A medical implant with a multifunctional coating and a method for producing the same

Abstract

This invention belongs to the field of surface modification technology for medical materials, specifically relating to a medical implant with a multifunctional coating and its preparation method. The multifunctional coating comprises, from bottom to top, a SiO2 transition layer, an antibacterial layer, and a superhydrophilic layer. The preparation method involves plasma cleaning of the implant substrate under a protective gas atmosphere; depositing a SiO2 transition layer onto the cleaned implant substrate using a vacuum evaporation process; applying an antibacterial material to the surface of the implant substrate with the SiO2 transition layer to form an antibacterial layer; applying a superhydrophilic material to the implant substrate with the antibacterial layer to form a superhydrophilic layer; and finally, low-temperature curing to obtain the medical implant with the multifunctional coating. This invention solves the technical problems of existing medical implant surface coatings, such as an imbalance between antibacterial properties and biocompatibility, uncontrolled release of heavy metal ions, poor adhesion, and insufficient durability under body fluid environments and disinfection processes.

Description

Technical Field

[0001] This invention belongs to the field of surface modification technology for medical materials, specifically relating to a medical implant with a multifunctional coating and its preparation method. Background Technology

[0002] In recent years, medical implants and implantable devices have become increasingly widely used in clinical practice. At the same time, post-implantation infection is one of the major risks associated with implants. During the healing process from implantation to the surrounding wound, the implant surface and the spaces between the implant and surrounding tissues are easily invaded by bacteria. If the implant surface lacks sufficient antibacterial properties, bacteria can easily and irreversibly adhere to the implant surface and rapidly secrete a highly resistant biofilm (mainly composed of fibrin, polysaccharide matrix, etc.). To address implant infection, antibiotics are often used clinically for prevention and treatment. However, antibiotic use has drawbacks such as bacterial resistance and reduced efficacy due to the presence of biofilms. Therefore, against this backdrop, surface modification of medical implants, endowing the implant surface with a multifunctional coating that possesses good biocompatibility and long-lasting sustained-release antibacterial and anti-inflammatory properties, is of significant clinical importance for the clinical application of implants.

[0003] Existing technologies, such as Chinese Patent Publication No. CN115282342A, provide a medical implant coating and its preparation method, as well as a medical implant. This method involves rapidly reacting tannic acid and silver nitrate solution through a layer-by-layer self-assembly process to generate a tannic acid-silver nanoparticle coating based on a metal-polyphenol system. Subsequently, a malic acid-1,8-octanediol polymer obtained from the reaction of 1,8-octanediol and L-malic acid is encapsulated on the outer layer of the tannic acid-silver nanoparticles and then subjected to thermal crosslinking. The phenolic hydroxyl groups of tannic acid crosslink with the carboxyl groups of polymalic acid, further stabilizing the silver nanoparticles within the composite coating.

[0004] However, the existing technology still has the following technical bottlenecks: On the one hand, traditional antibacterial coatings often use high content of heavy metals such as Ag and Cu as dopants, the release rate of metal ions is uncontrollable, easily produces cytotoxicity, has poor biocompatibility, and the coating thickness is too large, which can easily cause immune rejection; on the other hand, hydrophilic coatings only focus on biocompatibility and lack antibacterial function, and use conventional coating processes, which have weak adhesion to medical substrates, and are easy to fall off after long-term immersion in human body fluids and repeated disinfection, resulting in insufficient durability. Summary of the Invention

[0005] To address the technical problems of existing medical implant surface coatings, such as imbalance between antibacterial properties and biocompatibility, uncontrolled release of heavy metal ions, poor adhesion, and insufficient durability under body fluid environments and disinfection processes, this invention provides a medical implant with a multifunctional coating and its preparation method. By adopting an integrated process of plasma cleaning, vacuum SiO2 coating, antibacterial layer coating, SPC layer dip coating, and low-temperature curing, the above problems can be effectively solved.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] A method for preparing a medical implant with a multifunctional coating includes the following steps:

