CN115216108A - Hydrogel and preparation method and application thereof - Google Patents
Hydrogel and preparation method and application thereof Download PDFInfo
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- CN115216108A CN115216108A CN202210703027.1A CN202210703027A CN115216108A CN 115216108 A CN115216108 A CN 115216108A CN 202210703027 A CN202210703027 A CN 202210703027A CN 115216108 A CN115216108 A CN 115216108A
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- hydrogel
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Abstract
The invention discloses a hydrogel and a preparation method and application thereof. The hydrogel comprises raw materials including a metal nano-cluster, a methacrylic acylated hyaluronic acid substance and a recombinant human collagen modified by methacrylic anhydride, wherein the metal nano-cluster comprises at least one of a copper nano-cluster, a gold nano-cluster or a silver nano-cluster. The hydrogel disclosed by the invention has good antibacterial performance and good biocompatibility, and has good application prospects in the fields of biomedicine, tissue engineering and regenerative medicine.
Description
Technical Field
The invention relates to the technical field of new materials, in particular to hydrogel and a preparation method and application thereof.
Background
Hydrogel (Hydrogel) is a gel with water as a dispersion medium, is a polymer network system, is soft in property, can keep a certain shape, and can absorb a large amount of water. Due to their wet, soft nature and similarity to extracellular matrices, they are of great interest in the biomedical field. According to whether the hydrogel can respond to external stimulation or not, the hydrogel is divided into traditional hydrogel and intelligent hydrogel. The intelligent hydrogel can respond to the change of external conditions and is a highlight point in hydrogel research. Nowadays, there are many kinds of hydrogels, however, the conventional hydrogels have poor antibacterial properties, which greatly limits their application in biomedicine.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. Therefore, the invention provides the hydrogel which has the characteristic of good antibacterial performance.
The invention also provides a preparation method of the hydrogel.
The invention also provides the ultraviolet responsive hydrogel.
The invention also provides a preparation method of the ultraviolet responsive hydrogel.
The invention also provides a biomedical product.
The invention also provides the application of the hydrogel or the ultraviolet responsive hydrogel or the biomedical product.
In a first aspect of the present invention, a hydrogel is provided, where raw materials of the hydrogel include a metal nanocluster, a methacrylated hyaluronic acid substance, and a methacrylic anhydride-modified recombinant human collagen, and the metal nanocluster includes at least one of a copper nanocluster, a gold nanocluster, or a silver nanocluster.
The hydrogel provided by the embodiment of the invention has at least the following beneficial effects: the metal nano cluster has excellent antibacterial performance, so that the obtained hydrogel has good bacterial resistance, and can be used as an excellent antibacterial biological material. Meanwhile, the materials used by the hydrogel of the invention, namely the recombinant human collagen modified by methacrylic anhydride and the methacrylated hyaluronic acid, have good biocompatibility, so that the obtained hydrogel has good biocompatibility. In addition, the addition of the methacrylated hyaluronic acid substances (belonging to polysaccharides) enables the methacrylic anhydride modified recombinant human collagen (belonging to proteins) to be interacted with the methacrylic anhydride modified recombinant human collagen to be crosslinked to form a composite network, so that the hydrogel has high porosity and average pore size suitable for cell survival. Therefore, the hydrogel has a good application prospect in the fields of biomedicine, tissue engineering and regenerative medicine.
The methacrylic anhydride modified recombinant human collagen is abbreviated as: RHCMA; copper nanoclusters, abbreviated: cuNCs; gold nanoclusters, abbreviation: auNCs; silver nanoclusters, also known as silver nanoclusters (silver nano clusters), are abbreviated as: agNCs.
In some embodiments of the invention, the hydrogel has a killing effect on staphylococcus aureus.
In some embodiments of the invention, the metal nanoclusters have a particle size of 0.1 to 10nm.
In some embodiments of the invention, the methacrylated hyaluronic acid species comprises a methacrylated hyaluronic acid.
Methacryloylated hyaluronic acid, abbreviated as HAMA.
In some preferred embodiments of the present invention, the starting material for the preparation of methacrylated hyaluronic acid comprises hyaluronic acid and methacrylic anhydride.
Methacrylic anhydride, abbreviation: and (5) MA.
In some embodiments of the present invention, the raw material of the hydrogel further comprises water, and the amount of the methacrylic anhydride-modified recombinant human collagen added to the raw material of the hydrogel is (3-30)% g/mL based on the water.
In some preferred embodiments of the present invention, the amount of the methacrylated hyaluronic acid-based substance added to the raw material of the hydrogel is (1-20)% g/mL based on the water.
In some preferred embodiments of the present invention, the metal nanoclusters are added in an amount of 1 to 1000 μ g/mL based on the water in the raw material of the hydrogel.
In some embodiments of the present invention, in the raw material of the hydrogel, the ratio of the addition amount of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, and the metal nanocluster is (0.1-3) g: (0.1-3) g: (300-6000) mu g.
