Intelligent response type supramolecular hydrogel as well as preparation method and application thereof

Abstract

The invention discloses intelligent response type supramolecular hydrogel as well as a preparation method and application thereof, and the supramolecular hydrogel with pH / ROS / sugar responsiveness is constructed by carrying out supramolecular integration on G-quadruplex supramolecular hydrogel (G4) formed by lipoic acid (LA) and guanosine derivatives. According to the hydrogel, LA deprotonation is triggered through an alkaline environment of G4 to form LA salt, a three-dimensional cross-linked structure is constructed through ion hydrogen bonds and intermolecular hydrogen bonds of carboxyl and a G4 network, no harsh reaction conditions are needed in the preparation process, and the problem of inverse ring-closing depolymerization of an LA-based material is solved. The supramolecular hydrogel has the following advantages: (1) the supramolecular hydrogel has dynamic responsiveness to diabetes wound microenvironment (pH, ROS and sugar), and realizes on-demand drug release; (2) the beverage has the functions of resisting oxidation, resisting bacteria and reducing blood sugar; (3) the mechanical property is adjustable, and injection type or patch type dressings can be prepared; and (4) the wound dressing has high stability, can promote healing of diabetic wounds, has anti-inflammatory and antibacterial effects, and is suitable for development of intelligent wound dressings.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a smart responsive supramolecular hydrogel, its preparation method, and its application. Background Technology

[0002] Chronic wound healing disorders in diabetic patients pose a significant challenge in clinical treatment. Compared to non-diabetic patients, the wound healing process in diabetic patients is significantly delayed, with approximately 21-30% of cases developing into chronic skin ulcers. These ulcers are often accompanied by serious complications such as neuropathic pain, microbial infection, and tissue necrosis, and may ultimately lead to adverse consequences such as amputation. Traditional wound dressings are ill-suited to addressing the unique pathological microenvironment of diabetic wounds, including persistent hyperglycemia, excessive accumulation of reactive oxygen species (ROS), and acidic conditions.

[0003] Hydrogel materials demonstrate significant value in wound care due to their excellent biocompatibility, softness, and moisturizing properties. In particular, smart hydrogels with environmentally responsive characteristics can dynamically sense and adapt to changes in the wound microenvironment, providing new insights for the treatment of diabetic wounds. Supramolecular hydrogels exhibit unique stimulus-responsiveness due to their reversible nonvalent cross-linked networks. Among them, the G-quadruplex (G4) supramolecular structure, constructed based on guanosine (G) and its derivatives, exhibits excellent responsiveness to microenvironmental factors such as pH and ROS through cation coordination stabilization, making it an ideal substrate for diabetic wound dressings.

[0004] Lipoic acid (LA), as a natural antioxidant, possesses multiple biological activities, including scavenging ROS, regenerating endogenous antioxidants, and antibacterial activity, and has potential application value in the treatment of diabetic wounds. However, existing LA-based materials have significant drawbacks: (1) complex preparation processes often require harsh conditions such as high temperature and strong acid; (2) poor product stability, prone to reverse ring-closure depolymerization; and (3) limited functionality, lacking dynamic response capability to the wound microenvironment. These problems severely limit the practical application of LA-based materials in the treatment of diabetic wounds.

[0005] While some studies have attempted to combine LA with different carrier materials, most have failed to effectively address the aforementioned problems. For example, some studies have tried to improve the stability of LA-based materials by adding auxiliary components such as metal ions and double-bonded monomers, but these methods often introduce potential biosafety risks and make it difficult to achieve multifunctionality of the materials. Furthermore, most existing LA-based hydrogels lack targeted design for the complex pathological characteristics of diabetic wounds, and cannot achieve on-demand drug release and dynamic microenvironment regulation.

[0006] Therefore, developing a simple-to-prepare, stable, and multi-responsive LA-based hydrogel is of great significance for improving the treatment effect of diabetic chronic wounds. This invention successfully solves key problems in existing technologies by innovatively combining LA with a G4 supramolecular network. Summary of the Invention

[0007] In view of the above-mentioned shortcomings, this invention addresses the clinical challenge of chronic wound healing impairment in diabetic patients by providing a smart responsive hydrogel based on a composite of lipoic acid (LA) and G-quadruplex (G4) supramolecular network, along with its preparation method and applications. This hydrogel innovatively integrates the bioactivity of LA with the dynamic responsiveness of G4, effectively solving key problems in existing technologies such as poor material stability, limited functionality, and insufficient environmental responsiveness.

