Coating for cable tissue interface with adhesive antibacterial function and method for its production

Abstract

The application discloses a kind of coating for cable tissue interface with adhesive antibacterial function and preparation method thereof, belong to surface modification material field.The mixed aqueous solution of quaternary ammonium salt of chitosan, tannic acid and polyvinyl alcohol is first blended by centrifugation, and the solid polymer is separated and shaped into solid sheet, then after multiple freeze-thaw cycle treatment, freeze-drying can obtain adhesive antibacterial coating.Silica gel transdermal cable can be surface chemically modified to introduce active groups at the same time.Use, after spraying trace medical alcohol on the surface of coating, it is placed at the tissue interface of transdermal cable and adheres by pressing.The coating of the application can make medical transdermal silica gel cable and tissue interface produce good adhesion, and has antibacterial function, can effectively block the path of microbial invasion.The unique dry state storage and interface activation process makes the coating can realize the goal of stable storage and immediate adhesion sealing transdermal cable and tissue interface gap.

Description

Technical Field

[0001] This invention belongs to the field of surface modification materials, specifically relating to a coating with adhesive and antibacterial functions for cable interfaces and its preparation method. Background Technology

[0002] Percutaneous cables are crucial physical channels connecting implantable medical devices (such as artificial hearts, neurostimulators, and hemodialysis machines) to external control or power systems. With the rapid development of chronic disease treatment technologies, these devices play an irreplaceable role in prolonging patient life and improving quality of life. However, as a long-term implant that penetrates the skin, percutaneous cables disrupt this natural anatomical barrier, posing significant challenges to their clinical application.

[0003] 1. Weak Physical Connection: Traditional percutaneous cables are mostly made of inert medical-grade silicone, which has excellent chemical stability and biocompatibility, but it is difficult to achieve effective biointegration with surrounding tissues. This lack of mechanical connection results in tiny gaps between the cable and the tissue. 2. High Risk of Infection: Due to insufficient interfacial adhesion, human activity or external force can cause skin displacement along the cable. External bacteria can easily invade deeper tissues through these gaps, forming "sac-like" infections and biofilms, leading to persistent percutaneous pathway infections. 3. Chronic Inflammation: Continuous micro-movement and bacterial stimulation can lead to chronic inflammation and tissue fibrosis at the interface, not only failing to seal the wound but potentially accelerating device failure.

[0004] Currently, academia and industry are attempting to address these problems through surface modification, but significant drawbacks remain:

[0005] 1. Single Functionality: Most studies focus on single adhesion and antibacterial properties to skin tissue. However, while antibacterial dressings can kill bacteria in the short term, they cannot firmly bond to skin tissue and cables, failing to achieve physical sealing, allowing bacteria to continuously invade. Furthermore, the adhesion of some coatings rapidly diminishes in moist tissue environments. 2. Mechanical Mismatch: Existing hard coatings or physical etching methods easily lead to stress concentration on the cable surface, causing coating peeling or cracking during frequent bending. The mechanical properties of some coatings rapidly decline in moist tissue environments. The mismatch between the coating and skin modulus leads to delamination at the skin interface. 3. Poor Biocompatibility: Materials with good adhesion to both skin and cables, such as adhesives containing both cyano groups (for skin adhesion) and siloxane groups (for silicone cables), often exhibit cytotoxicity.

[0006] Extensive research has been conducted on composite antibacterial agents. For example, patent CN110790885A discloses a polyvinyl alcohol / chitosan quaternary ammonium salt self-healing hydrogel, which relies on boric acid chemical cross-linking. Its adhesion is primarily targeted at soft tissues with high water content. However, percutaneous cables (such as silicone) have extremely low surface polarity, resulting in weak adhesion of this hydrogel to the cable surface, failing to achieve "integrated gap filling" between the cable and tissue. Boric acid has certain cytotoxicity, posing a safety hazard to the interface of long-term implanted percutaneous cables. Furthermore, wet hydrogels are prone to dehydration or mold growth during storage, and active groups gradually deactivate upon long-term exposure to aqueous solutions, failing to meet the long-term pre-packaging requirements of clinical medical devices. Similarly, patent CN102481391A discloses an antimicrobial coating for invasive skin devices, focusing on sterilization of the cable surface but failing to address the physical gap between the cable and skin pores. Because the skin is dynamic, a "piston effect" occurs between the cable and the channel, allowing bacteria to enter the body with air and exudate, which cannot solve the problem of the cable's mismatch with the tissue modulus. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide a coating with adhesive and antibacterial functions for cable tissue interfaces, as well as a method for preparing the same. This coating can simultaneously and effectively adhere to modified silicone cables and skin tissue, exhibiting excellent mechanical compatibility, antibacterial properties, and biocompatibility. Furthermore, by employing a strategy of dry storage and interfacial activation, it solves the problems of poor storage stability and immediate intraoperative use of wet products.

[0008] The specific technical solution adopted in this invention is as follows:

[0009] In a first aspect, the present invention provides a method for preparing a coating with adhesive and antibacterial functions for cable interfacial structures, comprising the following steps:

[0010] S1: Mix 2wt%~4wt% of chitosan quaternary ammonium salt aqueous solution, 45wt%~55wt% of tannic acid aqueous solution and 8wt%~12wt% of polyvinyl alcohol aqueous solution in a mass ratio of 1:(0.5~1):(1~2), and complete the one-step polymerization reaction by centrifugal blending. After the reaction is completed, remove the supernatant and shape the lower solid polymer to obtain solid sheet polymer.

[0011] S2: After repeatedly subjecting the solid sheet polymer to freeze-thaw cycles, a dry adhesive antibacterial coating is obtained by freeze-drying.

