Plasma-modified polyurethane medical dressing and preparation method and application thereof

Abstract

The application discloses a plasma modified polyurethane medical dressing and a preparation method and application thereof, and relates to the technical field of medical dressings. The polyurethane sponge is cleaned and dried, and then is treated by using a plasma technology in an oxygen atmosphere to obtain treated polyurethane sponge; then, recombinant collagen with a HIS tag is prepared into a recombinant collagen solution; then, metal ions with antibacterial effects are added into the solution; the treated polyurethane sponge in step S1 is contacted with the recombinant collagen solution; finally, the modified polyurethane medical dressing is immersed into a high-molecular solution with a low isoelectric point and a negative charge under a neutral condition, and the medical dressing is obtained after drying and washing after immersion. The preparation method avoids the use of chemical cross-linking agents, ingeniously uses the tag of the recombinant collagen, simplifies an antibacterial substance loading process, and enables the antibacterial agent not to be excessive, so that the antibacterial agent can be used for a long time at a wound and can be safely applied to the fields of negative pressure drainage and wound care.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials technology, and particularly relates to a modified polyurethane medical dressing, its preparation method and application. Background Technology

[0002] Polyurethane (PU) is widely used in medical dressings, implantable devices, and other fields due to its excellent elasticity, abrasion resistance, and morphological stability. However, plain PU generally has poor surface biocompatibility, which may trigger an inflammatory response when in contact with wound tissue, and may cause partial adhesion during wound healing, resulting in secondary damage upon removal. Therefore, some products modify PU before use to increase the material's biocompatibility and reduce adhesion and friction.

[0003] Collagen, as a major component of the human extracellular matrix, possesses excellent biocompatibility and repair-promoting activity. However, it cannot be directly grafted onto PU surfaces and requires covalent cross-linking or physical embedding in polyurethane materials in the form of a gel followed by drying. Covalent cross-linking often requires the use of cross-linking agents, introducing additional safety risks, such as residual glutaraldehyde. Physical cross-linking of gels often requires very high collagen concentrations, and high concentrations of animal-derived components pose safety risks. Physical cross-linking of gels may also carry the risk of gel detachment and is unsuitable for sponges that require maintaining a porous structure, because animal collagen exhibits significant gelation upon contact with water, which can interfere with the aspiration of wound exudate.

[0004] Recombinant collagen raw materials can completely avoid animal-derived contamination and have excellent biocompatibility. How to graft recombinant collagen raw materials into polyurethane materials without the risk of cross-linking agents is a pressing technical challenge. Reference documents WO2025186007A8 or WO2025186007A1 mention using plasma to treat polymer scaffolds (including polyurethane) and then contacting them with collagen solutions to prepare a collagen-modified polyurethane material. However, for polyurethane and other foam materials, due to their porous structure and long-term use as drainage materials at wound sites, bacteria easily proliferate. The addition of collagen further promotes microbial growth, thus requiring the addition of antibacterial materials with long-term release capabilities. However, simply adding antibacterial agents to foam cannot achieve long-term sustained-release effects, cannot match the degradation cycle of recombinant collagen, and is prone to excessive addition leading to overly irritating effects. A comparative document (“bactericidal activity of elastin like polypetide biopolymer with polyhistidine domain and silver”, Kishore K. et al, *Collolids and Surfaces B: Biointerfaces*, 2014(119), 66-70, 20140316) mentions an elastin-like polypeptide polymer with multiple histidine domains and silver. Silver ions are loaded into the protein using the complexation of histidine with transition metal ions, creating an antibacterial material. The advantage lies in the ability to achieve a phase transition within a specific temperature range by altering the number of repeating structures in the sequence, forming a gel-like product where silver ions are trapped within the gel structure and slowly released over time. However, elastin currently lacks mature commercial applications due to its low expression levels leading to high costs. For applications loaded onto dressings, recombinant collagen, with its relatively lower cost, is a more suitable choice. It can also achieve antibacterial effects by introducing histidine regions to complex silver ions. However, recombinant collagen mostly lacks complex higher-order structures, typically existing in solution as random coils. After drying, it can be considered a random linear molecule. Therefore, directly introducing histidine sequences at both ends to chelate silver ions greatly increases the likelihood that the silver ions will directly contact the air and external environment, leading to their reduction to elemental silver or the formation of silver oxide. For dressing-type medical devices exposed to air and requiring long-term storage, this results in poor storage stability, easy discoloration, and a significant decrease in antibacterial efficacy over time. Therefore, how to leverage the low-cost advantage of recombinant collagen while improving the storage stability of its silver chelates presents a significant technical challenge. Summary of the Invention

