling properties and good adhesion in addition to good mechanical properties. In order to be able to fill the damaged area with a material, the hydrogel needs to have good fluidity, which is in great conflict with the good mechanical properties of the hydrogel. Although the injectable hydrogel is of great interest to researchers, the huge deformation of the hydrogel during injection and filling limits the energy dissipation caused by the deformation that the hydrogel must be mainly physically cross-linked during construction, resulting in poor rigidity and failure to maintain a good shape. Meanwhile, in general, the hydrogel has poor tissue adhesion to living bodies because the skeleton of the hydrogel can only form a weak physical action such as a hydrogen bond or van der waals force with an amino group, a carboxyl group, a hydroxyl group, or a thiol group on a protein contained in a living body tissue. Therefore, the hydrogel with good conformal filling capability, tissue adhesion and mechanical properties has good clinical requirements and wide application prospects, but faces huge challenges in synthesis and construction.
Disclosure of Invention
In view of the above, the invention provides a precursor of a high-strength hydrogel rapidly constructed in situ by visible light, and a preparation method and a use method thereof.
The invention specifically provides the following technical scheme:
1. a precursor of a high-strength hydrogel quickly constructed in situ by visible light comprises, by mass, 1-500 parts of a high-molecular framework with a double bond grafting rate of 20% -80%, 1-1000 parts of a toughening monomer, 0.001-10 parts of an initiator, 0-50 parts of a co-initiator and 1000-10000 parts of an aqueous solution.
Further, the polymer skeleton comprises natural polymers and synthetic polymers, the natural polymers are hyaluronic acid, sodium alginate, glucan, pullulan, agarose, chitosan, gelatin, collagen, silk fibroin, polypeptide and protein, and the synthetic polymers are poly (2-hydroxyethyl methacrylate), poly (2-hydroxyethyl acrylate), poly (N-hydroxyethyl acrylamide) and poly (ethylene glycol) methacrylate).
Further, the toughening monomer comprises: hydroxypropyl methacrylate, N-dimethylacrylamide, N-diethylacrylamide, N-isopropylacrylamide and 2-methoxyethyl acrylate.
Further, the initiator comprises: zinc porphyrin, eosin Y disodium salt or acid red 87 and ruthenium tris (bipyridyl) chloride hexahydrate.
Further, the coinitiator comprises: triethylamine and triethanolamine.
Further, the aqueous solution comprises: deionized water, normal saline and phosphate buffer solution.
2. The preparation method of the precursor of the high-strength hydrogel rapidly constructed in situ by visible light comprises the following steps:
1) preparing a double-bond-containing polymer skeleton, and controlling the double-bond grafting rate to be 20-80%; the polymer skeleton containing the double structure is a product obtained by reacting anhydride containing the double structure or epoxy compound containing the double structure with the polymer skeleton;
2) mixing the polymer framework obtained in the step 1), a toughening monomer, an initiator, a coinitiator and an aqueous solution to obtain a hydrogel precursor.
3. According to the application method of the precursor of the high-strength hydrogel rapidly constructed in situ by visible light, the hydrogel precursor is dripped on biological tissues and is irradiated by a visible light source, and the hydrogel precursor and the biological tissues can be rapidly gelatinized in situ.
Further, the visible light source comprises blue light, green light and yellow light, the wavelength of the blue light is 470nm, the wavelength of the green light is 530nm, the wavelength of the yellow light is 585 nm, and the irradiation time is within 120 seconds.
Further, the lapping-shearing tensile bearing strength of the gelatinized hydrogel on biological tissues is 50-120 kPa, the T-peeling tensile bearing strength is 10-50N/m, the tensile strength is 120-200 kPa, and the wound closure strength is 20-60 kPa.
The invention has the beneficial effects that:
1. the hydrogel precursor disclosed by the invention can be quickly gelled in 120 seconds under the condition of visible light irradiation, the used light sources are blue light, green light and yellow light visible light sources, and a near infrared light source with deep tissue penetrability or an ultraviolet light source capable of generating light damage to tissues is not required. Therefore, the visible light polymerization method can carry out in-situ polymerization at the tissue injury part, and has high biological safety, high gelling efficiency and convenient use.
