Mussel-like polylipoic acid-based hydrogel adhesive as well as preparation method and application thereof

Abstract

The invention relates to a mussel-like polylipoic acid-based hydrogel adhesive as well as a preparation method and application thereof, and the preparation method comprises the following steps: (1) uniformly mixing a sericin solution and a caffeic acid solution, then carrying out grafting reaction to obtain a reaction solution, and carrying out dialysis treatment and drying on the reaction solution to obtain sericin grafted caffeic acid; (2) adding lipoic acid into the lithium hydroxide solution, stirring until the lipoic acid is completely dissolved, then adding sericin grafted caffeic acid, and heating for reaction to obtain a PTALi-CAS mixture; and (3) cooling the PTALi-CAS mixture, so as to obtain the mussel-like polylipoic acid-based hydrogel adhesive. The dual-network PTALi-CAS hydrogel adhesive obtained in the invention realizes wet adhesion and rapid hemostasis, has excellent comprehensive performance, and is beneficial to providing a good repair environment for wounds as a wound dressing.

Description

Technical Field

[0001] The invention belongs to the field of hydrogel dressings, and in particular relates to a mussel-imitation polylipoic acid-based hydrogel adhesive and a preparation method and application thereof. Background Art

[0002] Hydrogels have high water content, excellent biocompatibility and good water retention properties; they have microstructures similar to extracellular matrix, softness and elastic mechanical properties; they are a type of biomedical material that is very close to living tissues, and therefore are increasingly used in the field of wound repair. At present, traditional hydrogel wound dressings are widely used for their high water absorption and breathability, which can effectively maintain a moist environment for wounds and promote healing. However, ordinary hydrogel dressings still have problems with insufficient wet adhesion, hemostasis and mechanical properties. Therefore, it is clinically necessary to develop a hydrogel wound dressing with wet adhesion, rapid hemostasis and good mechanical properties to seal wounds and promote wound healing.

[0003] Lipoic acid (TA) is a natural coenzyme present in mitochondria with good biocompatibility and antibacterial properties, and plays an important role in scavenging free radicals. Moreover, TA has hydrophobic 1,2-disulfane and alkyl chain groups and hydrophilic carboxylic acid groups, which can form a variety of non-covalent bonds, including hydrophobic aggregation, electrostatic interactions and hydrogen bonds. Therefore, its application in the field of wet adhesives has attracted more and more attention from researchers recently. However, poly(thioctic acid), PTA, prepared by TA ring-opening polymerization is metastable and easy to close the ring and depolymerize, which may affect its ability to adhere to wet tissues. Studies have shown that the introduction of catechol groups in polylipoic acid not only alleviates the depolymerization rate of PTA, but also significantly enhances the adhesive properties of hydrogels.

[0004] Caffeic acid (CA), a plant-derived catechol derivative that mimics mussels, can theoretically become the adhesive part of bioadhesive hydrogels through intermolecular interactions. However, the catechol group of CA is easily oxidized, which affects the adhesive properties of the hydrogel. Summary of the invention

[0005] The purpose of the present invention is to overcome the above technical deficiencies, provide a mussel-like polylipoic acid-based hydrogel adhesive and a preparation method and application thereof, and solve the technical problem in the prior art that ordinary hydrogel wound dressings are difficult to have both wet adhesion and rapid hemostasis properties.

[0006] In order to achieve the above technical purpose, the technical solution provided by the present invention is: In a first aspect, the present invention provides a method for preparing a mussel-like polylipoic acid-based hydrogel adhesive, comprising the following steps: (1) mixing a sericin solution and a caffeic acid solution evenly and then performing a grafting reaction to obtain a reaction solution, and the reaction solution is dialyzed and dried to obtain sericin grafted with caffeic acid; (2) adding lipoic acid to a lithium hydroxide solution and stirring until completely dissolved, then adding sericin grafted with caffeic acid, and heating the mixture to obtain a PTALi-CAS mixture; and (3) cooling the PTALi-CAS mixture to obtain a mussel-like polylipoic acid-based hydrogel adhesive.

[0007] In a second aspect, the present invention provides a mussel-like polylipoic acid-based hydrogel adhesive prepared by the above preparation method.

[0008] In a third aspect, the present invention provides a use of a mussel-mimicking polylipoic acid-based hydrogel adhesive as a wound dressing.

