Nanoparticle composite hydrogel material

Abstract

The invention relates to the technical field of biomedical materials, in particular to a nanoparticle composite hydrogel material. Comprising functional nanoparticles, a hydrogel base material, a light absorber, a photoinitiator and a binder, the preparation method comprises the following steps: 1, dissolving a hydrogel base material to obtain a hydrogel solution; 2, dissolving a photoinitiator and a light absorbent in the hydrogel solution to obtain a hydrogel precursor solution; step 3, adding functional nanoparticles into the hydrogel precursor solution to obtain an antibacterial nanoparticle composite hydrogel precursor solution; step 4, adding a binder into the antibacterial nano-particle composite hydrogel precursor solution, and carrying out curing treatment to obtain cured antibacterial nano-particle composite hydrogel; 5, freeze-drying treatment is conducted on the cured antibacterial nano-particle composite hydrogel, the interior of the material has a pore structure and a wrinkled structure, and the applicability and performance of the nano-particle composite hydrogel are effectively improved.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, and in particular to a nano-particle composite hydrogel material. Background Art

[0002] Bone defects are a huge challenge in clinical work, which are mainly caused by traffic accidents, nonunion of fractures, bone tumor resection and other factors. At present, more than 6 million people in China suffer from bone defects or dysfunction diseases every year, of which about 2 / 3 of patients need bone transplantation treatment. It is estimated that by 2050, the cost of bone defect treatment and care will reach 620 billion yuan. Bone defects can have a serious impact on the life and health of patients. Autologous transplantation is limited by the insufficient supply of donor sites. There are many challenges such as poor quality of donor bone, limited quantity, easy infection, difficult shape and size matching, and wound healing problems. In addition, there is also a huge demand for skin wound repair. During the wound repair process, since microorganisms can easily invade the wound, it may cause infection and hinder wound healing, and even cause tissue damage or death.

[0003] Currently, medical nanocomposite hydrogels have been introduced into tissue self-repair, but the current nanocomposite hydrogels still have shortcomings: although the nanoparticles are located inside the hydrogel, the hydrogel structure tightly encapsulates the nanoparticles, and the function of the nanoparticles can only be realized after the hydrogel is released, that is, only the drug-carrying function of the nanoparticles can be utilized. It can be seen that the current nanocomposite hydrogel functions are still limited and cannot target different injuries well. Summary of the invention

[0004] In order to solve the problems of poor quality and difficult shape matching of autologous bone and easy infection of skin wounds, the present invention proposes a nanoparticle composite hydrogel material. The nanoparticle composite hydrogel mixes functional nanoparticles with hydrogel and has a porous structure and a wrinkled structure inside, which effectively improves the applicability and performance of the nanoparticle composite hydrogel.

[0005] In order to achieve the above-mentioned purpose of the invention, the following technical solutions are provided:

[0006] A nanoparticle composite hydrogel material is provided, comprising the following raw materials in percentage by weight:

[0007] Functional nanoparticles 0.01%~30%

[0008] Hydrogel base material 1%~20%

[0009] Light absorber 0.01%~0.1%

[0010] Photoinitiator 0.1%~1%

[0011] Binder 0%~10%;

[0012] It is prepared by the following steps, including:

[0013] Step 1, dissolving the hydrogel substrate in deionized water to obtain a hydrogel solution;

[0014] Step 2: dissolving the photoinitiator and the light absorber in the hydrogel solution and fully shaking and mixing to obtain a hydrogel precursor solution;

[0015] Step 3, adding the functional nanoparticles into the hydrogel precursor solution, and mixing them thoroughly to make the functional nanoparticles evenly dispersed in the hydrogel precursor solution, to obtain a nanoparticle composite hydrogel precursor solution;

[0016] Step 4: adding a binder to the functional nanoparticle composite hydrogel precursor solution, mixing evenly, and then performing a curing treatment to obtain a cured functional nanoparticle composite hydrogel;

[0017] Step 5: freeze-drying the solidified functional nanoparticle composite hydrogel to form a pore structure and / or a wrinkle structure inside the solidified functional nanoparticle composite hydrogel.

[0018] In some embodiments, the hydrogel substrate includes a degradable hydrogel substrate and / or a non-degradable hydrogel substrate.

