CN114272427B - Preparation method of multifunctional colloid patch capable of being pasted with wet surface - Google Patents
Preparation method of multifunctional colloid patch capable of being pasted with wet surface Download PDFInfo
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Abstract
The invention relates to a preparation method of a multifunctional colloid patch capable of being pasted with a wet surface, which comprises a stem cell colloid patch capable of being pasted with the wet surface, an anti-inflammatory colloid patch capable of being pasted with the wet surface, a blood vessel repairing colloid patch capable of being pasted with the wet surface, a heart repairing colloid patch capable of being pasted with the wet surface and a skin repairing colloid patch capable of being pasted with the wet surface.
Description
Technical Field
The invention relates to a preparation method of a multifunctional colloid patch capable of being pasted with a wet surface, belonging to the technical field of biological materials.
Background
People are inevitably suffered from various diseases and accidental wounds in daily production life, so the life health of people is greatly troubled by the problems of tissue or organ damage, even function loss and the like, most commonly, the open wounds of skin, muscle and skeleton bring the consequences of blood outflow, tissue fluid outflow, severe pain and the like to people, and even cause secondary injuries such as infection, necrosis and the like. Tissue repair and reconstruction have become the most interesting clinical problem for humans today. In the traditional medical means, the injury to tissues or organs is almost limitless, only certain auxiliary means can be applied to avoid serious secondary injury such as wound infection, necrosis and the like, and then the patient can recover by self by means of the regulation mechanism of the body of the patient, so that the patient often suffers from long-time pain but the recovery condition is not good enough.
In recent years, tissue engineering, which is formed by crossing many disciplinary theories and technologies such as materials science, clinical medicine, cell biology, molecular biology and the like, provides new ideas and hopes for treating tissue or organ injuries. The tissue repair material used in the initial stage of tissue engineering is mainly hydrogel composed of natural materials and polymers derived from the natural materials, and because the physical properties of the materials are highly similar to those of extracellular matrix (ECM), the materials can well simulate human tissues to play a role in filling and supporting. With the gradual improvement of modern medical treatment level, people put forward higher requirements on tissue repair materials, and on one hand, the tissue repair materials are expected to not only provide certain mechanical support but also have more functions in the tissue repair process, so that the tissue repair materials play more roles and even directly become a part of an organism to participate in the life activity of the organism and finally degrade in the organism, and further, a flexible and efficient tissue repair scheme is realized. On the other hand, the probability of damage to tissues or organs of people in various environments such as natural disasters and wars is far higher than the daily production and living situations of people, the traditional tissue repair material has complex components, high storage difficulty and complicated use steps, and people urgently need a material which has flexible storage mode and simple and quick use method and can realize effective tissue repair in complex and critical environments.
Most adhesives adhere by intermolecular forces such as hydrogen bonding, electrostatic interactions, and van der waals interactions between two dry surfaces, but when wet surfaces such as human tissue, underwater equipment, etc. are involved, the water of the wet surfaces will separate the molecules of the two surfaces, thereby preventing the intermolecular interactions of the two surfaces. Therefore, the tissue repair material capable of realizing adhesion on a wet surface has wide application prospect.
Stem cells are insufficiently differentiated and immature cells, and have a potential function of regenerating into various tissues, organs and human cells. Stem cell transplantation therapy is an advanced medical technology, and the stem cell technology is classified as a third medical technology by the ministry of health in 2009. Stem cell transplantation therapy is the transplantation of healthy stem cells into a patient to repair or replace damaged cells or tissues, thereby achieving the purpose of healing. The stem cell transplantation has wide treatment range, and can generally treat nervous system diseases, immune system diseases and other internal and surgical diseases. Stem cells, known in the medical community as "universal cells," can differentiate into a variety of functional cells or tissue organs. Traditional stem cell implantation needs to be implanted in vivo by means of an instrument, and is high in cost and complex in process, and meanwhile, the stem cell implantation cannot be directly attached to a wound surface, so that the recovery effect is poor.