[0012] As a preferred embodiment of the first aspect above, the chitosan quaternary ammonium salt aqueous solution has a mass concentration of 3 wt%, the tannic acid aqueous solution has a mass concentration of 50 wt%, and the polyvinyl alcohol aqueous solution has a mass concentration of 10 wt%.

[0013] As a preferred embodiment of the first aspect above, in S1, the temperature during mixing and centrifugal blending is controlled at 20~60℃, the centrifugal speed during centrifugal blending is 6000~8000 rpm, and the centrifugation time is 3~10 min.

[0014] As a preferred embodiment of the first aspect above, in S2, the number of freeze-thaw cycles is at least 3, the temperature of each freezing process is -60°C to -20°C, and the time is ≥12h; the temperature of each thawing process is 15°C to 30°C, and the time is ≥12h.

[0015] As a preferred embodiment of the first aspect above, in step S2, the freeze-drying time is ≥72h.

[0016] In a second aspect, the present invention provides a coating for cable organization interfaces with adhesive and antibacterial functions, which is prepared by the coating preparation method for cable organization interfaces with adhesive and antibacterial functions as described in any of the first aspects above.

[0017] Thirdly, the present invention provides a method for activating the performance of a dry coating, wherein the dry coating is the coating with adhesive and antibacterial functions for cable tissue interfaces as described in the second aspect above. When activating the dry coating, it is soaked in water to soften it and then sprayed with alcohol on the surface to improve its flexibility and adhesion, and is used to press and adhere to the sheathed cable and / or tissue interface.

[0018] As a preferred embodiment of the third aspect above, the soaking and softening time is 5 to 20 minutes; the alcohol is medical alcohol with a mass concentration of 75%.

[0019] As a preferred embodiment of the third aspect above, the transcatheter cable is made of silicone and has undergone surface modification treatment to introduce amino groups onto its surface.

[0020] As a preferred embodiment of the third aspect above, the surface modification treatment method is as follows: first, the sheathed cable is subjected to plasma treatment to graft hydroxyl groups onto its surface; then, the treated cable is immersed in a silane coupling agent solution for surface chemical modification, and further grafted with amino groups.

[0021] Compared with the prior art, the present invention has the following advantages:

[0022] (1) Multifunctional synergistic interface adhesion: This invention achieves dual heavy adhesion of the coating to tissue (through the polyphenol groups of tannic acid) and modified silicone cable (through the interaction between the active groups of the coating and the amino groups on the cable surface) through the synergistic effect of chitosan quaternary ammonium salt (providing antibacterial properties), tannic acid (providing wet tissue adhesion) and polyvinyl alcohol (providing mechanical network), combined with the amylation modification of silicone cable, effectively blocking the microbial invasion channel at the transdermal interface.

[0023] (2) Matching and enhancement of mechanical properties: By enriching a high-density physically cross-linked condensed phase through centrifugal blending, the gel obtained through centrifugal blending has a higher cohesive energy compared to gels obtained by blending and then centrifuging. Combined with freeze-thaw cycle technology to induce the formation of polyvinyl alcohol microcrystalline regions, the cohesive energy and mechanical toughness of the coating are significantly enhanced. The modulus of the resulting coating is similar to that of human skin tissue, solving the problem of interfacial debonding caused by mechanical mismatch.

[0024] (3) Dry storage and transportation and interface activation: The present invention uses freeze-drying technology to make the coating into a dry state, which solves the problems of easy water loss, mold growth and deactivation of active groups in wet hydrogels during storage, and realizes long-term stable storage and transportation. When in use, the coating can be restored to its flexibility and the active groups can be quickly exposed by the convenient operation of "soaking in water to soften and then spraying with alcohol", so as to achieve immediate adhesion and sealing of the gap between the percutaneous cable and the tissue interface during surgery.

[0025] (4) Excellent biocompatibility and antibacterial properties: All coating components are physically cross-linked, avoiding the use of toxic chemical cross-linking agents. Cytotoxicity tests show that it has good biocompatibility. At the same time, the introduction of chitosan quaternary ammonium salt endows the coating with intrinsic contact bactericidal ability, which can effectively reduce the risk of infection.

[0026] (5) The preparation process is simple and the cost is low: the preparation method of the present invention does not require complex equipment, the process conditions are mild, and it is easy to realize industrial production and promotion. Attached Figure Description

[0027] Figure 1 The graph shows the adhesion strength of the adhesive coating to skin tissue in the dry state, corresponding to the mass ratio a:b:c of chitosan quaternary ammonium salt (QCS): tannic acid (TA): polyvinyl alcohol (PVA) in the solid polymer of the present invention.

[0028] Figure 2 This is a comparison diagram of the adhesion strength of coatings to skin tissue in a wet state between coatings that have undergone freeze-thaw cycles and those that have not undergone freeze-thaw cycles, as shown in the embodiments of the present invention.

[0029] Figure 3This is a comparison chart showing the adhesion strength of the coatings to modified silicone after being immersed in water for 72 hours, in an embodiment of the present invention, before and after the coatings underwent freeze-thaw cycle treatment and before the freeze-thaw cycle treatment.

[0030] Figure 4 This is a comparison diagram of the adhesion strength of the coating to skin tissue in dry and wet storage and interface activation in the embodiments of the present invention.

[0031] Figure 5 This is a comparison diagram showing the adhesion strength of the coating to skin tissue in a wet state between Comparative Example 1 and the coating in the embodiment of the present invention.

[0032] Figure 6 This is a comparison diagram showing the adhesion strength of the coating to skin tissue in a wet state between Comparative Example 2 and the embodiment of the present invention.

[0033] Figure 7 The rheological test diagram of the coating in this embodiment of the invention includes two types of results: strain scan and frequency scan.