In some embodiments of the present invention, the raw material of the hydrogel further includes water, and the ratio of the addition amount of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, the metal nanoclusters, and the water in the raw material of the hydrogel is (0.1-3) g: (0.1-3) g: (300-6000) μ g: (8-30) mL.
In some preferred embodiments of the present invention, in the raw material of the hydrogel, the ratio of the addition amounts of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, the metal nanoclusters, and the water is (0.5-2.7) g: (0.1-2) g: (510-5000) μ g: (10-30) mL.
In some embodiments of the present invention, the raw material for preparing the methacrylic anhydride modified recombinant human collagen comprises methacrylic anhydride and recombinant human collagen.
The recombinant human collagen is called as follows: and (4) RHC.
In a second aspect of the present invention, a method for preparing a hydrogel is provided, which comprises the following steps: and mixing a mixture I containing the methacrylic anhydride modified recombinant human collagen and water with a metal nano cluster and a methacrylic acylated hyaluronic acid substance to obtain the hydrogel.
The preparation method of the hydrogel provided by the embodiment of the invention has at least the following beneficial effects: the preparation method is simple, the preparation process is simple and mild, and the obtained hydrogel has antibacterial property and biocompatibility and has good application prospect in the fields of biomedicine, tissue engineering and regenerative medicine.
In some embodiments of the present invention, the methacrylic anhydride modified recombinant human collagen is mixed with water to obtain the mixture i.
In some embodiments of the invention, the freeze-dried powder of the methacrylic anhydride modified recombinant human collagen is mixed with water to obtain the mixture I.
In some embodiments of the present invention, the preparation method of the hydrogel comprises preparing the methacrylic anhydride modified recombinant human collagen, and specifically comprises the following operations: and mixing the recombinant human collagen dispersion liquid with methacrylic anhydride to obtain the methacrylic anhydride modified recombinant human collagen.
In some preferred embodiments of the present invention, methacrylic anhydride is added to the recombinant human collagen dispersion to obtain the methacrylic anhydride modified recombinant human collagen.
In some preferred embodiments of the present invention, the recombinant human collagen is mixed with the PBS solution to obtain the recombinant human collagen dispersion.
The PBS solution is also called phosphate buffered saline and has a pH of about 7.4.
In some more preferred embodiments of the present invention, the amount of the recombinant human collagen added is (1-25)% g/mL based on the PBS solution.
In some more preferred embodiments of the invention, the ratio of the volume of the methacrylic anhydride to the volume of the PBS solution is (1-20): 100.
in some preferred embodiments of the present invention, the recombinant human collagen dispersion is mixed with methacrylic anhydride, and neutralized to obtain the methacrylic anhydride modified recombinant human collagen.
In some preferred embodiments of the present invention, the recombinant human collagen dispersion is mixed with methacrylic anhydride, neutralized, dialyzed, and freeze-dried to obtain the methacrylic anhydride modified recombinant human collagen lyophilized powder.
In some preferred embodiments of the present invention, the recombinant human collagen dispersion is mixed with methacrylic anhydride to obtain a mixture ii, the pH is adjusted to 7-8, dialyzed, and freeze-dried to obtain the methacrylic anhydride modified recombinant human collagen.
In some more preferred embodiments of the present invention, methacrylic anhydride is added dropwise to the dispersion of the recombinant human-derived collagen to obtain the mixture ii.
The dropwise addition is preferably slow.
In a third aspect of the present invention, an ultraviolet-responsive hydrogel is provided, where raw materials of the ultraviolet-responsive hydrogel include a metal nanocluster, a methacrylated hyaluronic acid substance, a methacrylic anhydride-modified recombinant human collagen, and a photoinitiator, and the metal nanocluster includes at least one of a copper nanocluster, a gold nanocluster, or a silver nanocluster.
The ultraviolet-responsive hydrogel provided by the embodiment of the invention has at least the following beneficial effects:
according to the invention, a cross-linked body of two materials, namely a protein molecule (methacrylic anhydride modified recombinant human collagen) and a polysaccharide molecule (methacrylic acylated hyaluronic acid substance), is constructed, and the two materials are modified by methacrylic anhydride (modified with MA group) to endow hydrogel with high-efficiency and rapid ultraviolet responsiveness. Due to the added methacrylic anhydride modified Recombinant Human Collagen (RHCMA) and the methacrylic acylated hyaluronic acid substances, the obtained ultraviolet responsive hydrogel can respond to ultraviolet irradiation, and the ultraviolet response is efficient and rapid.