[0005] To overcome the problems in the prior art, this invention provides a plasma-modified polyurethane medical dressing, its preparation method, and its application. This invention avoids the use of chemical crosslinking agents while designing and utilizing the labeling and charged properties of recombinant collagen to simplify the antibacterial substance loading process. By forming ionizable composite molecules with negatively charged polymers, it extends the shelf life, ensures the storage stability of the product, and prevents excessive antibacterial agent use. It can be used for a long time at wound sites and can be safely applied in fields such as negative pressure drainage and wound care.

[0006] To solve the above-mentioned technical problems, the technical solution proposed by this invention is as follows:

[0007] This invention provides a method for preparing plasma-modified polyurethane medical dressings.

[0008] The preparation of the dressing includes the following steps:

[0009] S1. After cleaning and drying the polyurethane sponge, it is then treated with plasma technology in an oxygen atmosphere to obtain the treated polyurethane sponge.

[0010] S2. Prepare a recombinant collagen solution with HIS tag, then add metal ions with antibacterial effect to the solution, and contact the polyurethane sponge treated in step S1 with the recombinant collagen solution to obtain modified polyurethane medical dressing.

[0011] S3. The modified polyurethane medical dressing prepared in step S2 is immersed in a low isoelectric point, negatively charged polymer solution under neutral conditions. After immersion, the dressing is dried and washed to obtain the medical dressing.

[0012] This invention employs plasma technology to treat the surface of polyurethane foam in an oxygen atmosphere, introducing a large number of active groups onto the material surface. This provides sites for covalent cross-linking between the polyurethane foam and collagen. When the polyurethane foam comes into contact with a recombinant collagen solution, covalent grafting can occur directly without the need for other chemical cross-linking reagents. Unreacted active groups are also reduced by oxygen, nitrogen, and other molecules in the air, leaving no residue. This is a green and efficient surface modification method. The recombinant collagen used in this invention can load metal ions with antibacterial properties. The principle lies in the fusion tag inherent in the recombinant collagen sequence from the initial design stage. This tag consists of a 6*HIS or 8*HIS structure, which can complex with metal ions possessing antibacterial properties. When applied to wounds, in a bodily fluid environment, the degradation of the recombinant collagen and the exposure of the imidazole groups in the HIS tag lead to the slow release of silver ions, achieving a bactericidal effect. Simultaneously, leveraging the high isoelectric point of recombinant collagen, a negatively charged polymer with a low isoelectric point is introduced. Under neutral pH conditions, the collagen carries a positive charge while the polymer material carries a negative charge. During the drying process, electrostatic adsorption forms a composite structure that encapsulates the collagen molecules, thereby protecting the silver ions complexed with histidine. Furthermore, after drying, this composite molecule can block air, slowing down the oxidation of silver ions. In solution, the composite structure can rapidly ionize, significantly extending the product's shelf life without affecting the normal release of silver ions.

[0013] As an optional implementation, in the method provided by the present invention, in S2, the polyurethane sponge reacts with the recombinant collagen solution at a temperature of 60-80°C.

[0014] In this invention, the reaction is carried out at a temperature of 60-80°C, which is beneficial to promote the covalent grafting of recombinant collagen solution with the treated polyurethane sponge.

[0015] As an optional implementation, in the method provided by the present invention, in S2, the concentration of metal ions in the solution is 0.1-1%.

[0016] As an optional implementation, in the method provided by the present invention, in S2, the metal ion is selected from one or both of silver ions and zinc ions.

