Multifunctional biomedical coating material and preparation method and application thereof

Abstract

This invention provides a multifunctional biomedical coating material, its preparation method, and its application. The multifunctional biomedical coating material comprises a medical substrate, a polydopamine intermediate layer, and a polyphenol-metal network composite layer stacked together. The preparation method includes: (1) pretreating the medical substrate; (2) preparing a first buffer solution containing dopamine hydrochloride, immersing the medical substrate in the first buffer solution for a light-protected reaction, removing the substrate, washing and drying it to obtain a modified substrate; (3) preparing a second buffer solution containing polyphenols and metal ions, immersing the modified substrate in the second buffer solution for shaking incubation, removing the substrate, washing and drying it to obtain the multifunctional biomedical coating material. The multifunctional biomedical coating material provided by this invention is suitable for surface antibacterial and biocompatibility modification of various implantable / interventional devices, catheters, and medical textile materials, effectively solving the technical problems of clinical implant-related infections and poor cell compatibility.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, and relates to a multifunctional biomedical coating material, and more particularly to a multifunctional biomedical coating material, its preparation method and application. Background Technology

[0002] Implant-related infections and insufficient cell compatibility are core challenges restricting the clinical application of medical metals and polymer materials. Bacteria colonize, proliferate, and form biofilms on material surfaces, easily leading to implantation failure, revision surgeries, and complications. Globally, approximately 5%-15% of orthopedic implants and 20% of dental implants face the risk of implant-related infections.

[0003] Currently, existing antibacterial modifications mostly utilize silver, copper, and aluminum ions, which generally suffer from drawbacks such as high cytotoxicity, easy oxidation, uncontrollable release, and poor long-term biocompatibility. Furthermore, most coatings are only suitable for a single substrate and are difficult to adapt to mainstream clinical materials such as titanium alloys, polyurethane, and polyester.

[0004] Mussel-inspired polydopamine (PDA) can adhere firmly to the surface of almost all solid materials, and tannic acid (TA), a natural polyphenol, possesses antibacterial, antioxidant, and metal coordination capabilities, allowing the two to form a stable composite layer. However, the antibacterial efficacy of pure PDA / TA coatings is extremely limited.

[0005] Therefore, it is evident that providing a universal, mild, and scalable multi-substrate adaptable surface modification strategy that also ensures broad-spectrum and efficient antibacterial activity, excellent cell compatibility, and long-term physiological stability to meet the diverse clinical needs of implants, catheters, and medical textiles has become an urgent problem for those skilled in the art. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a multifunctional biomedical coating material, its preparation method, and its application. This material is suitable for surface antibacterial and biocompatibility modification of various implantable / interventional devices, catheters, and medical textile materials, effectively solving the technical problems of clinical implant-related infections and poor cell compatibility.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides a multifunctional biomedical coating material, comprising a medical substrate, a polydopamine intermediate layer, and a polyphenol-metal network composite layer stacked together.

[0009] This invention provides a polydopamine intermediate layer and a polyphenol-metal network composite layer on the surface of a medical substrate. The polydopamine can firmly adhere to the substrate surface, the metal ions can disrupt the integrity of bacterial cell membranes, and the polyphenols can inhibit bacterial metabolism. The three work synergistically to achieve long-lasting antibacterial function. Furthermore, the covalent and coordination bonds form a double network structure, resulting in minimal loss under physiological conditions and excellent durability. This invention is suitable for surface antibacterial and biocompatibility modification of various implantable / interventional devices, catheters, and medical textile materials.

[0010] Preferably, the material of the medical substrate includes at least one of titanium, polyurethane, or polyethylene terephthalate.

[0011] Preferably, the polyphenol-metal network composite layer includes a tannic acid-ytterbium ion composite layer.

[0012] Preferably, the total thickness of the polydopamine interlayer and the polyphenol-metal network composite layer is 110.3~131.2 nm.

[0013] Preferably, the water contact angle of the surface of the multifunctional biomedical coating material is 61°~63°.

[0014] Preferably, the thickness loss rate of the multifunctional biomedical coating material after immersion in phosphate buffer for 7 days is ≤8.1%.

