Alkannin-loaded self-healing hydrogel wound dressing as well as preparation method and application thereof

Abstract

The invention relates to a shikonin-loaded self-healing hydrogel wound dressing as well as a preparation method and application thereof. The method comprises the following steps: modifying TA on TOCNF to obtain TA-coated TOCNF; and compounding the TA-coated TOCNF with PVA, and sequentially adding an alkannin solution and a borax solution to prepare the hydrogel wound dressing. The hydrogel has the design characteristics that TA with a convergence effect on scalds and burns is introduced, so that the hydrogel is endowed with certain antibacterial activity and adhesion; on the basis of boric acid ester bonds formed by borax and PVA, the hydrogel is endowed with good self-healing property; meanwhile, the hydrogel is loaded with an active small molecular medicine shikonin with a repairing effect on scalds, so that the antibacterial activity and the oxidation resistance of the hydrogel are further enhanced. The preparation method is simple, can well adapt to irregular scald wounds, integrates antibacterial activity and oxidation resistance, and prepares the shikonin-loaded self-healing hydrogel wound dressing which can be produced on a large scale and has a good healing effect on scalds.

Description

Technical Field

[0001] This invention relates to a self-healing hydrogel wound dressing loaded with shikonin, its preparation method and application, belonging to the field of biomedical materials technology. Background Technology

[0002] As the largest organ in the human body, the skin plays a vital role in resisting external aggressors and maintaining internal homeostasis. However, trauma, burns, scalds, and surgical incisions often cause skin damage. Burns, in particular, result in irregular wounds with abundant exudate, necrotic tissue fragments, and a high susceptibility to infection, leading to slow healing and significant challenges in treatment. Hydrogels, as hydrophilic flexible materials with a three-dimensional network structure, not only absorb wound exudate and maintain a moist environment but also possess a structure similar to the natural extracellular matrix, which helps promote wound healing. Self-healing hydrogels, in particular, can spontaneously fill irregular wounds, preventing infection and releasing medication, making them especially suitable for burn treatment. However, self-healing hydrogels often suffer from insufficient adhesive design; excessively high viscosity can cause secondary damage during replacement, while excessively low viscosity requires external fixation.

[0003] Cellulose, as the most abundant natural polymer on Earth, boasts advantages such as low cost, renewability, biodegradability, good biocompatibility, and environmental friendliness. When used to prepare hydrogel wound dressings, its high water absorption helps absorb wound exudate and maintains a moist healing environment, promoting wound healing. However, cellulose hydrogels suffer from poor mechanical properties, easy degradation, and lack of antibacterial properties, limiting their further development. Summary of the Invention

[0004] The purpose of this invention is to provide a self-healing hydrogel wound dressing loaded with shikonin, its preparation method and application. The preparation process is simple, and it is formed in one step at room temperature. The prepared hydrogel wound dressing has good antibacterial, antioxidant, adhesive and self-healing properties. It can adapt well to the irregular wound shape of burns, increase the astringent effect on burns and accelerate the healing of burn wounds.

[0005] To achieve the above-mentioned objective, this invention provides a method for preparing a self-healing hydrogel wound dressing loaded with shikonin, comprising the following steps: (1) Add TA to TOCNF, mix well, adjust pH to 8.0, stir at room temperature in the dark for 10-14 hours to obtain TA@TOCNF; (2) Add PVA solution to the product obtained in step (1) and stir thoroughly until the mixture is homogeneous to form a uniform gel precursor solution; (3) Add shikonin solution to the precursor solution obtained in step (2), stir and mix well, then add borax solution and continue stirring until the system forms a gel, thus obtaining the self-healing hydrogel wound dressing.

[0006] In a preferred embodiment, in step (1), the mass ratio between TA and TOCNF is (1.25-3.5):1; and the stirring time is 12 hours.

[0007] In a preferred embodiment, in step (1), the concentration of the TOCNF solution is 1-1.25 wt%, and the dispersion medium is water.

[0008] In a preferred embodiment, in step (1), the pH is adjusted using a Tris-HCl buffer solution with a pH of 8.0.

[0009] In a preferred embodiment, in step (2), the mass ratio between PVA and TOCNF is (8-24):1; the concentration of the PVA solution is 5-15 wt%, and the dispersion medium is water.

[0010] In a preferred embodiment, in step (3), the mass ratio between shikonin and TOCNF is (0.48-1.2):1; the concentration of the shikonin solution is 20-50 mg / mL; and the dispersion medium is an ethanol / glycerol mixture.