[0017] As an optional implementation, in the method provided by the present invention, in S3, the negatively charged polymer solution is selected from sodium carboxymethyl cellulose solution, sodium hyaluronate solution, or sodium alginate solution.

[0018] As an optional implementation, in the method provided by the present invention, in S3, the concentration of the negatively charged polymer solution is 0.5-1%.

[0019] As an optional implementation, in the method provided by the present invention, in S2, the side of the treated polyurethane sponge intended to contact the wound is immersed in a recombinant collagen solution, the height of which is 3-5 mm.

[0020] As an optional implementation, in the method provided by the present invention, in S2, a recombinant collagen solution is sprayed onto the side of the treated polyurethane sponge that is expected to come into contact with the wound, and the spraying time is 30-60 seconds.

[0021] As an optional implementation, in the method provided by the present invention, in S2, the purity of the recombinant collagen is ≥95%, and the mass concentration of the recombinant collagen solution is 3-5%.

[0022] In this invention, the high-concentration collagen solution has poor solubility, while the low-concentration collagen solution has too large a reaction volume, resulting in insufficient total collagen load.

[0023] As an optional implementation, in the method provided by the present invention, in S1, the plasma treatment conditions are as follows: after sealing, the vacuum is evacuated to a vacuum degree of 10-30 Pa, a mixed reaction gas of argon and oxygen is introduced, the gas flow rate is controlled at 10-40 mL / min, the voltage is 8 kV, the frequency is 500 Hz, and the temperature is 25-30℃, and the plasma treatment is carried out for 5-10 min.

[0024] This invention ensures the number of activated polyurethane material groups is maintained by controlling the plasma processing conditions, guaranteeing that the number of activated groups is not insufficient. Adding an inert gas prevents the activated groups from reacting prematurely with other gas molecules in the air, and also prevents excessive oxygen oxidation of the material, which could negatively impact its properties.

[0025] As an optional implementation, in the method provided by the present invention, the volume ratio of argon to oxygen is 2:1.

[0026] In this invention, a mixture of argon and oxygen is used, and the inert gas is used to prevent the activated groups from reacting prematurely with other gas molecules in the air.

[0027] As an optional implementation, in the method provided by the present invention, the cleaning process of the polyurethane sponge in S1 is as follows: first, it is immersed in 75% anhydrous ethanol by volume and then ultrasonically cleaned, then ultrasonically rinsed with deionized water and dried.

[0028] As an optional implementation, in the method provided by the present invention, in S1, the covalently grafted polyurethane sponge is washed with buffer solution and then dried.

[0029] Based on the same technical concept, the present invention also provides modified polyurethane medical dressings prepared by the above-mentioned method for preparing plasma-modified polyurethane medical dressings.

[0030] Based on the same technical concept, the present invention also provides the application of the modified polyurethane medical dressing prepared by the above-mentioned plasma-modified polyurethane medical dressing in the preparation of wound repair dressings or tissue engineering scaffolds.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] (1) This invention employs a plasma-modified polyurethane covalent grafting method to recombinant collagen, utilizing the complexing ability of recombinant collagen to prepare a modified polyurethane medical antibacterial dressing. This dressing possesses mechanical support properties, drainage or liquid retention properties, as well as the biocompatibility and wound healing promotion capabilities of recombinant collagen. Simultaneously, it possesses antibacterial metal ions capable of killing pathogenic bacteria and reducing wound infection. Furthermore, by introducing a low isoelectric point polymer that carries a negative charge under neutral conditions to encapsulate collagen molecules, the silver ions complexed with histidine are protected. After drying, this composite molecule can block air, slowing down the oxidation of silver ions. In solution, the composite structure can rapidly ionize, significantly extending the product's shelf life without affecting the normal release of silver ions.

