A skin repair dressing and a method of making the same

Abstract

The application discloses a skin repair dressing and a preparation method thereof, and belongs to the technical field of medical dressings. The skin repair dressing comprises the following raw materials in parts by weight: carboxymethyl chitosan 4-6 parts, sodium alginate 2-4 parts, polyvinyl alcohol 8-10 parts, recombinant human collagen 1-2 parts, sodium hyaluronate 0.5-1 part, a crosslinking agent 1.5-2 parts, nano filler 0.1-0.5 part, an antioxidant 0.5-1 part and deionized water 80-90 parts; the crosslinking agent is prepared by reacting glutathione with dithio-bismaleimidyl ethane to obtain an intermediate 1, and then reacting with 4-formylphenylboronic acid. The skin repair dressing prepared by the application has excellent tensile properties and antibacterial properties.

Description

Technical Field

[0001] This invention relates to the field of medical dressing technology, specifically to a skin repair dressing and its preparation method. Background Technology

[0002] Skin is one of the most important organs in the human body, directly exposed to the external environment, sensing external stimuli, regulating body temperature, and protecting the body from external harm. Wound healing is a complex and dynamic process, and various factors can lead to a variety of wound healing problems, making wound repair difficult. Traditional dressings (such as gauze and absorbent cotton) only provide physical coverage and have drawbacks such as poor moisture retention, easy adhesion to the wound surface, and inability to actively fight bacteria. Synthetic polymer materials can provide a moist healing environment for the wound and have a certain barrier function, and are widely used in tissue engineering and drug delivery systems. However, they suffer from poor mechanical properties and a lack of active antibacterial capabilities, limiting their application and development as biomaterials.

[0003] Chinese invention patent CN112263708A discloses a multifunctional aerogel dressing for promoting wound healing and its preparation method. The preparation method includes the following steps: S1, dispersing amino acid derivatives, antimicrobial peptide derivatives, and natural polysaccharides in deionized water and heating to obtain a clear solution; S2, introducing the clear solution containing the three compounds (amino acid derivatives, antimicrobial peptide derivatives, and natural polysaccharides) into a mold and cooling to room temperature to form a hydrogel; S3, freeze-drying the hydrogel to obtain the multifunctional aerogel dressing. The multifunctional wound dressing material prepared by this invention can promote the proliferation of skin fibroblasts and endothelial cells and absorb exudate, but its mechanical properties are still insufficient. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the purpose of this invention is to provide a skin repair dressing and its preparation method.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A skin repair dressing comprises the following raw materials in parts by weight:

[0007] Carboxymethyl chitosan 4-6 parts, sodium alginate 2-4 parts, polyvinyl alcohol 8-10 parts, recombinant human collagen 1-2 parts, sodium hyaluronate 0.5-1 part, crosslinking agent 1.5-2 parts, nanofiller 0.1-0.5 parts, antioxidant 0.5-1 part, deionized water 80-90 parts;

[0008] The crosslinking agent is prepared by reacting glutathione with dithio-bismaleimide ethane to obtain intermediate 1, which is then reacted with 2-formylphenylboronic acid.

[0009] The crosslinking agent is prepared by the following method:

[0010] S1: stirring and mixing the solvent, glutathione and disulfide-bis-maleimide ethane, adding a photoinitiator, and under the irradiation of ultraviolet light, the reaction generates intermediate 1; the reaction equation is shown as follows:

[0011]

[0012] S2: stirring and mixing the buffer solution, intermediate 1 and 2-formyl phenylboronic acid, and the reaction generates the crosslinking agent; the reaction equation is shown as follows:

[0013]

[0014] In step S1, the molar ratio of the glutathione to disulfide-bis-maleimide ethane is (2.05-2.1):1.

[0015] In step S2, the molar ratio of the intermediate 1 to 2-formyl phenylboronic acid is 1:(2.1-2.2).

[0016] In step S1, the photoinitiator is 2,2-dimethoxy-2-phenylacetophenone.

[0017] In step S1, the solvent is DMF.

[0018] In step S2, the buffer solution is a phosphate buffer solution, and the pH is 7.4.

[0019] The nano filler is nano zinc oxide.

[0020] The antioxidant is vitamin E.