In addition, the main measures for maintaining cell growth, promoting cell differentiation and killing pathological cells in the traditional method are various biological reagents and cytokines, but various biological reagents and cytokines are often expensive and easily lose efficacy, and in recent years, people gradually discover that various inorganic nano materials have the effects of promoting cell differentiation and killing pathological cells, and the inorganic nano materials are low in price, stable in components and simple to store, and are good auxiliary substitutes for various biological reagents and cytokines.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of a multifunctional colloid patch capable of being pasted with a wet surface.
The multifunctional colloid patch comprises a stem cell colloid patch capable of being pasted with a wet surface, an anti-inflammatory colloid patch capable of being pasted with a wet surface, a blood vessel repairing colloid patch capable of being pasted with a wet surface, a heart repairing colloid patch capable of being pasted with a wet surface and a skin repairing colloid patch capable of being pasted with a wet surface, can be used for convenient and fast wound treatment and fast repair under various scenes, can be fast pasted with a wound on wet surfaces of human tissues, underwater equipment and the like, and achieves flexible and efficient tissue repair.
The invention is realized by the following technical scheme:
a preparation method of a multifunctional colloid patch capable of being pasted with a wet surface comprises the following steps:
1) Preparation of a wettable surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate and alpha-ketoglutaric acid into water for dissolving to obtain a mixed solution, filtering the mixed solution, and curing to obtain an adhesive wet surface hydrogel;
2) Preparation of multifunctional colloid patch capable of being pasted with wet surface
Directly adding the functional factors into the hydrogel capable of being adhered on the wet surface, uniformly mixing, and forming and curing a film; or dripping the hydrogel solution of the functional factor on the surface of the hydrogel film capable of being stuck on the wet surface, and drying to obtain the multifunctional colloid patch capable of being stuck on the wet surface.
Preferably according to the invention, in step 1), the mass concentration of acrylic acid in the mixed solution is 30-40%.
Preferably according to the invention, in step 1), the mass concentration of gelatin in the mixed solution is 3-10%.
Preferably, in step 1) according to the present invention, the mass concentration of N-hydroxysuccinimide acrylate in the mixed solution is 3-10% w/w.
Preferably according to the invention, in step 1), the mass concentration of α -ketoglutaric acid in the mixed solution is 0.5-2%.
Preferably, in step 1), the filtration is performed with a 0.22 μm filter.
According to the invention, in the step 1), the curing is performed for 20-40min under an ultraviolet lamp with a wavelength of 284nm and a power of 10W.
Preferably, in step 2), the functional factor is synthetic manganese dioxide nanoparticles and/or cephalo, basic Fiber Growth Factor (FGF), myocardial Growth Factor (MGF), epidermal Growth Factor (EGF) or stem cells.
Preferably, in step 2), the manganese dioxide nanoparticles are synthesized by the following method:
dissolving bovine serum albumin in pure water, and adding MnCl 2 And slowly dripping the solution into the system, adjusting the pH value to 10-11, reacting at room temperature for 1-3h, washing and drying the obtained product to obtain the manganese dioxide nano-particles.
Further preferably, the mass volume ratio of bovine serum albumin to pure water is 10mg:1-5mL of MnCl 2 The concentration of the solution is 0.05-0.3M 2 The volume ratio of the solution to pure water is 1: (1-5).
Further preferably, the mass volume ratio of bovine serum albumin to pure water is 10mg:1-3mL of MnCl 2 The concentration of the solution was 0.1M and MnCl was added 2 The volume ratio of the solution to pure water is 1:2.
preferably, in the step 2), when the functional factors are a mixture of synthetic manganese dioxide nanoparticles and cephalo, basic Fiber Growth Factor (FGF), myocardial Growth Factor (MGF) and Epidermal Growth Factor (EGF), the functional factors are directly added into the wettable wet surface hydrogel and uniformly mixed, poured into a template, cured by ultraviolet at room temperature for 20-40min, and dried at 60-70 ℃ for 8-10h, so as to obtain the multifunctional colloidal patch capable of being adhered to the wet surface.