[0019] In some embodiments, the degradable hydrogel substrate includes one or any two or more components selected from the group consisting of methacrylamide gelatin, chitosan, hydrolyzed hyaluronic acid methacrylamide, and polyethylene glycol diacrylate.

[0020] In some embodiments, the non-degradable hydrogel substrate includes one or any two or more components of polyvinyl alcohol, polyacrylamide, and polyurethane.

[0021] In some embodiments, the light absorber includes one or any two or more components of tartrazine, organic dyes, and nanoparticles.

[0022] In some embodiments, the photoinitiator includes one or any two or more components of sodium curcumin and lithium phenyl-2,4,6-trimethylbenzoyl phosphite.

[0023] In some embodiments, the functional nanoparticles include antibacterial nanoparticles, which include one or any two or more components of nanodiamond, nanosilver, and nanogold.

[0024] In some embodiments, the antibacterial nanoparticles have a diameter of about 2 nm to 900 nm.

[0025] In some embodiments, the binder includes one or any two or more components of N-hydroxysuccinimide acrylate, catechol, and tannic acid.

[0026] In some embodiments, in step 4, the curing method includes in-situ curing or mold curing, wherein the in-situ curing is performed by placing a light source of a specific wavelength at a distance of 1 cm to 30 cm from the antibacterial nanoparticle composite hydrogel precursor solution and irradiating for 10s to 210s;

[0027] Step 5: In the freeze-drying process, the freezing time is 2 to 15 hours, the freezing temperature is -80°C to -20°C, and the drying time is 30 hours to 60 hours.

[0028] Beneficial effects of the nanoparticle composite hydrogel material of the present invention:

[0029] (1) A nanoparticle composite hydrogel material of the present invention, which mixes hydrogel and functional nanoparticles and, in the process of preparing the nanoparticle composite hydrogel material, uses freeze-drying technology to make the nanoparticle composite hydrogel material have a porous structure inside. Among them, the hydrogel mechanics and mechanical capacity are improved by compounding the hydrogel with different nanoparticles; by regulating the curing means and freeze-drying technology, not only can the nanoparticle composite hydrogel material have a porous structure inside, but also the size of the pore structure and the proportion of the wrinkle structure are regulated, and the internal microstructure of the nanoparticle composite hydrogel material is increased, so that when the hydrogel absorbs the liquid exuded from the wound surface, the nanoparticles can also resist external bacteria, and the nanoparticles have a positive promoting effect on cell proliferation and cell adhesion. At the same time, the internal microstructure can form an oxygen exchange site, improve the functionality of the nanoparticles and enable the wound site to exchange oxygen in time, improve the repair effect of the nanoparticle composite hydrogel, so that the rice particle composite hydrogel can not only repair soft tissue, but also effectively improve the mechanical properties of the nanoparticle composite hydrogel, which is beneficial to the treatment of hard tissue.

[0030] (2) The nanoparticle composite hydrogel material of the present invention improves the performance, mechanical properties and other properties of the composite hydrogel by controlling the addition of functional nanoparticle components, and at the same time selects the type and ratio of the hydrogel substrate to enhance adhesion to the tissue so as to improve the repair ability of the biological tissue. Subsequently, by controlling the ratio of each component and the curing parameters, a new type of nanoparticle composite hydrogel material with controllable internal microscopic shape and adjustable performance is prepared.

[0031] (3) The nanoparticle composite hydrogel material of the present invention achieves the purpose of regulating the internal structure of the nanoparticle composite hydrogel by changing the nanoparticles and the post-processing technology of freeze-drying, and at the same time it can enhance the performance of the nanoparticle composite hydrogel. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Schematic diagram of cross-linking of the hydrogel of Experimental Example 1 of the present invention.

[0033] Figure 2 Schematic diagram of cross-linking of the nano-diamond composite hydrogel of Experimental Example 1 of the present invention.

[0034] Figure 3 Internal morphology of the nano-diamond composite hydrogel of Experimental Example 1 of the present invention.

[0035] Figure 4 Morphological diagram of the nano-diamond composite hydrogel promoting cell adhesion in Experimental Example 1 of the present invention.

[0036] Figure 5 A diagram showing the effect of the nano-diamond composite hydrogel of Experimental Example 1 of the present invention in promoting wound healing.