[0009] Compared with the prior art, the beneficial effects of the present invention include: The present invention obtains sericin grafted with caffeic acid (CAS) by grafting reaction between caffeic acid (CA) and sericin to simulate the catechol structure of mussels; in addition, lipoic acid (TA) is dissolved in a lithium hydroxide solution to prepare a supramolecular conductive polymer network of PTALi; and CAS is introduced into the polymer network to obtain a double-network PTALi-CAS hydrogel adhesive to achieve wet adhesion and rapid hemostasis. In addition, the hydrogel adhesive prepared by the present invention can also promote wound healing, has good antibacterial and mechanical properties, and excellent comprehensive performance. As a wound dressing, it can seal the wound and avoid wound infection, which is conducive to providing a good repair environment for the wound. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is a scanning electron microscope image of a mussel-like polylipoic acid-based hydrogel adhesive obtained in Example 1; Figure 2 is a scanning electron microscope image of the hydrogel adhesive obtained in Comparative Example 1; Figure 3 This is a diagram showing the effect of the hydrogel on Escherichia coli and Staphylococcus aureus in Test Example 2; Figure 4 This is a diagram showing the hemostatic performance of the hydrogel in Test Example 3; Figure 5 This is a diagram of the biocompatibility test results in Test Example 5, where the scale is 200 microns. DETAILED DESCRIPTION

[0011] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0012] In view of the fact that ordinary hydrogel wound dressings are difficult to have both wet adhesion and rapid hemostasis, and their mechanical properties are difficult to achieve compatibility with skin tissue, the present invention intends to learn from the adhesion strategy of marine mussels in a wet environment and design a polylipoic acid-sericin grafted caffeic acid (PTALi-CAS) composite hydrogel wound dressing with wet adhesion and rapid hemostasis. In the system of the present invention, the hydrogel surface has a large number of positively charged amino groups, which can promote platelet aggregation and achieve a pro-coagulation effect. In addition, caffeic acid (CA) with a phenolic hydroxyl structure can utilize the mussel adhesion mechanism to improve the wet adhesion of the hydrogel to its tissue and enhance its hemostasis; while sericin can provide sufficient grafting sites for CA and form hydrogen bonds with PTA, thereby forming a double cross-linked network structure to improve the mechanical properties of the hydrogel.

[0013] Therefore, the present invention provides a novel bionic multifunctional hydrogel adhesive, which mainly grafts caffeic acid (CA) onto sericin to obtain sericin grafted caffeic acid (CAS) to simulate the relevant structure of mussels, thereby promoting the improvement of hydrogel adhesion performance; in addition, lipoic acid (TA) is dissolved in lithium hydroxide solution to prepare a supramolecular conductive polymer network of PTALi; CAS is then introduced into the polymer network to achieve wet adhesion and rapid hemostasis. In addition, the hydrogel adhesive prepared by the present invention also has excellent self-healing properties, significant antibacterial properties, good mechanical properties and biocompatibility; these properties enable the hydrogel of the present invention to provide a good repair environment for wounds, accelerate the rapid healing of wounds, and is expected to be further clinically applied.

[0014] In a first aspect, the present invention provides a method for preparing a mussel-like polylipoic acid-based hydrogel adhesive, comprising the following steps: (1) The sericin solution and the caffeic acid solution are mixed evenly and then subjected to grafting reaction to obtain a reaction solution, and the reaction solution is dialyzed and dried to obtain sericin grafted with caffeic acid CAS; (2) adding lipoic acid to a lithium hydroxide solution and stirring until completely dissolved, then adding sericin grafted with caffeic acid, and heating the mixture to obtain a PTALi-CAS mixture; (3) The PTALi-CAS mixture is cooled to obtain a mussel-mimicking polylipoic acid-based hydrogel adhesive.

[0015] Preferably, in step (1), the mass ratio of sericin to caffeic acid is (1-2):(0.5-1).

[0016] Preferably, in step (1), the sericin solution is obtained by dissolving sericin in a MES buffer having a pH value of 4 to 6, and the ratio of sericin to MES buffer is (1 to 2) g: (40 to 60) mL.