Further preferably, when the functional factor is synthetic manganese dioxide nanoparticles and/or cephalosporins, the particle size of the manganese dioxide nanoparticles is 30 to 50nm, the amount of manganese dioxide added is 0.5 to 2% w/w, and the amount of cephalosporins added is 0.5 to 5% w/w. Can be used for resisting inflammation of wound area.
Further preferably, when the functional factor is basic Fiber Growth Factor (FGF), the amount added is 0.3-0.5% w/w. Can be used for repairing blood vessel.
Further preferably, when the functional factor is Myocardial Growth Factor (MGF), the amount added is 0.2-0.4% w/w. Can be used for heart repair.
Further preferably, when the functional factor is Epidermal Growth Factor (EGF), the amount added is 0.1-0.3% w/w. Can be used for repairing skin.
The functional factors of the present invention are not limited to the above.
According to the preferable selection of the invention, in the step 2), when the functional factors are stem cells, the stem cell suspension and the temperature-sensitive hydrogel solution are mixed according to the volume ratio of 1 (8-12) to obtain the stem cell composite temperature-sensitive hydrogel solution, the stem cell composite temperature-sensitive hydrogel solution is dripped on the surface of the hydrogel film capable of being adhered with the wet surface at the temperature of 2-4 ℃, and then the hydrogel film is placed in a carbon dioxide incubator at the temperature of 35-40 ℃ for standing for 10min to obtain the stem cell patch capable of being adhered with the wet surface.
The concentration of stem cells in the liquid of the stem cell suspension is 1X 10 7 /ml。
Further preferably, the temperature-sensitive hydrogel solution is prepared by the following method:
dissolving carboxymethyl chitosan into a hydrochloric acid aqueous solution with the concentration of 0.05-0.15mol/L, wherein the volume ratio of the mass of the carboxymethyl chitosan to the hydrochloric acid aqueous solution is 1; dissolving beta-sodium glycerophosphate into water, wherein the mass ratio of the beta-sodium glycerophosphate to the water is 0.005-0.15g/mL, and fully mixing a carboxymethyl chitosan solution and the beta-sodium glycerophosphate solution at the temperature of 4 ℃ according to the volume ratio of 3.
Further preferably, the attachable wet surface hydrogel sheet is a patterned attachable wet surface hydrogel sheet or a flat attachable wet surface hydrogel sheet.
Further preferably, the method for preparing the patterned attachable wet surface hydrogel film is as follows:
carrying out patterned etching treatment on the surface of the zirconia by utilizing laser etching, then carrying out sterilization treatment on the surface of the patterned zirconia template by utilizing a high-power ultraviolet light source, slowly dripping hydrogel solution on the surface of the patterned zirconia template, carrying out ultraviolet curing for 30min, then placing the cured hydrogel solution into a forced air drying oven, drying for 8h at the temperature of 60 ℃, and finally separating hydrogel from the patterned zirconia template to obtain the patterned adhesive wet surface hydrogel film.
The invention has the technical characteristics and advantages that:
1. the multifunctional colloid patch can be used for convenient and quick wound treatment and quick repair in various scenes, can be quickly adhered to a wound on wet surfaces of human tissues, underwater equipment and the like, has good adhesion, is not easy to fall off, and realizes flexible and efficient tissue repair.
2. The multifunctional colloid patch has the advantages of stronger tensile property, good deformability and better degradability.
3. The multifunctional colloid patch disclosed by the invention is used without an instrument, is low in cost, is directly attached to a wound surface, enables functional factors to better play a role, and achieves an efficient treatment effect.
