阅读说明：本技术 一种水凝胶及其制备方法和应用 (Hydrogel and preparation method and application thereof ) 是由 何苗苗 张莉 陈凌东 徐萍华 鲍娇慧 于 2021-09-14 设计创作，主要内容包括：本发明公开了一种水凝胶及其制备方法和应用,所述水凝胶包括2.5-20重量份甲基丙烯酸羟乙酯、5-25重量份甲基丙烯酰明胶、28-112重量份亲水性两性离子、0.02-2重量份引发剂、100重量份水。水凝胶具有优异的机械性能、保水性、高透光性及良好的生物相容性,拉伸强度最高可达0.88MPa,压缩强度最高可达1.2MPa,透光率＞90％。拓宽了水凝胶在生物材料领域的应用。(The invention discloses a hydrogel and a preparation method and application thereof, wherein the hydrogel comprises 2.5-20 parts by weight of hydroxyethyl methacrylate, 5-25 parts by weight of methacryl gelatin, 28-112 parts by weight of hydrophilic zwitterion, 0.02-2 parts by weight of initiator and 100 parts by weight of water. The hydrogel has excellent mechanical property, water retention property, high light transmittance and good biocompatibility, the highest tensile strength can reach 0.88MPa, the highest compressive strength can reach 1.2MPa, and the light transmittance is more than 90 percent. Widens the application of the hydrogel in the field of biological materials.)

1. The hydrogel is characterized by comprising 2.5-20 parts by weight of hydroxyethyl methacrylate, 5-25 parts by weight of methacryl gelatin, 28-112 parts by weight of hydrophilic zwitterion, 0.02-2 parts by weight of initiator and 100 parts by weight of water.

2. The hydrogel of claim 1, wherein the hydrophilic zwitterion is selected from one or more of the group consisting of carboxylic betaine acrylamide (CBAA), carboxybetaine methyl acrylate (CBMA), and thiobetaine methyl acrylate (SBMA), preferably thiobetaine methyl acrylate (SBMA).

3. The hydrogel according to claim 1, wherein the hydrogel further comprises an organic solvent for replacement with water, and further wherein the organic solvent is one or more selected from glycerol, sorbitol, isopropanol, ethanol, and ethylene glycol, and preferably glycerol.

4. The hydrogel of claim 1, wherein the hydrophilic zwitterion and the hydroxyethyl methacrylate are copolymerized into molecular chains, and the molecular chains are crosslinked by methacryl gelatin to form a multiple network.

5. The hydrogel according to claim 4, wherein the hydrogel is further soaked in an organic solvent for replacement after being subjected to ultraviolet light gel formation, and further, the organic solvent is one or more selected from glycerol, sorbitol, isopropanol, ethanol, and ethylene glycol.

6. A method of making a hydrogel, comprising:

mixing 2.5-20 parts by weight of hydroxyethyl methacrylate, 5-25 parts by weight of methacryl gelatin, 28-112 parts by weight of hydrophilic zwitterion, 0.02-2 parts by weight of initiator and 100 parts by weight of water;

and (3) after mixing, irradiating by ultraviolet light, carrying out copolymerization reaction on hydrophilic zwitterions and hydroxyethyl methacrylate to form molecular chains, and crosslinking the molecular chains through methacryl gelatin to form a multiple network.

7. The preparation method according to claim 6, wherein the initiator is one of phenyl (2,4, 6-trimethylbenzoyl) lithium phosphate, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone, ammonium persulfate serving as an oxidant, potassium persulfate and sodium bisulfite serving as a reducing agent, and the lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate is preferred.

8. The method according to claim 6, wherein the intensity of the UV light is 50-200w, preferably 200 w.

9. The method of claim 5, further comprising:

soaking the hydrogel in an organic solvent for replacement to obtain organic hydrogel; further, the organic solvent is selected from one or more of glycerol, sorbitol, isopropanol, ethanol and ethylene glycol.

10. Use of a hydrogel according to any one of claims 1 to 5 for 3D printing of biological material.

Technical Field

The application belongs to the technical field of biomedical materials, and particularly relates to hydrogel and a preparation method and application thereof.

Background

The medical dressing is used as an important part in wound care, not only provides a barrier protection function for a wound surface, but also constructs a favorable microenvironment for the wound, and improves the speed of wound healing to a certain extent. The dressing can be generally used for long-term care of wounds, such as the long-term care of chronic wounds caused by common bedsores, pressure sores and the like, and has obvious curative effect on scar repair after wound surgery or medical and cosmetic surgery.

The hydrogel is a novel material widely applied to the field of high-end medical dressings at present. The material is a three-dimensional network structure material containing a large amount of water molecules, is formed by crosslinking hydrophilic polymer chains, has the water content of over 99 percent, has biophysical characteristics similar to natural tissues, and has wide application prospects in the fields of biological tissues, drug carriers, bionic intelligent materials and the like. However, the traditional polymer hydrogel often has the defects of single structure, weak mechanical property and the like, thereby greatly limiting the practical application of the hydrogel.