2. The hydrogel precursor disclosed by the invention can be quickly formed into gel after illumination, wherein the mechanical properties of the hydrogel body are provided by natural polymers or synthetic polymers containing different double bond grafting rates and toughening monomers. After the polymerization reaction is initiated by illumination, natural macromolecules or synthetic macromolecules with a large number of double bonds on the molecular chain segment are polymerized to form a chemical bond cross-linked network as the skeleton of the hydrogel, so that rigidity is provided for the hydrogel. Meanwhile, the water-soluble toughening monomer can be driven to gather under the action of hydrogen bonds along with the increase of molecular weight in the polymerization process to form a polymerization-induced self-assembly body, and the self-assembly function as a physical-action crosslinking point of the hydrogel can provide good dissipation energy for the hydrogel and improve the toughness of the hydrogel. By constructing the hydrogel with the chemical crosslinking and physical crosslinking functions in situ, the hydrogel has good rigidity and toughness and high strength, and can be widely used for tissue repair.
3. The hydrogel disclosed by the invention can generate good adhesion to damaged tissues in the gelling process. The hydrogel comprises 1) physical action, a hydrogel framework and a crosslinking structure contain a large number of amino, carboxyl, hydroxyl and other groups, and the hydrogel framework and the crosslinking structure can form hydrogen bond action and van der Waals force action with the amino, carboxyl, hydroxyl, ether oxygen and other groups on skin tissues. 2) The chemical action is that the amino acid structure in human tissue contains sulfydryl group, which can generate click chemical reaction with the hydrogel precursor containing double bond under the condition of illumination, thus enhancing the interaction between the tissue and the hydrogel. 3) The mechanical action, the tissue surface is rough and not smooth, the hydrogel precursor has good fluidity, so that the gaps can be well filled, the gel filled in the gaps can form a complete interlocking macro topological structure with the gaps of the tissue in the process of light-irradiating the gel, and the mechanical interlocking action can provide strong adhesion.
4. The precursor of the hydrogel disclosed by the invention has good fluidity, and can fill the damaged part of the tissue along with the shape, fully fill the tissue gap and fully contact the wound surface of the tissue.
Drawings
In order to make the purpose, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings:
figure 1 is a photograph of the hydrogel precursor of example 1 in a vial.
Figure 2 is a gel forming picture of the hydrogel precursor of example 1 in a glass vial.
FIG. 3 is a scanning electron micrograph of the hydrogel precursor of example 1 after gelling in 5W green light illumination for 80 s.
Fig. 4 is a photograph of the administration on the pigskin tissue of example 1.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
Example 1
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1) dissolving 1g of hyaluronic acid (Mn is 300kDa) in 100mL of deionized water, adding 4mL of methacrylic anhydride, uniformly stirring, adjusting the pH to 8-9 by using 5moL/L of sodium hydroxide solution, reacting at 40 ℃ for 6h, dialyzing for 3d, performing suction filtration, and freeze-drying to obtain the methacrylic anhydride modified hyaluronic acid with the double bond grafting rate of 27% (the double bond grafting rate is 27%).
2) And (3) uniformly mixing 100mg of methacrylic anhydride modified hyaluronic acid (the double bond grafting rate is 27%) obtained in the step (1), 400mg of hydroxypropyl methacrylate, 10mg of triethanolamine and 0.05mg of eosin Y disodium salt in 5mL of deionized water solution to obtain a hydrogel precursor.
2. The hydrogel precursor is used as follows:
and (3) dropwise adding the hydrogel precursor onto the biological tissue, and illuminating for 80s by using 5W green light to enable the hydrogel to be gelatinized and tightly adhered to the biological tissue.
Figure 1 is a photograph of the hydrogel precursor of example 1 in a vial. The hydrogel precursor of example 1 was dropped into an upright transparent glass bottle without light, and the precursor flowed and tilted with the tilt of the glass bottle, so that it was found that the precursor could flow to fill different shapes of surfaces, and had good flowability with the mold filling ability.