[0034] Figure 8 This is a diagram showing the biocompatibility (cell viability) test results of the coating in an embodiment of the present invention. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with the accompanying drawings and embodiments. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0036] This invention provides a coating with adhesive and antibacterial functions for cable interfaces and its preparation method. The core of this method lies in constructing a dynamic network through physical cross-linking, combined with dry storage and transportation and interface activation strategies. The specific implementation steps of this coating preparation method are as follows:

[0037] S1: Mix 2wt%~4wt% of chitosan quaternary ammonium salt aqueous solution, 45wt%~55wt% of tannic acid aqueous solution and 8wt%~12wt% of polyvinyl alcohol aqueous solution in a mass ratio of 1:(0.5~1):(1~2), and complete the one-step polymerization reaction by centrifugal blending. After the reaction is completed, remove the supernatant and shape the lower solid polymer to obtain solid sheet polymer.

[0038] S2: After repeatedly subjecting the solid sheet polymer to freeze-thaw cycles, a dry adhesive antibacterial coating is obtained by freeze-drying.

[0039] In this preparation method, chitosan quaternary ammonium salt mainly provides antibacterial properties, tannic acid mainly provides wet tissue adhesion, and polyvinyl alcohol mainly provides a mechanical network; the three act synergistically. Furthermore, they directly polymerize during centrifugal blending, enriching a high-density physically cross-linked condensed phase with high cohesive energy. Combined with freeze-thaw cycling technology, this promotes the formation of polyvinyl alcohol microcrystalline regions, thereby improving the cohesive energy and mechanical toughness of the final coating. The coating is finally freeze-dried to a dry state, which allows for long-term stable preservation compared to wet hydrogels.

[0040] The process parameters in steps S1 and S2 of the above preparation method can be optimized and adjusted according to actual conditions.

[0041] As a preferred embodiment of the present invention, the mass concentration of the chitosan quaternary ammonium salt aqueous solution is recommended to be 3wt%, the mass concentration of the tannic acid aqueous solution is recommended to be 50wt%, the mass concentration of the polyvinyl alcohol aqueous solution is recommended to be 10wt%, and the mass ratio of the three solutions is recommended to be 1: (0.5~1): (1~2).

[0042] As a preferred embodiment of the present invention, in step S1, the temperature during mixing and centrifugal blending is recommended to be controlled at 20~60℃; the centrifugal speed during centrifugal blending is recommended to be set to 6000~8000 rpm, and the centrifugation time is recommended to be set to 3~10 min. More preferably, the chitosan quaternary ammonium salt aqueous solution, tannic acid aqueous solution, and polyvinyl alcohol aqueous solution need to be mixed rapidly, and can be premixed using a turbine stirrer, wherein the temperature of the chitosan quaternary ammonium salt aqueous solution and tannic acid aqueous solution is maintained at 20-60℃, and the temperature of the polyvinyl alcohol aqueous solution is maintained at 60℃. Under these conditions, a relatively thorough mixing of the three components can be ensured.

[0043] As a preferred embodiment of the present invention, in step S2, the number of freezing-thawing cycles is at least three (preferably three times), the temperature of each freezing process is -60℃ to -20℃, and the time is ≥12h; the temperature of each thawing process is 15℃ to 30℃, and the time is ≥12h.

[0044] In a preferred embodiment of the present invention, in step S2, the freeze-drying time is ≥72h to ensure that the coating is completely dry.

[0045] The preparation methods shown in S1 and S2 above produce a dry adhesive antibacterial coating (hereinafter referred to as dry coating). When used, the coating can be restored to its flexibility and the active groups can be quickly exposed through a simple operation of "soaking in water to soften and then spraying with alcohol". This coating is used to adhere and seal the gap between the percutaneous cable and the tissue interface.

[0046] Therefore, this invention also provides a method for activating the performance of a dry coating. Specifically, before use, the coating is first soaked in water to soften it, and then alcohol is sprayed onto its surface to improve its flexibility and adhesion, thus quickly activating its performance. In subsequent use, it is placed at the interface between the percutaneous cable and the tissue and pressed for a certain period of time to achieve adhesion.

[0047] In the above-mentioned dry coating performance activation method, the softening time varies depending on the coating thickness. Soaking the coating in water allows it to quickly soften from a dry, high-modulus state to a state close to the modulus of human skin, enabling better and seamless adhesion to irregular skin tissue. For a 1mm thick coating, the recommended softening time by soaking in water is 5–20 minutes.

[0048] Additionally, when using this product during surgery or in other situations where the skin is damaged, it is best to use medical alcohol with a recommended concentration of 75% for surface spraying. By spraying a small amount of alcohol, the active groups on the coating surface can be quickly exposed, improving the adhesion of the coating to skin tissue and silicone cables.

[0049] The activated coating of this invention can adhere well to the surface of skin tissue, and the surface of percutaneous cables can also be modified to enable them to adhere better to the activated coating of this invention.

[0050] As a preferred embodiment of the present invention, when the coating is used in conjunction with a perforated cable, it is recommended to use a silicone perforated cable. Furthermore, the silicone perforated cable needs to undergo plasma treatment to graft hydroxyl groups onto its surface. The treated cable is then immersed in a silane coupling agent solution for surface chemical modification, thereby further grafting amino groups. The silicone perforated cable with surface-grafted amino groups and the activated coating can have a stronger interaction.

[0051] In the modification of silicone-coated cables, the recommended plasma treatment time for the coated cables is 5–20 min. APTES is recommended as the silane coupling agent used for immersion. The silane coupling agent solution is prepared by mixing ethanol, water, APTES, and acetic acid in a mass ratio of 25:25:1:0.005. Furthermore, the surface chemical modification treatment temperature is 20–40 °C, and the treatment time is 6–8 h.