[0037] Figure 6 This is a cell fluorescence image of the nano-diamond composite hydrogel attached to the TPMS scaffold of Experimental Example 2 of the present invention.

[0038] Figure 7 This is a CT image of the bone defect repaired by the scaffold in Experimental Example 2 of the present invention. DETAILED DESCRIPTION

[0039] The preferred embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. Although the preferred embodiments of the present invention are shown in the accompanying drawings, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided to make the present invention more thorough and complete, and to fully convey the scope of the present invention to those skilled in the art.

[0040] The terms used in the present invention are only for the purpose of describing specific implementation regulations, and are not intended to limit the present invention. The singular forms "a", "the" used in the present invention and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings. It should also be understood that the term "and / or" used in this article refers to and includes any or all possible combinations of one or more associated listed items.

[0041] It should be understood that although the terms "first", "second", "third", etc. may be used to describe various information in the present invention, such information should not be limited to these terms. These terms are only used to distinguish the same type of information from each other. For example, without departing from the scope of the present invention, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information. Thus, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "multiple" is two or more, unless otherwise clearly and specifically defined.

[0042] Example 1

[0043] This embodiment discloses a nanoparticle composite hydrogel material, comprising the following raw materials in percentage by mass:

[0044] Functional nanoparticles 0.01%, the functional nanoparticles can be drug-carrying or antibacterial, and their specific functions can be selected according to actual needs. Functional nanoparticles are used to enrich the internal structure of the composite hydrogel.

[0045] Hydrogel base material 1%

[0046] Light absorber 0.01%

[0047] Photoinitiator 0.1%;

[0048] It is prepared by the following steps, including:

[0049] Step 1, dissolving the hydrogel substrate in deionized water to obtain a hydrogel solution, which has injectability and fluidity;

[0050] Step 2: dissolving the photoinitiator and the light absorber in the hydrogel solution and fully shaking and mixing to obtain a hydrogel precursor solution;

[0051] Specifically, the target content of photoinitiator and light absorber is dissolved in the hydrogel solution obtained in step 1 to obtain a complete hydrogel precursor solution. Its role is that, since free radicals are short-lived, the cross-linking reaction only occurs under specific lighting conditions, so by controlling the content of photoinitiator and light absorber, the wavelength of excitation light and the illumination time, the degree of photocuring can be accurately controlled. Further, the configured hydrogel precursor solution is fully oscillated to fully dissolve each material component in deionized water to obtain a uniform hydrogel precursor solution. Nanoparticles can improve the mechanical properties, swelling properties, degradation properties and other properties of the hydrogel. Secondly, nanoparticles can also play a functional role to realize the functionality of the material.

[0052] Step 3, adding the functional nanoparticles into the hydrogel precursor solution, and mixing them thoroughly to make the functional nanoparticles evenly dispersed in the hydrogel precursor solution, to obtain a nanoparticle composite hydrogel precursor solution;

[0053] The functional nanoparticles are evenly dispersed in the hydrogel precursor solution by means of an oscillator, ultrasonic dispersion, high-pressure homogenization, chemical dispersion, etc., with the aim of obtaining a more fully fused nanoparticle composite hydrogel precursor solution.

[0054] Step 4: adding a binder to the nanoparticle composite hydrogel precursor solution, mixing evenly, and then performing a curing treatment to obtain a cured antibacterial nanoparticle composite hydrogel;

[0055] Place the nanoparticle composite hydrogel precursor solution in a water bath or thermostat at about 37°C to keep it warm, then place a light source of a specific wavelength at 1 cm to irradiate for 10 seconds. The gel can be formed by in-situ curing, or the nanoparticle composite hydrogel precursor solution can be injected into the mold for curing. Different nanoparticle sizes and different mass proportions will produce reflection and refraction when the light source is irradiated and cured. Therefore, it is necessary to determine different cross-linking reaction times for nanoparticle composite hydrogel precursor solutions with different particle sizes and different mass proportions, and the cross-linking time varies from 10 seconds.

[0056] Step 5: freeze-drying the solidified nanoparticle composite hydrogel to form a pore structure and / or a wrinkle structure inside the solidified nanoparticle composite hydrogel.