Drawings
FIG. 1 is a drawing view of a multifunctional adhesive film for adhering a wet surface; a is before stretching, b is after stretching;
FIG. 2 is a graph of the degradation characteristics of a hydrogel;
FIG. 3 is a live-dead staining image of adipose-derived stem cells on the surface of a multifunctional colloid patch;
FIG. 4 is a schematic representation of manganese dioxide nanoparticles;
FIG. 5 is a TEM image of manganese dioxide;
FIG. 6 is a diagram of the procedure of example 1 for the protection of the wound bed and the reverse molding of the anti-bacterial and anti-inflammatory adhesive film;
FIG. 7 is a schematic diagram of a film for protecting wound surface and resisting bacteria and inflammation;
FIG. 8 is a diagram showing a model of skin wound of a rat in Experimental example 1;
FIG. 9 is a drawing of a multifunctional colloidal patch containing cephalosporin and manganese dioxide as a therapeutic substance in Experimental example 1;
FIG. 10 is a graph showing no indication of inflammation by HE staining 5 days after the treatment of Experimental example 1;
FIG. 11 is a graph showing the effect of experimental example 2 of a multifunctional gel patch with cephalosporin-doped wet surface on treating a rat wound;
fig. 12 is a bright field image of mesenchymal stem cells;
FIG. 13 is a staining pattern of bone marrow mesenchymal stem cells alive and dead in a stem cell patch;
FIG. 14 is a test chart of tensile properties of the patterned multifunctional stem cell patch, wherein a is before tensile and b is after tensile;
fig. 15 is a diagram of the effect of the patterned multifunctional stem cell patch on wound repair, wherein a is before repair and b is after repair.
Detailed Description
The present invention will be described in further detail with reference to the drawings and specific embodiments for illustrating the structural features and technical aspects of the present invention and achieving specific objects and functions.
Example 1
Preparing a colloidal patch for protecting a wound surface and resisting bacteria and inflammation:
1) Preparation of the adhesive wet surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid into water, dissolving to obtain mixed solution, and filtering with 0.22 μm filter. Curing for 20min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W to obtain the hydrogel capable of being stuck on the wet surface; the mixed solution has an acrylic acid concentration of 35% w/w, gelatin of 5% w/w, N-hydroxysuccinimide acrylic acid ester of 5% w/w, α -ketoglutaric acid of 1% w/w; the degradation characteristic of the hydrogel is shown in figure 2, and as can be seen from figure 2, the hydrogel can be completely degraded in about 7 days;
2) Synthesizing manganese dioxide nano particles:
10mg of bovine serum albumin was dissolved in 2ml of purified water, and 1ml of 0.1M MnCl was added 2 Slowly dripping the solution into the solution, adjusting the pH value of the solution to 10 by using 1M NaOH, reacting at room temperature for 2 hours, washing the reaction product with deionized water for three times, and drying to obtain manganese dioxide nanoparticles; a physical photograph of the manganese dioxide nanoparticles is shown in fig. 4, and a TEM image is shown in fig. 5;
3) Dispersing the cefaloxime and the synthesized manganese dioxide nano-particles in the step 2) in the hydrogel in the step 1) based on the hydrogel which can realize quick and strong adhesion on the wet surface in the step 1) to ensure that the concentration of the cefaloxime is 5 percent w/w and the concentration of the manganese dioxide is 0.5 percent w/w, thus obtaining the hydrogel for protecting the wound surface and resisting bacteria and inflammation;
4) Selecting an acrylic plate material, making a cuboid groove template with the length of 30cm, the width of 2cm and the depth of 2cm, fixing a spacer paper of a commercial double-sided adhesive tape with the width of 2cm at the bottom of the template, preparing 10ml of hydrogel liquid according to the existing component proportion, slowly pouring the hydrogel liquid into the template, carrying out ultraviolet curing for 30min at room temperature, and drying for 8h at 60 ℃ to obtain a film sticking product for protecting the wound surface and resisting bacteria and inflammation; the process of the reverse molding of the adhesive film for protecting the wound surface and resisting bacteria and inflammation is shown in fig. 6, and the obtained object of the adhesive film is shown in fig. 7.
Experimental example 1:
the adhesive film for protecting wound surface and resisting bacteria and inflammation of the example 1 is used for treating skin wound injury of rats.
The wounds were made on the skin of rats using a circular blade (see fig. 8), the adhesive bandage for wound protection and antibacterial and anti-inflammatory of example 1 was attached to the wound (see fig. 9), and after 5 days of rearing recovery, inflammatory reaction and recovery during observation, it was found that the rats using the multifunctional adhesive bandage showed no inflammatory reaction (see fig. 10).