[0015] Preferably, the pH value of the phosphate buffer solution is 7.2 to 7.4.

[0016] Preferably, the multifunctional biomedical coating material has an antibacterial rate of 83.9%~93.1% against Escherichia coli and Staphylococcus aureus over 24 hours.

[0017] Preferably, the multifunctional biomedical coating material has an antibacterial rate of 80.1% to 92.4% after 7 days of continuous bacterial challenge.

[0018] Preferably, the cell survival rate of the multifunctional biomedical coating material co-cultured with L929 mouse fibroblasts for 7 days is ≥80%.

[0019] In a second aspect, the present invention provides a method for preparing a multifunctional biomedical coating material as described in the first aspect, comprising the following steps:

[0020] (1) Pretreatment of the medical substrate;

[0021] (2) Prepare a first buffer solution containing dopamine hydrochloride, immerse the medical substrate obtained in step (1) in the first buffer solution for a light-protected reaction, remove the substrate, wash and dry it to obtain the modified substrate;

[0022] (3) Prepare a second buffer solution containing polyphenols and metal ions, immerse the modified substrate obtained in step (2) in the second buffer solution for shaking incubation, remove the substrate, clean and dry it to obtain the multifunctional biomedical coating material.

[0023] This invention employs a two-step immersion method to construct a composite coating on the surface of a medical substrate. It requires no complex equipment, and the preparation conditions are controllable, which is beneficial for large-scale industrial applications.

[0024] Optionally, the medical substrate in step (1) is made of titanium metal, and the pretreatment includes sandpaper polishing, ultrasonic cleaning and vacuum drying performed sequentially.

[0025] Optionally, the medical substrate in step (1) is made of polyurethane, and the pretreatment includes ultrasonic cleaning and vacuum drying performed sequentially.

[0026] Optionally, the medical substrate in step (1) is made of polyethylene terephthalate, and the pretreatment includes soaking, ultrasonic cleaning and vacuum drying in sequence.

[0027] Preferably, in step (2), the solute in the first buffer solution includes dopamine hydrochloride and tris(hydroxymethyl)aminomethane hydrochloride.

[0028] Preferably, the concentration of dopamine hydrochloride is 1.5~2.5 mg / mL, and the concentration of tris(hydroxymethyl)aminomethane hydrochloride is 8~12 mmol / L.

[0029] Preferably, in step (2), the pH value of the first buffer solution is 8 to 9.

[0030] Preferably, the temperature of the light-avoiding reaction in step (2) is 20~30℃ and the time is 20~30h.

[0031] Preferably, the polyphenol in step (3) includes tannic acid, and the metal ion includes ytterbium ion.

[0032] Preferably, the concentration of tannic acid is 1.5~2.5 mg / mL, and the concentration of ytterbium ions is 1.5~2.5 mmol / L.

[0033] Preferably, the pH value of the second buffer solution in step (3) is 5.5~6.5.

[0034] Preferably, the temperature for the oscillation incubation in step (3) is 25~35℃ and the time is 20~30h.

[0035] Thirdly, the present invention provides an application of the multifunctional biomedical coating material as described in the first aspect, specifically for manufacturing at least one of orthopedic implants, dental implants, interventional catheters, medical textiles, or antibacterial medical devices.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] (1) The present invention provides a polydopamine intermediate layer and a polyphenol-metal network composite layer on the surface of a medical substrate. The polydopamine can be firmly attached to the substrate surface, the metal ions can destroy the integrity of the bacterial cell membrane, and the polyphenols can inhibit bacterial metabolism. The three work together to achieve long-term antibacterial function. Furthermore, the covalent bonds and coordination bonds form a double network structure, which has less loss under physiological conditions and excellent durability. It is suitable for surface antibacterial and biocompatibility modification of various implantable / interventional devices, catheters, and medical textile materials.