[0033] (2) This invention avoids the use of chemical cross-linking agents and avoids the blockage of sponge pores by the gelation of animal glue raw materials. At the same time, it utilizes the complexing ability of recombinant collagen to load bactericides, thereby improving the utilization rate of recombinant collagen. It can be safely applied to negative pressure drainage, wound care and other fields. Attached Figure Description

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0035] Figure 1 The results of Fourier transform infrared (FTIR) spectroscopy of the recombinant collagen grafted modified polyurethane sponge medical dressing prepared for the example;

[0036] Figure 2 The standard curve obtained during the silver content detection process;

[0037] Figure 3 The results show the wound healing rate in rats;

[0038] Figure 4The image shows the comparison between the initial wound and the wound after healing on day 8 in rats. The left image shows the initial wound on day 0, and the right image shows the wound after healing on day 8. Detailed Implementation

[0039] To facilitate understanding of the present invention, the present invention will be described more fully and in detail below in conjunction with the specification and preferred embodiments, but the scope of protection of the present invention is not limited to the following specific embodiments.

[0040] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the invention.

[0041] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0042] Example 1

[0043] A method for preparing medical dressings using plasma-modified polyurethane includes the following steps:

[0044] (1) Polyurethane substrate: Prepare polyester polyurethane sponge with a pore size of 200-300μm (size 5cm×5cm×1cm), immerse the sponge in 75% anhydrous ethanol, clean it with an ultrasonic cleaner for 15-20 minutes, then rinse it with deionized water 2-3 times, 10 minutes each time. Place the cleaned polyurethane sponge in a vacuum drying oven and dry it at 60℃ for 2-4 hours for later use.

[0045] (2) Plasma treatment: The pretreated polyurethane substrate is placed in the reaction chamber of the plasma treatment instrument, sealed and evacuated to a vacuum degree of 10 Pa; Argon and oxygen mixed reaction gas is introduced, with a volume ratio of argon:oxygen = 2:1, the gas flow rate is controlled at 40 mL / min, voltage is 8 kV, frequency is 500 Hz, temperature is 25 ℃, and treatment is carried out for 10 minutes.

[0046] (3) Grafting reaction: Take 1g of recombinant type III collagen powder with a purity ≥95%. The recombinant collagen used should be derived from *Escherichia coli* or *Pichia pastoris*, and the sequence should contain the tail of a fusion tag. The fusion tag sequence is “HHHHHH”. Dissolve the recombinant collagen in 20mL of deionized water to prepare a 5% (w / w) recombinant collagen solution. Add silver nitrate to make the final silver ion concentration 1% (w / w). Mix evenly at room temperature for 5 minutes to form a recombinant collagen-silver ion complex. Add the prepared recombinant collagen-silver ion solution to a spray bottle and spray it onto the side of the polyurethane sponge that is expected to contact the wound using a repeated spraying method. The spraying volume is 50mL per sponge, and the spraying time is 1 minute. After spraying, react at 60℃ for 6 hours.

[0047] (4) Polymer treatment: Take the grafted dressing, immerse it in a 0.5% sodium carboxymethyl cellulose solution, keep it for 10 minutes and then take it out.

[0048] (5) Cleaning and drying: Take out the grafted polyurethane sponge and dry it at 60°C for 3 hours. Then wash it three times with 100 mL of 70% ethanol for 10 minutes each time; then dry it at 60°C for 3 hours to obtain a silver-containing polyurethane sponge medical dressing with recombinant collagen grafted and modified sodium carboxymethyl cellulose.

[0049] Example 2

[0050] A method for preparing medical dressings using plasma-modified polyurethane includes the following steps:

[0051] (1) Polyurethane substrate: Polyester polyurethane sponge with a pore size of 200-300μm (size 5cm×5cm×1cm). Immerse the polyester polyurethane sponge in 75% anhydrous ethanol and clean it with an ultrasonic cleaner for 15-20 minutes. Then rinse it with deionized water 2-3 times with ultrasonic cleaning, 10 minutes each time. Place the cleaned polyurethane sponge in a vacuum drying oven and dry it at 60℃ for 2-4 hours for later use.