The metal nano-cluster has excellent antibacterial performance, so that the obtained ultraviolet-responsive hydrogel has good bacterial resistance, and can be used as an excellent antibacterial biological material. Meanwhile, the materials used by the ultraviolet responsive hydrogel in the invention, namely the recombinant human collagen modified by methacrylic anhydride and the methacrylic acid-acidified hyaluronic acid substance, have good biocompatibility, and the obtained ultraviolet responsive hydrogel has good biocompatibility. In addition, the methacrylic acylated hyaluronic acid type substances (polysaccharide substances) are added, so that the methacrylic anhydride modified recombinant human collagen (protein substances) is interacted with the methacrylic anhydride modified recombinant human collagen to be crosslinked to form a composite network, and the ultraviolet responsive hydrogel has high porosity and average pore size suitable for cell survival.
Therefore, the obtained ultraviolet-responsive hydrogel has ultraviolet responsiveness, antibacterial property and biocompatibility, and has a good application prospect in the fields of 3D printing, biomedicine, tissue engineering and regenerative medicine.
In some embodiments of the invention, the UV-responsive hydrogel has a UV response time of 0.1 to 100 seconds.
The ultraviolet response time refers to the ultraviolet irradiation time required by curing and molding the ultraviolet response hydrogel from a sol state to a gel state.
In some preferred embodiments of the present invention, the UV-responsive hydrogel has a UV response time of 0.1 to 100s.
In some more preferred embodiments of the present invention, the UV-responsive hydrogel has a UV response time of 0.1 to 12s.
In some more preferred embodiments of the present invention, the UV-responsive hydrogel has a UV response time of 0.5 to 12s.
In some more preferred embodiments of the present invention, the UV-responsive hydrogel has a UV response time of 0.1 to 5s.
In some embodiments of the invention, the UV-responsive hydrogel responds with a UV light intensity of 1-20mW/cm 2 。
In some embodiments of the invention, the photoinitiator is a uv photoinitiator.
In some preferred embodiments of the invention, the photoinitiator comprises an I2959 photoinitiator.
In some preferred embodiments of the present invention, the photoinitiator is an aqueous solution of an I2959 photoinitiator, and the concentration of the I2959 photoinitiator in the aqueous solution of the I2959 photoinitiator is (0.1-5)% g/mL.
In some more preferred embodiments of the present invention, the raw material of the uv-responsive hydrogel further comprises water, and the volume ratio of the I2959 photoinitiator aqueous solution to the water in the raw material of the uv-responsive hydrogel is (1-20): 100.
in some embodiments of the invention, the uv-responsive hydrogel has a killing effect on staphylococcus aureus.
In some embodiments of the invention, the metal nanocluster has a particle size of 0.1 to 10nm.
In some embodiments of the invention, the methacrylated hyaluronic acid species comprises a methacrylated hyaluronic acid.
Methacryloylated hyaluronic acid, abbreviated as HAMA.
In some preferred embodiments of the present invention, the starting material for the preparation of methacrylated hyaluronic acid comprises hyaluronic acid and methacrylic anhydride.
In some embodiments of the present invention, the raw material of the uv-responsive hydrogel further comprises water, and the addition amount of the methacrylic anhydride-modified recombinant human collagen in the raw material of the uv-responsive hydrogel is (3-30)% g/mL based on the water.
In some preferred embodiments of the present invention, the amount of the methacrylated hyaluronic acid-based substance added to the raw material of the uv-responsive hydrogel is (1-20)% g/mL based on the water.
In some preferred embodiments of the present invention, the amount of the metal nanoclusters added to the raw material of the uv-responsive hydrogel is 1 to 1000 μ g/mL based on the water.
In some embodiments of the present invention, in the raw material of the uv-responsive hydrogel, the addition amount ratio of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, and the metal nanocluster is (0.1-3) g: (0.1-3) g: (300-6000) mu g.
In some embodiments of the present invention, in the raw material of the uv-responsive hydrogel, the ratio of the addition amounts of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, the metal nanocluster, and the photoinitiator is (0.1-3) g: (0.1-3) g: (300-6000) μ g: (0.1-1.2) mL.
In some embodiments of the present invention, the raw material of the hydrogel further includes water, and in the raw material of the uv-responsive hydrogel, the addition amount ratio of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, the metal nanoclusters, and the water is (0.1-3) g: (0.1-3) g: (300-6000) μ g: (8-30) mL.
In some embodiments of the present invention, the raw material of the hydrogel further includes water, and in the raw material of the uv-responsive hydrogel, the ratio of the addition amount of the methacrylic anhydride-modified recombinant human collagen, the methacrylated hyaluronic acid-based substance, the metal nanoclusters, the photoinitiator to the water is (0.1-3) g: (0.1-3) g: (300-6000) μ g: (0.1-1.2) mL: (8-30) mL.
In some preferred embodiments of the present invention, in the raw material of the uv-responsive hydrogel, the ratio of the addition amounts of the methacrylic anhydride-modified recombinant human-derived collagen, the methacrylated hyaluronic acid-based substance, the metal nanoclusters, the photoinitiator and the water is (0.5-2.7) g: (0.1-2) g: (510-5000) μ g: (0.1-1) mL: (10-30) mL.