[0021] A preparation method of a skin repair dressing, comprising the following steps:

[0022] (1) weighing by weight parts: carboxymethyl chitosan 4-6 parts, sodium alginate 2-4 parts, polyvinyl alcohol 8-10 parts, recombinant human collagen 1-2 parts, sodium hyaluronate 0.5-1 part, crosslinking agent 1.5-2 parts, nano filler 0.1-0.5 parts, antioxidant 0.5-1 part, deionized water 80-90 parts;

[0023] (2) mixing polyvinyl alcohol with deionized water, heating at 50-60℃, stirring for 20-30 min, cooling to room temperature, and then adding carboxymethyl chitosan, sodium alginate, recombinant human collagen, sodium hyaluronate, crosslinking agent, nano filler and antioxidant in sequence, continuing to stir, pouring into a mold, and performing irradiation sterilization to obtain the skin repair dressing.

[0024] By adopting the above technical solutions, the application has the following beneficial effects:

[0025] The skin repair dressing prepared by the application has excellent antibacterial efficiency, tensile property and self-repairing property. The crosslinking agent added in the component forms a crosslinking network through the formation of borate ester bond and strong hydrogen bond interaction, and cooperates with the disulfide bond and dynamic Schiff base to improve the tensile property, antibacterial property and self-repairing property of the dressing. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 High-resolution mass spectrum of the intermediate 1 prepared for Example 1.

[0027] Figure 2 High-resolution mass spectrum of the crosslinking agent prepared for Example 1. DETAILED DESCRIPTION

[0028] The application will be further described below in combination with examples, but the application is not limited to these examples.

[0029] Example 1: Preparation of a crosslinking agent

[0030] S1: 500ml of DMF, 0.205mol of glutathione, 0.1mol of disulfide-bis-maleimide ethane and 0.07g of a photoinitiator (2,2-dimethoxy-2-phenylphenylacetophenone) were added into a reaction kettle, stirred and uniformly mixed, and then irradiated under 100W 365nm ultraviolet light at room temperature for 10min. The reaction liquid was slowly added into 800ml of cold ether (0℃, same below), and the precipitate was stirred and separated, filtered and vacuum dried at 40℃ for 5h to obtain the intermediate 1, whose nuclear magnetic hydrogen spectrum data are as follows: 1 H NMR (300 MHz, Methanol- d 4) δ 12.44 (s, 2H), 9.46 (s, 2H), 8.58 - 8.47 (m, 4H), 6.78 (d, J =6.4 Hz, 4H), 4.48 - 4.28 (m, 4H), 4.06 - 3.68 (m, 10H), 3.22 - 2.56 (m, 12H),2.50 - 2.24 (m, 4H), 2.18 - 1.78 (m, 4H);its high-resolution mass spectrum is shown in Figure 1 HRMS (m / z): 927.1903 [M+H] + ;

[0031] S2: Add 500 ml of phosphate buffer (pH=7.4), 0.1 mol of intermediate 1, and 0.21 mol of 2-formylphenylboronic acid to a reaction vessel, stir and mix well, and react at room temperature for 12 h. Slowly pour the reaction solution into 800 ml of cold acetone, stir to precipitate, filter, and vacuum dry at 40 °C for 10 h to obtain the crosslinking agent. Its 1H NMR data are as follows: 1 H NMR (300 MHz, Methanol-) d 4) δ 13.08 (s, 2H), 12.44 (s, 2H), 8.76 (s, 2H), 8.58 - 8.46 (m, 4H), 7.88 - 7.79 (m, 2H), 7.59 (dd, J = 7.5, 1.5 Hz, 2H), 7.44 (s, 8H), 4.42 (dt, J = 8.1, 5.2 Hz, 2H), 4.32 (s, 2H), 4.19 (s, 2H), 4.04 - 3.76 (m, 8H), 3.22 – 2.01 (m, 20H); its high-resolution mass spectrum is shown below. Figure 2 As shown, HRMS (m / z): 1191.2694 [M+H] + .

[0032] Example 2: Preparation of crosslinking agent:

[0033] S1: Add 500 ml DMF, 0.208 mol glutathione, 0.1 mol dithio-bismaleimide ethane, and 0.07 g photoinitiator (2,2-dimethoxy-2-phenylacetophenone) to a reaction vessel, stir and mix well. Under stirring conditions, irradiate at room temperature under 100 W 365 nm ultraviolet light for 15 min. Slowly add the reaction solution to 800 ml cold diethyl ether, stir to precipitate, filter, and vacuum dry at 50 °C for 12 h to obtain intermediate 1.

