Preparation method of a self-healing hydrogel, product and application thereof

Abstract

The application discloses a preparation method of a self-healing hydrogel, a product and application thereof, and belongs to the technical field of biomedical materials. The self-healing hydrogel is prepared by taking gelatin as raw material and aldehyde functionalized diarylethene as a crosslinking agent for crosslinking reaction. The hydrogel prepared by the method has the functions of self-healing and light response regulation of mechanical properties, and has a potential application prospect in tissue engineering and wound repair.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a method for preparing a self-healing hydrogel, its products, and applications. Background Technology

[0002] Hydrogels, due to their soft properties and remarkably similarity to human soft tissue, are widely used in biomedicine, biomimetic materials, and other fields. However, conventional hydrogels often lose their original properties due to damage or fatigue during use, resulting in irreversible damage, which severely limits the expansion of their application areas and scenarios. Self-healing hydrogels, as functional hydrogels capable of self-repair after injury, achieve self-healing under external stimuli (light, heat, pH regulation, and self-healing agents) or the interaction of functional groups within the hydrogel (dynamic covalent bonds, etc.), effectively solving the problem of hydrogel damage during application and expanding its application range. For example, hydrogels are currently widely used in wound dressings, etc., and are easily deformed by environmental and skin changes during use; therefore, hydrogels with self-healing properties are urgently needed for wound repair. However, wound healing is a complex dynamic process, regulated by a combination of many stimuli, among which mechanical force plays a crucial role. Existing hydrogel dressings typically have fixed mechanical strength, which cannot meet the mechanical strength required for wound repair. Therefore, developing hydrogels with controllable and variable strength is beneficial for further expanding the application areas of hydrogels. Summary of the Invention

[0003] To address the problems in the prior art, this invention provides a method for preparing a self-healing hydrogel, its product, and its applications.

[0004] To achieve the above objectives, the present invention provides the following technical solution:

[0005] A method for preparing a self-healing hydrogel involves using gelatin (referred to as gel in this invention) as a raw material and aldehyde-functionalized diarylethylene as a crosslinking agent to carry out a crosslinking reaction, thereby obtaining a self-healing hydrogel.

[0006] Furthermore, the preparation method of the self-healing hydrogel includes the following specific steps:

[0007] 1) Dissolve gelatin in bicarbonate buffer solution to obtain gelatin aqueous solution;

[0008] 2) Dissolve aldehyde-functionalized diarylethylene in an organic solvent to obtain a crosslinking agent solution;

[0009] 3) Under ultrasonic oscillation in a water bath, a crosslinking agent solution is added to the obtained gelatin aqueous solution, and the mixture is allowed to stand to obtain a self-healing hydrogel (Gel-AFD).

[0010] Further, in step 1), the pH of the bicarbonate buffer solution is 8.5.

[0011] Further, in step 2), the aldehyde-functionalized diarylethylethylene is 4,4-(cyclopentadien-1-en-1,2-imide)di(5-methylthiophene-2-carboxaldehyde) (abbreviated as AFD); the organic solvent is dimethyl sulfoxide (DMSO).

[0012] Furthermore, the mass ratio of the gelatin to the aldehyde-functionalized diarylethylene is (10-20):(0.5-0.12).

[0013] Furthermore, in step 3), the water bath temperature is 50°C.

[0014] Further, in step 3), the volume ratio of the gelatin aqueous solution to the crosslinking agent solution is 1:1.

[0015] Furthermore, in step 3), the settling time is 12 hours.

[0016] The present invention also provides a self-healing hydrogel prepared using the above-described method for preparing self-healing hydrogel.

[0017] The present invention also provides an application of the above-mentioned self-healing hydrogel in the preparation of wound dressings.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0019] The purpose of this invention is to construct a self-healing hydrogel with photoresponsive, tunable mechanical properties and self-repairing capabilities. The preparation method utilizes readily available raw materials, is simple and rapid, and produces a hydrogel with excellent properties. In this invention, aldehyde-functionalized diarylethylene (4,4-(cyclopentadien-1-en-1,2-imidel)bis(5-methylthiophene-2-carboxaldehyde) is used as a crosslinking agent to link gelatin together to form a hydrogel. The self-healing ability and tunable mechanical properties of the formed hydrogel are then tested. The results show that the diarylethylene crosslinked gelatin hydrogel exhibits good self-healing ability and tunable mechanical properties.