In some embodiments of the present invention, the raw material for preparing the methacrylic anhydride modified recombinant human collagen comprises methacrylic anhydride and recombinant human collagen.
In a fourth aspect of the present invention, a method for preparing an ultraviolet responsive hydrogel is provided, comprising the following steps: and mixing the mixture I containing the methacrylic anhydride modified recombinant human collagen and water with a methacrylic acylated hyaluronic acid substance, a metal nano cluster and a photoinitiator to obtain the ultraviolet responsive hydrogel.
The preparation method of the ultraviolet-responsive hydrogel provided by the embodiment of the invention has at least the following beneficial effects: the preparation method is simple, the preparation process is simple and mild, and the obtained ultraviolet-responsive hydrogel has ultraviolet responsiveness, antibacterial property and biocompatibility and has good application prospects in the fields of 3D printing, biomedicine, tissue engineering and regenerative medicine.
In some embodiments of the present invention, the method for preparing the uv-responsive hydrogel comprises the following steps:
s1, mixing a mixture I containing methacrylic anhydride modified recombinant human collagen and water with a methacrylic acylated hyaluronic acid substance and a metal nano cluster to obtain a mixture III;
and S2, mixing the mixture III with a photoinitiator to obtain the ultraviolet-responsive hydrogel.
In some preferred embodiments of the present invention, in the step S2, the mixture iii is mixed with a photoinitiator to obtain a hydrogel precursor, and the ultraviolet-responsive hydrogel is obtained by ultraviolet irradiation.
In some more preferred embodiments of the present invention, in the step S2, the intensity of the ultraviolet irradiation is 1-20mW/cm 2 。
In some more preferred embodiments of the present invention, in the step S2, the time of the ultraviolet irradiation is 0.1 to 100S.
In some more preferred embodiments of the present invention, in the step S2, the time of the ultraviolet irradiation is 0.1 to 12S.
In some more preferred embodiments of the present invention, in the step S2, the time of the ultraviolet irradiation is 0.5 to 12S.
In some more preferred embodiments of the present invention, in the step S2, the time of the ultraviolet irradiation is 0.1 to 5S.
In some embodiments of the present invention, the methacrylic anhydride modified recombinant human collagen is mixed with water to obtain the mixture i.
In some embodiments of the invention, the freeze-dried powder of the methacrylic anhydride modified recombinant human collagen is mixed with water to obtain the mixture I.
In some embodiments of the present invention, the preparation method of the ultraviolet-responsive hydrogel includes preparing a methacrylic anhydride modified recombinant human collagen, and specifically includes the following operations: and mixing the recombinant human collagen dispersion liquid with methacrylic anhydride to obtain the recombinant human collagen modified by the methacrylic anhydride.
In some preferred embodiments of the present invention, methacrylic anhydride is added to the recombinant human collagen dispersion to obtain the methacrylic anhydride modified recombinant human collagen.
In some preferred embodiments of the present invention, the recombinant human collagen is mixed with the PBS solution to obtain the recombinant human collagen dispersion.
The PBS solution is also called phosphate buffer solution, and the pH value of the PBS solution is about 7.4.
In some more preferred embodiments of the present invention, the amount of the recombinant human collagen added is (1-25)% g/mL based on the PBS solution.
In some more preferred embodiments of the invention, the ratio of the volume of the methacrylic anhydride to the volume of the PBS solution is (1-20): 100.
in some preferred embodiments of the present invention, the recombinant human collagen dispersion is mixed with methacrylic anhydride, and neutralized to obtain the methacrylic anhydride modified recombinant human collagen.
In some preferred embodiments of the present invention, the recombinant human collagen dispersion is mixed with methacrylic anhydride, neutralized, dialyzed, and freeze-dried to obtain the methacrylic anhydride modified recombinant human collagen lyophilized powder.
In some preferred embodiments of the present invention, the recombinant human collagen dispersion is mixed with methacrylic anhydride to obtain a mixture ii, the pH is adjusted to 7-8, dialyzed, and freeze-dried to obtain the methacrylic anhydride modified recombinant human collagen.
In some more preferred embodiments of the present invention, methacrylic anhydride is added dropwise to the recombinant human collagen dispersion to obtain the mixture ii.
The dropwise addition is preferably slow.
In some embodiments of the present invention, the metal nanoclusters are silver nanoclusters, and the method of preparing the silver nanoclusters includes: mixing a mixture IV containing silver nitrate, bovine serum albumin and sodium hydroxide with NaBH 4 And (3) mixing alkaline solutions to obtain the silver nanoclusters.
In some preferred embodiments of the invention, the NaBH is 4 The alkaline solution is NaBH taking 0.1mol/L NaOH aqueous solution as solvent 4 And (4) dissolving the solution.
In a fifth aspect of the invention, a biomedical article is provided comprising the above-described uv-responsive hydrogel.
In a sixth aspect of the present invention, the application of the hydrogel or the ultraviolet responsive hydrogel or the biomedical article in the biomedical field is provided.