[0034] S2: Add 500 ml of phosphate buffer (pH=7.4), 0.1 mol of intermediate 1 and 0.215 mol of 2-formylphenylboronic acid to the reaction vessel, stir and mix well, react at room temperature for 14 h, slowly pour the reaction solution into 800 ml of cold acetone, stir to precipitate, filter, and vacuum dry at 40 °C for 10 h to obtain the crosslinking agent.

[0035] Example 3: Preparation of crosslinking agent:

[0036] S1: 500 ml of DMF, 0.21 mol glutathione, 0.1 mol dithio-bismaleimidoethane, 0.07 g of photoinitiator (2,2-dimethoxy-2-phenylphenylacetophenone) were added to the reaction kettle, stirred and mixed, and irradiated under 100 W 365 nm ultraviolet light at room temperature for 20 min. The reaction solution was slowly added to 800 ml of cold ether, and the precipitate was separated by stirring, filtered, and vacuum dried at 50°C for 12 h to obtain intermediate 1.

[0037] S2: 500 ml of phosphate buffer (pH = 7.4), 0.1 mol of intermediate 1 and 0.22 mol of 2-formylphenylboronic acid were added to the reaction kettle, stirred and mixed, and reacted at room temperature for 15 h. The reaction solution was slowly poured into 800 ml of cold acetone, and the precipitate was separated by stirring, filtered, and vacuum dried at 40°C for 10 h to obtain the crosslinking agent.

[0038] Example 4 Preparation of a skin repair dressing:

[0039] (1) Take: carboxymethyl chitosan 4 g, sodium alginate 2 g, polyvinyl alcohol 8 g, recombinant human collagen 1 g, sodium hyaluronate 0.5 g, crosslinking agent (prepared in Example 1) 1.5 g, nano filler (nano zinc oxide) 0.1 g, antioxidant (vitamin E) 0.5 g, deionized water 80 g;

[0040] (2) The polyvinyl alcohol was mixed with deionized water and heated to 50°C, stirred for 30 min, cooled to room temperature, and then carboxymethyl chitosan, sodium alginate, recombinant human collagen, sodium hyaluronate, crosslinking agent, nano filler and antioxidant were added in turn. Continue to stir for 4 h to obtain a mixed slurry, pour into a mold (30 mm x 10 mm x 5 mm), sterilize with γ-rays (irradiation dose 25 kGy) for 2 h, demold, and obtain a skin repair dressing.

[0041] Example 5 Preparation of a skin repair dressing:

[0042] (1) Take: carboxymethyl chitosan 4 g, sodium alginate 2 g, polyvinyl alcohol 8 g, recombinant human collagen 1 g, sodium hyaluronate 0.5 g, crosslinking agent (prepared in Example 1) 1.5 g, nano filler (nano zinc oxide) 0.1 g, antioxidant (vitamin E) 0.5 g, deionized water 80 g;

[0043] (2) The polyvinyl alcohol is mixed with deionized water and heated to 55°C, stirred for 25 min, cooled to room temperature, and then carboxymethyl chitosan, sodium alginate, recombinant human collagen, sodium hyaluronate, crosslinking agent, nano filler, antioxidant are added in turn, and stirring is continued for 5 h to obtain a mixed slurry, which is poured into a mold (30 mm x 10 mm x 5 mm), sterilized by γ-ray irradiation (irradiation dose 25 kGy) for 2 h, demolded, and the skin repair dressing is obtained.

[0044] Example 6 Preparation of a skin repair dressing:

[0045] (1) Weigh: carboxymethyl chitosan 6g, sodium alginate 4g, polyvinyl alcohol 10g, recombinant human collagen 2g, sodium hyaluronate 1g, crosslinking agent (prepared in example 3) 2g, nano filler (nano zinc oxide) 0.5g, antioxidant (vitamin E) 1g, deionized water 90g;

[0046] (2) The polyvinyl alcohol is mixed with deionized water and heated to 60°C, stirred for 20 min, cooled to room temperature, and then carboxymethyl chitosan, sodium alginate, recombinant human collagen, sodium hyaluronate, crosslinking agent, nano filler, antioxidant are added in turn, and stirring is continued for 6 h to obtain a mixed slurry, which is poured into a mold (30 mm x 10 mm x 5 mm), sterilized by γ-ray irradiation (irradiation dose 25 kGy) for 2 h, demolded, and the skin repair dressing is obtained.

