Gelatin modified polyacrylamide gel as well as preparation method and application thereof

Abstract

The invention discloses gelatin modified polyacrylamide gel as well as a preparation method and application thereof. The method comprises the following steps: dissolving gelatin in water at 37 DEG C, then adding protocatechualdehyde, and reacting for 1 hour to obtain a gelatin Schiff base solution; then, directly adding an acrylamide monomer, N, N '-methylene bisacrylamide, tetramethylethylenediamine and ammonium persulfate into the solution, and reacting at 60 DEG C until the mixed solution is gelatinized to form a first layer of cross-linked network; and finally, cooling the hydrogel in a refrigerator at 4 DEG C for 30 minutes to form a second layer of cross-linked network, thereby obtaining the gel. The gel has high mechanical strength and adhesion, also has excellent properties such as oxidation resistance, photo-thermal antibiosis, swelling, moisturizing and sensing monitoring, can meet the performance requirements of wound recovery, is firm in adhesion and not easy to damage, can significantly promote wound healing, and is suitable for wound repair, wound monitoring, sensing detection and plugging materials.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials and also to the field of chemical engineering materials, and particularly relates to a gelatin-modified polyacrylamide gel and its preparation method and application. Background Art

[0002] Wound repair is an extremely complex process, including requirements in multiple aspects such as hemostasis and antibacterial. Adhesive antibacterial gels are expected to be used in fields such as the above-mentioned wound repair. However, there are some problems to be solved in practical applications. On the one hand, in the traditional method, adhesive functional groups (such as caffeic acid, etc.) are first introduced to synthesize adhesive polymers, and then separated and purified before preparing adhesive hydrogels. The whole process is complex, time-consuming, laborious, and costly. On the other hand, the adhesiveness of adhesive hydrogels mainly stems from the number of adhesive functional groups. The traditional synthesis method is through coupling reactions using 1-ethyl-(3-dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide, but the number of coupled adhesive functional groups is very limited. In addition, in application scenarios such as wounds, adhesive hydrogels often need to withstand effects such as extrusion and stretching, but the mechanical strength of general hydrogels themselves is not high, resulting in easy damage under external effects during adhesive use. Summary of the Invention

[0003] The purpose of the present invention is to solve the problems existing in the prior art, and provides a gelatin-modified polyacrylamide gel and its preparation method and application. The present invention first uses gelatin as a raw material to prepare gelatin Schiff base; then, acrylamide monomers are added, and a cross-linking agent, a catalyst, and an initiator are sequentially added to cross-link polyacrylamide to form a gel; finally, the above gel is cooled in a 4°C refrigerator to obtain a physical cross-linking network. This modification can improve the comprehensive performance of the gel, including adhesive strength, antioxidant property, antibacterial property, and stability, etc., and can significantly improve the mechanical strength of the gel, and can achieve temperature-dependent adhesion through its own structural changes.

[0004] To achieve the above purpose, the technical solution of the present invention is as follows:

[0005] The present invention provides a gelatin-modified polyacrylamide gel. The raw materials of the gel include gelatin, protocatechuic aldehyde, and acrylamide monomers; a chemical cross-linking network is formed by polymerization under the action of a cross-linking agent, an initiator, and a catalyst to obtain a hydrogel, and it is cooled to obtain a physical cross-linking network, wherein the dosage of protocatechuic aldehyde is 1% - 20% of the mass of gelatin, and the dosage of acrylamide monomers is 1% - 200% of the mass of gelatin;

[0006] The chemical cross-linking agent is N,N'-methylenebisacrylamide, the catalyst is tetramethylethylenediamine, and the initiator is ammonium persulfate.

[0007] Furthermore, the dosage of protocatechuic aldehyde is 5% - 15% of the mass of gelatin, and the dosage of acrylamide monomer is 50% - 150% of the mass of gelatin.

[0008] Still further, the dosage of the cross-linking agent is 0.01% - 0.1% of the mass of gelatin; the dosage of the initiator is 2% of the mass of gelatin; the dosage of the catalyst is 0.78% of the mass of gelatin.