[0038] (2) The present invention uses a two-step immersion method to construct a composite coating on the surface of a medical substrate. It does not require complex equipment, the preparation conditions are controllable, and it is conducive to large-scale industrial application. Attached Figure Description

[0039] Figure 1 The results are the chemical composition characterization results of the coating materials obtained in Example 1; (a) are the infrared experimental results of PDA, PDA / TA, and PDA / TA-Yb; (b) are the XPS experimental results of Ti, Ti / PDA, and Ti / PDA / TA-Yb; (c) are the C 1s high-resolution XPS spectra and peak fitting results of the PDA coating; (d) are the C 1s high-resolution XPS spectra and peak fitting results of the PDA / TA-Yb coating; (e) are the N 1s high-resolution XPS spectra and peak fitting results of the PDA coating; and (f) are the N 1s high-resolution XPS spectra and peak fitting results of the PDA / TA-Yb coating.

[0040] Figure 2 These are the scanning electron microscope (SEM) experimental results of the materials obtained in Examples 1-3 and Comparative Examples 1-3.

[0041] Figure 3 These are the atomic force microscopy (AFM) experimental results of the materials obtained in Examples 1-3 and Comparative Examples 1-3.

[0042] Figure 4 The results are the surface performance characterization results of the materials obtained in Examples 1-3 and Comparative Examples 1-3; where (a) is the surface roughness of the sample; (b) is the contact angle test diagram of the sample; (c) is the contact angle test result of the sample; and (d) is the coating thickness test result of the sample.

[0043] Figure 5The results are the 24-hour antibacterial test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3; among them, (a) is an optical photograph of the colony formation of Escherichia coli and Staphylococcus aureus after co-culturing with each material for 24 hours; (b) is the quantitative colony count of Escherichia coli on the surface of different materials; (c) is the quantitative colony count of Staphylococcus aureus on the surface of different materials.

[0044] Figure 6 These are the 7D antibacterial test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3; where (a) is the result of changing 1.0 × 10⁻⁶ ppm of the antibacterial agent daily for 7 consecutive days. 6 (a) The relative bacterial count of Escherichia coli on different material surfaces under continuous bacterial challenge conditions with CFU / mL fresh bacterial suspension; (b) The relative bacterial count of Staphylococcus aureus on different material surfaces under the same continuous bacterial challenge conditions.

[0045] Figure 7 The results are the cytotoxicity test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3; (a) is the fluorescence image of live / dead cells stained with Calcein-AM / PI after L929 mouse fibroblasts were co-cultured with each material for 24 h; (b) is the fluorescence image of live / dead cells stained with Calcein-AM / PI after L929 mouse fibroblasts were co-cultured with each material for 72 h; (c) is the quantitative result of cell viability of L929 mouse fibroblasts after co-cultured with each material for 24 h as determined by CCK-8 assay; (d) is the quantitative result of cell viability of L929 mouse fibroblasts after co-cultured with each material for 72 h as determined by CCK-8 assay. Detailed Implementation

[0046] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0047] One embodiment of the present invention provides a multifunctional biomedical coating material, comprising a medical substrate, a polydopamine (PDA) interlayer, and a polyphenol-metal network composite layer stacked together.

[0048] This invention provides a polydopamine intermediate layer and a polyphenol-metal network composite layer on the surface of a medical substrate. The polydopamine can firmly adhere to the substrate surface, the metal ions can disrupt the integrity of bacterial cell membranes, and the polyphenols can inhibit bacterial metabolism. The three work synergistically to achieve long-lasting antibacterial function. Furthermore, the covalent and coordination bonds form a double network structure, resulting in minimal loss under physiological conditions and excellent durability. This invention is suitable for surface antibacterial and biocompatibility modification of various implantable / interventional devices, catheters, and medical textile materials.

[0049] In some embodiments, the medical substrate is made of at least one of titanium (Ti), polyurethane (PU), or polyethylene terephthalate (PET).

[0050] This invention enables uniform film formation on the surface of medical substrates of different materials, effectively overcoming the limitation of traditional coatings using a single substrate.

[0051] In some embodiments, the polyphenol-metal network composite layer includes a tannic acid-ytterbium ion (TA-Yb) composite layer.