[0052] (2) Plasma treatment: The pretreated polyurethane substrate is placed in the reaction chamber of the plasma treatment instrument, sealed and evacuated to a vacuum degree of 28 Pa; Argon and oxygen mixed reaction gas is introduced, with a volume ratio of argon:oxygen = 2:1, and the gas flow rate is controlled at 15 mL / min, voltage 8 kV, frequency 500 Hz, temperature 25 ℃, and treatment time is 5 minutes.

[0053] (3) Grafting reaction: Take 1g of recombinant type III collagen powder with a purity ≥95%. The recombinant collagen used should be derived from *Escherichia coli* or *Pichia pastoris*, and the sequence should contain a tail of a fusion tag with 6 histidine residues. Dissolve the recombinant collagen in 20mL of deionized water to prepare a 5% (w / w) recombinant collagen solution. Add silver nitrate to make the final silver ion concentration 0.1% (w / w). Mix thoroughly at room temperature for 5 minutes to form a recombinant collagen-silver ion complex. Add the prepared recombinant collagen-silver ion solution to a spray bottle and spray it onto the side of the polyurethane sponge that is expected to contact the wound using a repeated spraying method. The spraying volume is 75mL per sponge, and the spraying time is 1 minute. After spraying, react at 80℃ for 12 hours.

[0054] (4) Polymer treatment: Take the grafted dressing, immerse it in a 0.5% sodium hyaluronate solution, keep it for 10 minutes and then take it out.

[0055] (5) Cleaning and drying: Take out the grafted polyurethane sponge and dry it at 60°C for 3 hours. Then wash it three times with 100 mL of 70% ethanol for 10 minutes each time; then dry it at 60°C for 3 hours to obtain a silver-containing polyurethane sponge medical dressing with recombinant collagen grafted and modified sodium hyaluronate.

[0056] Example 3

[0057] A method for preparing medical dressings using plasma-modified polyurethane includes the following steps:

[0058] (1) Polyurethane substrate: Polyester polyurethane foam with a pore size of 200-300μm (size 5cm×5cm×1cm). Immerse the polyester polyurethane foam in 75% anhydrous ethanol and clean it with an ultrasonic cleaner for 15-20 minutes. Then rinse it with deionized water 2-3 times with ultrasonic cleaning, 10 minutes each time. Place the cleaned polyurethane foam in a vacuum drying oven and dry it at 60℃ for 2-4 hours for later use.

[0059] (2) Plasma treatment: The pretreated polyurethane substrate is placed in the reaction chamber of the plasma treatment instrument, sealed and evacuated to a vacuum degree of 22 Pa; a mixture of argon and oxygen reaction gas is introduced, wherein the ratio of argon to oxygen is 2:1, the flow rate is 25 mL / min, the voltage is 8 kV, the frequency is 500 Hz, the temperature is 30 ℃, and the treatment lasts for 7 minutes.

[0060] (3) Grafting reaction: Take 1g of recombinant type III collagen powder with a purity ≥95%. The recombinant collagen used should be derived from engineered bacteria such as Escherichia coli and Pichia pastoris, and the sequence should contain an HIS tail or head with 8 histidine residues. Dissolve the recombinant collagen in 33mL of deionized water to prepare a 3% (w / w) recombinant collagen solution. Add silver nitrate to make the final silver ion concentration 0.5% (w / w). Mix evenly at room temperature for 5 minutes to form a recombinant collagen-silver ion complex. Add the prepared recombinant collagen-silver ion solution to a spray bottle and spray the solution onto the side of the polyurethane sponge that is expected to contact the wound using a repeated spraying method. The spraying volume is 75mL per sponge, and the spraying time is 0.5 minutes. After spraying, react at 70℃ for 2 hours.

[0061] (4) Polymer treatment: Take the grafted dressing, immerse it in a 1% sodium alginate solution, keep it for 10 minutes and then take it out.

[0062] (5) Cleaning and drying: Take out the polyurethane sponge after step four and dry it at 60°C for 3 hours. Then wash it three times with 100mL of 70% ethanol for 10 minutes each time; then dry it at 60°C for 3 hours to obtain a silver-containing polyurethane sponge medical dressing with recombinant collagen grafted and modified sodium alginate blocked.