[0020] This invention crosslinks gelatin with aldehyde-functionalized diarylethylene (4,4-(cyclopentadien-1-en-1,2-pyridyl)bis(5-methylthiophene-2-carboxaldehyde) via dynamic covalent bonds to form a hydrogel. The amino groups in the gelatin and the aldehyde groups in the diarylethylene form Schiff base bonds under alkaline conditions. This chemical bond is dynamically reversible, endowing the hydrogel with self-healing properties. Simultaneously, aldehyde-functionalized diarylethylene (4,4-(cyclopentadien-1-en-1,2-pyridyl)bis(5-methylthiophene-2-carboxaldehyde) undergoes a reversible ring-opening-closing change under UV-Vis light, resulting in a reversible elongation-shortening change in its molecular structure. This change in molecular structure induces changes in the size of the gaps in the hydrogel network, thereby reversibly altering the hardness and volume of the hydrogel. The hydrogel prepared by this method possesses self-healing capabilities and photoresponsive mechanical property regulation, showing potential applications in tissue engineering and wound repair. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 Fourier transform infrared spectroscopy analysis was performed on gelatin, diarylethylene, and the assembled Gel-AFD hydrogel.

[0023] Figure 2 Figure 1 shows the rapid self-healing properties of Gel-AFD hydrogel and pure gelatin.

[0024] Figure 3 Rheological test of the self-healing ability of Gel-AFD hydrogel before UV irradiation;

[0025] Figure 4 Rheological test of the self-healing ability of Gel-AFD hydrogel after UV irradiation;

[0026] Figure 5 Micromechanical testing of the photoresponse-regulated mechanical properties of Gel-AFD hydrogel;

[0027] Figure 6 Rheological testing of the photoresponse-regulated mechanical properties of Gel-AFD hydrogel;

[0028] Figure 7 Micromechanical testing to assess the photoresponse-regulated mechanical properties of Gelatin hydrogel;

[0029] Figure 8Rheological testing to assess the photoresponsiveness of the mechanical properties of gelatin hydrogels. Detailed Implementation

[0030] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0031] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0032] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0033] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This application specification and embodiments are merely exemplary.

[0034] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0035] A method for preparing a self-healing hydrogel involves using gelatin (referred to as gel in this invention) as a raw material and aldehyde-functionalized diarylethylene as a crosslinking agent to carry out a crosslinking reaction, thereby obtaining a self-healing hydrogel.

[0036] In some preferred embodiments, the preparation method includes the following specific steps:

[0037] 1) Dissolve gelatin in bicarbonate buffer solution to obtain gelatin aqueous solution;

[0038] 2) Dissolve aldehyde-functionalized diarylethylene in an organic solvent to obtain a crosslinking agent solution;

[0039] 3) Under ultrasonic oscillation in a water bath, a crosslinking agent solution is added to the obtained gelatin aqueous solution to react until the solution is uniform and clear, and then allowed to stand to obtain self-healing hydrogel (Gel-AFD).

[0040] In some preferred embodiments, in step 1), the pH of the bicarbonate buffer solution is 8.5. The bicarbonate buffer solution is a 10 mM sodium bicarbonate buffer solution.

[0041] In some preferred embodiments, in step 2), the aldehyde-functionalized diarylethene is 4,4-(cyclopentadien-1-en-1,2-imide)di(5-methylthiophene-2-carboxaldehyde) (abbreviated as AFD); and the organic solvent is dimethyl sulfoxide (DMSO).

[0042] In some preferred embodiments, the mass ratio of gelatin to aldehyde-functionalized diarylethylene is (10-20):(0.5-0.12). Preferably, it is 10:0.5 or 20:0.12.

[0043] In some preferred embodiments, in step 3), the water bath temperature is 50°C.

[0044] In some preferred embodiments, in step 3), the volume ratio of the gelatin aqueous solution to the crosslinking agent solution is 1:1.

[0045] In some preferred embodiments, in step 3), the settling time is 12 hours.

[0046] The present invention also provides a self-healing hydrogel prepared using the above-described method for preparing self-healing hydrogel.

[0047] The present invention also provides an application of the above-mentioned self-healing hydrogel in the preparation of wound dressings.

[0048] All raw materials used in this invention were purchased from McLean.

[0049] Unless otherwise specified, "room temperature" in this invention refers to 25°C.

[0050] Example 1

[0051] Preparation of Gel-AFD hydrogel:

[0052] 1) Dissolve gelatin in sodium bicarbonate buffer solution at pH 8.5 to obtain a gelatin aqueous solution with a mass concentration of 200 mg / mL;

[0053] 2) Dissolve 4,4-(cyclopentadien-1-ene-1,2-imidel)bis(5-methylthiophene-2-carboxaldehyde) (AFD) in dimethyl sulfoxide (DMSO) to obtain a crosslinking agent solution with a mass concentration of 10 mg / mL;

[0054] 3) Under ultrasonic oscillation in a water bath at 50℃, a crosslinking agent solution is slowly added dropwise to the obtained gelatin aqueous solution and the reaction is carried out for 30 minutes. The volume ratio of the gelatin aqueous solution to the crosslinking agent solution is 1:1 until the solution is uniform and clear.