[0052] This invention specifically selects a tannic acid-ytterbium ion composite layer because tannic acid, as a natural polyphenol, possesses antibacterial, antioxidant, and metal coordination capabilities, while rare earth ytterbium ions (Yb...)... 3+ With a stable electronic structure, it can regulate osteogenic differentiation and inhibit inflammatory responses. Furthermore, it can form stable coordination structures with polyphenolic hydroxyl groups, thereby achieving controlled sustained release, making it an ideal alternative to traditional antibacterial metal ions. Moreover, compared to Ag⁺ and Cu²⁺, the Yb selected in this invention… 3+ It exhibits extremely low cytotoxicity, fully meeting the non-cytotoxic requirements for medical implants.

[0053] In some embodiments, the total thickness of the polydopamine interlayer and the polyphenol-metal network composite layer is 110.3~131.2 nm, for example, it can be 110.3 nm, 116.8 nm, 120.5 nm, 124.1 nm, 127.9 nm or 131.2 nm, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0054] In some embodiments, the water contact angle of the surface of the multifunctional biomedical coating material is 61° to 63°, for example, 61°, 61.4°, 61.9°, 62.3°, 62.7°, or 63°, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0055] In some embodiments, the thickness loss rate of the multifunctional biomedical coating material after immersion in phosphate-buffered saline (PBS) for 7 days is ≤8.1%, for example, it may be 0.2%, 1.5%, 3.1%, 4.8%, 6.5%, 7.3% or 8.1%, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0056] In some embodiments, the phosphate buffer solution comprises at least one of sodium chloride (NaCl), potassium chloride (KCl), disodium hydrogen phosphate (Na2HPO4), or potassium dihydrogen phosphate (KH2PO4).

[0057] In some embodiments, the pH of the phosphate buffer solution is 7.2 to 7.4, for example, 7.2, 7.23, 7.28, 7.31, 7.36, 7.39 or 7.4, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0058] In some embodiments, the 24-hour antibacterial rate of the multifunctional biomedical coating material against Escherichia coli and Staphylococcus aureus is 83.9% to 93.1%, for example, it can be 83.9%, 85.2%, 87.6%, 89.1%, 91.5%, 92.4% or 93.1%, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0059] In some embodiments, the multifunctional biomedical coating material exhibits an antibacterial rate of 80.1% to 92.4% during a continuous bacterial challenge of 7 days (7D), for example, 80.1%, 82.7%, 85.3%, 87.9%, 90.2%, 91.6%, or 92.4%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0060] In some embodiments, the cell viability of the multifunctional biomedical coating material co-cultured with L929 mouse fibroblasts for 7 days is ≥80%, for example, it can be 80%, 84.2%, 88.7%, 91.3%, 95.6%, 98.1% or 99.5%, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0061] One embodiment of the present invention also provides a method for preparing the multifunctional biomedical coating material described in any of the above embodiments, comprising the following steps:

[0062] (1) Pretreatment of the medical substrate;

[0063] (2) Prepare a first buffer solution containing dopamine hydrochloride, immerse the medical substrate obtained in step (1) in the first buffer solution for a light-protected reaction, remove the substrate, wash and dry it to obtain the modified substrate;

[0064] (3) Prepare a second buffer solution containing polyphenols and metal ions, immerse the modified substrate obtained in step (2) in the second buffer solution for shaking incubation, remove the substrate, clean and dry it to obtain the multifunctional biomedical coating material.

[0065] This invention employs a two-step immersion method to construct a composite coating on the surface of a medical substrate. It requires no complex equipment, and the preparation conditions are controllable, which is beneficial for large-scale industrial applications.

[0066] In some embodiments, the medical substrate in step (1) is made of titanium metal, and the pretreatment includes sandpaper polishing, ultrasonic cleaning and vacuum drying in sequence, specifically: polishing with 400#, 1000# and 2000# metallographic sandpaper, ultrasonic cleaning with acetone, anhydrous ethanol and deionized water for 15 min each, and vacuum drying at 45°C for 8 h.