[0009] The present invention also provides a gelatin-modified polyacrylamide gel, comprising the following steps:

[0010] (1) Dissolve gelatin in deionized water to obtain a gelatin solution;

[0011] (2) Add protocatechuic aldehyde to the gelatin solution and react to obtain a gelatin Schiff base solution;

[0012] (3) Dissolve N,N'-methylenebisacrylamide in deionized water to obtain an N,N'-methylenebisacrylamide solution;

[0013] (4) Add acrylamide monomer to the gelatin Schiff base solution in step (2), and sequentially add the N,N'-methylenebisacrylamide solution, tetramethylethylenediamine and ammonium persulfate, stir evenly, and carry out a water bath reaction to obtain a chemically cross-linked network gel;

[0014] (5) Cool the chemically cross-linked network gel to obtain a physically and chemically double cross-linked network gelatin-modified polyacrylamide gel.

[0015] Furthermore, in the step (1), the concentration of the gelatin solution is 0.1 - 0.3 g·mL -1 , and the dissolution temperature is 37°C.

[0016] Still further, in the step (2), the dosage of protocatechuic aldehyde is 1% - 20% of the mass of gelatin, the reaction temperature is 37°C, and the reaction time is 1 hour.

[0017] Still further, in the step (3), the concentration of N,N'-methylenebisacrylamide is 0.01 g·mL -1 .

[0018] Still further, in the step (4), the dosage of acrylamide monomer is 1% - 200% of the mass of gelatin, the dosage of the cross-linking agent is 0.01% - 0.1% of the mass of gelatin, the dosage of the catalyst is 0.78% of the mass of gelatin, and the dosage of the initiator is 2% of the mass of gelatin; the water bath reaction temperature is 60°C, and the reaction time is 1 hour.

[0019] Still further, in the step (5), the cooling temperature is 4°C, and the cooling time is 30 minutes.

[0020] The present invention also provides an application of the above-mentioned gelatin-modified polyacrylamide gel in the preparation of wound repair, wound monitoring, sensing detection, and plugging materials.

[0021] Preparation mechanism of the gelatin-modified polyacrylamide gel of the present invention:

[0022] Both gelatin and polyacrylamide are commonly used substrates for preparing gels. Among them, gelatin is derived from animal connective tissues and hard bone tissues. As a commonly used pharmaceutical excipient, it is mainly applied in the food and pharmaceutical industries, including as a raw material for capsules. Polyacrylamide is an important biomedical polymer material. Its hydrogel is colorless and transparent, soft and elastic, and is widely used in the fields of biomedical materials and so on. The present invention couples protocatechuic aldehyde with gelatin molecules and composites polyacrylamide to obtain a double-crosslinked high-strength adhesive gel. The catechol group is coupled to the gelatin molecule by the Schiff base reaction, and the rich side chain groups of gelatin are retained, endowing the gel with excellent adhesion and antioxidant properties. The mechanical strength of the gel is enhanced through a double-layer network. The acrylamide monomer is chemically crosslinked after initiation polymerization to obtain a tough gel with a chemical crosslinked network. Finally, the gelatin physical crosslinked network is reorganized by cooling to obtain the gelatin-modified polyacrylamide gel. Strong hydrogen bond interactions, Schiff base bonds, chemical crosslink bonds, and π-π interactions enable the gel to form a dense and stable crosslinked network.

[0023] Advantages of the present invention:

[0024] 1. The present invention provides a novel gelatin-modified polyacrylamide gel, and the modification helps to improve its comprehensive properties such as adhesion and antioxidant properties.

[0025] 2. The gelatin-modified polyacrylamide gel provided by the present invention exhibits strong adhesion, solving the problem of insufficient adhesion of ordinary gels as materials for wound repair and the like.

[0026] 3. On the basis of adhesion, the gelatin-modified polyacrylamide gel provided by the present invention has excellent mechanical strength at the same time, and can solve the problem that materials for wound repair and the like are easily damaged during use.

[0027] 4. On the basis of high-strength adhesion, the gelatin-modified polyacrylamide gel provided by the present invention has outstanding antibacterial properties at the same time, and can significantly reduce the risk of wound infection.

[0028] 5. On the basis of high-strength adhesion, the gelatin-modified polyacrylamide gel provided by the present invention has wound monitoring performance at the same time, and can identify the movement state of the wound.

[0029] 6. The gelatin Schiff base is obtained by the Schiff base reaction of the gelatin-modified polyacrylamide gel provided by the present invention, which helps to greatly improve the adhesion.