[0047] Comparative Example 1

[0048] The raw material composition and preparation method of the skin repair dressing are basically the same as those of Example 5, except that the crosslinking agent is replaced by an equal amount of crosslinking agent prepared by the following method:

[0049] The preparation method of the crosslinking agent is basically the same as that of Example 2, except that the glutathione in step S1 is replaced by an equal molar amount of L-cysteine.

[0050] Comparative Example 2

[0051] The raw material composition and preparation method of the skin repair dressing are basically the same as those of Example 5, except that the crosslinking agent is replaced by an equal amount of crosslinking agent prepared by the following method:

[0052] The preparation method of the crosslinking agent is basically the same as that of Example 2, except that the disulfide-bis-maleimide ethane in step S1 is replaced by an equal molar amount of N,N'-cyclohexane bis-maleimide.

[0053] Comparative Example 3

[0054] The raw material composition and preparation method of the skin repair dressing are basically the same as those of Example 5, except that the crosslinking agent is replaced by an equal mass of a crosslinking agent prepared by the following method:

[0055] The preparation method of the crosslinking agent is basically the same as that of Example 2, except that the bisulfide-bismaleimide ethane in step S1 is replaced by an equal molar amount of diallyl disulfide.

[0056] Comparative Example 4

[0057] The raw material composition and preparation method of the skin repair dressing are basically the same as those of Example 5, except that the crosslinking agent is replaced by an equal mass of a crosslinking agent prepared by the following method:

[0058] S1: 500 ml of DMF, 0.208 mol of glutathione, 0.1 mol of bisulfide-bismaleimide ethane, and 0.07 g of a photoinitiator (2,2-dimethoxy-2-phenylphenylacetophenone) were added to a reaction kettle, stirred and mixed, and irradiated at room temperature under 100 W of 365 nm ultraviolet light for 15 min. The reaction solution was slowly added to 800 ml of cold ether, and the precipitate was stirred and separated. After filtration, the precipitate was vacuum dried at 50°C for 12 h to obtain intermediate 1.

[0059] S2: 500 ml of anhydrous DMF and 0.215 mol of 2-carboxyphenylboronic acid were added to a reaction kettle, stirred and mixed, and 0.23 mol of 1-hydroxybenzotriazole and 0.25 mol of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride were added. The mixture was stirred at room temperature for 50 min, and 0.1 mol of intermediate 1 was added. The mixture was reacted at room temperature for 5 h, and the reaction solution was slowly poured into 800 ml of cold ether. The precipitate was stirred and separated, filtered, and vacuum dried at 40°C for 10 h to obtain the crosslinking agent.

[0060] Comparative Example 5

[0061] The raw material composition and preparation method of the skin repair dressing are basically the same as those of Example 5, except that the crosslinking agent is replaced by an equal mass of a crosslinking agent prepared by the following method:

[0062] The preparation method of the crosslinking agent is basically the same as that of Example 2, except that the 2-formylphenylboronic acid in step S2 is replaced by an equal molar amount of 4-formylphenylboronic acid.

[0063] The degree of substitution of the carboxymethyl chitosan used in the examples and comparative examples of the present application is 80%, and the number average molecular weight is 9000 Da; the type of sodium alginate is LYF, the particle size is 60 mesh, and it is produced by Qingdao Mingyue Seaweed Group Co., Ltd.; the type of polyvinyl alcohol is PVA-1799; the type of recombinant human collagen is recombinant human type III collagen, and it is produced by Zhuhai Jibai Kang Biological Technology Co., Ltd.; the type of sodium hyaluronate is SH-MDI, and it is produced by Shandong Jiaofeng Furuida Biological Co., Ltd.; the nano zinc oxide is a medical grade nano zinc oxide, the type is NKS134, the average particle size is 20 nm, and it is produced by Qingdao Nakasen New Material Technology Co., Ltd.; the phosphate buffer (pH = 7.4) is prepared by the following method: 7.63 g of dipotassium hydrogen phosphate and 9.83 g of potassium dihydrogen phosphate are weighed and added to 1000 ml of deionized water, stirred and dissolved, and the pH is adjusted to 7.4 with 0.1 M HCl or 0.1 M NaOH solution to obtain the phosphate buffer.