[0067] In some embodiments, the medical substrate in step (1) is made of polyurethane, and the pretreatment includes sequential ultrasonic cleaning and vacuum drying, specifically: ultrasonic cleaning with isopropanol, anhydrous ethanol and deionized water for 15 min each, followed by vacuum drying at 35°C for 10 h.

[0068] In some embodiments, the medical substrate in step (1) is made of polyethylene terephthalate. The pretreatment includes soaking, ultrasonic cleaning and vacuum drying in sequence, specifically: soaking in ethanol / deionized water (v / v=1:1) for 30 min, ultrasonic cleaning in deionized water, acetone and anhydrous ethanol for 20 min each, and vacuum drying at 40°C for 6 h.

[0069] In some embodiments, the solute in the first buffer solution in step (2) includes dopamine hydrochloride and tris-hydroxymethylaminomethane hydrochloride (Tris-HCl).

[0070] In some embodiments, the concentration of dopamine hydrochloride is 1.5 to 2.5 mg / mL, for example, it can be 1.5 mg / mL, 1.62 mg / mL, 1.85 mg / mL, 2.07 mg / mL, 2.29 mg / mL, 2.41 mg / mL or 2.5 mg / mL, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0071] In some embodiments, the concentration of the tris(hydroxymethyl)aminomethane hydrochloride is 8 to 12 mmol / L, for example, it can be 8 mmol / L, 8.7 mmol / L, 9.5 mmol / L, 10.3 mmol / L, 11.1 mmol / L, 11.6 mmol / L or 12 mmol / L, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0072] In some embodiments, the pH value of the first buffer solution in step (2) is 8 to 9, for example, it can be 8, 8.12, 8.35, 8.51, 8.74, 8.86 or 9, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0073] In some embodiments, the temperature of the light-shielding reaction in step (2) is 20~30°C, for example, it can be 20°C, 21.6°C, 23.1°C, 25.5°C, 27.8°C, 29.2°C or 30°C, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0074] In some embodiments, the light-avoidance reaction time in step (2) is 20 to 30 hours, for example, 20 hours, 22.3 hours, 24.7 hours, 26.1 hours, 27.9 hours, 29.4 hours or 30 hours, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0075] In some embodiments, the polyphenol in step (3) includes tannic acid, and the metal ion includes ytterbium ion.

[0076] In some embodiments, the concentration of tannic acid is 1.5 to 2.5 mg / mL, for example, it may be 1.5 mg / mL, 1.68 mg / mL, 1.92 mg / mL, 2.11 mg / mL, 2.35 mg / mL, 2.44 mg / mL or 2.5 mg / mL, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0077] In some embodiments, the concentration of ytterbium ions is 1.5 to 2.5 mmol / L, for example, it can be 1.5 mmol / L, 1.64 mmol / L, 1.87 mmol / L, 2.03 mmol / L, 2.26 mmol / L, 2.41 mmol / L or 2.5 mmol / L, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0078] In some embodiments, the pH value of the second buffer solution in step (3) is 5.5 to 6.5, for example, it can be 5.5, 5.63, 5.81, 6.05, 6.27, 6.42 or 6.5, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0079] In some embodiments, the temperature for the oscillation incubation in step (3) is 25~35°C, for example, it can be 25°C, 26.4°C, 28.9°C, 30.2°C, 32.7°C, 34.1°C or 35°C, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0080] In some embodiments, the oscillation incubation time in step (3) is 20 to 30 hours, for example, it can be 20 hours, 21.5 hours, 23.8 hours, 25.2 hours, 27.6 hours, 28.9 hours or 30 hours, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0081] One embodiment of the present invention also provides an application of the multifunctional biomedical coating material described in any of the above embodiments, specifically for manufacturing at least one of orthopedic implants, dental implants, interventional catheters, medical textiles, or antibacterial medical devices.

[0082] The numerical range described in this invention includes not only the point values ​​listed above, but also any point values ​​within the numerical ranges not listed above. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific point values ​​included in the range.

[0083] Example 1

[0084] This embodiment provides a multifunctional biomedical coating material and its preparation method, specifically including the following steps:

[0085] (1) Select a 10mm×10mm×1mm metal titanium sheet as a medical substrate, polish it with 400#, 1000# and 2000# metallographic sandpaper in sequence, clean it with acetone, anhydrous ethanol and deionized water for 15min each, and vacuum dry it at 45℃ for 8h.