Disclosure of Invention

The embodiment of the application aims to provide a hydrogel and a preparation method and application thereof, so as to solve the technical problem of weak toughness of the hydrogel in the related art.

According to a first aspect of embodiments of the present invention, there is provided a hydrogel comprising 2.5 to 20 parts by weight of hydroxyethyl methacrylate, 5 to 25 parts by weight of methacryl gelatin, 28 to 112 parts by weight of a hydrophilic zwitterion, 0.02 to 2 parts by weight of an initiator, and 100 parts by weight of water.

Optionally, the hydrophilic zwitterion is selected from one or more of carboxylic betaine acrylamide (CBAA), carboxybetaine methyl acrylate (CBMA), and thiobetaine methyl acrylate (SBMA), preferably thiobetaine methyl acrylate (SBMA).

Optionally, the hydrogel further comprises an organic solvent for replacement with water, and further, the organic solvent is one or more selected from glycerol, sorbitol, isopropanol, ethanol and ethylene glycol, wherein glycerol is preferred.

Optionally, the hydrophilic zwitterion and hydroxyethyl methacrylate are subjected to copolymerization to form a molecular chain, and the molecular chain is crosslinked through methacryl gelatin to form a multiple network.

Optionally, the hydrogel is further soaked in an organic solvent for replacement after being subjected to ultraviolet light to form a gel, and it should be noted that the replacement may be partial replacement or complete replacement, specifically determined by the properties of the hydrogel composition before replacement.

Optionally, the organic solvent is one or more selected from glycerol, sorbitol, isopropanol, ethanol, and ethylene glycol.

According to a second aspect of embodiments of the present invention, there is provided a method of preparing a hydrogel, the method comprising:

mixing 2.5-20 parts by weight of hydroxyethyl methacrylate, 5-25 parts by weight of methacryl gelatin, 28-112 parts by weight of hydrophilic zwitterion, 0.02-2 parts by weight of initiator and 100 parts by weight of water;

and (3) after mixing, irradiating by ultraviolet light, carrying out copolymerization reaction on hydrophilic zwitterions and hydroxyethyl methacrylate to form molecular chains, and crosslinking the molecular chains through methacryl gelatin to form a multiple network.

Optionally, the molecular weight of the methacrylyl gelatin is 4w-5w, and the substitution degree is 50% -90%.

Optionally, the initiator is one of phenyl (2,4, 6-trimethylbenzoyl) lithium phosphate, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone, ammonium persulfate serving as an oxidant, potassium persulfate and sodium bisulfite serving as a reducing agent, wherein the phenyl (2,4, 6-trimethylbenzoyl) lithium phosphate is preferred.

Optionally, the intensity of the ultraviolet light is 50-200 w.

Optionally, the method further includes: soaking the hydrogel in an organic solvent for replacement to obtain organic hydrogel; further, the organic solvent is selected from one or more of glycerol, sorbitol, isopropanol, ethanol and ethylene glycol.

According to a third aspect of embodiments of the present invention there is provided a use of the hydrogel of the first aspect in 3D printing of biological material.

The technical scheme provided by the embodiment of the application can have the following beneficial effects:

according to the embodiment, the preparation process is simple, the methacrylyl gelatin and the hydrophilic zwitterion are directly dissolved in deionized water, and the prepared hydrogel has good biocompatibility and excellent mechanical property. The hydrogel is further soaked in an organic solvent for replacement to obtain the organic hydrogel, which has high toughness and excellent water retention property and has a wide application prospect in the field of biomedicine.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the application.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and together with the description, serve to explain the principles of the application.

FIG. 1 is a stress-strain curve of the tensile strength of the hydrogels obtained in examples 1-3 of the present invention;

FIG. 2 is a stress-strain curve of the tensile strength of the hydrogels obtained in examples 4-6 of the present invention;

FIG. 3 is a stress-strain curve of the tensile of the hydrogels obtained in examples 7-9 of the present invention;

FIG. 4 is a stress-strain curve of the tensile of the hydrogels obtained in examples 10-12 of the present invention;

FIG. 5 is a graph showing the transmittance of hydrogels obtained in examples 1 to 3 of the present invention before and after soaking in glycerol;

FIG. 6 is a graph showing the transmittance of hydrogels obtained in examples 4 to 6 of the present invention before and after soaking in glycerol;

FIG. 7 is a graph showing the transmittance of hydrogels obtained in examples 7 to 9 of the present invention before and after soaking in glycerol;

FIG. 8 is a graph showing the compressive properties of the hydrogel obtained in example 5 of the present invention;

FIG. 9 shows the water retention properties of the hydrogel obtained in example 5 of the present invention.

Detailed Description

The following detailed description of embodiments of the present invention is provided, but the scope of the present invention is not limited thereto.

Example 1

(1) 5g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 1, the tensile strength is 0.21MPa, and the breaking strain is 211%. The transmittance in the visible wavelength range is shown in fig. 5, with good transmittance (> 90%).

Example 2

(1) 10g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 1, the tensile strength is 0.88MPa, and the breaking strain is 222%. The transmittance in the visible wavelength range is shown in fig. 5, with good transmittance (> 90%).