[0011] In a preferred embodiment, in step (3), the mass ratio between borax and TOCNF is (0.8-1.4):1; the concentration of the borax solution is 0.02-0.035 g / mL; and the dispersion medium is water.

[0012] To achieve the above-mentioned objectives, the present invention also provides a self-healing hydrogel wound dressing loaded with shikonin prepared by the above-mentioned preparation method.

[0013] To achieve the above-mentioned objectives, the present invention also provides the application of the self-healing hydrogel wound dressing loaded with shikonin in biomedical dressings.

[0014] Compared with the prior art, the present invention has the following beneficial effects: This invention modifies TOCNF with TA, which has astringent effects on scalds and burns, endowing the hydrogel with certain adhesive and antibacterial properties. PVA is introduced through physical blending, and the hydrogen bonding between PVA and TOCNF, as well as the borate ester crosslinking formed between PVA and borax, achieve the preparation of a uniformly structured, self-healing TA@TOCNF / PVA hydrogel and the loading of the active small molecule drug shikonin. The preparation process involves only a simple mixing process, one-step molding at room temperature, requiring no complex equipment, thus simplifying the production process. Furthermore, the raw material configuration is flexible, and the preparation cost is controllable, facilitating large-scale production and practical application. The prepared hydrogel wound dressing exhibits excellent antibacterial, antioxidant, adhesive, and self-healing properties, making it suitable for irregular wounds caused by burns and scalds. Simultaneously, the presence of TA and shikonin also promotes the healing of burn and scald wounds, showing potential application in the fields of medicine and flexible materials. Attached Figure Description

[0015] Figure 1 The image shows the actual product of the TA@TOCNF / PVA self-healing hydrogel loaded with shikonin obtained in Example 1. Figure 2 The images show the self-healing properties of the TA@TOCNF / PVA self-healing hydrogel loaded with shikonin obtained in Example 2 (a) and the TA@TOCNF / PVA hydrogel of Comparative Example 2 (b), as well as a microscopic image of the junction between the two hydrogels. Figure 3 The adhesion of the TA@TOCNF / PVA self-healing hydrogel loaded with shikonin obtained in Example 2 to glass, aluminum, copper, and silicon wafers is shown in the figure. Figure 4 The image shows the antibacterial activity of the TA@TOCNF / PVA self-healing hydrogel loaded with shikonin obtained in Example 2 against Staphylococcus aureus. Figure 5 The image shows the wound healing effect of the TA@TOCNF / PVA self-healing hydrogel loaded with shikonin obtained in Example 2 as a dressing for burn wounds. Detailed Implementation

[0016] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0017] In this invention, "TOCNF" stands for "2,2,6,6-tetramethylpiperidine-N-oxygen radical oxidized cellulose nanofibers", "2,2,6,6-tetramethylpiperidine-N-oxygen radical" is abbreviated as "TEMPO", and "cellulose nanofibers" is abbreviated as "CNF". Therefore, TOCNF is also called "TEMPO oxidized CNF".

[0018] In this invention, "TA" represents "tannic acid"; "Tris-HCl buffer" represents "tris(hydroxymethyl)aminomethane-hydrochloric acid buffer"; and "PVA" represents "polyvinyl alcohol".

[0019] Example 1 A method for preparing a self-healing hydrogel wound dressing loaded with shikonin includes the following steps: (1) Add 0.125 g TA to 10.0 g of 1.00 wt% TOCNF aqueous solution, mix well and adjust the pH of the system to 8.0 with Tris-HCl buffer solution of pH=8. Stir at room temperature in the dark for 12 hours to obtain TA@TOCNF; (2) Add 20 g of 5 wt% PVA aqueous solution to the product obtained in step (1) and stir thoroughly until the mixture is homogeneous to form a homogeneous gel precursor solution. (3) Add 3 mL of 20 mg / mL shikonin glycerol-ethanol dispersion to the precursor solution obtained in step (2), stir and mix well, then add 5 mL of 0.02 g / mL borax aqueous solution, and continue stirring until the system forms a gel, thus obtaining the self-healing hydrogel wound dressing.

[0020] Example 2 Unlike Example 1, in step (1), 0.1875 g of TA and 10.0 g of TOCNF with a concentration of 1.25 wt% were mixed to form TA@TOCNF and stirred at room temperature in the dark for 10 h; in step (2), 10 g of PVA aqueous solution with a concentration of 10 wt% was added and mixed with TA@TOCNF to obtain a precursor solution; in step (3), the concentration of glycerol-ethanol dispersion of shikonin was 50 mg / mL and the concentration of borax solution was 0.035 g / mL. Other steps and the conditions and parameters involved in the steps were the same as in Example 1.