Drawings
The invention is further described with reference to the following figures and examples, in which:
FIG. 1 is a photograph of a UV-responsive hydrogel cured by UV light in example 1 of the present invention;
FIG. 2 is a graph showing the microstructure test results of the UV-responsive hydrogel in example 1 of the present invention;
FIG. 3 is a graph showing the results of bacteriostatic experiments on the UV-responsive hydrogel of example 1 of the present invention and the hydrogel of comparative example 1;
FIG. 4 is a graph showing the results of the biocompatibility test of the UV-responsive hydrogel in example 1 of the present invention.
Detailed Description
The concept and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and those skilled in the art can obtain other embodiments without inventive effort based on the embodiments of the present invention, and all embodiments are within the protection scope of the present invention.
The details of the raw materials used in the examples of the present invention are as follows:
recombinant Human Collagen (RHC): jiangsu Jiangshan Congregation Biotechnology Inc., 2290S001;
HA:Lifecore Biomedical(Chaska,MN,USA);
MA:Sigma-Aldrich(St.Louis,MO,USA);
i2959 photoinitiator: sigma-Aldrich (St. Louis, MO, USA);
preparation of HAMA:
HA (hyaluronic acid) was dissolved in deionized water, and after sufficiently stirred and dissolved at room temperature, MA (methacrylic anhydride) was added dropwise with stirring, and the pH was adjusted to neutral (pH = 8) with continued stirring using 1mol/L aqueous NaOH solution. Transferring to dialysis bag, dialyzing, and freeze drying to obtain HAMA. Wherein the molar ratio of HA, water and MA is about 1:2107:5.
preparation of AgNCs: mixing AgNO 3 Mixing with BSA under stirring for 10min; adding solid NaOH, and stirring for 15min; dropwise addition of NaBH 4 Solution (NaBH using 0.1mol/L NaOH aqueous solution as solvent) 4 Dissolving solution), stirring for 1h; and (5) purifying by using an ultrafiltration tube to obtain AgNCs. Wherein AgNO 3 、BSA、NaOH、NaBH 4 In a molar ratio of 1:0.00074:6:0.504. the grain diameter of the obtained AgNCs is 0.1-10nm.
Wherein, BSA: namely, bovine Serum Albumin, which is known in Chinese as Bovine Serum Albumin.
In addition, according to the experimental needs, a proper amount of HAMA or AgNCs can be prepared according to the preparation method.
The PBS solution is also called phosphate buffered saline and has a pH of about 7.4.
Example 1
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 1.5g of RHC powder was added to 10mL of PBS solution and stirred well to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 1mL of MA into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHC MA solution, neutralizing the solution, transferring the solution to a dialysis bag for dialysis, and freeze-drying to obtain the RHC MA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 1.5g of RHCMA lyophilized powder to 10mL of aqueous solution, stirring thoroughly, then adding 1.5g of HAMA and 510. Mu.g of AgNCs, stirring thoroughly mechanically, adding 0.5mL of I2959 photoinitiator aqueous solution (wherein the concentration of I2959 photoinitiator in the I2959 photoinitiator aqueous solution is 2% g/mL), and obtaining the antibacterial UV-responsive hydrogel.
The ultraviolet responsive hydrogel is subjected to ultraviolet light (the wavelength is 365nm, and the intensity is 11 mW/cm) 2 ) The setting process can be completed by irradiating for 10 s.
FIG. 1 is a photograph of a hydrogel cured after UV irradiation; FIG. 2 is an SEM image of a cured UV-responsive hydrogel showing high porosity (about 53.166%) and an average pore size suitable for cell survival (about 28.7 μm) as calculated by ImageJ software.
This example also discloses a biomedical article comprising the uv-responsive hydrogel prepared in this example.
Example 2
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 0.5g of RHC powder was added to 10mL of PBS solution and sufficiently stirred to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 0.5mL of MA into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHCMA solution, neutralizing the solution, transferring the solution into a dialysis bag for dialysis, and freeze-drying to obtain the RHCMA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 0.5g RHCMA lyophilized powder to 10mL of the aqueous solution, stirring thoroughly, then adding 0.1g HAMA and 510 μ g AgNCs, stirring thoroughly mechanically, adding 0.5mL of the aqueous solution of I2959 photoinitiator (wherein the concentration of I2959 photoinitiator in the aqueous solution of I2959 photoinitiator is 0.5% g/mL), and obtaining the antibacterial UV-responsive hydrogel.
The ultraviolet responsive hydrogel is subjected to ultraviolet light (the wavelength is 365nm, and the intensity is 11 mW/cm) 2 ) The setting process can be completed by irradiating for 3 s.