[0052] The technical solution and effects of the present invention will be further illustrated below through several specific embodiments. Unless otherwise specified, the commercial silicone sheets used in the embodiments of the present invention are made of the same silicone material as those used in medical percutaneous cables, and are used for simulation testing. The chitosan quaternary ammonium salt (QCS) used in the following embodiments of the present invention to prepare the aqueous solution of chitosan quaternary ammonium salt (QCS) is a commercially available reagent, brand name: MACKLIN, catalog number: C768944-100g, lot number / Lot#: C17171747, CAS: NONE6321, hereinafter referred to as MACKLIN NONE6321. The degree of substitution of this chitosan quaternary ammonium salt is 40%, and its structural formula is as follows:

[0053] In this structural formula, the terminal structure of the intermediate monomer is connected to a group after -NH as -CH2-CH(OH)-CH2-N⁺(CH3)3 Cl⁻, where the nitrogen quaternary ammonium ion N + It is attached to three methyl groups and adsorbs chloride ions (Cl) through ionic bonds. - However, this chitosan quaternary ammonium salt is only an optional reagent, and other commercially available reagents can be used instead. The tannic acid used in the following embodiments of the present invention has the CAS number 1401-55-4, and the polyvinyl alcohol used has the CAS number 9002-89-5.

[0054] Example 1

[0055] In this embodiment, a coating with adhesive and antibacterial functions for cable organization interfaces is prepared, specifically including the following steps:

[0056] (1) Prepare 3wt% chitosan quaternary ammonium salt (QCS) aqueous solution, 50wt% tannic acid (TA) aqueous solution, and 10wt% polyvinyl alcohol (PVA) aqueous solution, respectively. Preheat the QCS and TA aqueous solutions in a 37℃ constant temperature oven, and heat the PVA aqueous solution to 60℃ to dissolve it. Then, mix the three solutions quickly in a centrifuge tube at a mass ratio of QCS aqueous solution:TA aqueous solution:PVA aqueous solution = 1:1:2, and immediately place them in a centrifuge. Centrifuge at 8000 rpm for 3 min. Remove the centrifuge tube, discard the supernatant, and collect the lower solid polymer. Place the solid polymer between two glass plates, with a 1mm thick hollow silicone pad placed around the area where the solid polymer is placed between the glass plates to control the molding thickness. After pressing the two glass plates together, fix them with clamps for 5 min to obtain a solid sheet polymer with a thickness of 1mm.

[0057] (2) The solid sheet polymer after molding was immersed in deionized water for 72 hours to remove unreacted monomers. After removal, it was placed in a sealed bag and subjected to three freeze-thaw cycles: each time it was frozen at -20°C for 12 hours and then thawed at 20°C for 12 hours. Finally, the polymer that had completed the three freeze-thaw cycles was placed in an open container and freeze-dried for 72 hours to obtain a dry coating, which was then sealed and dried for storage.

[0058] (3) The commercial silicone sheet was subjected to plasma treatment for 10 min. Then it was immersed in a modified solution prepared by ethanol, deionized water, APTES and acetic acid in a mass ratio of 25:25:1:0.005 and reacted at 25°C for 8 h. After removing the silicone sheet, it was thoroughly cleaned with ethanol and deionized water and dried in an oven at 60°C for later use.

[0059] (4) Take the dry coating and soak it in deionized water for 10 minutes to soften it. After taking it out, spray a small amount of 75% medical alcohol evenly on the surface of the coating and immediately place it on the surface of the silicone sheet (used to simulate modified cable) or pigskin tissue treated in step (3). Press with your finger for 15 seconds to adhere it.

[0060] Example 2

[0061] In this embodiment, a coating with adhesive and antibacterial functions for cable organization interfaces is prepared, specifically including the following steps:

[0062] (1) Prepare 3wt% chitosan quaternary ammonium salt (QCS) aqueous solution, 50wt% tannic acid (TA) aqueous solution and 10wt% polyvinyl alcohol (PVA) aqueous solution respectively. Preheat the QCS and TA solutions in a constant temperature oven at 37℃, and heat the PVA solution to 60℃ to dissolve. Then, mix the three solutions quickly in a centrifuge tube at a mass ratio of QCS aqueous solution:TA aqueous solution:PVA aqueous solution = 1:0.5:2, and immediately place them in a centrifuge. Centrifuge at 8000 rpm for 3 min. Remove the centrifuge tube, discard the supernatant, and collect the lower solid polymer. Place the solid polymer between two glass plates. Place a 1 mm thick hollow silicone pad around the area where the solid polymer is placed between the glass plates to control the molding thickness. After pressing the two glass plates together, fix them with clamps for 5 min to obtain a solid sheet polymer with a thickness of 1 mm.

[0063] (2) The solid sheet polymer after molding was immersed in deionized water for 72 hours to remove unreacted monomers. After removal, it was placed in a sealed bag and subjected to three freeze-thaw cycles: each time it was frozen at -20°C for 12 hours and then thawed at 20°C for 12 hours. Finally, the polymer that had completed the three freeze-thaw cycles was placed in an open container and freeze-dried for 72 hours to obtain a dry coating, which was then sealed and dried for storage.

[0064] (3) The commercial silicone sheet was subjected to plasma treatment for 10 min. Then it was immersed in a modified solution prepared by ethanol, deionized water, APTES and acetic acid in a mass ratio of 25:25:1:0.005 and reacted at 25°C for 8 h. After removing the silicone sheet, it was thoroughly cleaned with ethanol and deionized water and dried in an oven at 60°C for later use.

[0065] (4) Take the dry coating and soak it in deionized water for 10 minutes to soften it. After taking it out, spray a small amount of 75% medical alcohol evenly on the surface of the coating and immediately place it on the surface of the silicone sheet (used to simulate modified cable) or pigskin tissue treated in step (3). Press with your finger for 15 seconds to adhere it.