[0021] Example 3 Unlike Example 1, in step (1), 0.25 g of TA and 10.0 g of TOCNF with a concentration of 1.25 wt% were mixed to form TA@TOCNF and stirred at room temperature in the dark for 14 h; in step (2), 10 g of PVA aqueous solution with a concentration of 15 wt% was added and mixed with TA@TOCNF to form a gel precursor solution; in step (3), the concentration of borax solution was 0.025 g / mL, and the other steps and the conditions and parameters involved in the steps were the same as in Example 1.

[0022] Example 4 Unlike Example 1, in step (1), 0.3125 g of TA was mixed with 10.0 g of TOCNF with a concentration of 1.25 wt% to form TA@TOCNF; in step (2), 10 g of PVA aqueous solution with a concentration of 20 wt% was added and mixed with TA@TOCNF to form a gel precursor solution. The other steps and the conditions and parameters involved in the steps were the same as in Example 1.

[0023] Example 5 Unlike Example 1, in step (1), 0.4375 g of TA was mixed with 10.0 g of TOCNF with a concentration of 1.25 wt% to form TA@TOCNF; in step (2), 10 g of PVA aqueous solution with a concentration of 30 wt% was added and mixed with TA@TOCNF to form a gel precursor solution; the other steps and the conditions and parameters involved in the steps were the same as in Example 1.

[0024] Comparative Example 1 A method for preparing a hydrogel wound dressing includes the following steps: Take 10.0 g of 1.00 wt% TOCNF aqueous solution, then add 20 g of 5 wt% PVA aqueous solution, and stir thoroughly until homogeneous to form a uniform gel precursor solution; then add 5 mL of 0.03 g / mL borax aqueous solution, and continue stirring until the system forms a gel, thus obtaining the hydrogel wound dressing.

[0025] Comparative Example 2 Unlike Example 1, step (3) of adding 3 mL of shikonin (20 mg / mL) in a glycerol-ethanol dispersion to the precursor solution was omitted. The other steps and the conditions and parameters involved in the steps were the same as in Example 1.

[0026] As an example, Example 1 demonstrates the preparation of a TA@TOCNF / PVA hydrogel loaded with shikonin. For example... Figure 1 As shown, the TA@TOCNF / PVA hydrogel loaded with shikonin has a uniform color and does not flow down in an inverted glass bottle, proving that borax and the precursor solution of the gel were successfully cross-linked, achieving uniform loading of shikonin.

[0027] As examples, Example 2 and Comparative Example 2 respectively demonstrate the preparation of TA@TOCNF / PVA hydrogels loaded with and unloaded with shikonin. Figure 2As shown in Figure a, when TA@TOCNF / PVA hydrogel loaded with shikonin (purple) and TA@TOCNF / PVA hydrogel without shikonin (yellow) are bonded together, based on the borate ester bonds formed between PVA and borax, the two can re-establish a cross-linked network within seconds at room temperature without any external force, forming a complete whole. This is demonstrated under a microscope. Figure 2 Figure b shows more clearly that the two hydrogels are tightly bound together, and there is a clear boundary between the two gels.

[0028] The adhesiveness of the self-healing TA@TOCNF / PVA hydrogel loaded with shikonin prepared in Example 2 is as follows: Figure 3 As shown in the figure, the prepared hydrogel exhibits good adhesion to gloves, glass, aluminum sheets, copper sheets, and silicon wafers.

[0029] The antibacterial properties of the self-healing TA@TOCNF / PVA hydrogel loaded with shikonin prepared in Example 2 are as follows: Figure 4 As shown in the figure, after co-culturing the hydrogel loaded with shikonin with Staphylococcus aureus for 24 h, obvious inhibition zones were formed around it. The size of the inhibition zones is shown in Table 1. After co-culturing the hydrogels prepared in other examples and comparative examples with Staphylococcus aureus for 24 h, obvious inhibition zones were formed around the hydrogels prepared in the examples, while no inhibition zone was formed around the hydrogel prepared in Comparative Example 1. An inhibition zone was formed around the hydrogel prepared in Comparative Example 2, but the size of the inhibition zone was smaller. The specific size of the inhibition zone is shown in Table 1. This proves that the TA@TOCNF / PVA hydrogel loaded with shikonin has good antibacterial activity against Staphylococcus aureus.