[0086] (2) Prepare a 10 mmol / L Tris-HCl buffer (pH=8.5), degas it under vacuum for 15 min; add dopamine hydrochloride to a concentration of 2 mg / mL, stir to dissolve, and obtain the first buffer; vertically immerse the titanium sheet in the buffer, let it stand at 25°C in the dark for 24 h, take it out and ultrasonically clean it with deionized water for 5 min, and vacuum dry it at 40°C for 6 h to obtain the PDA modified substrate;

[0087] (3) Prepare a 2 mg / mL tannic acid solution, add ytterbium nitrate hexahydrate, and control Yb. 3+ The final concentration was 2.0 mmol / L; then the pH of the solution was adjusted to 6.0 with 0.1 mol / L NaOH to obtain the second buffer solution; the modified substrate was vertically immersed in the buffer solution and incubated with shaking at 30℃ and 50 rpm for 24 h. After removal, it was thoroughly rinsed with deionized water 3 times and vacuum dried at 50℃ for 8 h to obtain the Ti / PDA / TA-Yb multifunctional biomedical coating material.

[0088] Example 2

[0089] This embodiment provides a multifunctional biomedical coating material and its preparation method. Except for replacing the medical substrate in step (1) with polyurethane of the same specification (polymerization degree of 1500), the other steps and conditions are the same as in Example 1, so they will not be repeated here.

[0090] The multifunctional biomedical coating material obtained in this embodiment is denoted as PU / PDA / TA-Yb.

[0091] Example 3

[0092] This embodiment provides a multifunctional biomedical coating material and its preparation method. Except for replacing the medical substrate in step (1) with polyethylene terephthalate (polymerization degree of 130) of the same specification, the other steps and conditions are the same as in Example 1, so they will not be repeated here.

[0093] The multifunctional biomedical coating material obtained in this embodiment is denoted as PET / PDA / TA-Yb.

[0094] Comparative Example 1

[0095] This comparative example directly uses a 10mm×10mm×1mm titanium sheet, denoted as bare Ti.

[0096] Comparative Example 2

[0097] This comparative example directly uses polyurethane with a specification of 10mm×10mm×1mm (degree of polymerization of 1500), denoted as barePU.

[0098] Comparative Example 3

[0099] This comparative example directly uses polyethylene terephthalate (degree of polymerization 130) with a specification of 10mm×10mm×1mm, denoted as bare PET.

[0100] Performance testing:

[0101] (1) Coating thickness: The coating thickness was measured using a spectroscopic ellipsometry (M-2000v, JA Woolliam, USA). The test method was in accordance with GB / T40272-2021 "Determination of film thickness by spectroscopic ellipsometry". Before the test, all samples were equilibrated for 24 hours at room temperature (25℃) and relative humidity of 50%. The test wavelength range was 380~1000nm, and the incident angle was set to 65°, 70°, and 75°. Five different locations were randomly selected for each sample for testing, and the average value was taken as the final coating thickness. The result is expressed as "mean ± standard deviation (SD)".

[0102] (2) Water contact angle: The water contact angle was measured using a contact angle meter (DSAHT1600, KRUSS GmbH, Germany). The test method was in accordance with GB / T30693-2014 "Determination of water contact angle of plastic films and sheets" and ISO15989:2004 "Measurement of water contact angle of plastic films and sheets". The test environment was controlled at room temperature of 25℃ and relative humidity of 50%. 2μL of ultrapure water (18.2MΩ・cm) was added to the sample surface using a micro-syringe. The contact angle value was recorded after the droplet stabilized for 3s. Three different locations were randomly selected for parallel testing of each sample. The average value was taken as the final water contact angle. The result is expressed as "mean ± standard deviation (SD)".