Example 3

(1) 25g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 1, the tensile strength is 1.20MPa, and the breaking strain is 155%. The transmittance in the visible wavelength range is shown in fig. 5, with good transmittance (> 90%).

Example 4

(1) 15g of methacrylyl gelatin, 2.5g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred well. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 2, the tensile strength is 0.92MPa, and the breaking strain is 91%. The transmittance in the visible wavelength range is shown in fig. 6, with good transmittance (> 90%).

Example 5

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 2, the tensile strength is 0.88MPa, and the breaking strain is 222%. The transmittance in the visible wavelength range is shown in fig. 6, with good transmittance (> 90%).

Example 6

(1) 15g of methacrylyl gelatin, 20g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 2, the tensile strength is 0.45MPa, and the breaking strain is 44%. The transmittance in the visible wavelength range is shown in fig. 5, with good transmittance (> 90%).

Example 7

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 28g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 3, the tensile strength is 0.33MPa, and the breaking strain is 166%. The transmittance in the visible wavelength range is shown in fig. 7, with good transmittance (> 90%).

Example 8

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 84g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 3, the tensile strength is 1.00MPa, and the breaking strain is 176%. The transmittance in the visible wavelength range is shown in fig. 7, with good transmittance (> 90%).

Example 9

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 112g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 3h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 3, the tensile strength is 0.75MPa, and the breaking strain is 44%. The transmittance in the visible wavelength range is shown in fig. 7, with good transmittance (> 90%).

Example 10

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 15min to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 4, the tensile strength is 0.03MPa, and the breaking strain is 16%.

Example 11

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 2h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 4, the tensile strength is 0.66MPa, and the breaking strain is 222%.

Example 12

(1) 15g of methacrylyl gelatin, 10g of hydroxyethyl methacrylate and 56g of thiobetaine methyl acrylate were added to 100mL of deionized water and stirred uniformly. It should be noted that the deionized water can be replaced by ordinary water, but deionized water is also preferred, and the density of the deionized water is 1 g/mL.

(2) And (3) adding 2g of lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate initiator into the solution, uniformly stirring, and performing ultrasonic treatment until air bubbles in the solution are completely removed.

(3) Injecting the solution into a sealed glass mold, irradiating with 365nm and 200w of ultraviolet light at room temperature for 1min, finishing the reaction, soaking the obtained gel in glycerol for 4h to obtain the methacrylyl gelatin/hydroxyethyl methacrylate/SBMA/glycerol hydrogel, wherein the tensile stress-strain curve is shown in figure 4, the tensile strength is 0.67MPa, and the breaking strain is 64%.

Material characterization and Performance testing

(1) Testing the tensile mechanical property: a hydrogel sample strip with the length of 60mm and the width of 10mm is prepared by using a glass mold with the thickness of 2mm, and the hydrogel sample strip with the gauge length of 50mm, the width of 4mm and the thickness of 2mm is prepared by using a dumbbell-shaped cutter. Taking a water gel sample strip to perform a mechanical tensile test on a CMT4101 microcomputer controlled electronic universal tester, measuring the mechanical property at the tensile speed of 50 mm/min.

(2) Compression mechanical property test: preparing a cylindrical hydrogel sample with the height of 8mm by using a glass mold with the diameter of 8mm, carrying out a mechanical tensile test on a water gel sample strip on an Instron 5966 universal material testing machine, measuring the mechanical property at a compression speed of 5 mm/min.

(3) Water retention: preparing cylindrical hydrogel, placing the cylindrical hydrogel in water baths at Room Temperature (RT) and 37 ℃, weighing the hydrogel once without time, and evaluating the water retention performance of the hydrogel by calculating the mass change rate of the hydrogel. Three samples were measured per group and averaged.

(4) Transmittance experiment: a circular hydrogel sample having a diameter of 2.5cm was prepared, and the light transmittance of the sample was measured using an ultraviolet/visible/near-infrared spectrophotometer.

It should be noted that the thiobetaine methyl acrylate (SBMA) in the above embodiments may be replaced by one or more of carboxylic betaine acrylamide (CBAA), carboxybetaine methyl acrylate (CBMA), and thiobetaine methyl acrylate; the lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate salt can be replaced by one of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone (I2959)/ammonium persulfate as an oxidant, potassium persulfate and sodium bisulfite as a reducing agent. The glycerol can be replaced by one or more of glycerol, sorbitol, isopropanol, ethanol, and ethylene glycol. The intensity of the ultraviolet light may be between 50 and 200w, with 200w being most preferred. The ultraviolet irradiation time is 1min, and the hydrogel is soaked in glycerol for 3h, wherein the irradiation time and the glycerol soaking time are not limited to 1min and 3h, and are specifically determined by the gelling condition and the required mechanical property of the hydrogel.

It will be understood that the present application is not limited to the precise arrangements described above and shown in the drawings and that various modifications and changes may be made without departing from the scope thereof. The scope of the application is limited only by the appended claims.