[0030] The self-healing TA@TOCNF / PVA hydrogel loaded with shikonin prepared in Example 2, as a wound dressing, showed the following effect in promoting the healing of burn wounds: Figure 5 As shown in Table 1 and Figure 5 As can be seen, after applying the hydrogel to a burn wound with a diameter of approximately 1 cm, the wound size significantly decreased after 3 days, and it was basically healed after 14 days, with a wound area of ​​only 0.178 cm². 2 The hydrogels prepared in other examples and comparative examples were used as wound dressings to promote the healing of burn wounds. After applying the hydrogel prepared in the examples to burn wounds approximately 1 cm in diameter, the wound size significantly decreased after 3 days and was basically healed after 14 days, with a wound area ranging from 0.162 to 0.199 cm². 2 After applying the hydrogels prepared in Comparative Example 1 and Comparative Example 2 to burn wounds approximately 1 cm in diameter, the wound areas were 0.456 cm² after 14 days. 2 0.208 cm 2This demonstrates that the TA@TOCNF / PVA hydrogel loaded with shikonin has a significant effect on promoting the healing of burn wounds.

[0031] Table 1. Size of the inhibition zone and wound area after 14 days In summary, the hydrogels prepared in Examples 1-5 respectively possess good self-healing properties, adhesion, antibacterial properties, and the ability to promote burn wound healing. The self-healing property is demonstrated by the ability of both TA@TOCNF / PVA hydrogels loaded with and unloaded with shikonin to self-heal into a single unit. The adhesion property is demonstrated by the ability of the TA@TOCNF / PVA hydrogel loaded with shikonin to adhere to the surfaces of materials such as glass, aluminum sheets, copper sheets, and silicon wafers. The antibacterial property is demonstrated by the fact that Comparative Example 1 had no antibacterial effect against Staphylococcus aureus, while Comparative Example 2, with the introduction of TA, showed a significant improvement in antibacterial effect. Further addition of shikonin further enhanced the antibacterial activity against Staphylococcus aureus. The promotion of burn wound healing is demonstrated by the fact that, compared to Comparative Example 1, the introduction of TA and shikonin significantly improved the healing effect of burn wounds; after 14 days, the wounds treated with the shikonin-loaded hydrogel wound dressing were essentially healed.

[0032] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for preparing a self-healing hydrogel wound dressing loaded with shikonin, characterized in that, Includes the following steps: (1) Add TA to the TOCNF solution, mix well, adjust the pH to 8.0, and stir at room temperature in the dark for 10-14 hours to obtain TA@TOCNF; (2) Add PVA solution to the product obtained in step (1) and stir thoroughly until the mixture is homogeneous to form a uniform gel precursor solution; (3) Add shikonin solution to the precursor solution obtained in step (2), stir and mix well, then add borax solution and continue stirring until the system forms a gel, thus obtaining the self-healing hydrogel wound dressing.

2. The method for preparing a self-healing hydrogel wound dressing loaded with shikonin according to claim 1, characterized in that, In step (1), the mass ratio between TA and TOCNF is (1.25-3.5):1; the stirring time is 12 hours.

3. A method for preparing a self-healing hydrogel wound dressing loaded with shikonin according to claim 1 or 2, characterized in that, In step (1), the concentration of the TOCNF solution is 1-1.25 wt%, and the dispersion medium is water.

4. A method for preparing a self-healing hydrogel wound dressing loaded with shikonin according to claim 1 or 2, characterized in that, In step (1), the pH is adjusted using Tris-HCl buffer solution with a pH of 8.

0.

5. A method for preparing a self-healing hydrogel wound dressing loaded with shikonin according to claim 1 or 2, characterized in that, In step (2), the mass ratio between PVA and TOCNF is (8-24):1; the concentration of the PVA solution is 5-15 wt%, and the dispersion medium is water.

6. A method for preparing a self-healing hydrogel wound dressing loaded with shikonin according to claim 1 or 2, characterized in that, In step (3), the mass ratio between shikonin and TOCNF is (0.48-1.2):1; the concentration of the shikonin solution is 20-50 mg / mL, and the dispersion medium is an ethanol / glycerol mixture.

7. A method for preparing a self-healing hydrogel wound dressing loaded with shikonin according to claim 1 or 2, characterized in that, In step (3), the mass ratio between borax and TOCNF is (0.8-1.4):1; the concentration of the borax solution is 0.02-0.035 g / mL; and the dispersion medium is water.

8. A self-healing hydrogel wound dressing loaded with shikonin, characterized in that, It is prepared by the method described in any one of claims 1-7.

9. The application of the self-healing hydrogel wound dressing loaded with shikonin as described in claim 8 in biomedical dressings.

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