[0063] Example 4

[0064] A method for preparing medical dressings using plasma-modified polyurethane includes the following steps:

[0065] (1) Polyurethane substrate: Polyester polyurethane foam with a pore size of 200-300μm (size 5cm×5cm×1cm). Immerse the polyester polyurethane foam in 75% anhydrous ethanol and clean it with an ultrasonic cleaner for 15-20 minutes. Then rinse it with deionized water 2-3 times with ultrasonic cleaning, 10 minutes each time. Place the cleaned polyurethane foam in a vacuum drying oven and dry it at 60℃ for 2-4 hours for later use.

[0066] (2) Plasma treatment: The pretreated polyurethane substrate is placed in the reaction chamber of the plasma treatment instrument, sealed and evacuated to a vacuum degree of 22 Pa; a mixture of argon and oxygen reaction gas is introduced, wherein the ratio of argon to oxygen is 2:1, the flow rate is 25 mL / min, the voltage is 8 kV, the frequency is 500 Hz, the temperature is 30 ℃, and the treatment lasts for 7 minutes.

[0067] (3) Grafting reaction: Take 1g of recombinant type III collagen powder with a purity ≥95%. The recombinant collagen used should be from engineered bacteria such as Escherichia coli and Pichia pastoris, and the sequence should contain the HIS tail or head with 8 histidine residues. Dissolve the recombinant collagen in 25mL of deionized water to prepare a 4% recombinant collagen solution. Add silver nitrate to make the final silver ion concentration 0.1% (mass concentration). Mix evenly at room temperature for 5 minutes to form a recombinant collagen-silver ion complex. Take a clean and sterilized stainless steel tray, adjust the level, and add the recombinant collagen solution prepared in step 3 to make the liquid level 3-5mm. Immerse the side of the treated polyurethane sponge that is expected to contact the wound in the solution and react at 60℃ for 12 hours to obtain a recombinant collagen grafted modified polyurethane sponge medical antibacterial dressing.

[0068] (4) Polymer treatment: Take the grafted dressing, immerse it in a 0.5% sodium carboxymethyl cellulose solution, keep it for 10 minutes and then take it out.

[0069] (5) Cleaning and drying: Take out the grafted polyurethane sponge and dry it at 60°C for 3 hours. Then wash it three times with 100 mL of 70% ethanol for 10 minutes each time; then dry it at 60°C for 3 hours to obtain a silver-containing polyurethane sponge medical dressing with recombinant collagen grafted and modified sodium carboxymethyl cellulose.

[0070] Comparative Example 1

[0071] The difference from Example 1 is that no silver ions were added in step (3), but the rest is the same as in Example 1.

[0072] Comparative Example 2

[0073] The difference from Example 1 is that step (4) is omitted, while the rest is the same as in Example 1.

[0074] Performance testing

[0075] The recombinant collagen-grafted modified polyurethane sponge medical dressing prepared in the examples was analyzed by Fourier transform infrared spectroscopy (FTIR), and the results are as follows: Figure 1 As shown, at 1652cm -1 (Amide I band, C=O stretching) and 1541cm -1 The presence of characteristic peaks (amide II band, NH bending) indicates that the recombinant collagen white and polyurethane sponge underwent covalent grafting.

[0076] sterilization experiment

[0077] According to the test method for soluble antibacterial component impregnation test in Appendix E of GB15979-2024, Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa were used as test bacterial solutions. The recombinant collagen grafted modified polyurethane sponge medical antibacterial dressings prepared in Examples 1 and 4 were used as samples, and Comparative Example 1 was used as a control for the bactericidal test. The specific steps are as follows:

[0078] (1) Sample preparation

[0079] Take the sponges prepared in Examples 1 and 4, cut several circular samples with a diameter of 5.0 cm, and place three samples into three conical flasks respectively, then seal the flasks for later use. Similarly, cut two samples of the control standard from Comparative Example 1, place them into two conical flasks respectively, seal the flasks, and sterilize at 121℃ for 15 min for later use.