The film for protecting the wound surface and resisting bacteria and inflammation of example 1 is subjected to a tensile test, and the tensile test effect is shown in fig. 1b, which shows that the film for protecting the wound surface and resisting bacteria and inflammation of the wound surface has stronger tensile property.
Example 2
Preparing a colloidal patch for protecting a wound surface and resisting bacteria and inflammation:
1) Preparation of a wettable surface hydrogel:
dissolving acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid in water to obtain a mixed solution, and filtering with a 0.22 μm filter. Curing for 20min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W to obtain the hydrogel capable of being stuck on the wet surface; the mixed solution had an acrylic acid concentration of 30% w/w, a gelatin concentration of 3% w/w, an N-hydroxysuccinimide acrylic acid ester of 3% w/w, an α -ketoglutaric acid of 1% w/w;
2) Dispersing the cephalosporins in the hydrogel obtained in the step 1) on the basis of the hydrogel which can realize quick and strong adhesion on the wet surface in the step 1) to ensure that the concentration of the cephalosporins is 1 percent w/w, and obtaining the hydrogel for protecting the wound surface and resisting bacteria and inflammation;
4) An acrylic plate material is selected to be used as a cuboid groove template with the length of 30cm, the width of 2cm and the depth of 2cm, isolation paper of a commercial double faced adhesive tape with the width of 2cm is fixed at the bottom of the template, 10ml of hydrogel liquid is prepared according to the existing component proportion, then the hydrogel liquid is slowly poured into the template, ultraviolet curing is carried out for 30min at room temperature, and drying is carried out for 8h at the temperature of 60 ℃, thus obtaining the adhesive film product for protecting the wound surface and resisting bacteria and inflammation.
Experimental example 2
The adhesive film for protecting wound surface and resisting bacteria and inflammation of the example 2 is used for treating skin wound injury of rats.
The wound was made on the skin of a rat using a circular blade (see fig. 8), and the adhesive film for protecting the wound surface and resisting bacteria and inflammation of example 2 was attached to the wound (see fig. 9), and the adhesive film was easily detached after healing (see fig. 11).
Example 3
Preparation of a colloidal patch for vascular repair:
1) Preparation of a wettable surface hydrogel:
dissolving acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid in water to obtain a mixed solution, and filtering with a 0.22 μm filter. Curing for 20min under an ultraviolet lamp with wavelength of 284nm and power of 10W to obtain the adhesive wet surface hydrogel; the acrylic acid concentration of the mixed solution was 35% w/w, gelatin was 5% w/w, N-hydroxysuccinimide acrylate was 5% w/w, and α -ketoglutaric acid was 1% w/w;
2) Based on the hydrogel capable of realizing rapid and strong adhesion on a wet surface in the step 1), adding basic Fiber Growth Factor (FGF) into the hydrogel, and uniformly mixing to ensure that the concentration of the basic Fiber Growth Factor (FGF) is 0.4 percent, so as to obtain the hydrogel for vascular repair;
3) Selecting an acrylic plate material, making a cuboid groove template with the length of 30cm, the width of 2cm and the depth of 2cm, fixing a piece of isolation paper of a commercial double-sided adhesive tape with the width of 2cm at the bottom of the template, preparing 10ml of hydrogel liquid according to the existing component proportion, slowly pouring the hydrogel liquid into the template, carrying out ultraviolet curing for 30min at room temperature, and drying for 8h at 60 ℃ to obtain the film pasting product for repairing blood vessels.