Figure 2 is a gel forming picture of the hydrogel precursor of example 1 in a glass vial. The hydrogel precursor of example 1 was dropped into an upright transparent glass bottle, and irradiated with 5W of green light for 80 seconds, whereby the hydrogel precursor formed a hydrogel and remained in an inclined state without flowing. Therefore, the precursor can be quickly gelled in 80 s.
FIG. 3 is a scanning electron micrograph of the hydrogel precursor of example 1 after being gelled in 5W green light illumination for 80s, and it can be seen from FIG. 3 that the crosslinked pore structure is inside the hydrogel. The porous structure is filled with water, so that cell migration is promoted, and the air exchange between wound tissues and the outside is facilitated. The formed holes are uniformly distributed, which shows that the hydrogel frameworks are uniformly distributed in the hydrogel, can reduce stress concentration and provide better mechanical property. Meanwhile, the surfaces of the pores are closed, the pores are separated from each other by a solid framework, when the gel bears external force, the pores are extruded or stretched and deformed along the stress direction, and the deformed parts are absorbed by the adjacent pore walls, so that the elastic modulus of the gel is increased, and the mechanical property is enhanced.
Fig. 4 is a photograph of the administration on the pigskin tissue of example 1. Dripping the hydrogel precursor into the gap between two pieces of pigskin tissues, and then irradiating to form gel. After gelling, reddish high-strength hydrogel can be observed between pigskin tissue gaps, and meanwhile, the hydrogel can be seen to have good adhesion on the edges of the pigskin tissue.
Example 2
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1) dissolving 1g of sodium alginate (600cps) in 100mL of deionized water, adding 3mL of methacrylic anhydride, uniformly stirring, adjusting the pH to 8-9 by using a 5moL/L sodium hydroxide solution, reacting for 6h at 40 ℃, dialyzing for 3d, performing suction filtration, and freeze-drying to obtain the methacrylic anhydride modified sodium alginate with the double bond grafting rate of 20% (the double bond grafting rate is 20%).
2) And (3) uniformly mixing 100mg of methacrylic anhydride modified sodium alginate obtained in the step (1) (the double bond grafting rate is 20%), 600mg of N, N-dimethylacrylamide, 30mg of triethanolamine and 0.1mg of eosin Y disodium salt in 5mL of normal saline to obtain a hydrogel precursor.
2. The hydrogel precursor is used as follows:
dropping the hydrogel precursor onto biological tissue, and illuminating with 0.1W green light for 120s to make the hydrogel gel and adhere to the biological tissue.
Example 3
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)5g of dextran (Mn ═ 400kDa) was dissolved in 45mL of DMSO, and then 1g of 4- (dimethylamino) pyridine and 5g of glycidyl methacrylate were added, and the mixture was reacted at room temperature for 48 hours, followed by addition of hydrochloric acid to terminate the reaction, dialysis and lyophilization, whereby glycidyl methacrylate-modified dextran having a double bond graft ratio of 35% (double bond graft ratio of 35%) was obtained.
2) Uniformly mixing 100mg of glycidyl methacrylate glucan (the double bond grafting rate is 35%) obtained in the step 1, 10mg of N, N-isopropylacrylamide and 0.8mg of terpyridine ruthenium chloride hexahydrate in 10mL of phosphate buffer solution to obtain a hydrogel precursor.
2. The hydrogel precursor is used as follows:
and (3) dropwise adding the hydrogel precursor onto the biological tissue, and illuminating for 10s by using 50W blue light to enable the hydrogel to be gelatinized and tightly adhered to the biological tissue.
Example 4
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)20g of pullulan (Mn ═ 350kDa dissolved in 110mL of DMSO), 2.4g of 4- (dimethylamino) pyridine and 23g of glycidyl methacrylate were added, the mixture was reacted at room temperature for 48 hours, hydrochloric acid was added to terminate the reaction, and the reaction solution was dialyzed and lyophilized to obtain glycidyl methacrylate-modified pullulan having a double bond graft ratio of 43% (double bond graft ratio of 43%).
2) And (3) uniformly mixing 100mg of glycidyl methacrylate modified pullulan obtained in the step (1) (the double bond grafting rate is 43%), 1000mg of 2-methoxyethyl acrylate and 0.2mg of zinc porphyrin in 5mL of deionized water to obtain the precursor.