[0055] The mass ratio of gelatin to aldehyde-functionalized diarylethylene is 10:0.5.

[0056] 4) Let the obtained gel solution stand for 12 hours to obtain the self-healing hydrogel (Gel-AFD).

[0057] Figure 1 Fourier transform infrared spectroscopy analysis was performed on gelatin, AFD, and the assembled Gel-AFD hydrogel. The transmission peak at 1641 shown in the figure is the characteristic peak of the dynamic covalent bond (imine bond) after the formation of the Gel-AFD hydrogel.

[0058] Example 2

[0059] Preparation of Gel-AFD hydrogel:

[0060] 1) Dissolve gelatin in sodium bicarbonate buffer solution at pH 8.5 to obtain a gelatin aqueous solution with a mass concentration of 400 mg / mL;

[0061] 2) Dissolve 4,4-(cyclopentadien-1-ene-1,2-imidel)bis(5-methylthiophene-2-carboxaldehyde) (AFD) in dimethyl sulfoxide (DMSO) to obtain a crosslinking agent solution with a mass concentration of 2.4 mg / mL;

[0062] 3) Under ultrasonic oscillation in a water bath at 50℃, a crosslinking agent solution is slowly added dropwise to the obtained gelatin aqueous solution and the reaction is carried out for 30 minutes. The volume ratio of the gelatin aqueous solution to the crosslinking agent solution is 1:1 until the solution is uniform and clear.

[0063] The mass ratio of gelatin to aldehyde-functionalized diarylethylene is 20:0.12.

[0064] 4) Let the obtained gel solution stand for 12 hours to obtain the self-healing hydrogel (Gel-AFD).

[0065] 1. The repair performance test of the Gel-AFD hydrogel and raw material gelatin prepared in this embodiment was carried out. Specifically, the gel liquid formed in step 3) was placed in the mold under heating (50°C). After it cooled to room temperature and formed a gel, it was cut in half and reattached. After standing at room temperature for 3 minutes, it was observed whether the gel could be picked up from one side. Then, it was observed again by irradiating with ultraviolet light for 2 minutes and standing at room temperature for 1 minute.

[0066] As a control, try the above steps again using a separate gelatin solution.

[0067] Figure 2 The graph shows the rapid self-healing properties of Gel-AFD hydrogel and pure gelatin. As can be seen from the graph, Gel-AFD hydrogel has rapid self-healing properties, while under the same conditions, hydrogel formed by pure gelatin does not have self-healing properties.

[0068] 2. The Gel-AFD hydrogel prepared in this embodiment was subjected to ultraviolet light irradiation to observe its self-healing rheological properties. Specifically, the gel liquid formed in step 3) was placed in a mold under heating (50°C). After it cooled to room temperature and formed a gel, it was placed on a test platform for rheological testing. The test was repeated after irradiation with ultraviolet light for 2 minutes. At the same time, low strain and high strain cyclic tests were performed using the time scan mode of the rheometer, with a cycle period of 30 minutes.

[0069] Figure 3 and Figure 4 These are rheological test diagrams of the self-healing ability of Gel-AFD hydrogel before and after ultraviolet light irradiation.

[0070] from Figure 3 As can be seen, before UV irradiation, in the low-strain test, the storage modulus was higher than the loss modulus, indicating that it was in a gel state. Conversely, in the high-strain test, the loss modulus was higher than the storage modulus, indicating that the gel state was damaged. After standing for 3 minutes, low-strain and high-strain tests were repeated. The results showed that in the first cycle, the storage modulus recovered to about 60% of the initial value, and in the second cycle, it recovered to about 40%. This indicates that the Gel-AFD hydrogel can still recover a certain degree of modulus after its physical structure is damaged, demonstrating self-healing ability.

[0071] from Figure 4It can be seen that after UV irradiation, the modulus recovery rate of Gel-AFD hydrogel after the physical structure is damaged increases. The storage modulus of the first cycle can recover to about 80% of the initial test state, and the second cycle can recover to about 70%, showing stronger self-healing ability. Moreover, in each cycle test, the storage modulus after irradiation is higher than that before irradiation, indicating that the strength of hydrogel is improved after irradiation.

[0072] Figure 3 and Figure 4 This demonstrates that the Gel-AFD hydrogel prepared in this embodiment can stably recover its modulus under low and high strain cycles, and its healing ability is further enhanced after ultraviolet irradiation.

[0073] 3. The photomechanical properties of the Gel-AFD hydrogel prepared in this embodiment were tested. Specifically, the gel solution formed in step 3) was placed in a mold under heating (50°C). After cooling to room temperature to form a gel, it was subjected to ultraviolet irradiation and visible light irradiation, and then placed on a micromechanical testing platform for micromechanical testing (see [link to micromechanical test platform]). Figure 5 ).