[0066] Example 3

[0067] In this embodiment, a coating with adhesive and antibacterial functions for cable organization interfaces is prepared, specifically including the following steps:

[0068] (1) Prepare 3wt% chitosan quaternary ammonium salt (QCS) aqueous solution, 50wt% tannic acid (TA) aqueous solution and 10wt% polyvinyl alcohol (PVA) aqueous solution respectively. Preheat the QCS and TA solutions in a constant temperature oven at 37℃, and heat the PVA solution to 60℃ to dissolve. Then, mix the three solutions quickly in a centrifuge tube at a mass ratio of QCS aqueous solution:TA aqueous solution:PVA aqueous solution = 1:0.5:1, and immediately place them in a centrifuge. Centrifuge at 8000 rpm for 3 min. Remove the centrifuge tube, discard the supernatant, and collect the lower solid polymer. Place the solid polymer between two glass plates. Place a 1 mm thick hollow silicone pad around the area where the solid polymer is placed between the glass plates to control the molding thickness. After pressing the two glass plates together, fix them with clamps for 5 min to obtain a solid sheet polymer with a thickness of 1 mm.

[0069] (2) The solid sheet polymer after molding was immersed in deionized water for 72 hours to remove unreacted monomers. After removal, it was placed in a sealed bag and subjected to three freeze-thaw cycles: each time it was frozen at -20°C for 12 hours and then thawed at 20°C for 12 hours. Finally, the polymer that had completed the three freeze-thaw cycles was placed in an open container and freeze-dried for 72 hours to obtain a dry coating, which was then sealed and dried for storage.

[0070] (3) The commercial silicone sheet was subjected to plasma treatment for 10 min. Then it was immersed in a modified solution prepared by ethanol, deionized water, APTES and acetic acid in a mass ratio of 25:25:1:0.005 and reacted at 25°C for 8 h. After removing the silicone sheet, it was thoroughly cleaned with ethanol and deionized water and dried in an oven at 60°C for later use.

[0071] (4) Take the dry coating and soak it in deionized water for 10 minutes to soften it. After taking it out, spray a small amount of 75% medical alcohol evenly on the surface of the coating and immediately place it on the surface of the silicone sheet (used to simulate modified cable) or pigskin tissue treated in step (3). Press with your finger for 15 seconds to adhere it.

[0072] Example 4

[0073] In this embodiment, a coating with adhesive and antibacterial functions for cable organization interfaces is prepared, specifically including the following steps:

[0074] (1) Prepare 3wt% chitosan quaternary ammonium salt (QCS) aqueous solution, 50wt% tannic acid (TA) aqueous solution, and 10wt% polyvinyl alcohol (PVA) aqueous solution, respectively. Preheat the QCS and TA solutions in a 37℃ constant temperature oven, and heat the PVA solution to 60℃ to dissolve. Then, mix the three solutions quickly in a centrifuge tube at a mass ratio of QCS aqueous solution:TA aqueous solution:PVA aqueous solution = 1:1:2, and immediately place them in a centrifuge. Centrifuge at 8000 rpm for 3 min. Remove the centrifuge tube, discard the supernatant, and collect the lower layer of solid polymer. Place the solid polymer between two glass plates, with a 1mm thick hollow silicone pad placed around the area where the solid polymer is placed between the glass plates to control the molding thickness. After pressing the two glass plates together, fix them with clamps for 5 min to obtain a solid sheet polymer with a thickness of 1mm.

[0075] (2) The solid sheet polymer after molding was immersed in deionized water for 72 hours to remove unreacted monomers. After removal, it was placed in a sealed bag and subjected to three freeze-thaw cycles: each time it was frozen at -20°C for 12 hours and then thawed at 20°C for 12 hours. Finally, the polymer that had completed the three freeze-thaw cycles was placed in an open container and freeze-dried for 72 hours to obtain a dry coating, which was then sealed and dried for storage.

[0076] (3) The commercial silicone sheet was subjected to plasma treatment for 10 min. Then it was immersed in a modified solution prepared by ethanol, deionized water, APTES and acetic acid in a mass ratio of 25:25:1:0.005 and reacted at 25°C for 8 h. After removing the silicone sheet, it was thoroughly cleaned with ethanol and deionized water and dried in an oven at 60°C for later use.

[0077] (4) Take the dry coating and soak it in water until it swells to equilibrium. After taking it out, spray a small amount of 75% medical alcohol evenly on the surface of the coating. Completely immerse the silicone sheet (used to simulate modified cables) or pigskin treated in step (3) in water and then take it out. Place the coating that has swelled to equilibrium and sprayed with a small amount of 75% medical alcohol on the surface of the silicone sheet or pigskin tissue, and press it with your finger for 15 seconds to adhere it.

[0078] Example 5

[0079] In this embodiment, a coating with adhesive and antibacterial functions for cable organization interfaces is prepared, specifically including the following steps:

[0080] (1) Prepare 3wt% chitosan quaternary ammonium salt (QCS) aqueous solution, 50wt% tannic acid (TA) aqueous solution and 10wt% polyvinyl alcohol (PVA) aqueous solution respectively. Preheat the QCS and TA solutions in a constant temperature oven at 37℃, and heat the PVA solution to 60℃ to dissolve. Then, mix the three solutions quickly in a centrifuge tube at a mass ratio of QCS aqueous solution:TA aqueous solution:PVA aqueous solution = 1:1:2, and immediately place them in a centrifuge. Centrifuge at 8000 rpm for 3 min. Remove the centrifuge tube, discard the supernatant, and collect the lower solid polymer. Place the solid polymer between two glass plates. Place a 1mm thick hollow silicone pad around the area where the solid polymer is placed between the glass plates to control the molding thickness. After pressing the two glass plates together, fix them with clamps for 5 min to obtain a solid sheet polymer with a thickness of 1mm.