[0008] To achieve the above-mentioned technical effects, the present invention employs the following technical means:

[0009] This invention first discloses a smart responsive supramolecular hydrogel, composed of the following raw materials by mass percentage:

[0010] Lipoic acid: 7.80% ± 0.5%;

[0011] Potassium hydroxide: 0.10% ± 0.02%;

[0012] Guanosine: 0.71%-1.89%;

[0013] Boric acid compounds: 0.37%-1.89%;

[0014] The remainder consists of aminoglycoside antibiotics: 0.46%-0.58% (w / w).

[0015] Where: K + Guanosine, boric acid compounds, and aminoglycoside antibiotics together constitute the G-quadruplex supramolecular structure, while lipoic acid forms a three-dimensional network structure through disulfide bonds.

[0016] Furthermore, the boric acid compound is selected from at least one of the following: boric acid, terephthaloboric acid, hyaluronic acid grafted with 3-aminophenylboronic acid, or 2-formylphenylboronic acid.

[0017] Furthermore, the aminoglycoside antibiotic is selected from at least one of the following: amikacin, netilmicin, simomicin, sisomicin, streptomycin, kanamycin, tobramycin, neomycin, or spectinomycin.

[0018] Furthermore, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5.

[0019] The molar ratio of guanosine to boric acid compounds is 1:1 to 1:1.2.

[0020] This invention also discloses a method for preparing any of the above-mentioned smart responsive supramolecular hydrogels, comprising:

[0021] (1) Dissolve lipoic acid and potassium hydroxide in water in a certain proportion to prepare a precursor solution;

[0022] (2) Add guanosine, boric acid compounds and aminoglycoside antibiotics to the precursor solution to obtain a mixed solution;

[0023] (3) The mixed solution was reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, and then cooled to 25℃±2℃ to obtain the intelligent responsive supramolecular hydrogel.

[0024] The present invention also discloses a smart responsive supramolecular hydrogel prepared according to the above preparation method.

[0025] Furthermore, the total solid mass percentage of the smart responsive supramolecular hydrogel is 1.5-2.5%; the pH value of the smart responsive supramolecular hydrogel is 7.5-8.5.

[0026] Furthermore, the total solid mass percentage in the intelligent responsive supramolecular hydrogel is 1.8-2.2%.

[0027] The present invention also discloses the application of any of the above-described smart responsive supramolecular hydrogels in the preparation of smart wound dressings.

[0028] Furthermore, the application includes:

[0029] Applications in the preparation of dressings for treating chronic wounds of diabetes or other chronic wounds.

[0030] The beneficial effects of this invention are as follows:

[0031] The hydrogel prepared in this invention triggers LA deprotonation in the alkaline environment of G4 to form LA salt, and constructs a three-dimensional cross-linked structure through ionic hydrogen bonds and intermolecular hydrogen bonds between carboxyl groups and the G4 network. The preparation process does not require harsh reaction conditions and solves the problem of reverse ring-closure depolymerization of LA-based materials. This supramolecular hydrogel has the following advantages: (1) dynamic responsiveness to the microenvironment (pH, ROS, sugar) of diabetic wounds, enabling on-demand drug release; (2) possessing antioxidant, antibacterial, and hypoglycemic functions; (3) adjustable mechanical properties, which can be made into injectable or patch dressings; (4) high stability, which can promote the healing of diabetic wounds and has anti-inflammatory and antibacterial effects, making it suitable for the development of smart wound dressings. Attached Figure Description

[0032] Figure 1Photos of wounds taken at different healing stages. Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The following embodiments are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall be followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0034] Example 1

[0035] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 1.89% ± 0.2% (w / w) guanosine and 0.50% ± 0.1% (w / w) boric acid were added as structural units, wherein K + Guanosine and boric acid together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, the molar ratio of guanosine to boric acid is 1:1 to 1:1.2, and the pH of the reaction system is controlled within the range of 7.5-8.5.

[0036] The resulting hydrogel is transparent and maintains stable mechanical properties at room temperature, showing broad application prospects in wound dressings, drug delivery, wearable devices, and other fields.

[0037] Example 2

[0038] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 1.89% ± 0.2% (w / w) guanosine and 1.89% ± 0.1% (w / w) terephthalic acid were added as structural units, wherein K + Guanosine and terephthalobolic acid together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, the molar ratio of guanosine to terephthalobolic acid is 1:1 to 1:1.2, and the pH of the reaction system is controlled within the range of 7.5-8.5.