[0064] The skin repair dressings prepared in Examples 4-6 and Comparative Examples 1-5 are subjected to antibacterial performance testing, tensile property testing, and self-repairing performance testing, and the test results are shown in Table 1.

[0065] In the antibacterial test, gram-positive Staphylococcus aureus (S. aureus, ATCC 6538) is selected as the inoculated strain. The concentration of the inoculated bacterial solution is about 10 6 CFU / mL, and the antibacterial performance of the sample is tested by plate counting method: 20 μL of the bacterial solution is inoculated on the surface of the sample (30 mm x 10 mm x 5 mm), and another sample of the same size is overlaid on top. A 50 g sterile weight is used to press tightly to ensure that the sample is in full contact with the bacterial solution. After the sample is in contact with the bacterial solution for 2 h, the sample is immersed in 5 mL of sterile phosphate solution, and the bacteria are eluted by vortexing for 250 s. Then the eluted phosphate solution is diluted 100 times, and 50 μL of the diluted solution is evenly dropped onto the surface of the agar plate. After incubation in a 37°C constant temperature incubator for 24 h, the number of colonies is calculated. All test samples are subjected to ultraviolet lamp disinfection treatment for 1 h before the experiment, and the antibacterial efficiency is calculated: antibacterial efficiency = (N0-N1) / N0 x 100%, wherein N0 represents the number of surviving bacteria of the bacterial solution without contact with the sample (20 μL of the bacterial solution is taken and placed on the surface of a petri dish for 2 h, 5 mL of sterile phosphate solution is added, diluted 100 times, 50 μL of the diluted solution is evenly dropped onto the surface of the agar plate, and the number of colonies is calculated after incubation in a 37°C constant temperature incubator for 24 h), and N1 represents the number of surviving bacteria after contact with the sample.

[0066] The tensile properties were tested by a tensile testing machine (CTM2050), and the sample (30mmx10mmx5mm) was stretched at a loading rate of 10mm / min, and the tensile strength at break was calculated as the maximum tensile force during the stretching / the cross-sectional area, and the elongation at break was calculated as (the length at break-the initial length) / the initial lengthx100%.

[0067] Self-repairing test of the sample: one side of the sample (formed by 30mmx10mm) was vertically cut by a blade at the center of the side to form two symmetrical cross-shaped incisions (each with a depth of 0.5mm and a length of 6mm), and the intersection of the cross-shaped incisions was located at the center of the side; then the sample was immersed in 50ml of PBS buffer solution at 37℃ and pH=7.4, soaked for 24h, taken out, and the surface moisture was wiped off with a wrung wet towel to obtain the repaired skin repair dressing, and the tensile strength was tested.

[0068] Table 1: Performance test data table

[0069]

[0070] As can be seen from the data of examples 4, 5 and 6 in table 1, the skin repair dressing prepared by the application has excellent antibacterial efficiency, tensile properties and self-repairing properties.

[0071] The crosslinking agent added in the skin repair dressing prepared by the application contains boric acid, carboxyl, disulfide bond and Schiff base structure, wherein the boric acid and carboxyl in the crosslinking agent will form a crosslinking network with the hydroxyl (-OH) in the dressing matrix through boric acid ester bond and strong hydrogen bond, respectively, to improve the tensile strength of the dressing; the dynamic reversibility of the boric acid ester bond allows the molecular chain to slip under stress, thereby improving the elongation at break of the material; the dynamic disulfide bond and the Schiff base structure promote the self-healing process through the synergistic reversible rupture and recombination, thereby realizing self-repairing; at the same time, the Schiff base structure can interact with the proteins or lipids on the bacterial cell membrane, increase the permeability of the cell membrane, and then affect the growth and reproduction of the bacteria, thereby improving the antibacterial efficiency; further, the ortho boric acid in the crosslinking agent forms a stable five-membered ring ligand with the Schiff base, which has high chemical stability and mechanical strength, and endows the dressing with excellent mechanical properties. The synergistic effect of various structures in the crosslinking agent jointly constructs a crosslinking network with high strength, self-adaptability and antibacterial effect, thereby making the skin repair dressing exhibit good antibacterial efficiency, tensile properties and self-repairing properties.