[0057] Specifically, the formed nanoparticle composite hydrogel is then post-processed by freeze drying, and the internal pores and other structures of the nanoparticle composite hydrogel sample are adjusted by freeze drying. The post-processing technology includes but is not limited to freeze drying, electrical stimulation, thermal stimulation, etc. The nanoparticle composite hydrogel is freeze-dried, and the internal structure of the nanoparticle composite hydrogel can be regulated by adjusting parameters such as freezing time, freezing temperature, drying time, and drying temperature to obtain repair capabilities for different scenarios.

[0058] In this embodiment, the hydrogel substrate includes a degradable hydrogel substrate and / or a non-degradable hydrogel substrate.

[0059] In this embodiment, the degradable hydrogel substrate includes one or any two or more components selected from methacrylamide gelatin, chitosan, hydrolyzed hyaluronic acid methacrylamide, and polyethylene glycol diacrylate. The specific components can be selected according to actual needs and are not limited here.

[0060] In this embodiment, the non-degradable hydrogel substrate includes one or any two or more components of polyvinyl alcohol, polyacrylamide, and polyurethane. The specific components can be selected according to actual needs and are not limited here.

[0061] In this embodiment, the light absorber includes one or any two or more components of lemon yellow, organic dyes, and nanoparticles, which can be selected according to actual needs and are not limited here.

[0062] In this embodiment, the photoinitiator includes one or any two or more components selected from sodium curcuma and phenyl-2,4,6-trimethylbenzoyl lithium phosphite. The specific selection can be made according to actual needs and is not limited here.

[0063] In this embodiment, the functional nanoparticles are antibacterial nanoparticles, which include one or any two or more components of nanodiamond, nanosilver, and nanogold. The specific selection can be made according to actual needs and is not limited here.

[0064] In this embodiment, the functional nanoparticles are antibacterial nanoparticles, and the diameter of the antibacterial nanoparticles is about 2nm to 900nm.

[0065] In this embodiment, in step 4, the curing method includes in-situ curing or mold curing, which can be selected according to actual needs and is not limited here.

[0066] The in-situ curing is performed by placing a light source of a specific wavelength at a distance of 1 cm from the composite hydrogel precursor solution to which the antibacterial nanoparticles are added and irradiating for 10 seconds;

[0067] Step 5: In the freeze-drying process, the freezing time is 2 hours, the freezing temperature is -80°C and the drying time is 30 hours.

[0068] Example 2

[0069] This embodiment discloses a nanoparticle composite hydrogel material, comprising the following raw materials in percentage by mass:

[0070] Functional nanoparticles 30%, the functional nanoparticles can be drug-carrying or antibacterial, and their specific functions can be selected according to actual needs. Functional nanoparticles are used to enrich the internal structure of the composite hydrogel and control the performance of the composite hydrogel.

[0071] Hydrogel base material 20%

[0072] Light absorber 0.1%

[0073] Light 1%

[0074] Binder 10%;

[0075] It is prepared by the following steps, including:

[0076] Step 1, dissolving the hydrogel substrate in deionized water to obtain a hydrogel solution, which has injectability and fluidity;

[0077] Step 2: dissolving the photoinitiator and the light absorber in the hydrogel solution and fully shaking and mixing to obtain a hydrogel precursor solution;

[0078] Specifically, the target content of photoinitiator and light absorber is dissolved in the hydrogel solution obtained in step one to obtain a complete hydrogel precursor solution. Its function is that, since free radicals are short-lived, the cross-linking reaction only occurs under specific lighting conditions. Therefore, by controlling the content of photoinitiator and light absorber, the wavelength of excitation light and the illumination time, the degree of photocuring can be accurately controlled. Further, the configured hydrogel precursor solution is fully oscillated so that each material component is fully dissolved in deionized water to obtain a uniform hydrogel precursor solution. Step three, add functional nanoparticles to the hydrogel precursor solution, mix thoroughly, so that the functional nanoparticles are evenly dispersed in the hydrogel precursor solution, and obtain a nanoparticle composite hydrogel precursor solution;

[0079] The functional nanoparticles are evenly dispersed in the hydrogel precursor solution by means of an oscillator, ultrasonic dispersion, high-pressure homogenization, chemical dispersion, etc., with the aim of obtaining a more fully fused nanoparticle composite hydrogel precursor solution.