[0030] 7. The present invention realizes temperature-dependent adhesion through the structural change of gelatin, facilitating the regulation of the adhesion and de-adhesion properties of the hydrogel.

[0031] 8. The gelatin-modified polyacrylamide gel provided by the present invention can be prepared by a one-pot method without complex separation and purification processes.

[0032] 9. The preparation of the gelatin-modified polyacrylamide gel provided by the present invention is simple, the process conditions are mild, the production cost is low, and it is convenient to realize industrialization.

[0033] 10. The gelatin-modified polyacrylamide gel provided by the present invention has good biocompatibility and can effectively promote the healing of wound surfaces. Description of the Drawings

[0034] Figure 1 Shows the effect of the gelatin-modified polyacrylamide gel in promoting wound healing. Detailed Embodiments

[0035] The present invention will be further described in detail below in conjunction with specific embodiments for those skilled in the art to understand.

[0036] Example 1

[0037] (1) Dissolve 1.0 g of gelatin in 5 mL of deionized water, stir and dissolve at 37 °C until uniform to obtain a gelatin solution.

[0038] (2) Weigh 0.1 g of protocatechuic aldehyde and dissolve it in the above gelatin solution, stir and react at 37 °C for 1 hour to obtain a gelatin Schiff base solution.

[0039] (3) Weigh 0.1 g of N,N'-methylenebisacrylamide and dissolve it in 10 mL of deionized water to obtain a chemical cross-linking agent solution.

[0040] (4) Weigh 1.5 g of acrylamide and dissolve it in the above gelatin Schiff base solution, and successively add 60 μL of the chemical cross-linking agent solution, 10 μL of tetramethylethylenediamine and 0.02 g of ammonium persulfate, stir quickly and evenly, and react in a 60 °C water bath until a gel is formed.

[0041] (5) Place the above gel in a 4 °C refrigerator and cool for 30 minutes to obtain gelatin-modified polyacrylamide gel 1.

[0042] The compressive strength of the gel 1 obtained by the above method reaches 3.1 MPa, and the tensile strength is 290.5 kPa. Its adhesion performance is outstanding, and it can firmly adhere to different substrates (plastic, rubber, glass, pig skin, and kidneys and lungs), with a wide range of applicable materials. Its adhesion strength to the skin (pig skin, the same below) reaches 153.5 kPa; the scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals is 95.8%; the antibacterial rate against Escherichia coli is 98.9%, and the antibacterial rate against Staphylococcus aureus is 90.6%. After being irradiated by near-infrared light for 300 seconds, the gel 1 heats up by 21 °C, and at this time, the antibacterial rates against the above two bacteria are as high as 99%. It can not only promote wound healing but also reduce the possibility of wound infection. If other processes remain unchanged and only the dosage of protocatechuic aldehyde is adjusted to 0 g, the adhesion strength drops to 48.3 kPa, the scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals is only 5.0%, the antibacterial rate against Escherichia coli is 58.7%, and the antibacterial rate against Staphylococcus aureus is 64.7%. The results show that protocatechuic aldehyde plays a significant role in the gel 1 for wound repair, mainly manifested in enhancing adhesion, antioxidant properties, and antibacterial properties, etc.

[0043] The gel 1 showed stable temperature-triggered adhesion and detachment during 5 cycles, indicating that the gel has stable temperature-responsive adhesion, which is sufficient to meet daily needs. The gel 1 can maintain a high instantaneous adhesion strength at 37 °C (body temperature), while completely losing its adhesion force below 10 °C. This thermoresponsive adhesion ability provides the possibility for the gel to be separated by local temperature changes when necessary, and can also avoid the inconvenience brought by other interfaces outside the adhered tissue.

[0044] The gel 1 can be used as a flexible sensor to monitor strain-related movements of various parts of the human body, such as finger bending and straightening, wrist and ankle activities, elbow and knee bending and straightening, etc. The test results show that the gel 1 can make a significant, rapid, and reversible electrical signal response to limb movements. In addition, due to the unique soft, sticky, and deformable properties of the gel 1 sensor, it can adhere tightly to various parts of the body without additional adhesives.