[0072] The crosslinking agent used in Comparative Example 1 has a low carboxyl content, resulting in a low crosslinking density and affecting the mechanical properties; the crosslinking agents used in Comparative Examples 2 and 4 do not contain dynamic disulfide bonds and Schiff bases, respectively, resulting in a decrease in self-repairing performance; the crosslinking agent used in Comparative Example 3 does not have a maleimide rigid ring, and when subjected to external force, it is prone to tearing and deformation, resulting in a decrease in tensile strength. The crosslinking agent used in Comparative Example 5 is difficult to form a five-membered ring ligand with the Schiff base and boric acid, resulting in a decrease in the tensile strength of the dressing.

[0073] The above is only a preferred embodiment of the present application and is not intended to limit the present application; however, for those of ordinary skill in the art, some minor changes, modifications, and equivalent changes made to the above disclosed technical content without departing from the scope of the technical solutions of the present application are equivalent embodiments of the present application; at the same time, any equivalent changes, modifications, and evolution of the above embodiments made in accordance with the essential technology of the present application are still within the protection scope of the technical solutions of the present application.

Claims

1. A skin repair dressing, characterized by, The raw materials include the following components by weight: carboxymethyl chitosan 4-6 parts, sodium alginate 2-4 parts, polyvinyl alcohol 8-10 parts, recombinant human collagen 1-2 parts, sodium hyaluronate 0.5-1 part, crosslinking agent 1.5-2 parts, nano filler 0.1-0.5 parts, antioxidant 0.5-1 part, and deionized water 80-90 parts; The crosslinking agent is prepared by reacting glutathione with dithio-bismaleimidyl ethane to obtain intermediate 1, and then reacting with 2-formylphenylboronic acid.

2. The skin repair dressing according to claim 1, wherein The crosslinking agent is prepared by the following method: S1: stirring and mixing the solvent, glutathione and dithio-bismaleimidyl ethane, adding a photoinitiator, and reacting under the irradiation of ultraviolet light to obtain intermediate 1; S2: stirring and mixing the buffer, intermediate 1 and 2-formylphenylboronic acid, and reacting for 12-15 hours to obtain the crosslinking agent.

3. A dressing for skin repair according to claim 2, wherein In step S1, the molar ratio of glutathione to dithio-bismaleimidyl ethane is (2.05-2.1):

1.

4. The skin repair dressing according to claim 2, wherein In step S2, the molar ratio of intermediate 1 to 2-formylphenylboronic acid is 1:(2.1-2.2).

5. The skin repair dressing according to claim 2, wherein In step S1, the photoinitiator is 2,2-dimethoxy-2-phenylphenylacetophenone.

6. The skin repair dressing according to claim 2, wherein In step S1, the solvent is DMF.

7. The skin repair dressing according to claim 2, wherein In step S2, the buffer is phosphate buffer with a pH of 7.

4.

8. The skin repair dressing according to claim 1, wherein The nano filler is nano zinc oxide.

9. The skin repair dressing of claim 1, wherein The antioxidant is vitamin E.

10. A method of preparing the skin repair dressing as claimed in any one of claims 1 to 9, characterized in that, The method includes the following steps: (1) weighing the following components by weight: carboxymethyl chitosan 4-6 parts, sodium alginate 2-4 parts, polyvinyl alcohol 8-10 parts, recombinant human collagen 1-2 parts, sodium hyaluronate 0.5-1 part, crosslinking agent 1.5-2 parts, nano filler 0.1-0.5 parts, antioxidant 0.5-1 part, and deionized water 80-90 parts; (2) mixing polyvinyl alcohol with deionized water, heating to 50-60°C, stirring for 20-30 minutes, cooling to room temperature, and then sequentially adding carboxymethyl chitosan, sodium alginate, recombinant human collagen, sodium hyaluronate, crosslinking agent, nano filler, and antioxidant, continuing to stir, pouring into a mold, and performing irradiation sterilization to obtain the skin repair dressing.

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