Example 4
Preparation of colloidal patch for cardiac repair:
1) Preparation of a wettable surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid into water, dissolving to obtain mixed solution, and filtering with 0.22 μm filter. Curing for 20min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W to obtain the hydrogel capable of being stuck on the wet surface; the mixed solution has an acrylic acid concentration of 35% w/w, gelatin of 5% w/w, N-hydroxysuccinimide acrylic acid ester of 5% w/w, α -ketoglutaric acid of 1% w/w;
2) Based on the hydrogel capable of realizing rapid and strong adhesion on a wet surface in the step 1), adding a Myocardial Growth Factor (MGF) into the hydrogel, and uniformly mixing to ensure that the concentration of the Myocardial Growth Factor (MGF) is 0.3 percent w/w, so as to obtain the hydrogel for repairing the heart;
3) An acrylic plate material is selected, a cuboid groove template with the length of 30cm, the width of 2cm and the depth of 2cm is manufactured, isolation paper with the width of 2cm of a commercial double faced adhesive tape is fixed at the bottom of the template, 10ml of hydrogel liquid is prepared according to the existing component proportion, then the hydrogel liquid is slowly poured into the template, ultraviolet curing is carried out for 30min at room temperature, and drying is carried out for 8h at the temperature of 60 ℃, so that the film pasting product for heart repair can be obtained.
Example 5
Preparation of a colloidal patch for skin repair:
1) Preparation of the adhesive wet surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid into water, dissolving to obtain mixed solution, and filtering with 0.22 μm filter. Curing for 20min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W to obtain the hydrogel capable of being stuck on the wet surface; the acrylic acid concentration of the mixed solution was 35% w/w, gelatin was 5% w/w, N-hydroxysuccinimide acrylate was 5% w/w, and α -ketoglutaric acid was 1% w/w;
2) Adding Epidermal Growth Factor (EGF) to the hydrogel based on the hydrogel of step 1) capable of achieving rapid and strong adhesion on a wet surface, and mixing uniformly so that the concentration of the EGF is 0.2% w/w, to obtain a hydrogel for skin repair;
3) Selecting an acrylic plate material, making a cuboid groove template with the length of 30cm, the width of 2cm and the depth of 2cm, fixing a piece of isolation paper of a commercial double-sided adhesive tape with the width of 2cm at the bottom of the template, preparing 10ml of hydrogel liquid according to the existing component proportion, slowly pouring the hydrogel liquid into the template, carrying out ultraviolet curing for 30min at room temperature, and drying for 8h at 60 ℃ to obtain the film pasting product for skin repair.
Example 6
Preparing a stem cell patch capable of being adhered to a wet surface:
1) Preparation of the adhesive wet surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid into water, dissolving to obtain mixed solution, and filtering with 0.22 μm filter. Curing for 20min under an ultraviolet lamp with wavelength of 284nm and power of 10W to obtain the adhesive wet surface hydrogel; the acrylic acid concentration of the mixed solution was 35% w/w, gelatin was 5% w/w, N-hydroxysuccinimide acrylate was 5% w/w, and α -ketoglutaric acid was 1% w/w;
2) Selecting acrylic plate material, making a cuboid groove template with the length of 30cm, the width of 2cm and the depth of 2cm, fixing isolation paper of commercial double-sided adhesive tape with the width of 2cm at the bottom of the template, slowly pouring hydrogel into the template, carrying out ultraviolet curing for 30min at room temperature, and drying for 8h at 60 ℃ to obtain a film;
3) Mixing the stem cell suspension and the temperature-sensitive hydrogel solution according to the volume ratio of 1 7 Per ml; obtaining a stem cell composite temperature-sensitive hydrogel solution, dripping the stem cell composite temperature-sensitive hydrogel solution on the surface of the hydrogel film which can be adhered to the wet surface in the step 2) at the temperature of 2-4 ℃, and then placing the hydrogel film in a carbon dioxide incubator at the temperature of 35-40 ℃ for standing for 10min to obtain dry fine hydrogel which can be adhered to the wet surfaceCell sticking sheets; live and dead staining of mesenchymal stem cells in the stem cell patch is shown in fig. 13.