[0074] from Figure 5 As can be seen, the recovery force required to compress the Gel-AFD hydrogel a certain distance in the initial state is about 12000 μN, while the recovery force required to compress the Gel-AFD hydrogel after ultraviolet (UV) irradiation increases to 18000 μN, and the recovery force required to compress the Gel-AFD hydrogel after visible light (Vis) irradiation decreases to 12000 μN. This indicates that the strength of Gel-AFD can be controllably regulated through UV-Vis.

[0075] 4. The photoresponse mechanical strength of the Gel-AFD hydrogel prepared in this embodiment was tested using rheological methods. Specifically, the gel solution formed in step 3) was placed in a mold under heating (50°C), and after cooling to room temperature to form a gel, it was irradiated with ultraviolet light and visible light respectively. Then, it was placed on a test platform and tested using a rheometer in frequency scanning mode (see [link to test procedure]). Figure 6 ).

[0076] from Figure 6 As can be seen, after ultraviolet irradiation, the modulus of the Gel-AFD hydrogel (including storage modulus and loss modulus, with storage modulus represented by solid icons and loss modulus by hollow icons) increased, while after irradiation under visible light, the modulus decreased to some extent. This indicates that ultraviolet-visible light can controllably regulate the intensity of Gel-AFD.

[0077] 5. The photoresponsive mechanical properties of the isolated gelatin hydrogel prepared in this embodiment for use as a control were subjected to micromechanical testing. Specifically, the gel solution formed in step 3) was placed in a mold under heating (50°C), and after cooling to room temperature to form a gel, it was subjected to ultraviolet irradiation and visible light irradiation, and then placed on a micromechanical testing platform for micromechanical testing (see...). Figure 7 ).

[0078] from Figure 7 As can be seen, the recovery force required to compress gelatin gel a certain distance in the initial state is about 13000 μN, while the recovery force required to compress gelatin gel after ultraviolet (UV) irradiation remains at 14000 μN, and the recovery force required to compress gelatin gel after visible light (Vis) irradiation is still 14000 μN. This indicates that the strength of simple gelatin gel cannot be controlled by UV-Vis.

[0079] 6. The simple gelatin hydrogel prepared in this embodiment as a control was subjected to rheological testing of its photoresponsive mechanical strength. Specifically, the gel solution formed in step 3) was placed in a mold under heating (50°C), and after cooling to room temperature to form a gel, it was irradiated with ultraviolet light and visible light respectively. Then, it was placed on a testing platform and tested using a rheometer in frequency scanning mode (see [link to relevant documentation]). Figure 8 ).

[0080] from Figure 8 As can be seen, the modulus (including storage modulus and loss modulus, with storage modulus represented by a solid icon and loss modulus by a hollow icon) of pure gelatin hydrogel did not change after ultraviolet irradiation, and the modulus also did not show significant change after irradiation under visible light. This indicates that ultraviolet-visible light cannot controllably regulate the strength of pure gelatin hydrogel.

[0081] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a self-healing hydrogel, characterized in that, A self-healing hydrogel was obtained by cross-linking gelatin as raw material and aldehyde-functionalized diarylethylene as cross-linking agent; the mass ratio of gelatin to aldehyde-functionalized diarylethylene was (10-20):(0.5-0.12). The preparation method includes the following specific steps: 1) Dissolve gelatin in bicarbonate buffer solution to obtain gelatin aqueous solution; 2) The aldehyde-functionalized diarylethylene is dissolved in an organic solvent to obtain a crosslinking agent solution; the aldehyde-functionalized diarylethylene is 4,4-(cyclopentadien-1-en-1,2-imidel)bis(5-methylthiophene-2-carboxaldehyde); the organic solvent is dimethyl sulfoxide; 3) Under ultrasonic oscillation in a water bath, the crosslinking agent solution is added to the gelatin aqueous solution and allowed to stand to obtain a self-healing hydrogel.

2. The method for preparing the self-healing hydrogel according to claim 1, characterized in that, In step 1), the pH of the bicarbonate buffer solution is 8.

5.

3. The method for preparing the self-healing hydrogel according to claim 1, characterized in that, In step 3), the water bath temperature is 50°C.

4. The method for preparing the self-healing hydrogel according to claim 1, characterized in that, In step 3), the volume ratio of the gelatin aqueous solution to the crosslinking agent solution is 1:

1.

5. The method for preparing the self-healing hydrogel according to claim 1, characterized in that, In step 3), the settling time is 12 hours.

6. A self-healing hydrogel prepared using the preparation method of the self-healing hydrogel according to any one of claims 1-5.

7. The application of the self-healing hydrogel as described in claim 6 in the preparation of wound dressings.

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