[0081] (2) The solid sheet polymer after shaping was immersed in deionized water for 72 hours to remove unreacted monomers. After removing the polymer, it was placed in an open container and freeze-dried for 72 hours to obtain a dry coating. The coating was then sealed and dried for storage.

[0082] (3) The commercial silicone sheet was subjected to plasma treatment for 10 min. Then it was immersed in a modified solution prepared by ethanol, deionized water, APTES and acetic acid in a mass ratio of 25:25:1:0.005 and reacted at 25°C for 8 h. After removing the silicone sheet, it was thoroughly cleaned with ethanol and deionized water and dried in an oven at 60°C for later use.

[0083] (4) Take the dry coating and soak it in water until it swells to equilibrium. After taking it out, spray a small amount of 75% medical alcohol evenly on the surface of the coating. Completely immerse the silicone sheet (used to simulate modified cables) or pigskin treated in step (3) in water and then take it out. Place the swelled and balanced coating with a small amount of 75% medical alcohol on the surface of the silicone sheet or pigskin tissue, and press it with your finger for 15 seconds to adhere it.

[0084] Comparative Example 1

[0085] In this embodiment, a polyvinyl alcohol hydrogel material was prepared. The specific preparation method includes the following steps:

[0086] (1) Add 1 g of chitosan quaternary ammonium salt (HACC) to 9 g of deionized water and stir magnetically overnight at room temperature until the chitosan quaternary ammonium salt is completely dissolved, and the resulting chitosan quaternary ammonium salt solution with a concentration of 10 wt% is ready for use.

[0087] (2) Weigh 5.0 g of polyvinyl alcohol (PVA) and add it to 40.0 g of deionized water. Stir magnetically in a 90 ℃ water bath for 1 h until the polyvinyl alcohol (PVA) dissolves. Weigh 5.0 g of the chitosan quaternary ammonium salt solution obtained in step (1) above and add it to the polyvinyl alcohol (PVA) solution. Stir magnetically in a 90 ℃ water bath for 2 h to obtain a mixed solution of polyvinyl alcohol (PVA) and chitosan quaternary ammonium salt (HACC) for later use.

[0088] (3) The polyvinyl alcohol (PVA) and chitosan quaternary ammonium salt (HACC) mixed solution obtained in step (2) above is sonicated in an ultrasonic instrument until the bubbles disappear; then the mixed solution is poured into a mold, frozen for 12 h, and then taken out and thawed for 12 h. This freeze-thaw cycle is repeated three times to obtain polyvinyl alcohol / chitosan quaternary ammonium salt gel for later use.

[0089] (4) Add 10 g of tannic acid (TA) to 90 g of deionized water and stir magnetically at room temperature until completely dissolved to obtain a 10 wt% tannic acid solution for later use.

[0090] (5) The polyvinyl alcohol / chitosan quaternary ammonium salt gel obtained in step (3) above is soaked in the tannic acid solution obtained in step (4) above for 48 hours to finally obtain a double network structure hydrogel wound dressing.

[0091] Comparative Example 2

[0092] In this embodiment, a coating with adhesive and antibacterial functions for cable organization interfaces is prepared, specifically including the following steps:

[0093] (1) Prepare 3wt% chitosan quaternary ammonium salt (QCS) aqueous solution, 50wt% tannic acid (TA) aqueous solution and 10wt% polyvinyl alcohol (PVA) aqueous solution respectively. Preheat the QCS and TA solutions in a constant temperature oven at 37℃, and heat the PVA solution to 60℃ to dissolve. Then, mix the three solutions in a beaker at a mass ratio of QCS aqueous solution:TA aqueous solution:PVA aqueous solution = 1:1:2, stir for 12h, and centrifuge at 8000 rpm for 3min. Remove the centrifuge tube, discard the supernatant, and collect the lower solid polymer. Place the solid polymer between two glass plates, with a 1mm thick hollow silicone pad placed around the area where the solid polymer is placed between the glass plates to control the molding thickness. After pressing the two glass plates together, fix them with clamps for 5min to obtain a solid sheet polymer with a thickness of 1mm.

[0094] (2) The solid sheet polymer after molding was immersed in deionized water for 72 hours to remove unreacted monomers. After removal, it was placed in a sealed bag and subjected to three freeze-thaw cycles: each time it was frozen at -20°C for 12 hours and then thawed at 20°C for 12 hours. Finally, the polymer that had completed the three freeze-thaw cycles was placed in an open container and freeze-dried for 72 hours to obtain a dry coating, which was then sealed and dried for storage.

[0095] (4) Take the dry coating and soak it in water until it swells to equilibrium. After removing it, spray a small amount of 75% medical alcohol evenly on the surface of the coating. Completely immerse the pigskin in water and then remove it. Place the swollen and balanced coating, sprayed with a small amount of 75% medical alcohol, on the surface of the moist tissue and press it with your finger for 15 seconds to allow it to adhere.

[0096] To demonstrate the effect of the coating prepared by the present invention, more detailed performance tests were conducted on the coatings with adhesive and antibacterial functions for cable tissue interfaces prepared in Examples 1-5, as well as the dressings or coatings prepared in Comparative Examples 1-2. The specific test process is as follows:

[0097] 1. Adhesion performance test

[0098] (1) The coatings from Examples 1-3 were cut into sheets measuring 1cm*0.5cm*0.1mm. Pigskin was cut into sheets measuring 3cm*1cm*0.2mm. A layer of anti-deformation tape was adhered to the surface of the pigskin using commercial adhesive. The coatings, softened by soaking in water for 10 minutes, were sprayed with a small amount of medical alcohol, placed on the surface of the pigskin tissue, pressed with a finger for 15 seconds, and left for 15 minutes before testing. The adhesion test type was an overlap shear adhesion test, with a tensile rate of 5mm / min. The results are as follows: Figure 1 As shown, the coating prepared in Example 3 exhibited the best adhesion performance, with an adhesion strength of 83.9 ± 13.7 kPa. The coating with the best performance (Example 3) was then tested on the modified silicone sheet in the same manner as described above, and the silicone adhesion strength was 250 kPa.