[0080] Step 4: adding a binder to the nanoparticle composite hydrogel precursor solution, mixing evenly, and then performing a curing treatment to obtain a cured nanoparticle composite hydrogel;

[0081] Place the nanoparticle composite hydrogel precursor solution in a water bath or thermostat at about 37°C to keep it warm, then place a light source of a specific wavelength at 30cm and irradiate for 210s. The gel can be formed by in-situ curing, or the nanoparticle composite hydrogel precursor solution can be injected into the mold for curing. Different nanoparticle sizes and different mass proportions will produce reflection and refraction when the light source is irradiated and cured. Therefore, it is necessary to determine different cross-linking reaction times for nanoparticle composite hydrogel precursor solutions with different particle sizes and different mass proportions, and the cross-linking time varies from 300s.

[0082] Step 5: freeze-drying the solidified nanoparticle composite hydrogel to form a pore structure and / or a wrinkle structure inside the solidified antibacterial nanoparticle composite hydrogel.

[0083] Specifically, the formed nanoparticle composite hydrogel is then post-processed by freeze drying, and the internal pores and other structures of the nanoparticle composite hydrogel sample are adjusted by freeze drying. The post-processing technology includes but is not limited to freeze drying, electrical stimulation, thermal stimulation, etc. The nanoparticle composite hydrogel is freeze-dried, and the internal structure of the nanoparticle composite hydrogel can be adjusted by adjusting parameters such as freezing time, freezing temperature, drying time, and drying temperature to obtain repair capabilities for different scenarios. Nanoparticles can improve the mechanical properties, swelling properties, degradation properties, etc. of the hydrogel. Secondly, nanoparticles can also play a functional role to realize the functionality of the material.

[0084] In this embodiment, the hydrogel substrate includes a degradable hydrogel substrate and / or a non-degradable hydrogel substrate.

[0085] In this embodiment, the degradable hydrogel substrate includes one or any two or more components selected from the group consisting of methacrylamide gelatin, chitosan, hydrolyzed hyaluronic acid methacrylamide, and polyethylene glycol diacrylate.

[0086] In this embodiment, the non-degradable hydrogel substrate includes one or any two or more components of polyvinyl alcohol, polyacrylamide, and polyurethane. The specific components can be selected according to actual needs and are not limited here.

[0087] In this embodiment, the light absorber includes one or any two or more components of lemon yellow, organic dyes, and nanoparticles. The specific components can be selected according to actual needs and are not limited here.

[0088] In this embodiment, the photoinitiator includes one or any two or more components selected from sodium curcuma and phenyl-2,4,6-trimethylbenzoyl lithium phosphite, which can be selected according to actual needs and are not limited here.

[0089] In this embodiment, the functional nanoparticles are antibacterial nanoparticles, which include one or any two or more components of nanodiamond, nanosilver, and nanogold. The specific components can be selected according to actual needs and are not limited here.

[0090] In this embodiment, the functional nanoparticles are antibacterial nanoparticles, and the diameter of the antibacterial nanoparticles is about 2nm-900nm.

[0091] In this embodiment, the binder includes one or any two or more components of acrylic acid N-hydroxysuccinimide ester, catechol, and tannic acid.

[0092] In this embodiment, in step 4, the curing method includes in-situ curing or mold curing, wherein the in-situ curing is to place a light source of a specific wavelength at a distance of 1 cm from the antibacterial nanoparticle composite hydrogel precursor solution and irradiate for 10 seconds;

[0093] Step 5: In the freeze-drying process, the freezing time is 15 hours, the freezing temperature is -20°C and the drying time is 60 hours.

[0094] Example 3

[0095] This embodiment discloses a nanoparticle composite hydrogel material, comprising the following raw materials in percentage by mass:

[0096] Functional nanoparticles 0.01-30%, the functional nanoparticles can be drug-carrying or antibacterial, and their specific functions can be selected according to actual needs. Functional nanoparticles are used to enrich the internal structure of the composite hydrogel and control the performance of the composite hydrogel.