[0080] (2) Preparation of bacterial suspension

[0081] The preserved bacterial strain was streaked onto nutrient agar medium and incubated at 36℃±1℃ for 24 h. Typical colonies were then inoculated into Erlenmeyer flasks containing broth and incubated at 36℃±1℃ for 18 h–24 h. The cultured bacterial solution was then diluted with broth to a concentration of 1E5–5E5 cfu / mL.

[0082] (2) Experimental steps

[0083] Take 1.0 mL of bacterial suspension and add it to two prepared conical flasks containing the sample and one containing the control, ensuring even distribution and no excess liquid in the flasks. Seal the flasks to prevent evaporation and bacterial death. Add 100 mL of neutralizing agent (0.1% sodium thiosulfate) to one conical flask containing the inoculated bacterial suspension and the other containing the control fabric. Vortex for 1 min to wash the bacteria. Take 1.0 mL and perform a 10-fold serial dilution. Select an appropriate dilution and inoculate it into a petri dish using the pour method. This serves as the bacterial count on the "0" contact time sample and control fabric. Incubate another conical flask containing the inoculated bacterial suspension sample at 36℃±1℃ for 20 h±2 h. Add 100 mL of neutralizing agent and vortex for 1 min to wash the bacteria. Take 1.0 mL and perform a 10-fold serial dilution. Select an appropriate dilution and inoculate it into a petri dish using the pour method. This serves as the experimental group.

[0084] Negative control group: No bacterial suspension was inoculated into the sample. 100 mL of neutralizing agent was added at the "0" contact time, and the sample was vortexed for 1 min before inoculating onto a Petri dish. Positive control group: Another Erlenmeyer flask containing control fabric was inoculated with 1.0 mL of bacterial suspension and incubated at 36℃±1℃ for 20 h±2 h. 100 mL of PBS was added, and the bacteria were washed by vortexing for 1 min. 1.0 mL of the solution was serially diluted 10-fold, and an appropriate dilution was inoculated onto Petri dishes using the pour method. The Petri dishes inoculated with the negative and positive control samples and the test group samples were incubated together at 36℃±1℃ for 48 h, and the colony count was performed. The test was repeated three times. The testing method for the product's antibacterial effect against Candida albicans and other microorganisms was the same as above, selecting the appropriate strains, culture media, and culture conditions.

[0085] The sterilization rate was calculated according to the formula in GB15979-2024, and the results are shown in Table 1.

[0086] Table 1. Sterilization rate test of dressings

[0087]

[0088] As shown in Table 1, the recombinant collagen grafted modified polyurethane sponge medical antibacterial dressing prepared in this invention has excellent bactericidal effect, and the bactericidal efficiency is not affected after polymer treatment, indicating that the release of silver is not affected.

[0089] Silver content testing

[0090] The silver content of samples from different embodiments was measured by atomic broad-spectrum absorption. Samples measuring 3*3*1 cm were used, and the silver content was measured using a microwave digestion method following nitric acid treatment. The results are shown in Table 2 below, and the standard curve for the detection process is shown in the figure. Figure 2 As shown.

[0091] Table 2: Silver content detection results

[0092]

[0093] Table 2 shows that silver loading was successful, and silver ions were successfully loaded onto the foam.

[0094] Stability test

[0095] The sponges prepared in Examples 1-4 were placed in an accelerated aging chamber and aged at 55°C and 60% humidity. Their color changes were observed, and the valence state of silver was analyzed by X-ray photoelectron spectroscopy (XPS).

[0096] Table 3. XPS binding energy, peak width, and color under accelerated aging conditions in different embodiments.

[0097]

[0098] Table 3 shows that the maximum binding energy and color remained consistent in Examples 1-4 under accelerated aging conditions. The peak width increased on days 14 and 31, indicating that the proportion of silver ions remained at a stable high level within 7 days. The proportions of silver oxide and elemental silver increased from days 7 to 14. In contrast, Comparative Example 2, used as a control, showed an increased peak width on day 3 and a larger maximum absorption energy on day 7, indicating that the proportion of silver ions began to decrease on day 3, while the content of silver oxide and elemental silver increased, manifested as a brownish color change. This comparison demonstrates that the complex formed after adsorption of recombinant collagen and polymers can significantly delay the reduction or oxidation of silver ions, thus improving product stability.