Example 3
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 1g of RHC powder was added to 12mL of PBS solution and stirred well to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 0.3mL of MA solution into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHCMA solution, neutralizing the solution, transferring the solution into a dialysis bag for dialysis, and freeze-drying to obtain the RHCMA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 1.5g of RHCMA lyophilized powder to 10mL of the aqueous solution, stirring thoroughly, then adding 0.3g of HAMA and 700. Mu.g of AgNCs, stirring thoroughly mechanically, adding 0.2mL of I2959 photoinitiator aqueous solution (wherein the concentration of I2959 photoinitiator in the I2959 photoinitiator aqueous solution is 1 g/mL), and obtaining the antibacterial UV-responsive hydrogel.
Ultraviolet ray (wavelength 365nm, intensity 5 mW/cm) 2 ) The 12s irradiation completes the setting process.
This example also discloses a biomedical article comprising the uv-responsive hydrogel prepared in this example.
The experimental results of this example are comparable to example 1.
Example 4
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 1g of RHC powder was added to 25mL of PBS solution and stirred well to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 0.6mL of MA into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHCMA solution, neutralizing the solution, transferring the solution to a dialysis bag for dialysis, and freeze-drying to obtain the RHCMA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 2.5g of RHCMA lyophilized powder to 30mL of aqueous solution, stirring thoroughly, then adding 0.8g of HAMA and 780. Mu.g of AgNCs, stirring thoroughly mechanically, adding 0.1mL of I2959 photoinitiator aqueous solution (wherein the concentration of I2959 photoinitiator in the I2959 photoinitiator aqueous solution is 2% g/mL), and obtaining the antibacterial ultraviolet responsive hydrogel.
Ultraviolet ray (wavelength 365nm, intensity 15 mW/cm) 2 ) The setting process can be completed by irradiating for 10 s.
This example also discloses a biomedical article comprising the uv-responsive hydrogel prepared in this example.
The experimental results of this example are comparable to example 1.
Example 5
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 1g of RHC powder was added to 8mL of PBS solution and stirred well to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 0.8mL of MA into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHCMA solution, neutralizing the solution, transferring the solution to a dialysis bag for dialysis, and freeze-drying to obtain the RHCMA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 2.5g of RHCMA lyophilized powder to 10mL of the aqueous solution, stirring thoroughly, then adding 1.1g of HAMA and 1800. Mu.g of AgNCs, stirring thoroughly mechanically, adding 0.6mL of I2959 photoinitiator aqueous solution (wherein the concentration of I2959 photoinitiator in the I2959 photoinitiator aqueous solution is 3% g/mL), and obtaining the antibacterial UV-responsive hydrogel.
Ultraviolet ray (wavelength 365nm, intensity 5 mW/cm) 2 ) The setting process can be completed by irradiating for 6 s.
This example also discloses a biomedical article comprising the uv-responsive hydrogel prepared in this example.
The experimental results of this example are comparable to example 1.
Example 6
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 1.8g of RHC powder was added to 21mL of PBS solution and stirred well to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 0.9mL of MA into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHCMA solution, neutralizing the solution, transferring the solution to a dialysis bag for dialysis, and freeze-drying to obtain the RHCMA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 2.7g of RHCMA lyophilized powder to 10mL of the aqueous solution, stirring thoroughly, then adding 2g of HAMA and 3000. Mu.g of AgNCs, stirring thoroughly mechanically, adding 1mL of I2959 photoinitiator aqueous solution (wherein the concentration of I2959 photoinitiator in the I2959 photoinitiator aqueous solution is 1.5% g/mL), and obtaining the antibacterial UV-responsive hydrogel.
By ultraviolet light (wavelength 365nm, intensity 5 mW/cm) 2 ) The setting process can be completed by irradiating for 5s.
This example also discloses a biomedical article comprising the UV-responsive hydrogel prepared in this example.
The experimental results of this example are comparable to example 1.
Example 7
The embodiment discloses an ultraviolet responsive hydrogel, which is prepared by the following steps:
(I) 2.7g of RHC powder was added to 21mL of PBS solution and sufficiently stirred to obtain a uniform RHC dispersion.
And (II) slowly dropwise adding 0.6mL of MA into the RHC dispersion liquid, fully stirring until the reaction is complete to obtain an RHCMA solution, neutralizing the solution, transferring the solution into a dialysis bag for dialysis, and freeze-drying to obtain the RHCMA freeze-dried powder. Wherein the neutralization treatment is to adjust the pH to be about 7-8 by using 1mol/L NaOH aqueous solution.
(III) adding 2.7g of RHCMA lyophilized powder to 10mL of the aqueous solution, sufficiently stirring, subsequently adding 2g of HAMA and 5000. Mu.g of AgNCs, sufficiently mechanically stirring, and adding 1mL of an I2959 photoinitiator aqueous solution (wherein the concentration of the I2959 photoinitiator in the I2959 photoinitiator aqueous solution is 0.3% g/mL), thereby obtaining the antibacterial UV-responsive hydrogel.
By ultraviolet light (wavelength 365nm, intensity 16 mW/cm) 2 ) The setting process can be completed by irradiating for 0.5 s.