[0045] The hemolysis rate of the gel 1 is less than 5%, and the cytocompatibility test shows its excellent biocompatibility, which is suitable for biomedical materials. The wound repair performance of the gel was evaluated by the wound healing of a rat Staphylococcus aureus infection model. The anesthetized rats were shaved with a hair clipper to form circular wounds on the back. Figure 1To investigate the effect of gelatin-modified polyacrylamide gel on promoting wound healing. In the control group, the wounds of rats were wiped with normal saline; in the gel group, the prepared gel was directly adhered to the wounds of rats; in the gel + near-infrared group, the gel was directly adhered to the wounds of rats and irradiated with 808 nm near-infrared light for sterilization. After seven days, it could be seen that, compared with the control group, the gel group significantly promoted wound healing. On the 11th day, the wound healing rates of the gel group and the hydrogel + near-infrared group exceeded 80%, while the control group could reach a wound healing rate of 80% only on the 14th day, indicating that Gel 1 has excellent performance in promoting wound repair.

[0046] Example 2

[0047] (1) Dissolve 1.0 g of gelatin in 5 mL of deionized water, and stir and dissolve it at 37 °C until uniform to obtain a gelatin solution.

[0048] (2) Weigh 0.1 g of protocatechuic aldehyde and dissolve it in the above gelatin solution, and stir and react at 37 °C for 1 hour to obtain a gelatin Schiff base solution.

[0049] (3) Weigh 0.1 g of N,N'-methylenebisacrylamide and dissolve it in 10 mL of deionized water to obtain a chemical cross-linking agent solution.

[0050] (4) Weigh 1.0 g of acrylamide and dissolve it in the above gelatin Schiff base solution, and successively add 60 μL of the chemical cross-linking agent solution, 10 μL of tetramethylethylenediamine, and 0.02 g of ammonium persulfate, stir quickly and evenly, and react in a 60 °C water bath until a gel is formed.

[0051] (5) Place the above gel in a 4 °C refrigerator and cool it for 30 minutes to obtain gelatin-modified polyacrylamide gel 2.

[0052] The compressive strength of Gel 2 obtained by the above method reaches 2.9 MPa, and the tensile strength is 375.5 kPa; the adhesion strength to the skin is 122.4 kPa; the swelling rate in deionized water is 112.9%, and its water absorption and moisture retention are good.

[0053] Example 3

[0054] (1) Dissolve 1.0 g of gelatin in 5 mL of deionized water, and stir and dissolve it at 37 °C until uniform to obtain a gelatin solution.

[0055] (2) Weigh 0.1 g of protocatechuic aldehyde and dissolve it in the above gelatin solution, and stir and react at 37 °C for 1 hour to obtain a gelatin Schiff base solution.

[0056] (3) Weigh 0.1 g of N,N'-methylenebisacrylamide and dissolve it in 10 mL of deionized water to obtain a chemical cross-linking agent solution.

[0057] (4) Weigh 2.0 g of acrylamide and dissolve it in the above-mentioned gelatin Schiff base solution. Then, add 60 μL of the chemical cross-linking agent solution, 10 μL of tetramethylethylenediamine, and 0.02 g of ammonium persulfate in sequence, and stir rapidly and evenly. React in a water bath at 60 °C until a gel is formed.

[0058] (5) Place the above gel in a refrigerator at 4 °C and cool for 30 minutes to obtain gelatin-modified polyacrylamide gel 3.

[0059] The compressive strength of gel 3 obtained by the above method is 3.2 MPa, and the tensile strength is 106.8 kPa; the results show that the compressive and tensile properties of gel 3 can be adjusted by changing the amount of acrylamide used. The adhesion strength to the skin is 125.8 kPa.

[0060] Example 4

[0061] (1) Dissolve 1.0 g of gelatin in 5 mL of deionized water, and stir and dissolve it evenly at 37 °C to obtain a gelatin solution.

[0062] (2) Weigh 0.05 g of protocatechuic aldehyde and dissolve it in the above-mentioned gelatin solution, and stir and react at 37 °C for 1 hour to obtain a gelatin Schiff base solution.

[0063] (3) Weigh 0.1 g of N,N'-methylenebisacrylamide and dissolve it in 10 mL of deionized water to obtain a chemical cross-linking agent solution.