2. The hydrogel precursor is used as follows:
dripping the hydrogel precursor onto the biological tissue, and illuminating with 15W yellow light for 60s to make the hydrogel gel and adhere to the biological tissue tightly.
Example 5
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)1g of carboxymethyl chitosan was dissolved in 80ml of 0.1mol of 2-morpholinoethanesulfonic acid (MES, pH 6.0-8.0), and 10mmol of N- (3-dimethylaminopropyl) -N' -Ethylcarbodiimide (EDC) and 10mmol of N-hydroxysuccinimide (NHS) were added to activate the carboxyl groups for 1 h. Adding 0.6g of aminoethyl methacrylate, stirring at 4 ℃ for 24h, dialyzing, and freeze-drying to obtain the aminoethyl methacrylate modified carboxymethyl chitosan with 14% of double bond grafting rate (14% of double bond grafting rate).
2) And (2) uniformly mixing 100mg of aminoethyl methacrylate modified carboxymethyl chitosan (the double bond grafting rate is 14%) obtained in the step (1), 200mg of 2-methoxyethyl acrylate and 0.2mg of zinc porphyrin in 5mL of deionized water to obtain the precursor.
2. The hydrogel precursor is used as follows:
dripping the hydrogel precursor onto the biological tissue, and illuminating with 185W yellow light for 60s to make the hydrogel gel and adhere to the biological tissue tightly.
Example 6
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)10g of gelatin (derived from cold water fish skin) was dissolved in 100mL of DPBS, heated at 60 ℃ for 1 hour, 20mL of methacrylic anhydride was added dropwise to the gelatin solution with stirring, reacted at 50 ℃ for 3 hours, diluted, dialyzed at 50 ℃ for 5 days in deionized water, filtered, and lyophilized for 3 days to obtain methacrylic anhydride-modified gelatin with a double bond grafting rate of 56% (double bond grafting rate of 56%).
2) And (2) uniformly mixing 100mg of methacrylic anhydride modified gelatin (the double bond grafting rate is 56%) obtained in the step (1), 800mg of N, N-diethylacrylamide, 37.5mg of triethylamine and 0.15mg of eosin Y disodium salt in 10mL of phosphate buffer solution to obtain a precursor.
2. The hydrogel precursor is used as follows:
dropping the hydrogel precursor onto biological tissue, and illuminating with 20W green light for 100s to make the hydrogel gel and adhere to the biological tissue tightly.
Example 7
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)130g of 2-hydroxyethyl methacrylate, 0.122g of methyl 2-chloropropionate and 0.78L of distilled water were charged into a 1L flask, degassed by three cycles of freeze-pump-thaw, left under nitrogen, added with 0.149mg of cuprous bromide and 0.345g of tris [2- (dimethylamino) ethyl ] amine, reacted at 25 ℃ for 1h, exposed to air after the reaction was completed, precipitated with methanol, and oven-dried at 65 ℃ to obtain poly (2-hydroxyethyl methacrylate (Mn 130 kDa).
2)5g of poly (2-hydroxyethyl methacrylate) (Mn 130kDa) was dissolved in 45mL of DMSO, and then 1g of 4- (dimethylamino) pyridine and 4.806g of glycidyl methacrylate were added to react at room temperature for 48 hours, followed by addition of hydrochloric acid to terminate the reaction, dialysis, and lyophilization, to obtain glycidyl methacrylate-modified poly (2-hydroxyethyl methacrylate) having a double bond grafting ratio of 88%.
3) And (3) uniformly mixing 100mg of glycidyl methacrylate modified poly (2-hydroxyethyl methacrylate) (the double bond grafting rate is 88%) obtained in the step (2), 100mg of N, N-diethyl acrylamide, 37.5mg of triethylamine and 0.15mg of eosin Y disodium salt in 10mL of phosphate buffer solution to obtain the precursor.
2. The hydrogel precursor is used as follows:
dropping the hydrogel precursor onto biological tissue, and illuminating with 250W green light for 60s to make the hydrogel gel and adhere to the biological tissue tightly.