[0103] (3) Antibacterial properties: The colony forming unit (CFU) counting method was used for determination. The test method refers to GB / T21866-2008 "Determination of antibacterial properties and antibacterial effects of antibacterial coatings (films)" and ISO22196:2011 "Determination of antibacterial activity of plastics and other non-porous surfaces". The specific steps are as follows:

[0104] ① Preparation of bacterial suspension: Gram-negative Escherichia coli (E. coli, ATCC25922) and Gram-positive Staphylococcus aureus (S. aureus, ATCC29213) were inoculated into LB liquid medium and cultured at 37°C with shaking at 150 rpm for 12 h until the logarithmic growth phase was reached; the bacterial concentration was adjusted to 1.0 × 10⁻⁶ using sterile phosphate-buffered saline (PBS, pH=7.4). 6 CFU / mL (OD) 600 ≈0.1) Reserved.

[0105] ② Sample preparation: All samples (Examples 1-3, Comparative Examples 1-3) were sterilized by irradiation with 254nm ultraviolet light for 30 min and then aseptically transferred to 24-well plates.

[0106] ③ 24h antibacterial test: Add 400μL of the above bacterial suspension to each well, ensuring complete coverage of the sample surface; after incubation at 37℃ for 24h, gently wash the sample 3 times with sterile PBS to remove non-adhesive bacteria; transfer the sample to a centrifuge tube containing 4mL sterile PBS, vortex at 2000rpm for 5min to completely elute adhesive bacteria; perform 10-fold serial dilutions of the eluent, take 100μL of the appropriate dilution and spread it evenly on LB agar plates, incubate upside down at 37℃ for 18~24h, and then count the number of colonies.

[0107] ④ 7-day long-term antibacterial test: Under the same culture conditions, the old bacterial culture was completely aspirated and replaced with an equal volume of fresh 1.0×10⁻⁶ bacteria every 24 hours. 6 After a 7-day challenge with CFU / mL bacterial suspension, the same steps as the 24-hour antimicrobial test described above were followed for elution, dilution, plating, and colony counting.

[0108] The test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3 are detailed in Table 1 below.

[0109] Table 1

[0110]

[0111] In Table 1 above, antibacterial rate A refers to the antibacterial rate against Escherichia coli, and antibacterial rate B refers to the antibacterial rate against Staphylococcus aureus.

[0112] Taking the coating material obtained in Example 1 as an example, the infrared experimental results of PDA, PDA / TA, and PDA / TA-Yb are shown in [reference needed]. Figure 1 (a); XPS experimental results for Ti, Ti / PDA, and Ti / PDA / TA-Yb are shown in [reference needed]. Figure 1 (b)

[0113] The SEM experimental results of the materials obtained in Examples 1-3 and Comparative Examples 1-3 are shown in the figure. Figure 2 The AFM experimental results are shown below. Figure 3 .

[0114] The surface roughness, contact angle test diagrams, and contact angle test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3 are shown in the corresponding figures. Figure 4 (a)~ Figure 4 (c) The coating thickness test results of the materials obtained in Examples 1-3 are shown in [the table]. Figure 4 (d)

[0115] The 24-hour antibacterial test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3 are shown in the figure. Figure 5 The results of the 7D antibacterial experiment are shown in [link to experiment]. Figure 6 .

[0116] The cytotoxicity test results of the materials obtained in Examples 1-3 and Comparative Examples 1-3 are shown in the figure. Figure 7 .

[0117] Therefore, this invention provides a polydopamine intermediate layer and a polyphenol-metal network composite layer on the surface of a medical substrate. The polydopamine can firmly adhere to the substrate surface, the metal ions can disrupt the integrity of bacterial cell membranes, and the polyphenols can inhibit bacterial metabolism. The three work synergistically to achieve long-lasting antibacterial function. Furthermore, the covalent and coordination bonds form a double network structure, resulting in minimal loss under physiological conditions and excellent durability. This invention is suitable for surface antibacterial and biocompatibility modification of various implantable / interventional devices, catheters, and medical textile materials.

[0118] Furthermore, this invention employs a two-step immersion method to construct a composite coating on the surface of a medical substrate, requiring no complex equipment and allowing for controllable preparation conditions, which is beneficial for large-scale industrial applications.