[0064] (4) Weigh 1.5 g of acrylamide and dissolve it in the above-mentioned gelatin Schiff base solution. Then, add 60 μL of the chemical cross-linking agent solution, 10 μL of tetramethylethylenediamine, and 0.02 g of ammonium persulfate in sequence, and stir rapidly and evenly. React in a water bath at 60 °C until a gel is formed.

[0065] (5) Place the above gel in a refrigerator at 4 °C and cool for 30 minutes to obtain gelatin-modified polyacrylamide gel 4.

[0066] The compressive strength of gel 4 obtained by the above method is 3.2 MPa, and the tensile strength is 340.7 kPa; the adhesion strength to the skin is 97.1 kPa; the scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals is 95.7%; after being irradiated by near-infrared light for 300 seconds, the temperature of this gel 4 rises by 19.1 °C, indicating its excellent photothermal performance. The hemolysis rate of this gel 4 is less than 5%, and the cell compatibility test shows its excellent biocompatibility, indicating that this gel 4 is safe and non-toxic and can be used as a biomedical material.

[0067] Other parts not described in detail are all prior arts. Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments according to these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A gelatin-modified polyacrylamide gel, characterized in that: The raw materials of the gel include gelatin, protocatechuic aldehyde and acrylamide monomer; the gel is formed under the joint action of a chemical crosslinking agent, a catalyst and an initiator, wherein the amount of protocatechuic aldehyde is 1% to 20% of the mass of the gelatin, and the amount of acrylamide monomer is 1% to 200% of the mass of the gelatin; The chemical cross-linking agent is N,N'-methylenebisacrylamide, the catalyst is tetramethylethylenediamine, and the initiator is ammonium persulfate.

2. The gelatin-modified polyacrylamide gel according to claim 1, characterized in that: The amount of protocatechuic aldehyde used is 5% to 15% of the mass of gelatin, and the amount of acrylamide monomer used is 50% to 150% of the mass of gelatin.

3. The gelatin-modified polyacrylamide gel according to claim 1, characterized in that: The amount of the cross-linking agent is 0.01% to 0.1% of the mass of gelatin; the amount of the initiator is 2% of the mass of gelatin; and the amount of the catalyst is 0.78% of the mass of gelatin.

4. A gelatin-modified polyacrylamide gel, characterized in that: The following steps are involved: (1) dissolving gelatin in deionized water to obtain a gelatin solution; (2) adding protocatechuic aldehyde to a gelatin solution to react and obtain a gelatin Schiff base solution; (3) dissolving N,N'-methylenebisacrylamide in deionized water to obtain an N,N'-methylenebisacrylamide solution; (4) adding acrylamide monomer to the gelatin Schiff base solution in step (2), and sequentially adding N,N'-methylenebisacrylamide solution, tetramethylethylenediamine and ammonium persulfate, stirring evenly, and reacting in a water bath to obtain a chemically cross-linked network hydrogel; (5) Cooling the chemically cross-linked network hydrogel to obtain a gelatin-modified polyacrylamide gel with a physical and chemical double cross-linked network.

5. The preparation method according to claim 4, characterized in that: In the step (1), the concentration of the gelatin solution is 0.1 to 0.3 g·mL -1 , the melting temperature is 37℃.

6. The preparation method according to claim 4, characterized in that: In the step (2), the amount of protocatechuic aldehyde used is 1% to 20% of the mass of gelatin, the reaction temperature is 37° C., and the reaction time is 1 hour.

7. The preparation method according to claim 4, characterized in that: In step (3), the concentration of N,N'-methylenebisacrylamide is 0.01 g·mL -1 .

8. The preparation method according to claim 4, characterized in that: In the step (4), the amount of acrylamide monomer is 1% to 200% of the mass of gelatin, the amount of cross-linking agent is 0.01% to 0.1% of the mass of gelatin, the amount of catalyst is 0.78% of the mass of gelatin, and the amount of initiator is 2% of the mass of gelatin; the water bath reaction temperature is 60° C., and the reaction time is 1 hour.

9. The preparation method according to claim 4, characterized in that: In the step (5), the cooling temperature is 4° C. and the cooling time is 30 minutes.

10. Use of the gelatin-modified polyacrylamide gel according to claim 1 in preparing wound repair, wound monitoring, sensor detection and plugging materials.

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