Example 7
Preparing a patterned colloid patch:
1) Preparation of a wettable surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid into water, dissolving to obtain mixed solution, and filtering with 0.22 μm filter. Curing for 20min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W to obtain the hydrogel capable of being stuck on the wet surface; the mixed solution has an acrylic acid concentration of 35% w/w, gelatin of 5% w/w, N-hydroxysuccinimide acrylic acid ester of 5% w/w, α -ketoglutaric acid of 1% w/w;
2) Carrying out patterned etching treatment on the surface of the zirconia by utilizing laser etching, then carrying out sterilization treatment on the surface of the patterned zirconia template by utilizing a high-power ultraviolet light source, slowly dripping hydrogel onto the surface of the patterned zirconia template, carrying out ultraviolet curing for 30min, then placing the cured hydrogel into a forced air drying oven, drying for 8h at the temperature of 60 ℃, and finally separating the hydrogel from the patterned zirconia template to obtain a patterned adhesive wet surface hydrogel film;
3) Mixing the stem cell suspension and the temperature-sensitive hydrogel solution according to the volume ratio of 1 7 Per ml; and (3) obtaining a stem cell composite temperature-sensitive hydrogel solution, dripping the stem cell composite temperature-sensitive hydrogel solution on the surface of the patterned sticky wet surface hydrogel film obtained in the step 2) at the temperature of 2-4 ℃, and standing for 10min in a carbon dioxide incubator at the temperature of 35-40 ℃ to obtain the patterned sticky wet surface stem cell patch.
Experimental example 3:
the patterned gel patch of example 7 was used for skin wound injury treatment in rats.
The annular blade is adopted to make wounds on the skin of a rat, the patterned multifunctional stem cell patch wound repairing paste is pasted at the wound, and after 5 days of feeding and rehabilitation, the repairing effect of the patterned multifunctional stem cell patch on the wounds is shown in figure 15.
The patterned gel patch of example 7 was subjected to a tensile test, the effect of which is shown in fig. 14b, indicating that the patch has strong tensile properties.
Example 8
The preparation of the colloidal patch for wound protection, antibiosis and anti-inflammatory described in example 1 is different in that:
in step 1), preparation of the adhesive wet surface hydrogel: dissolving acrylic acid, gelatin, N-hydroxysuccinimide acrylate, and alpha-ketoglutaric acid in water to obtain a mixed solution, and filtering with a 0.22 μm filter. Curing for 20min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W to obtain the hydrogel capable of being stuck on the wet surface; the mixed solution was subjected to the process of example 1 except that the acrylic acid concentration was 40% w/w, the gelatin was 10% w/w, the N-hydroxysuccinimide acrylate was 10% w/w, and the α -ketoglutaric acid was 1% w/w.
Claims (7)
1. A preparation method of a multifunctional colloid patch capable of being pasted with a wet surface comprises the following steps:
1) Preparation of a wettable surface hydrogel:
adding acrylic acid, gelatin, N-hydroxysuccinimide acrylate and alpha-ketoglutaric acid into water for dissolving to obtain a mixed solution, filtering the mixed solution, and curing to obtain an adhesive wet surface hydrogel;
2) Preparation of multifunctional colloid patch capable of being pasted with wet surface
The functional factors are a mixture of synthetic manganese dioxide nanoparticles and cephalosporins, synthetic manganese dioxide nanoparticles, cephalosporins, basic fiber growth factors FGF, cardiac muscle growth factors MGF, epidermal cell growth factors EGF or stem cells;
when the functional factors are a mixture of synthetic manganese dioxide nanoparticles and cephalosporins, synthetic manganese dioxide nanoparticles, cephalosporins, basic fiber growth factor FGF, myocardial growth factor MGF and epidermal growth factor EGF, directly adding the functional factors into the wettable moist surface hydrogel, uniformly mixing, pouring into a template, carrying out ultraviolet curing at room temperature for 20-40min, and drying at 60-70 ℃ for 8-10h to obtain the multifunctional colloid patch capable of adhering a moist surface;
when the functional factor is stem cells, mixing the stem cell suspension and the temperature-sensitive hydrogel solution in a volume ratio of 1 (8-12) to obtain a stem cell composite temperature-sensitive hydrogel solution, dripping the stem cell composite temperature-sensitive hydrogel solution onto the surface of the hydrogel film capable of being adhered with the wet surface at 2-4 ℃, and then placing the hydrogel film in a carbon dioxide incubator at 35-40 ℃ for standing for 10min to obtain the stem cell patch capable of being adhered with the wet surface; the concentration of stem cells in the liquid of the stem cell suspension is 1X 10 7 /ml。
2. The production method as claimed in claim 1, wherein, in the step 1), the mass concentration of acrylic acid in the mixed solution is 30-40%; the mass concentration of gelatin in the mixed solution is 3-10%; the mass concentration of the N-hydroxysuccinimide acrylate in the mixed solution is 3-10% w/w; the mass concentration of alpha-ketoglutaric acid in the mixed solution is 0.5-2%; the filtration is carried out by using a 0.22 mu m filter; the curing is carried out for 20-40min under an ultraviolet lamp with the wavelength of 284nm and the power of 10W.