[0099] animal experiments

[0100] Rat wound model: After circumferential incision of a full-thickness defect in rats, the area was measured. The left side of the wound was covered with pure PU sponge, and the right side with PU sponge grafted with recombinant collagen (prepared in Example 1). The sponges were removed daily to calculate the wound healing area and healing rate. Results showed that after 8 days of coverage, the collagen-grafted PU sponge healed significantly faster than the ungrafted PU sponge, with a final wound healing rate exceeding 90% (compared to 82% in the pure PU group). Figure 3 As shown.

[0101] Comparison of initial wound and wound after healing on day 8 in rats Figure 4 As shown, the left side is pure PU treatment, and the right side is PU treatment after grafting with recombinant collagen. After healing on the 8th day, there was no obvious inflammation or residual exudate in the wound.

[0102] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. However, it should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. A method of preparing a plasma-modified polyurethane medical dressing, characterized by, Includes the following steps: S1. After cleaning and drying the polyurethane sponge, it is then treated with plasma technology in an oxygen atmosphere to obtain the treated polyurethane sponge. S2. Prepare a recombinant collagen solution with HIS tag, then add metal ions with antibacterial effect to the solution, and contact the polyurethane sponge treated in step S1 with the recombinant collagen solution to obtain modified polyurethane medical dressing. S3. The modified polyurethane medical dressing prepared in step S2 is immersed in a low isoelectric point, negatively charged polymer solution under neutral conditions. After immersion, the dressing is dried and washed to obtain the medical dressing.

2. The method for preparing plasma-modified polyurethane medical dressings according to claim 1, characterized in that, In S2, polyurethane sponge reacts with recombinant collagen solution at a temperature of 60-80℃.

3. The method for preparing plasma-modified polyurethane medical dressing according to claim 1, characterized in that, In S2, the concentration of metal ions in the solution is 0.1-1%.

4. The method of claim 1, wherein the plasma-modified polyurethane medical dressing is prepared by the steps of: In S2, the metal ion is selected from one or both of silver ions and zinc ions.

5. The method for preparing plasma-modified polyurethane medical dressings according to claim 1, characterized in that, In S3, the polymer solution is selected from sodium carboxymethyl cellulose solution, sodium hyaluronate solution, or sodium alginate solution, and the concentration of the negatively charged polymer solution is 0.5-1%.

6. The method for preparing plasma-modified polyurethane medical dressing according to claim 1, characterized in that, In step S2, the recombinant collagen solution is sprayed onto the side of the treated polyurethane sponge that is expected to come into contact with the wound for 30-60 seconds. Alternatively, the side of the treated polyurethane sponge that is expected to come into contact with the wound is immersed in the recombinant collagen solution to a height of 3-5 mm.

7. The method for preparing plasma-modified polyurethane medical dressing according to claim 1, characterized in that, In S2, the purity of the recombinant collagen is ≥95%, and the mass concentration of the recombinant collagen solution is 3-5%.

8. The method of claim 1, wherein the plasma-modified polyurethane medical dressing is prepared by the steps of: In S1, the plasma treatment conditions are as follows: after sealing, the vacuum is evacuated to a vacuum degree of 10-30 Pa, a mixture of argon and oxygen reaction gas is introduced, the gas flow rate is controlled at 10-40 mL / min, the voltage is 8 kV, the frequency is 500 Hz, and the temperature is 25-30℃, and the plasma treatment lasts for 5-10 min.

9. A modified polyurethane medical dressing prepared by the method for preparing plasma-modified polyurethane medical dressing as described in any one of claims 1-8.

10. The application of a modified polyurethane medical dressing prepared by the method of any one of claims 1-8 in the preparation of wound repair dressings or tissue engineering scaffolds.

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