[0017] Preferably, in step (1), the caffeic acid solution is obtained by dissolving caffeic acid in ethanol, and the ratio between caffeic acid and ethanol is (0.5-1) g: (20-30) mL; the caffeic acid solution also contains 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS), wherein the mass ratio of caffeic acid, EDC and NHS is (0.5-1): (0.15-0.25): (0.08-0.13). When preparing the caffeic acid solution, if the caffeic acid is excessive, it will precipitate and affect the adhesion performance of the hydrogel.

[0018] Preferably, in step (1), the sericin solution and the caffeic acid solution are stirred in an ice bath for 30 to 50 minutes to be uniformly mixed; and the grafting reaction is carried out under nitrogen protection and stirred at room temperature for 10 to 15 hours.

[0019] Preferably, in step (1), the dialysis treatment uses a dialysis bag with a molecular weight of 3000 to 4000, the dialysis time is 3 to 5 days, and the deionized water is replaced every 12 to 15 hours.

[0020] Preferably, in step (1), the drying is performed by freeze drying.

[0021] Preferably, in step (2), the mass ratio of lipoic acid to lithium hydroxide is (5-8): (0.05-0.1); the mass ratio of sericin grafted caffeic acid to lithium hydroxide is (0.2-0.3): (0.05-0.1). Excessive lipoic acid will result in the inability to prepare hydrogel.

[0022] Preferably, in step (2), the lithium hydroxide solution is formed by dissolving lithium hydroxide in deionized water, and the ratio of lithium hydroxide to deionized water is (0.05-0.1) g: (20-30) mL.

[0023] Preferably, in step (2), lipoic acid is added to a lithium hydroxide solution at 60-80°C and stirred until completely dissolved, and then sericin grafted with caffeic acid is added and stirred at 60-80°C for 2-3 h to obtain a PTALi-CAS mixture. Wherein, too long a stirring time or too high a temperature will affect the mechanical properties of the hydrogel.

[0024] Preferably, in step (3), the temperature is cooled to 20-30°C.

[0025] In a second aspect, the present invention provides a mussel-like polylipoic acid-based hydrogel adhesive prepared by the above preparation method.

[0026] In a third aspect, the present invention provides a use of a mussel-mimicking polylipoic acid-based hydrogel adhesive as a wound dressing.

[0027] The main mechanism of action and advantages of the present invention: (1) Sericin, as the main component of silk, not only has excellent biocompatibility, but also provides abundant amino grafting sites for modifying caffeic acid, which can effectively prevent the oxidation of CA. Sericin can also form hydrogen bonds with PTA, thereby increasing the cross-linking density of the hydrogel.

[0028] (2) Since CA has phenolic hydroxyl groups, these hydrogels also exhibit antibacterial and hemostatic abilities through electrostatic interactions, which not only leads to bacterial growth inhibition and death but also activates coagulation factor XII to initiate the coagulation cascade reaction, thereby achieving rapid hemostasis.

[0029] (3) The present invention not only prepared sericin grafted with caffeic acid CAS for the first time, but also constructed a double-network PTALi-CAS hydrogel adhesive, which not only enhanced the antibacterial properties of the hydrogel, but also improved the sealing and hemostatic properties of the hydrogel adhesive for wounds, thereby promoting wound healing; in this system, CAS provides wet adhesion and rapid hemostasis; the disulfide bonds in polylipoic acid give the hydrogel self-healing properties; and lipoic acid lithium provides conductivity; the present invention achieves the repair of traumatic wounds by preparing PTALi-CAS multifunctional hydrogel.

[0030] The hydrogel adhesive prepared according to the method of the present invention has excellent self-healing properties, significant antibacterial properties, good mechanical properties and biocompatibility, and is a multifunctional hydrogel adhesive; more importantly, the hydrogel can quickly and timely seal wounds and stop bleeding to avoid wound infection. These properties enable the hydrogel of the present invention to be used as an adhesive to provide a good repair environment for wounds and provide effective antibacterial treatment, thereby accelerating the rapid healing of traumatic wounds.

[0031] The present invention is further described in detail below through specific examples; the materials, reagents, etc. used therein, unless otherwise specified, can be obtained from commercial sources, for example, sericin is purchased from MacLean. Unless otherwise specified, the concentration of a solution prepared with a liquid is expressed in volume ratio (v / v), and the concentration of a solution prepared with a solid is expressed in mass volume ratio (w / v).