[0039] The resulting hydrogel is transparent and maintains stable mechanical properties at room temperature, showing broad application prospects in wound dressings, drug delivery, wearable devices, and other fields.

[0040] Example 3

[0041] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.49% ± 0.1% (w / w) amikacin were added as structural units, wherein K + Guanosine, 2-formylphenylboronic acid, and amikacin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0042] The resulting hydrogel is transparent and maintains stable mechanical properties at room temperature, showing broad application prospects in wound dressings, drug delivery, wearable devices, and other fields.

[0043] Example 4

[0044] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 1.89% ± 0.2% (w / w) guanosine and 1.89% ± 0.1% (w / w) 3-aminophenylboronic acid-grafted hyaluronic acid were added as structural units, wherein K + The hyaluronic acid grafted with guanosine and 3-aminophenylboronic acid forms a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, the molar ratio of guanosine to 3-aminophenylboronic acid grafted hyaluronic acid is 1:1 to 1:1.2, and the pH of the reaction system is controlled within the range of 7.5-8.5.

[0045] Example 5

[0046] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.46% ± 0.1% (w / w) netilmicin were added as structural units, wherein K + Guanosine, 2-formylphenylboronic acid, and netilmicin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0047] Example 6

[0048] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.47% ± 0.1% (w / w) small nomicin were added as structural units, wherein K + Guanosine, 2-formylphenylboronic acid, and phenomicin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0049] Example 7

[0050] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.48% ± 0.1% (w / w) sisomicin were added as structural units, wherein K +Guanosine, 2-formylphenylboronic acid, and sisomicin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0051] Example 8

[0052] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid, and 0.58% ± 0.1% (w / w) streptomycin were added as structural units. K + Guanosine, 2-formylphenylboronic acid, and streptomycin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0053] Example 9

[0054] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.48% ± 0.1% (w / w) kanamycin were added as structural units. K + Guanosine, 2-formylphenylboronic acid, and kanamycin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0055] Example 10

[0056] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.47% ± 0.1% (w / w) tobramycin were added as structural units. K + Guanosine, 2-formylphenylboronic acid, and tobramycin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0057] Example 11

[0058] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.47% ± 0.1% (w / w) tobramycin were added as structural units. K + Guanosine, 2-formylphenylboronic acid, and tobramycin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0059] Example 12

[0060] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid, and 0.57% ± 0.1% (w / w) neomycin were added as structural units. K +Guanosine, 2-formylphenylboronic acid, and neomycin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0061] Example 13

[0062] First, an aqueous solution containing 7.80% ± 0.5% (w / w) lipoic acid and 0.10% ± 0.02% (w / w) potassium hydroxide was prepared as a precursor; then, 0.71% ± 0.2% (w / w) guanosine, 0.37% ± 0.1% (w / w) 2-formylphenylboronic acid and 0.50% ± 0.1% (w / w) spectinomycin were added as structural units. K + Guanosine, 2-formylphenylboronic acid, and spectinomycin together constitute a G-quadruplex supramolecular structure. The mixed solution is reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, then cooled to 25℃±2℃ to form a solid hydrogel with a three-dimensional network structure. Preferably, the molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5, and the total solid content of the gel is controlled at 1.5-2.5% (w / w), more preferably 1.8-2.2% (w / w). The pH of the reaction system is controlled within the range of 7.5-8.5.

[0063] Application Example 1

[0064] This application example tests the therapeutic effect of the gel dressing prepared in Example 1 in a diabetic wound model according to the following steps.

[0065] Experimental rats were randomly assigned to three groups: a diabetic model control group (PBS group) and a gel dressing treatment group, with 6 rats in each group. The modeling process for diabetic rats was as follows: First, all rats were fed a high-sugar, high-fat diet, and were alternately provided with regular drinking water and 10% sucrose water (rotating every 12 hours) for one week. Subsequently, streptozotocin (STZ, dose 60 mg / kg) was injected intraperitoneally for five consecutive days, and the rats were fasted before each injection. Throughout the modeling period, a high-sugar, high-fat diet and sugary drinking water were maintained. One week after the completion of STZ injection, when blood glucose levels tended to stabilize, rats with fasting blood glucose levels exceeding 11.1 mmol / L were defined as diabetic models and included in subsequent experiments.