[0097] Hydrogel base material 15%

[0098] Light absorber 0.05%

[0099] Photoinitiator 0.7%

[0100] Binder 5%;

[0101] It is prepared by the following steps, including:

[0102] Step 1, dissolving the hydrogel substrate in deionized water to obtain a hydrogel solution, which has injectability and fluidity;

[0103] Step 2: dissolving the photoinitiator and the light absorber in the hydrogel solution and fully shaking and mixing to obtain a hydrogel precursor solution;

[0104] Specifically, the target content of photoinitiator and light absorber is dissolved in the hydrogel solution obtained in S1 to obtain a complete hydrogel precursor solution. Its role is that, since free radicals are short-lived, the cross-linking reaction only occurs under specific lighting conditions. Therefore, by controlling the content of photoinitiator and light absorber, the wavelength of excitation light and the illumination time, the degree of photocuring can be accurately controlled. Further, the configured hydrogel precursor solution is fully oscillated so that each material component is fully dissolved in deionized water to obtain a uniform hydrogel precursor solution.

[0105] Step 3, adding the functional nanoparticles into the hydrogel precursor solution, and mixing them thoroughly to make the functional nanoparticles evenly dispersed in the hydrogel precursor solution, to obtain a nanoparticle composite hydrogel precursor solution;

[0106] The functional nanoparticles are evenly dispersed in the hydrogel precursor solution by means of an oscillator, ultrasonic dispersion, high-pressure homogenization, chemical dispersion, etc., with the aim of obtaining a more fully fused nanoparticle composite hydrogel precursor solution.

[0107] Step 4: adding a binder to the nanoparticle composite hydrogel precursor solution, mixing evenly, and then performing a curing treatment to obtain a cured nanoparticle composite hydrogel;

[0108] Place the nanoparticle composite hydrogel precursor solution in a water bath or thermostat at about 37°C to keep it warm, then place a light source of a specific wavelength at 20cm and irradiate for 200s. The gel can be formed by in-situ curing, or the nanoparticle composite hydrogel precursor solution can be injected into the mold for curing. Different nanoparticle sizes and different mass proportions will produce reflection and refraction when the light source is irradiated and cured. Therefore, it is necessary to determine different cross-linking reaction times for nanoparticle composite hydrogel precursor solutions of different particle sizes and different mass proportions, and the cross-linking time varies from 200s.

[0109] Step 5: freeze-drying the solidified nanoparticle composite hydrogel to form a pore structure and / or a wrinkle structure inside the solidified nanoparticle composite hydrogel.

[0110] Specifically, the formed nanoparticle composite hydrogel is then post-processed by freeze drying, and the internal pores and other structures of the nanoparticle composite hydrogel sample are adjusted by freeze drying. The post-processing technology includes but is not limited to freeze drying, electrical stimulation, thermal stimulation, etc. The nanoparticle composite hydrogel is freeze-dried, and the internal structure of the nanoparticle composite hydrogel can be adjusted by adjusting parameters such as freezing time, freezing temperature, drying time, and drying temperature to obtain repair capabilities for different scenarios. Nanoparticles can improve the mechanical properties, swelling properties, degradation properties, etc. of the hydrogel. Secondly, nanoparticles can also play a functional role to realize the functionality of the material.

[0111] In this embodiment, the hydrogel substrate includes a degradable hydrogel substrate and / or a non-degradable hydrogel substrate.

[0112] In this embodiment, the degradable hydrogel substrate includes one or any two or more components selected from the group consisting of methacrylamide gelatin, chitosan, hydrolyzed hyaluronic acid methacrylamide, and polyethylene glycol diacrylate.

[0113] In this embodiment, the non-degradable hydrogel substrate includes one or any two or more components of polyvinyl alcohol, polyacrylamide, and polyurethane. The specific components can be selected according to actual needs and are not limited here.

[0114] In this embodiment, the light absorber includes one or any two or more components of lemon yellow, organic dyes, and nanoparticles. The specific components can be selected according to actual needs and are not limited here.

[0115] In this embodiment, the photoinitiator includes one or any two or more components selected from sodium curcuma and phenyl-2,4,6-trimethylbenzoyl lithium phosphite, which can be selected according to actual needs and are not limited here.

[0116] In this embodiment, the functional nanoparticles are antibacterial nanoparticles, which include one or any two or more components of nanodiamond, nanosilver, and nanogold. The specific components can be selected according to actual needs and are not limited here.

[0117] In this embodiment, the functional nanoparticles are antibacterial nanoparticles, and the diameter of the antibacterial nanoparticles is about 2nm to 900nm.