[0099] (2) Cut the coatings from Examples 4-5 into sheets measuring 1cm*0.5cm*0.1mm. Cut pigskin into sheets measuring 3cm*1cm*0.2cm. Apply a layer of anti-deformation tape to the surface of the pigskin using commercial adhesive. Spray a small amount of medical alcohol onto the coating that has been soaked in water until it reaches swelling equilibrium. Place the coating on the surface of the moist pigskin tissue, press it with your finger for about 15 seconds, and then test it after 15 minutes. The adhesion test type is the overlap shear adhesion test, and the tensile rate is 5mm / min. The results are as follows: Figure 2As shown, the wet skin tissue adhesion strength of the coating without freeze-thaw cycles (the coating prepared in Example 5) was only 28.1 ± 1.7 kPa. In contrast, the wet skin tissue adhesion strength of the coating with freeze-thaw cycles (the coating prepared in Example 4) was 54.8 ± 4.3 kPa. The coatings from Examples 4 and 5 were tested on modified silicone sheets in the same manner as described above, with the silicone sheets immersed in water for 72 hours after adhesion. The results are as follows. Figure 3 As shown, the wet silicone adhesive strength of the coating without freeze-thaw cycles (the coating prepared in Example 5) was only 13.9 ± 1.0 kPa. In contrast, the wet silicone adhesive strength of the coating with freeze-thaw cycles (the coating prepared in Example 4) was 46.3 ± 0.07 kPa. This demonstrates that the freeze-thaw cycles introduced in this invention have a significant impact on improving the wet adhesion and mechanical properties of the polymer.

[0100] (3) Cut the coating prepared in Example 3 into sheets of 1cm*0.5cm*0.1mm. Cut the pigskin into sheets of 3cm*1cm*0.2cm. Apply a layer of anti-deformation tape to the surface of the pigskin with commercial adhesive. Set up 6 experimental groups for the coating in Example 3. Among them, the wet storage-interface activation alcohol 0 means that the coating prepared in Example 3 was soaked in water for 30 days before adhesion, and no alcohol activation was required before use. It was pressed on the skin tissue interface for 15s. The wet storage-interface activation alcohol 37.5% means that the coating prepared in Example 3 was soaked in water for 30 days before adhesion, and activated with 37.5% alcohol before use. It was pressed on the skin tissue interface for 15s. The wet storage-interface activation alcohol 75% means that the coating prepared in Example 3 was soaked in water for 30 days before adhesion, and activated with 75% alcohol before use. It was pressed on the skin tissue interface for 15s. The dry-stored-interface-activated alcohol 0% coating, prepared in Example 3, was stored in a dry state for 30 days before adhesion. No alcohol activation was required before use; it was pressed onto the skin tissue interface for 15 seconds. The dry-stored-interface-activated alcohol 37.5% coating, prepared in Example 3, was stored in a dry state for 30 days before adhesion. It was activated with 37.5% alcohol before use and pressed onto the skin tissue interface for 15 seconds. The dry-stored-interface-activated alcohol 75% coating, prepared in Example 3, was stored in a dry state for 30 days before adhesion. It was activated with 75% alcohol before use and pressed onto the skin tissue interface for 15 seconds. The results of the six experimental groups are as follows: Figure 4As shown, the results indicate that the coating prepared in Example 3 exhibits greater adhesion strength in dry storage than in wet storage. Specifically, the coating's adhesion to skin tissue increases with increasing alcohol concentration. Alcohol rapidly disrupts the physical cross-linking interactions of the coating, activating interfacial functional groups to form adhesion with skin tissue. Without alcohol for interfacial activation, the coating cannot rapidly develop adhesion. This experiment demonstrates the crucial role of dry storage-alcohol interfacial activation in achieving stable storage and transportation, as well as immediate adhesion and sealing of the coating.

[0101] (4) Cut the coating prepared in Comparative Example 1 into sheets measuring 1cm*0.5cm*0.1mm. Cut pigskin into sheets measuring 3cm*1cm*0.2cm. Apply a layer of anti-deformation tape to the surface of the pigskin using commercial adhesive. Spray a small amount of medical alcohol onto the coating, which has been soaked in water until it reaches swelling equilibrium. Place the coating on the moist pigskin tissue surface, press it with your finger for approximately 15 seconds, and then test it after 15 minutes. The adhesion test type is lap shear adhesion test, and the tensile rate is 5mm / min. Figure 5 As shown, the coating prepared in Comparative Example 1 exhibited an adhesion strength of 12.4 ± 3.8 kPa to moist skin tissue, while the coating in Example 4 exhibited an adhesion strength of 54.8 ± 4.3 kPa to moist skin tissue. The adhesion strength of the coating prepared in Example 4 to the skin was significantly greater than that of the comparative example. The comparative example was prepared using a two-step method, with a preparation time exceeding 48 hours. In contrast, Example 4 employed a one-step method, resulting in fewer preparation steps and a shorter reaction time, yet exhibiting stronger adhesion properties. This superior adhesion performance is primarily attributed to the separation of polymer and water during the blending and centrifugation process, leading to an increase in polymer density and providing excellent cohesiveness. Within a certain range, increased polymer cohesiveness leads to increased polymer adhesion strength.