[0066] Next, hair was removed from the back of the rats, and under isoflurane inhalation anesthesia, a circular full-thickness skin defect with a diameter of 10 mm was created on the back to complete the establishment of the animal model.

[0067] In the diabetic model control group, only wounds were created in rats without any treatment intervention. In the gel dressing group, the wounds were covered with the gel dressing prepared in Example 1, and the dressing was changed daily for continuous treatment. The wounds were photographed every other day to record the healing progress. Figure 1 As shown, during the 20-day observation period, the healing rate of diabetic wounds in rats treated with the drug-loaded gel dressing was significantly higher than that of the blank control group and the PBS control group, and also superior to the single-component LA group and the G4 hydrogel group. During the inflammatory response phase on postoperative day 5, the wounds in the blank control group and the PBS control group showed obvious purulent discharge and an expanding wound margin, indicating bacterial infection; in contrast, the LA@G4 and E... 0.5 In the LA@G4 group, only a small amount of yellow purulent exudate was observed, indicating mild infection. By day 10, LA@G4 and E... 0.5 The LA@G4 group showed no purulent discharge and a significant reduction in wound area. Furthermore, compared to the commercially available Shunaimei recombinant type III humanized collagen dressing, LA@G4 and E... 0.5 LA@G4 still exhibited superior wound healing efficiency. These results demonstrate that the drug-loaded gel dressing can effectively promote the repair process of diabetic wounds.

[0068] The above description and specific embodiments are intended to demonstrate the practical application of the technical solution provided by this invention and should not be construed as limiting the scope of protection of this invention. Those skilled in the art can make various modifications, equivalent substitutions, or improvements within the spirit and principle of this invention. The scope of protection of this invention is defined by the appended claims.

Claims

1. A smart responsive supramolecular hydrogel, composed of the following raw materials in weight percentages: Lipoic acid: 7.80% ± 0.5%; Potassium hydroxide: 0.10% ± 0.02%; Guanosine: 0.71%-1.89%; Boric acid compounds: 0.37%-1.89%; The remainder consists of aminoglycoside antibiotics; Among them, K⁺, guanosine, borate compounds and aminoglycoside antibiotics together constitute the G-quadruplex supramolecular structure, and lipoic acid forms a three-dimensional network structure through disulfide bonds.

2. The smart responsive supramolecular hydrogel according to claim 1, wherein: The boric acid compound is selected from at least one of the following: boric acid, terephthaloboric acid, hyaluronic acid grafted with 3-aminophenylboronic acid, or 2-formylphenylboronic acid.

3. The smart responsive supramolecular hydrogel according to claim 1, wherein: The aminoglycoside antibiotics are selected from at least one of the following: amikacin, netilmicin, simomicin, sisomicin, streptomycin, kanamycin, tobramycin, neomycin, or spectinomycin.

4. The smart responsive supramolecular hydrogel according to claim 1, wherein: The molar ratio of lipoic acid to potassium hydroxide is 1:1 to 1:1.5; The molar ratio of guanosine to boric acid compounds is 1:1 to 1:1.

2.

5. A method for preparing a smart responsive supramolecular hydrogel according to any one of claims 1-4, comprising: (1) Dissolve lipoic acid and potassium hydroxide in water in a certain proportion to prepare a precursor solution; (2) Add guanosine, boric acid compounds and aminoglycoside antibiotics to the precursor solution to obtain a mixed solution; (3) The mixed solution was reacted at 90℃±2℃ and 500rpm±50rpm for 2 hours±10 minutes, and then cooled to 25℃±2℃ to obtain the intelligent responsive supramolecular hydrogel.

6. A smart responsive supramolecular hydrogel prepared by the preparation method according to claim 5.

7. The smart responsive supramolecular hydrogel according to any one of claims 1 to 4 or 6, wherein: The total solid mass percentage of the aforementioned intelligent responsive supramolecular hydrogel is 1.5-2.5%. The pH value of the intelligent responsive supramolecular hydrogel is 7.5-8.

5.

8. The smart responsive supramolecular hydrogel according to claim 7, wherein: The total solid mass percentage of the smart responsive supramolecular hydrogel is 1.8-2.2%.

9. The application of a smart responsive supramolecular hydrogel according to any one of claims 1 to 4 or 8 in the preparation of smart wound dressings, comprising: Applications in the preparation of dressings for treating chronic wounds of diabetes or other chronic wounds.

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