[0118] In this embodiment, the binder includes one or any two or more components of acrylic acid N-hydroxysuccinimide ester, catechol, and tannic acid. The specific components can be selected according to actual needs and are not limited here.

[0119] In this embodiment, in step 4, the curing method includes in-situ curing or mold curing, wherein the in-situ curing is to place a light source of a specific wavelength at a distance of 20 cm from the antibacterial nanoparticle composite hydrogel precursor solution and irradiate for 200 seconds;

[0120] Step 5: In the freeze-drying process, the freezing time is 10 hours, the freezing temperature is -70°C and the drying time is 50 hours.

[0121] Efficacy verification

[0122] To further illustrate the function of the nanoparticle composite hydrogel material of the present invention, the following experiments were performed:

[0123] Test Example 1

[0124] Weigh 5% methacryloyl alum, 0.25% phenyl-2,4,6-trimethylbenzoyl lithium phosphite, 0.05% tartrazine, and phosphate buffer, mix the materials, place in a 37°C water bath away from light, and then shake and stir evenly to obtain a completely uniform hydrogel precursor solution without precipitates.

[0125] The nano-diamonds were dried and sterilized, and then 0.1% by mass of 100 nm nano-diamond particles were added to the hydrogel precursor solution. An oscillator was used to completely disperse the nano-diamond particles in the precursor solution, thereby obtaining a complete nano-diamond composite hydrogel precursor solution.

[0126] The uniformly mixed nanodiamond composite hydrogel precursor solution is placed in the material tank of the photocuring biological 3D printer for printing and molding. Figure 2 The schematic diagram of the structure of the obtained cured nanodiamond composite hydrogel is shown in FIG. Figure 1 Compared to the hydrogel shown, Figure 2 The nanoparticles were uniformly distributed in the hydrogel. The samples were then frozen for 6 hours and dried for 48 hours. Figure 3 As shown, a composite hydrogel with rich multi-level pore structure was obtained.

[0127] The mechanical properties of the composite hydrogel were tested, and the tensile strength of the composite hydrogel exceeded 80KPa, which is more than twice that of the porous hydrogel without NDs (nanoparticles), and the fracture strain reached 200%, which is also about twice that of the porous hydrogel without NDs. The freeze-dried samples were analyzed for swelling behavior in different acid-base environments. Especially in alkaline environments, the swelling rate of the 100nm, 0.1% nanodiamond composite hydrogel sample reached a maximum of 62.26%, which is related to the increase in the chemical reaction rate of the environment.

[0128] like Figure 5 As shown, the nanodiamond composite hydrogel is then sterilized. The nanodiamond composite hydrogel precursor solution can cover the irregularly shaped wound and adhere tightly to the wound through in situ gelation. At the same time, the strong hygroscopicity of the dressing can effectively absorb the exudate on the mouse wound, which helps promote wound healing.

[0129] According to the results of the mouse wound repair animal experiment, the healing of the mouse wound showed a significant gap on the 3rd day, and showed a significant healing effect on the 5th day, with the highest wound area healing rate reaching 56.71%. In addition, through staining, it was found that mice using nano-diamond composite hydrogel dressings had more obvious collagen fibers and epidermal keratinization and spinous layer thickening. After 14 days, the wound treated with nano-diamond composite hydrogel dressings showed obvious skin regeneration, and the skin showed a continuous phenomenon with the maximum epidermal thickness of about 325μm. It shows that the nanoparticle composite hydrogel material has a significant repair effect.

[0130] In addition, if Figure 4 As shown, the nano-diamond composite hydrogel was subjected to in vitro cell culture to obtain the effect of the nano-diamond composite hydrogel in promoting cell adhesion.

[0131] Test Example 2

[0132] This test example uses two light curing steps to compound the nano-diamond composite hydrogel precursor solution with the three-dimensional scaffold into a new scaffold, and its mass fraction components and preparation method are as follows:

[0133] Weigh 10% methacryloyl gelatin, 0.5% phenyl-2,4,6-trimethylbenzoyl lithium phosphite, 0.05% tartrazine, and phosphate buffer, mix and stir the materials evenly to obtain a completely uniform hydrogel precursor solution without precipitates.