[0119] The above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A multifunctional biomedical coating material, characterized by, The multifunctional biomedical coating material comprises a medical substrate, a polydopamine intermediate layer, and a polyphenol-metal network composite layer stacked together.

2. The multifunctional biomaterial coating according to claim 1, wherein The material of the medical substrate includes at least one of titanium, polyurethane, or polyethylene terephthalate. And / or, the polyphenol-metal network composite layer includes a tannic acid-ytterbium ion composite layer.

3. The multifunctional biomaterial coating material according to claim 1 or 2, wherein, The total thickness of the polydopamine interlayer and the polyphenol-metal network composite layer is 110.3~131.2 nm; And / or, the water contact angle of the surface of the multifunctional biomedical coating material is 61°~63°.

4. The multifunctional biomaterial coating material according to claim 1 or 2, wherein, The thickness loss rate of the aforementioned multifunctional biomedical coating material after immersion in phosphate buffer for 7 days is ≤8.1%. The pH value of the phosphate buffer solution is 7.2~7.

4.

5. The multifunctional biomedical coating material according to claim 1 or 2, characterized in that, The multifunctional biomedical coating material exhibits an antibacterial rate of 83.9%~93.1% against Escherichia coli and Staphylococcus aureus within 24 hours. And / or, the multifunctional biomedical coating material exhibits an antibacterial rate of 80.1% to 92.4% after 7 days of continuous bacterial challenge; And / or, the cell survival rate of the multifunctional biomedical coating material co-cultured with L929 mouse fibroblasts for 7 days is ≥80%.

6. A method for preparing the multifunctional biomaterial coating material according to any one of claims 1 to 5, characterized by, The preparation method includes the following steps: (1) Pretreatment of the medical substrate; (2) Prepare a first buffer solution containing dopamine hydrochloride, immerse the medical substrate obtained in step (1) in the first buffer solution for a light-protected reaction, remove the substrate, wash and dry it to obtain the modified substrate; (3) Prepare a second buffer solution containing polyphenols and metal ions, immerse the modified substrate obtained in step (2) in the second buffer solution for shaking incubation, remove the substrate, clean and dry it to obtain the multifunctional biomedical coating material.

7. The method for preparing the multifunctional biomedical coating material according to claim 6, characterized in that, The medical substrate in step (1) is made of titanium metal, and the pretreatment includes sandpaper polishing, ultrasonic cleaning and vacuum drying in sequence; Alternatively, the medical substrate in step (1) is made of polyurethane, and the pretreatment includes sequential ultrasonic cleaning and vacuum drying. Alternatively, the medical substrate in step (1) is made of polyethylene terephthalate, and the pretreatment includes soaking, ultrasonic cleaning and vacuum drying performed sequentially.

8. The method for preparing the multifunctional biomedical coating material according to claim 6, characterized in that, Step (2) The solutes in the first buffer solution include dopamine hydrochloride and tris(hydroxymethyl)aminomethane hydrochloride; Wherein, the concentration of dopamine hydrochloride is 1.5~2.5 mg / mL, and the concentration of tris(hydroxymethyl)aminomethane hydrochloride is 8~12 mmol / L; And / or, in step (2), the pH value of the first buffer solution is 8~9; And / or, the temperature of the light-protected reaction in step (2) is 20~30℃ and the time is 20~30h.

9. The method for preparing the multifunctional biomedical coating material according to claim 6 or 8, characterized in that, The polyphenols in step (3) include tannic acid, and the metal ions include ytterbium ions; The concentration of tannic acid is 1.5~2.5 mg / mL, and the concentration of ytterbium ions is 1.5~2.5 mmol / L. And / or, in step (3), the pH of the second buffer solution is 5.5 to 6.5; And / or, the temperature of the oscillation incubation in step (3) is 25~35℃ and the time is 20~30h.

10. Use of the multifunctional biomaterial coating according to any one of claims 1 to 5, characterized in that, The multifunctional biomedical coating material is used to manufacture at least one of orthopedic implants, dental implants, interventional catheters, medical textiles, or antibacterial medical devices.

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