Example 8
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)116g of 2-hydroxyethyl acrylate, 0.364g of 2- (dodecyltrithiocarbonate) -2-methylpropanoic acid, 32.8mg of azobisisobutyronitrile, 0.54g of paraldehyde and 133g of dioxane were added to a 200mL flask, nitrogen was introduced for 30min, the reaction was carried out at 65 ℃ for 5h, the reaction was quenched by immersion in ice water and exposure to air, ether precipitation was carried out, and drying was carried out in a vacuum oven at 45 ℃ to obtain poly (2-hydroxyethyl acrylate) (Mn 120 kDa).
2)5g of poly (2-hydroxyethyl acrylate) (Mn 120kDa) was dissolved in 45mL of DMSO, and then 1g of 4- (dimethylamino) pyridine and 4.27g of glycidyl methacrylate were added to react at room temperature for 48 hours, followed by addition of hydrochloric acid to terminate the reaction, dialysis, and lyophilization, thereby obtaining glycidyl methacrylate-modified poly (2-hydroxyethyl acrylate) having a double bond grafting ratio of 70%.
3) And (3) uniformly mixing 100mg of glycidyl methacrylate modified poly (2-hydroxyethyl acrylate) (the double bond grafting rate is 70%) obtained in the step (2), 900mg of hydroxypropyl methacrylate, 25mg of triethylamine and 0.1mg of eosin Y disodium salt in 5mL of deionized water to obtain the precursor.
2. The hydrogel precursor is used as follows:
dropping the hydrogel precursor onto biological tissue, and illuminating with 20W green light for 120s to make the hydrogel gel and adhere to the biological tissue tightly.
Example 9
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1)200g N-hydroxyethyl acrylamide, 0.122g of methyl 2-chloropropionate and 1.12L of distilled water were charged into a 1.5L flask, degassed by three freeze-pump-thaw cycles, left under nitrogen, charged with 0.149mg of cuprous bromide and 0.345g of tris [2- (dimethylamino) ethyl ] amine, reacted at 25 ℃ for 1h, exposed to air after the reaction was complete, precipitated with methanol, and oven-dried at 65 ℃ to give poly (N-hydroxyethyl acrylamide) (Mn 180 kDa).
2)5g of poly (N-hydroxyethyl acrylamide) (Mn 180kDa) was dissolved in 45mL of DMSO, and then 1g of 4- (dimethylamino) pyridine and 3.786g of glycidyl methacrylate were added to react at room temperature for 48 hours, followed by addition of hydrochloric acid to terminate the reaction, dialysis, and lyophilization, thereby obtaining glycidyl methacrylate-modified poly (N-hydroxyethyl acrylamide) having a double bond grafting rate of 62%.
3) And (3) uniformly mixing 100mg of glycidyl methacrylate modified poly (N-hydroxyethyl acrylamide) (the double bond grafting rate is 62%) obtained in the step (2), 1000mg of N, N-dimethylacrylamide and 0.2mg of terpyridine ruthenium chloride hexahydrate in 5mL of normal saline to obtain the precursor.
2. The hydrogel precursor is used as follows:
and (3) dropwise adding the hydrogel precursor onto the biological tissue, and illuminating for 90s by using 30W blue light to enable the hydrogel to be gelatinized and tightly adhered to the biological tissue.
Example 10
1. The preparation method for rapidly constructing the high-strength hydrogel precursor in situ by visible light comprises the following steps:
1) adding 180g of poly (ethylene glycol) methacrylate, 0.279g of 4-cyano-4- (phenylcarbonylthio) pentanoic acid, 0.41g of azobisisobutyronitrile and 200g of dioxane into a 250mL flask, introducing nitrogen for 30min, reacting at 70 ℃ for 16h, cooling at-20 ℃ after the reaction is finished, exposing in air, precipitating n-hexane, and drying in vacuum to obtain poly (ethylene glycol) methacrylate) (Mn is 180 kDa).