[0032] Example 1 A method for preparing a mussel-like polylipoic acid-based hydrogel adhesive comprises the following steps: (1) Dissolve 1.0 g of sericin in 50 mL of MES buffer (pH 5) and stir magnetically at room temperature until the sericin is completely dissolved to obtain a sericin solution; 0.5 g of CA was dissolved in 25 mL of ethanol and stirred magnetically at room temperature until completely dissolved; EDC (0.19 g) and NHS (0.11 g) were then added and stirred in an ice bath for 30 min to obtain a caffeic acid solution; The sericin solution and the caffeic acid solution were added into a three-necked flask, and the reaction was continued with stirring for 12 hours under the protection of N2 to obtain a reaction solution, which was poured into a dialysis bag (molecular weight 3500) and dialyzed with deionized water for 3 days, with the deionized water replaced every 12 hours; finally, the sericin grafted caffeic acid CAS was obtained by freeze drying as a white cotton-like solid.

[0033] (2) Disperse 0.05 g of lithium hydroxide in 25 mL of deionized water to obtain a lithium hydroxide solution, and heat it to 70°C; 5 g of lipoic acid was added to a lithium hydroxide solution at 70°C and stirred continuously until completely dissolved to obtain a PTALi complex; 0.275 g of sericin grafted with caffeic acid CAS obtained in step (1) was then added, and the mixture was stirred at 70°C for 2 h to obtain a PTALi-CAS mixture; (3) Pour the PTALi-CAS mixture into a mold and cool it to 25 °C to obtain a mussel-like polylipoic acid-based hydrogel adhesive.

[0034] The scanning electron microscope image of the product obtained in this example is shown in Figure 1 , indicating that a hydrogel adhesive with a three-dimensional network structure, microporous characteristics, and high porosity is obtained, and the pores of the hydrogel product are uniform and moderate, so the obtained hydrogel has good mechanical properties while ensuring air permeability.

[0035] Comparative Example 1 A method for preparing a hydrogel adhesive, which differs from Example 1 in that CAS is not added, and other steps and conditions are the same as those of Example 1; specifically, the method comprises the following steps: 0.05 g lithium hydroxide was dispersed in 25 mL deionized water and heated to 70 °C; then 5 g lipoic acid was added to the 70 °C lithium hydroxide solution and stirred continuously for 2 h to mix into a gel, thereby obtaining PTALi hydrogel.

[0036] The scanning electron microscope image of the hydrogel product obtained in this comparative example is shown in Figure 2 The pores of the hydrogel product are uneven and the pore size is relatively large, which will lead to a decrease in the mechanical properties of the hydrogel.

[0037] Comparative Example 2 The only difference from Example 1 is that the amount of CA is adjusted to 0.1 g or 1.5 g, respectively, and the other steps and conditions are the same as Example 1.

[0038] The results show that the amount of caffeic acid grafted on sericin affects the adhesion properties of the hydrogel, and too much or too little CA has adverse effects. The preferred mass ratio of sericin to caffeic acid in the present invention is (1-2): (0.5-1), and more preferably (1-2): 0.5.

[0039] Comparative Example 3 The only difference from Example 1 is that the amount of TA is adjusted to 1 g or 10 g, respectively, and the other steps and conditions are the same as Example 1.

[0040] The results show that too little lipoic acid will result in the inability to prepare the hydrogel, which will be viscous; excessive lipoic acid will affect the cross-linking inside the hydrogel, thereby affecting the mechanical properties of the hydrogel. Therefore, too much or too little TA has adverse effects. The preferred mass ratio of lipoic acid to lithium hydroxide in the present invention is (5-8): (0.05-0.1).

[0041] Comparative Example 4 The only difference from Example 1 is that after CAS is added, the reaction temperature is adjusted to 30° C. or 90° C., and the other steps and conditions are the same as in Example 1.

[0042] The results show that when the temperature is 30°C, the hydrogel cannot be formed; when the temperature is 90°C, the hydrogel hardens and the wet adhesion performance decreases. Therefore, too high or too low a temperature has adverse effects. The preferred reaction temperature of the present invention is 60-80°C, more preferably 70°C.

[0043] Test Example 1 The antibacterial efficiency of the mussel-like polylipoic acid-based hydrogel adhesive of the present invention against Escherichia coli and Staphylococcus aureus was evaluated.