This example also discloses a biomedical article comprising the UV-responsive hydrogel prepared in this example.
The experimental results of this example are comparable to example 1.
Comparative example 1
This comparative example discloses an ultraviolet-responsive hydrogel, which is different from example 1 in that AgNCs are not added in step (III) of this comparative example.
Test examples
This test example was subjected to a performance test on the ultraviolet-responsive hydrogels prepared in example 1 and comparative example 1. The method comprises the following steps:
(1) And (3) testing the bacteriostatic effect:
the method specifically comprises the following steps: LB solid Medium-coated Staphylococcus aureus (about 10) 8 CFU/mL of 100 mu L of bacteria), placing hydrogel blocks of a control group (comparative example 1) and an experimental group (example 1), and observing and recording the size of the inhibition zone after 36 h.
Wherein, the staphylococcus aureus is purchased from Beijing biological collection center, and the strain number is ATCC25923.
The experimental results of the zone of inhibition for the uv-responsive hydrogels of example 1 and comparative example 1 are shown in fig. 3:
the size of the zone of inhibition was observed, and the diameter of the zone of inhibition was read by a ruler, the zone of inhibition was not generated in the control group (comparative example 1, left side) (zone of inhibition diameter is 0 mm), and the zone of inhibition diameter in the experimental group (example 1, right side) was about 18mm. Therefore, the bacteriostatic effect of the uv-responsive hydrogel in example 1 was significantly better than that of the hydrogel in comparative example 1.
(2) And (3) testing the biocompatibility:
the method specifically comprises the following steps: adding 100 μ L of 4 × 10 concentration into 96-well plate 4 After each/mL of NIH3T3 cell suspension (NIH 3T3 cells, extracted by the inventor's laboratory), a common culture medium and a hydrogel immersion liquid are respectively added into a control group and a hydrogel group (each group is provided with 3 repeated holes), CCK8 solution is added after 3 days of culture for incubation for 2 hours, and then the absorption value at the wavelength of 450nm is measured.
Wherein, the common culture medium is RPMI 1640 basic medium +10% Fetal Bovine Serum (FBS) +1% penicillin/streptomycin, that is, the volume ratio of the RPMI 1640 basic medium, the fetal bovine serum and the penicillin/streptomycin is 89.
In the hydrogel group, the hydrogel immersion liquid was obtained by immersing the ultraviolet-responsive hydrogel obtained in example 1 in a common medium.
The measured biocompatibility results are shown in fig. 4: the ultraviolet-responsive hydrogel obtained in example 1 has better biocompatibility.
In conclusion, the invention constructs the cross-linked body of two materials, namely a protein molecule (methacrylic anhydride modified recombinant human collagen) and a polysaccharide molecule (methacrylic acylated hyaluronic acid substance), wherein the two materials are both modified by methacrylic anhydride (modified by MA group) to endow hydrogel with high-efficiency and quick ultraviolet responsiveness. Due to the addition of methacrylic anhydride modified Recombinant Human Collagen (RHCMA) and methacrylic acid hyaluronic acid (HAMA), the RHCMA and the HAMA can simultaneously respond to ultraviolet, the obtained ultraviolet responsive hydrogel can respond to ultraviolet irradiation, the ultraviolet response is efficient and quick, and the irradiation intensity is 1-20W/cm 2 Under the condition of (2), the curing can be realized only in 0.1-100s.
The metal nano-cluster has excellent antibacterial performance, so that the obtained ultraviolet responsive hydrogel has good bacterial resistance, and can be used as an excellent antibacterial biological material. Meanwhile, the materials used in the ultraviolet responsive hydrogel of the invention, namely the recombinant human collagen modified by methacrylic anhydride and the methacrylic acid hyaluronic acid, have good biocompatibility, and the obtained ultraviolet responsive hydrogel has good biocompatibility. In addition, HAMA and RHCMA are proteins and polysaccharides, respectively, which interact to crosslink (e.g., via covalent and electrostatic bonds) to form a complex network, such that the uv-responsive hydrogel has high porosity and an average pore size suitable for cell survival.
Meanwhile, the preparation method of the ultraviolet responsive hydrogel is simple, and the preparation process is simple and mild.
In conclusion, the ultraviolet-responsive hydrogel disclosed by the invention has multiple advantages of ultraviolet responsiveness, antibacterial property, biocompatibility and the like, and has a good application prospect in the fields of 3D printing, biomedicine, tissue engineering and regenerative medicine.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is specific and detailed, but not to be understood as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention.
Claims (10)
1. The hydrogel is characterized in that raw materials of the hydrogel comprise metal nanoclusters, a methacrylic acylated hyaluronic acid substance and methacrylic anhydride modified recombinant human collagen, wherein the metal nanoclusters comprise at least one of copper nanoclusters, gold nanoclusters or silver nanoclusters.