2) Dissolving 1g of poly (ethylene glycol) methacrylate) (Mn ═ 180kDa) in 100mL of deionized water, adding 1.5mL of methacrylic anhydride, uniformly stirring, adjusting the pH to 8-9, reacting in an oil bath kettle at 40 ℃ for 6 hours, dialyzing for 3d, filtering, and freeze-drying to obtain methacrylic anhydride ester modified poly (ethylene glycol) methacrylate with the double bond grafting rate of 38%. 3) And (3) sequentially adding 300mg of N, N-isopropylacrylamide and 0.53mg of zinc porphyrin in 10mL of deionized water into 100mg of methacrylic anhydride modified poly (ethylene glycol) methacrylate) (the double bond grafting rate is 38%) obtained in the step (2) and uniformly mixing to obtain the precursor.
2. The hydrogel precursor is used as follows:
and dripping the hydrogel precursor onto the biological tissue, and illuminating for 30s by using 40W yellow light to enable the hydrogel to be gelatinized and tightly adhered to the biological tissue.
Example 11
The hydrogels formed according to examples 1-9 were tested for lap-shear tensile load strength, T-peel tensile load strength, tensile strength, and wound closure strength according to YY/T0729 "test method for tissue adhesive bonding Performance", to obtain the data in Table 1.
TABLE 1 hydrogel mechanical Properties testing
As can be seen from table 1, the examples within the scope of the claimed invention (examples 1, 2, 3, 4, 6, 8, 9 and 10) all have good lap-shear tensile load-bearing strength, T-peel tensile load-bearing strength, tensile strength and wound closure strength, satisfying the need for biological tissue adhesion, by mechanical property testing of the examples. This is because the hydrogel precursor formulation claimed in the present invention simultaneously defines the double bond grafting rate and the fraction of the toughening monomer of the hydrogel framework material. The double bonds of the hydrogel framework material provide rigidity and mechanical support, and meanwhile, physical action crosslinking points formed by the toughening monomers in the polymerization process can provide good dissipation energy for the hydrogel, so that the toughness of the hydrogel is improved. The combination of hydrogel stiffness and toughness provides the overall lap-shear tensile load strength, T-peel tensile load strength, tensile strength, and wound closure strength of the hydrogel.
When the grafting ratio of the double bonds of the hydrogel skeleton is too low (example 5), the crosslinking points which can be participated in by the hydrogel skeleton are partially reduced, so that the rigidity of the hydrogel is weaker, and the polymerization effect with a toughening monomer is reduced, so that the mechanical property of the hydrogel is poor. When the grafting ratio of the double bonds of the hydrogel skeleton is too high (example 7), the crosslinking density of the hydrogel is too high, and the high crosslinking degree limits the rapid arrangement of the polymer chains along with stress, so that the breakage of the polymer chains and the final breakage of the hydrogel material can be caused under slight external force, and relevant mechanical tests cannot be carried out.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.
Claims (10)
1. A precursor of a high-strength hydrogel quickly constructed in situ by visible light is characterized by comprising 1-500 parts by mass of a high-molecular framework with a double bond grafting rate of 20-80%, 1-1000 parts by mass of a toughening monomer, 0.001-10 parts by mass of an initiator, 0-50 parts by mass of a co-initiator and 1000-10000 parts by mass of an aqueous solution.
2. The precursor of the visible light in-situ fast-constructed high-strength hydrogel according to claim 1, wherein the polymer skeleton comprises natural polymers and synthetic polymers, the natural polymers are hyaluronic acid, sodium alginate, dextran, pullulan, agarose, chitosan, gelatin, collagen, silk fibroin, polypeptides and proteins, and the synthetic polymers are poly (2-hydroxyethyl methacrylate), poly (2-hydroxyethyl acrylate), poly (N-hydroxyethyl acrylamide) and poly (ethylene glycol) methacrylate).
3. The precursor of a high-strength hydrogel capable of being rapidly constructed in situ by visible light according to claim 1, wherein the toughening monomer comprises: hydroxypropyl methacrylate, N-dimethylacrylamide, N-diethylacrylamide, N-isopropylacrylamide and 2-methoxyethyl acrylate.
4. The precursor of a visible light in-situ fast-built high-strength hydrogel according to claim 1, wherein the initiator comprises: zinc porphyrin, eosin Y disodium salt or acid red 87 and ruthenium tris (bipyridyl) chloride hexahydrate.