[0102] (5) The coating prepared in Comparative Example 2 is adhered using the method described above. For example... Figure 6 As shown, the coating prepared in Comparative Example 2 exhibited an adhesion strength of 30.7 ± 1.3 kPa to moist skin tissue, while the coating prepared in Example 4 showed an adhesion strength of 54.8 ± 4.3 kPa to moist skin tissue. The coating prepared in Example 4 showed significantly greater adhesion strength to skin than the coating prepared in Comparative Example 2. The comparative examples employed a method of blending followed by centrifugation, which, although separating the polymer and water through centrifugation and increasing the polymer density, resulted in a lower polymer density compared to the centrifugal blending method used in this invention. This invention, through simultaneous centrifugation and blending, allows the polymer chains to interact under high-speed extrusion, resulting in closer polymer chain spacing and a higher polymer density.

[0103] (6) The coating prepared in Example 3 was applied to commercially available cardiac medical silicone cables (modified according to the above requirements) and skin tissue as described above. Under continuous strong water flow impact, the adhesion interface was stable and no debonding was observed.

[0104] 2. Rheological test

[0105] The coating with the best performance (i.e., the coating prepared in Example 3) was subjected to rheological testing after swelling equilibrium. For example... Figure 7 As shown, the strain scanning range is 0.1%-10%, and the frequency is fixed at 1Hz. A linear strain scanning region is selected, with a fixed strain of 0.1% and a frequency scanning range of 0.1-100Hz. The storage modulus G' and loss modulus G'' are both close to the actual modulus of human skin tissue. This ensures that the mechanical properties of the coating match those of skin tissue, preventing debonding.

[0106] 3. Biocompatibility testing

[0107] The freeze-dried coating was ground into powder after being added to liquid nitrogen and then sterilized. The treated coating powder was co-cultured with cell culture medium for 24 hours, followed by co-culture with human fibroblasts for 24 hours. 3000 human fibroblasts per well were placed in a 96-well plate. To demonstrate the difference in coating performance due to different raw material ratios, the formulation of the precursor solution (3 wt% chitosan quaternary ammonium salt aqueous solution, 50 wt% tannic acid aqueous solution, and 10 wt% polyvinyl alcohol aqueous solution in a mass ratio of 1:0.5:1) was adjusted based on the best-performing coating prepared in Example 3. The concentrations of tannic acid were changed to 25 wt% and 16.7 wt%, while the concentrations of the other two solutions and the mass ratios remained unchanged. Based on the adjusted precursor solutions, two other coatings with different proportions were prepared using the same method as in Example 3 (but with different precursor solution formulations). A blank control group without coating powder was also included. Biocompatibility tests were performed on the above coatings with different proportions, and the results are as follows: Figure 8 As shown, the cell viability is above 98%, indicating good biocompatibility.

[0108] 4. Antibacterial performance test

[0109] The coating with the best performance (i.e., the coating prepared in Example 3) was selected. The lyophilized coating was ground into powder with liquid nitrogen and sterilized. 0.5 mg, 1 mg, and 5 mg of the treated coating powder were dissolved in 20 μL of DMSO, and each was mixed with 1 mL of LB cell culture medium. 100 μL of each powder was mixed with 10 μL of DH5α cultured overnight, incubated for 6 h, diluted 200 times, and plated on LB agar plates for overnight incubation. The blank control group received 20 μL of DMSO but no coating powder. As the polymer content increased, the number of bacteria decreased, demonstrating that the coating itself possesses certain antibacterial properties.

[0110] The embodiments described above are merely some preferred implementations of the present invention and are not intended to limit the invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all technical solutions obtained through equivalent substitution or transformation fall within the protection scope of the present invention.

Claims

1. A method for activating the properties of a dry coating, characterized in that, The dry coating is a coating with adhesive and antibacterial functions for cable tissue interface. When the dry coating is activated, it is soaked in water to soften it and then sprayed with alcohol on the surface to improve its flexibility and adhesion, and is used to press and adhere to the transcatheter cable and / or tissue interface. The method for preparing a coating with adhesive and antibacterial functions for cable interfaces includes the following steps: S1: Mix 2wt%~4wt% of chitosan quaternary ammonium salt aqueous solution, 45wt%~55wt% of tannic acid aqueous solution and 8wt%~12wt% of polyvinyl alcohol aqueous solution in a mass ratio of 1:(0.5~1):(1~2), and complete the one-step polymerization reaction by centrifugal blending. After the reaction is completed, remove the supernatant and shape the lower solid polymer to obtain solid sheet polymer. S2: After repeatedly subjecting the solid sheet polymer to freeze-thaw cycles, a dry adhesive antibacterial coating is obtained by freeze-drying. The alcohol is 75% medical alcohol by mass concentration; the percutaneous cable is made of silicone and has undergone surface modification treatment to introduce amino groups onto its surface; the surface modification treatment method is as follows: first, the percutaneous cable is subjected to plasma treatment to graft hydroxyl groups onto its surface; then, the treated cable is immersed in a silane coupling agent solution for surface chemical modification to further graft amino groups.

2. The method for activating the performance of a dry coating as described in claim 1, characterized in that, The chitosan quaternary ammonium salt aqueous solution has a mass concentration of 3 wt%, the tannic acid aqueous solution has a mass concentration of 50 wt%, and the polyvinyl alcohol aqueous solution has a mass concentration of 10 wt%.

3. The method for activating the performance of a dry coating according to claim 1, characterized in that, In step S1, the temperature during mixing and centrifugal blending is controlled at 20~60℃, the centrifugal speed during centrifugal blending is 6000~8000 rpm, and the centrifugation time is 3~10 min.

4. The method for activating the performance of a dry coating according to claim 1, characterized in that, In S2, the freezing-thawing cycle is performed at least 3 times, with each freezing process taking a temperature of -60°C to -20°C and a time of ≥12 hours; and each thawing process taking a temperature of 15°C to 30°C and a time of ≥12 hours.

5. The method for activating the performance of a dry coating according to claim 1, characterized in that, In step S2, the freeze-drying time is ≥72h.

6. The method for activating the performance of a dry coating according to claim 1, characterized in that, The soaking and softening time is 5 to 20 minutes.

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