2. A method for preparing the hydrogel of claim 1, comprising the steps of: and mixing a mixture I containing the methacrylic anhydride modified recombinant human collagen and water with a metal nano cluster and a methacrylic acylated hyaluronic acid substance to obtain the hydrogel.
3. The ultraviolet-responsive hydrogel is characterized in that raw materials of the ultraviolet-responsive hydrogel comprise a metal nanocluster, a methacryloylated hyaluronic acid substance, a methacrylic anhydride modified recombinant human collagen and a photoinitiator, wherein the metal nanocluster comprises at least one of a copper nanocluster, a gold nanocluster or a silver nanocluster.
4. The UV-responsive hydrogel according to claim 3, wherein the UV-responsive hydrogel has a UV response time of 0.1 to 100s.
5. The uv-responsive hydrogel according to claim 3, wherein the methacrylated hyaluronic acid-like substance comprises methacrylated hyaluronic acid; preferably, the raw material of the ultraviolet-responsive hydrogel further comprises water, and the addition amount of the methacrylic anhydride-modified recombinant human collagen in the raw material of the ultraviolet-responsive hydrogel is (3-30)% g/mL based on the water; preferably, in the raw material of the ultraviolet responsive hydrogel, the addition amount of the methacrylated hyaluronic acid-based substance is (1-20)% g/mL based on the water; preferably, in the raw material of the ultraviolet-responsive hydrogel, the addition amount of the metal nanoclusters is 1-1000 μ g/mL based on the water.
6. A method for preparing the uv-responsive hydrogel of claim 3, comprising the steps of: and mixing the mixture I containing the methacrylic anhydride modified recombinant human collagen and water with a methacrylic acylated hyaluronic acid substance, a metal nano cluster and a photoinitiator to obtain the ultraviolet responsive hydrogel.
7. The method for producing an ultraviolet-responsive hydrogel according to claim 6, comprising the steps of:
s1, mixing a mixture I containing methacrylic anhydride modified recombinant human collagen and water with a methacrylic acylated hyaluronic acid substance and a metal nano cluster to obtain a mixture III;
and S2, mixing the mixture III with a photoinitiator to obtain the ultraviolet-responsive hydrogel.
8. The method for preparing the ultraviolet-responsive hydrogel according to claim 6, wherein the method for preparing the ultraviolet-responsive hydrogel comprises the step of preparing the methacrylic anhydride modified recombinant human collagen, and specifically comprises the following operations: and mixing the recombinant human collagen dispersion liquid with methacrylic anhydride to obtain the methacrylic anhydride modified recombinant human collagen.
9. A biomedical article comprising the uv-responsive hydrogel of any of claims 3 to 5 or the uv-responsive hydrogel produced by the method of any of claims 6 to 8.
10. Use of a hydrogel according to claim 1 or a hydrogel prepared by the method of claim 2 or a uv-responsive hydrogel according to any one of claims 3 to 5 or a uv-responsive hydrogel prepared by the method of any one of claims 6 to 8 or a biomedical article according to claim 9 in the biomedical field.
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117339016A (en) * | 2023-12-04 | 2024-01-05 | 北京大学口腔医学院 | Bionic composite material containing nano gold clusters and preparation method and application thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105733032A (en) * | 2016-02-26 | 2016-07-06 | 湖北大学 | Preparation method and application of silver nanocluster gel |
CN110790950A (en) * | 2019-10-21 | 2020-02-14 | 南京理工大学 | Photo-crosslinking recombinant collagen hydrogel, preparation method and application thereof in 3D bioprinting |
CN114524953A (en) * | 2022-03-20 | 2022-05-24 | 山西医科大学 | Silk fibroin/hyaluronic acid composite hydrogel, preparation method and application |
-
2022
- 2022-06-21 CN CN202210703027.1A patent/CN115216108A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105733032A (en) * | 2016-02-26 | 2016-07-06 | 湖北大学 | Preparation method and application of silver nanocluster gel |
CN110790950A (en) * | 2019-10-21 | 2020-02-14 | 南京理工大学 | Photo-crosslinking recombinant collagen hydrogel, preparation method and application thereof in 3D bioprinting |
CN114524953A (en) * | 2022-03-20 | 2022-05-24 | 山西医科大学 | Silk fibroin/hyaluronic acid composite hydrogel, preparation method and application |
Non-Patent Citations (1)
Title |
---|
HUAN XIAO ET.AL.: "《Nursing effect of hyaluronic acid/silver nanoclusters on patients after total laryngectomy》", 《NANOSCIENCE AND NANOTECHNOLOGY LETTERS》, vol. 12, pages 1406 - 1412 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117339016A (en) * | 2023-12-04 | 2024-01-05 | 北京大学口腔医学院 | Bionic composite material containing nano gold clusters and preparation method and application thereof |
CN117339016B (en) * | 2023-12-04 | 2024-03-01 | 北京大学口腔医学院 | Bionic composite material containing nano gold clusters and preparation method and application thereof |
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