5. The precursor of a visible light in-situ fast-built high-strength hydrogel according to claim 1, wherein the co-initiator comprises: triethylamine and triethanolamine.
6. A precursor of a visible light fast in situ built high strength hydrogel according to claim 1 wherein said aqueous solution comprises: deionized water, normal saline and phosphate buffer solution.
7. The method for preparing the precursor of the high-strength hydrogel rapidly constructed in situ by visible light according to any one of claims 1 to 6, which is characterized by comprising the following steps:
1) preparing a double-bond-containing polymer skeleton, and controlling the double-bond grafting rate to be 20-80%; the polymer skeleton containing the double structure is a product obtained by reacting anhydride containing the double structure or epoxy compound containing the double structure with the polymer skeleton;
2) mixing the polymer framework obtained in the step 1), a toughening monomer, an initiator, a coinitiator and an aqueous solution to obtain a hydrogel precursor.
8. The use method of the precursor of the visible light in-situ fast constructed high-strength hydrogel as claimed in any one of claims 1 to 6, wherein the hydrogel precursor is dripped on the biological tissue and irradiated by the visible light source, and the hydrogel precursor and the biological tissue can realize in-situ fast gelation.
9. The method as claimed in claim 8, wherein the visible light source comprises blue light, green light and yellow light, the blue light wavelength is 450-470nm, the green light wavelength is 515-530nm, the yellow light wavelength is 585-600nm, and the irradiation time is within 120 seconds.
10. The use method of the precursor of the high-strength hydrogel rapidly constructed in situ by visible light according to claim 8, wherein the overlap-shear tensile load-bearing strength of the hydrogel after being gelled to biological tissues is 50-120 kPa, the T-peel tensile load-bearing strength is 10-50N/m, the tensile strength is 120-200 kPa, and the wound closure strength is 20-60 kPa.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114163658A (en) * | 2021-10-08 | 2022-03-11 | 西北大学 | High-adhesion toughness hydrogel based on rapid controllable orthogonal photochemical reaction and preparation method thereof |
| CN114392387A (en) * | 2021-09-24 | 2022-04-26 | 中山大学中山眼科中心 | Visible light curing biological tissue adhesive material based on natural macromolecules and preparation method and application thereof |
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| CN105131315A (en) * | 2014-11-27 | 2015-12-09 | 华东理工大学 | Non-radical photochemical crosslinked hydrogel material preparation method, product and application |
| CN110818921A (en) * | 2018-08-13 | 2020-02-21 | 中国科学院苏州纳米技术与纳米仿生研究所 | Rapidly-curable double-crosslinked hydrogel and preparation method and application thereof |
| US20200262939A1 (en) * | 2017-11-15 | 2020-08-20 | Zhongshan Guanghe Medical Technology Co., Ltd. | Photo-coupled synergistically crosslinked hydrogel material and its composition, preparation method, use, product, and preparation kit |
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| CN105131315A (en) * | 2014-11-27 | 2015-12-09 | 华东理工大学 | Non-radical photochemical crosslinked hydrogel material preparation method, product and application |
| US20200262939A1 (en) * | 2017-11-15 | 2020-08-20 | Zhongshan Guanghe Medical Technology Co., Ltd. | Photo-coupled synergistically crosslinked hydrogel material and its composition, preparation method, use, product, and preparation kit |
| CN110818921A (en) * | 2018-08-13 | 2020-02-21 | 中国科学院苏州纳米技术与纳米仿生研究所 | Rapidly-curable double-crosslinked hydrogel and preparation method and application thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114392387A (en) * | 2021-09-24 | 2022-04-26 | 中山大学中山眼科中心 | Visible light curing biological tissue adhesive material based on natural macromolecules and preparation method and application thereof |
| CN114163658A (en) * | 2021-10-08 | 2022-03-11 | 西北大学 | High-adhesion toughness hydrogel based on rapid controllable orthogonal photochemical reaction and preparation method thereof |
| CN114163658B (en) * | 2021-10-08 | 2024-01-19 | 西北大学 | High-adhesion toughness hydrogel based on rapid controllable orthogonal photochemical reaction and preparation method thereof |
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