[0134] Add 1% by mass of 500nm diamond particles to the above precursor solution, and use an oscillator to completely disperse the nanodiamonds in the precursor solution to obtain a complete nanodiamond composite hydrogel precursor solution. Use a water bath at a constant temperature of 37°C to keep the nanodiamond composite hydrogel precursor solution in a liquid state. During the constant temperature process, the solution needs to be kept away from light to prevent visible light from affecting the solution.

[0135] The three-dimensional bracket was formed by high-precision printing equipment. After forming, the bracket was put into ultrasonic cleaning for 3 minutes to completely remove the residual liquid in the holes and flow channels.

[0136] like Figure 6 As shown, cells were placed in a nanodiamond composite hydrogel precursor solution and then attached to the obtained scaffold for in vitro cell growth analysis. The cells gradually adhered to the TPMS scaffold, which showed a good positive growth-promoting effect.

[0137] like Figure 7 As shown, the scaffold was verified by in vivo experiments. Compared with the blank group, the scaffold group had better therapeutic effect and more new bone tissue. It can be seen that the nanoparticle composite hydrogel material of the present invention has a good growth-promoting effect.

[0138] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A nanoparticle composite hydrogel material, characterized in that: The following raw materials are included in the following mass percentages: Functional nanoparticles 0.01%~30% Hydrogel base material 1%~20% Light absorber 0.01%~0.1% Photoinitiator 0.1%~1% Binder 0%~10%; It is prepared by the following steps, including: Step 1, dissolving the hydrogel substrate in deionized water to obtain a hydrogel solution; Step 2: dissolving the photoinitiator and the light absorber in the hydrogel solution and fully shaking and mixing to obtain a hydrogel precursor solution; Step 3, adding the functional nanoparticles into the hydrogel precursor solution, and mixing them thoroughly to make the functional nanoparticles evenly dispersed in the hydrogel precursor solution, to obtain a nanoparticle composite hydrogel precursor solution; Step 4: adding a binder to the functional nanoparticle composite hydrogel precursor solution, mixing evenly, and then performing a curing treatment to obtain a cured functional nanoparticle composite hydrogel; Step 5: freeze-drying the solidified functional nanoparticle composite hydrogel to form a pore structure and / or a wrinkle structure inside the solidified functional nanoparticle composite hydrogel.

2. The nanoparticle composite hydrogel material according to claim 1, characterized in that: The hydrogel substrate includes a degradable hydrogel substrate and / or a non-degradable hydrogel substrate.

3. The nanoparticle composite hydrogel material according to claim 2, characterized in that: The degradable hydrogel substrate comprises one or any two or more components of methacrylamide gelatin, chitosan, hydrolyzed hyaluronic acid methacrylamide, and polyethylene glycol diacrylate.

4. The nanoparticle composite hydrogel material according to claim 2, characterized in that: The non-degradable hydrogel substrate comprises one or any two or more components of polyvinyl alcohol, polyacrylamide and polyurethane.

5. The nanoparticle composite hydrogel material according to claim 1, characterized in that: The light absorber includes one or any two or more components of lemon yellow, organic dyes, and nanoparticles.

6. The nanoparticle composite hydrogel material according to claim 1, characterized in that: The photoinitiator includes one or any two or more components of sodium curcuma and phenyl-2,4,6-trimethylbenzoyl lithium phosphite.

7. The nanoparticle composite hydrogel material according to claim 1, characterized in that: The functional nanoparticles include antibacterial nanoparticles, which include one or any two or more components of nanodiamond, nanosilver, and nanogold.

8. The nanoparticle composite hydrogel material according to claim 1, characterized in that: The diameter of the antibacterial nanoparticles is about 2nm to 900nm.

9. The nanoparticle composite hydrogel material according to claim 1, characterized in that: The binder includes one or any two or more components of acrylic acid N-hydroxysuccinimide ester, catechol, and tannic acid.

10. The nanoparticle composite hydrogel material according to claim 1, characterized in that: In step 4, the curing method includes in-situ curing or mold curing, wherein the in-situ curing is to place a light source of a specific wavelength at a distance of 1 cm to 30 cm from the antibacterial nanoparticle composite hydrogel precursor solution and irradiate for 10s to 210s; Step 5: In the freeze-drying process, the freezing time is 2 to 15 hours, the freezing temperature is -80°C to -20°C, and the drying time is 30 hours to 60 hours.

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