[0044] The hydrogel prepared in Example 1 was added to a 24-well cell culture plate and sterilized with ultraviolet light for 24 hours to obtain a sterilized hydrogel. 20 μL of the diluted bacterial suspension (108 CFU / mL) was added to the sterilized hydrogel as a test group.

[0045] The hydrogel prepared in Comparative Example 1 (without CAS) was added to a 24-well cell culture plate instead of the hydrogel in Example 1, and other sterilization and addition of diluted bacterial suspension were performed in the same manner as above, serving as a control group; And 20 μL of diluted bacterial suspension was directly added to the 24-well cell culture plate as a blank group.

[0046] Then, after culturing in a shaking incubator at 100 rpm / min and 37°C for 2 hours, each group of materials was washed with 1 mL of sterile PBS. Then, 100 μL of bacterial suspension was evenly dispersed on the agar plate and cultured in a constant temperature shaking incubator for 12 hours. Finally, the antibacterial properties of the materials were analyzed by taking pictures and counting the colonies on the agar plate.

[0047] The number of colonies on agar plates is shown in Figure 3 , among which the test group had the least colonies, indicating that the mussel-like polylipoic acid-based hydrogel adhesive of the present invention has excellent antibacterial properties.

[0048] Test Example 2 The adhesion properties of the hydrogels were further evaluated by shear tests using a universal testing machine. These hydrogels were applied to two pieces of two substrate sizes (50 mm long × 20 mm wide) and an adhesion area of ​​20 × 20 mm. Subsequently, the samples were immersed in PBS solution. Finally, the samples were measured at a speed of 10 mm / min. The results of the hydrogel test data are shown in Table 1.

[0049] Table 1 Hydrogel adhesion performance data

[0050] From the results in Table 1, it can be seen that the adhesion performance of the hydrogel obtained in Example 1 is better than that in Comparative Example 1, which indicates that the hydrogel adhesive of the present invention has excellent wet adhesion performance.

[0051] Test Example 3 A blank 96-well plate was used as the blank group; 25 mg of gauze was deposited in a 96-well plate as the control group; and 25 mg of the PTALi-CAS hydrogel obtained in Example 1 was deposited in a 96-well plate as the test group.

[0052] Then, 50 μL of refractory rat blood was added to the wells of each group of well plates. After the specified time, the wells of the mixture were washed several times with 0.9 wt% NaCl solution in sequence. Specifically, the first column of wells in the three groups were washed in the first minute, and the second column of wells in the three groups were washed in the second minute. Seven columns of samples were washed in sequence. After the test was completed, the final coagulation time was recorded, and the thrombus photos were imaged with a digital camera. The results of the hydrogel test data are shown in Figure 4 .

[0053] Depend on Figure 4 It can be seen that blood coagulation occurs in Example 1 at 1 minute, blood coagulation occurs in the control group at about 2 minutes, and blood coagulation occurs in the blank group at about 5 minutes, which shows that the hydrogel in Example 1 can promote blood coagulation and form thrombus, indicating that the hydrogel adhesive of the present invention has the performance of rapid hemostasis.

[0054] Test Example 4 The wound healing experiment was conducted using Kunming rats (female, obtained from Wuhan Center for Disease Control and Prevention, 200-250 g) wound model.

[0055] First, SD rats were randomly divided into three groups: a blank group, a control group (using the PTALi hydrogel of Comparative Example 1), and a test group (using the PTALi-CAS hydrogel of Example 1).

[0056] First, the rats were paralyzed with 3% sodium pentobarbital. The hair on the back of the rats was shaved, and 20 mm transverse skin wounds were made on both sides of the midline. After surgery, different materials were used as wound dressings to cover the wound surface according to the grouping, and the blank group was not treated. The wound area was photographed on the 3rd, 6th and 9th days, and the wound healing rate was calculated based on the wound area. The wound healing rate of mice is shown in Table 2.

[0057] Table 2 Wound healing rate of mice

[0058] From the results in Table 2, it can be seen that the healing rate of the wound covered with the hydrogel obtained in Example 1 as a dressing is significantly higher than that of the blank group and the hydrogel of Comparative Example 1, which shows that the mussel-like polylipoic acid-based hydrogel adhesive of the present invention can effectively promote the healing of skin wounds.