3. The method of claim 1, wherein the step 2) of synthesizing manganese dioxide nanoparticles is performed by:
dissolving bovine serum albumin in pure water, and adding MnCl 2 Slowly dripping the solution into the system, adjusting the pH value to 10-11, reacting at room temperature for 1-3h, washing and drying the obtained product to obtain manganese dioxide nano-particles;
the mass volume ratio of the bovine serum albumin to the pure water is 10mg:1-5mL of MnCl 2 The concentration of the solution is 0.05-0.3M 2 The volume ratio of the solution to pure water is 1: (1-5).
4. The method of claim 1, wherein when the functional factor is a mixture of synthetic manganese dioxide nanoparticles and cephalo, synthetic manganese dioxide nanoparticles, cephalo, manganese dioxide nanoparticles having a particle size of 30 to 50nm, manganese dioxide addition amount of 0.5 to 2% w/w, and cephalo addition amount of 0.5 to 5% w/w, for anti-inflammation of wound area;
when the functional factor is basic fiber growth factor FGF, the addition amount is 0.3-0.5% w/w, and the functional factor can be used for vascular repair;
when the functional factor is myocardial growth factor MGF, it is added in an amount of 0.2-0.4% w/w, and can be used for heart repair;
when the functional factor is epidermal growth factor EGF, the addition amount is 0.1-0.3% w/w, and can be used for skin repair.
5. The method according to claim 1, wherein the temperature-sensitive hydrogel solution is prepared by:
dissolving carboxymethyl chitosan into a hydrochloric acid aqueous solution with the concentration of 0.05-0.15mol/L, wherein the volume ratio of the mass of the carboxymethyl chitosan to the hydrochloric acid aqueous solution is 1; dissolving beta-sodium glycerophosphate into water, wherein the mass ratio of the beta-sodium glycerophosphate to the water is 0.005-0.15g/mL, and fully mixing a carboxymethyl chitosan solution and the beta-sodium glycerophosphate solution at the temperature of 4 ℃ according to the volume ratio of 3.
6. The method of claim 1, wherein the attachable wet surface hydrogel sheet is a patterned attachable wet surface hydrogel sheet or a flat attachable wet surface hydrogel sheet.
7. The method of claim 6, wherein the patterned attachable wet surface hydrogel sheet is prepared by: carrying out patterned etching treatment on the surface of the zirconia by utilizing laser etching, then carrying out sterilization treatment on the surface of the patterned zirconia template by utilizing a high-power ultraviolet light source, slowly dripping hydrogel solution on the surface of the patterned zirconia template, carrying out ultraviolet curing for 30min, then placing the cured hydrogel solution into a forced air drying oven, drying for 8h at the temperature of 60 ℃, and finally separating hydrogel from the patterned zirconia template to obtain the patterned adhesive wet surface hydrogel film.
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| US20030175328A1 (en) * | 2002-03-06 | 2003-09-18 | Adi Shefer | Patch for the controlled delivery of cosmetic, dermatological, and pharmaceutical active ingredients into the skin |
| CN102718928B (en) * | 2012-07-04 | 2014-11-05 | 天津工业大学 | Hydrogel for intelligent desorption of cell sheet layer and application of hydrogel |
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| AU2020275382A1 (en) * | 2019-05-10 | 2022-01-06 | Massachusetts Institute Of Technology | Dry double-sided material for adhesion of wet tissues and devices |
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