[0059] Test Example 5 The biocompatibility of L929 cells was tested by CCK-8 live-dead staining. 3 cells / well, 100 μL of L929 cell suspension was inoculated in a 96-well plate and placed in a 37°C incubator. After 24 hours, 100 μL of the hydrogel obtained in Example 1 was refilled as the test group; the hydrogel of Comparative Example 1 was filled as the control group, and the one without hydrogel was used as the blank group.

[0060] Each group of cells was then incubated for another day, stained with calcein / propidium iodide dye for 30 minutes, and the fluorescence of the stained cells was observed under a microscope.

[0061] The results are as follows Figure 5 As shown, compared with the blank group, both the control group and the experimental group had a certain proliferation effect on cells and showed good biocompatibility.

[0062] The present invention provides a mussel-like polylipoic acid-based hydrogel adhesive and a preparation method thereof. First, a sericin-grafted caffeic acid complex is prepared, and then the complex is added to a polylipoic acid solution to obtain a bionic multifunctional hydrogel adhesive. The hydrogel adhesive prepared by the present invention has excellent self-healing properties, significant antibacterial properties, good mechanical properties and biocompatibility. More importantly, the hydrogel adopts a mussel-like strategy to improve wet adhesion properties, can quickly and timely seal wounds and quickly stop bleeding in a short time, and these properties enable the hydrogel to provide a good repair environment for wounds and provide effective antibacterial treatment, thereby accelerating the rapid healing of traumatic wounds. Therefore, the hydrogel adhesive has broad application prospects in the field of wound repair.

[0063] The specific implementation of the present invention described above does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A method for preparing a mussel-like polylipoic acid-based hydrogel adhesive, characterized in that: The steps include: (1) mixing a sericin solution and a caffeic acid solution uniformly and performing a grafting reaction to obtain a reaction solution, and dialyzing and drying the reaction solution to obtain sericin grafted with caffeic acid; (2) adding lipoic acid to a lithium hydroxide solution and stirring until completely dissolved, then adding sericin grafted with caffeic acid, and heating the mixture to obtain a PTALi-CAS mixture; (3) The PTALi-CAS mixture is cooled to obtain a mussel-mimicking polylipoic acid-based hydrogel adhesive.

2. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (1), the mass ratio of sericin to caffeic acid is (1-2): (0.5-1).

3. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (1), the sericin solution is obtained by dissolving sericin in a MES buffer solution having a pH value of 4 to 6, and the ratio between sericin and MES buffer solution is (1 to 2) g: (40 to 60) mL.

4. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (1), the caffeic acid solution is obtained by dissolving caffeic acid in ethanol, and the ratio of caffeic acid to ethanol is (0.5-1) g: (20-30) mL; The caffeic acid solution also contains EDC and NHS, wherein the mass ratio of caffeic acid, EDC and NHS is (0.5-1): (0.15-0.25): (0.08-0.13).

5. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (1), the sericin solution and the caffeic acid solution are mixed evenly by stirring for 30 to 50 minutes in an ice bath; and the grafting reaction is carried out under nitrogen protection and stirred at room temperature for 10 to 15 hours.

6. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (1), the dialysis treatment uses a dialysis bag with a molecular weight of 3000 to 4000, the dialysis time is 3 to 5 days, and the deionized water is replaced every 12 to 15 hours.

7. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (2), the mass ratio of lipoic acid to lithium hydroxide is (5-8): (0.05-0.1); the mass ratio of sericin grafted caffeic acid to lithium hydroxide is (0.2-0.3): (0.05-0.1).

8. The method for preparing the mussel-like polylipoic acid-based hydrogel adhesive according to claim 1, characterized in that: In step (2), the lithium hydroxide solution is formed by dissolving lithium hydroxide in deionized water, and the ratio of lithium hydroxide to deionized water is (0.05-0.1) g: (20-30) mL; The specific preparation steps of the PTALi-CAS mixture include: adding lipoic acid to a lithium hydroxide solution at 60-80° C. and stirring until completely dissolved, then adding sericin grafted with caffeic acid, and stirring at 60-80° C. for 2-3 h to obtain the PTALi-CAS mixture; In step (3), the mixture is cooled to a temperature of 20 to 30°C.

9. The mussel-like polylipoic acid-based hydrogel adhesive prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the mussel-like polylipoic acid-based hydrogel adhesive as claimed in claim 9 as a wound dressing.

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