[0008] Step 1: Placing the implant substrate under a protective gas atmosphere for plasma cleaning;

[0009] Step 2: Deposit a SiO2 transition layer onto the cleaned implant substrate using a vacuum evaporation process;

[0010] Step 3: Apply an antibacterial material to the surface of the implant substrate coated with the SiO2 transition layer to form an antibacterial layer;

[0011] Step 4: After coating the antibacterial layer, the implant substrate is dipped in a superhydrophilic material to form a superhydrophilic layer;

[0012] Step 5: After the superhydrophilic layer is coated, it is cured at low temperature to obtain a medical implant with a multifunctional coating.

[0013] Furthermore, in step one, the protective gas is an argon / oxygen mixture with a volume ratio of 4:1, and the total flow rate of the protective gas is 12-18 sccm; the plasma cleaning power is 100-150 W, the cleaning time is 4-6 min, and the cleaning vacuum degree is 0.08-0.12 Pa. In this invention, plasma cleaning can thoroughly remove the oxide layer, oil, and fine impurity particles from the substrate surface, while also improving the surface activity and roughness of the substrate, creating conditions for the subsequent application of a multifunctional layer.

[0014] Furthermore, the vacuum evaporation process parameters in step two are: background vacuum degree ≤ 5×10⁻³Pa, deposition temperature 180-200℃, and evaporation rate 0.1-0.2nm / s.

[0015] Furthermore, step three, the dip coating, includes the following steps: transferring the implant substrate to the coating station, controlling the dip coating speed to 3-5 mm / s to dip in the antibacterial material, allowing it to air dry naturally for 5-10 minutes after dip coating, and then curing it at 180-200℃ for 10-15 minutes. During the curing process, oxygen is introduced at a flow rate of 5-8 sccm. In this invention, introducing oxygen during the curing process can control the Ag release rate to 0.1-0.3 μg / (cm²·d), making it compliant with the ISO 10993-5 biocompatibility standard.

[0016] Furthermore, in step four, the viscosity of the superhydrophilic material is 5-8 mPa·s, and the dipping speed is 1-2 mm / s. Controlling the viscosity of the superhydrophilic material in this invention ensures a uniform coating.

[0017] Furthermore, the low-temperature curing in step five includes the following steps: naturally air-drying the implant substrate in an ultra-clean environment with a temperature of 25±5℃ and a humidity of 40-60% for 5-10 minutes, and then placing it in a constant temperature curing environment of 80-100℃ for 3-5 minutes.

[0018] The present invention also provides a medical implant with a multifunctional coating, wherein the medical implant is any one of a medical titanium alloy substrate, a medical stainless steel substrate, or a medical cobalt chromium alloy substrate, and the multifunctional coating comprises a SiO2 transition layer, an antibacterial layer, and a superhydrophilic layer arranged sequentially from bottom to top.

[0019] Furthermore, the SiO2 transition layer has a thickness of 8-12 nm. In this invention, the SiO2 transition layer can enhance the interfacial bonding between the substrate and the subsequent antibacterial layer. At the same time, SiO2 material has excellent biocompatibility and is a widely used biomaterial, providing a guarantee for the safe use of subsequent products.

[0020] Furthermore, the antibacterial layer has a thickness of 40-60 nm, and the antibacterial material used in the antibacterial layer includes nano-Ag-doped hydroxyapatite liquid, wherein the nano-Ag doping amount in the nano-Ag-doped hydroxyapatite liquid is 3-5 wt%, and the nano-Ag particle size is 20-50 nm.

[0021] Furthermore, the thickness of the superhydrophilic layer is 2-4 nm, and the content of hydroxyl and amino groups on the surface of the superhydrophilic material used in the superhydrophilic layer is ≥30%.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. This invention provides a medical implant with a multifunctional coating that possesses excellent antibacterial properties while ensuring bioactivity. The antibacterial layer exhibits an antibacterial rate of ≥99.9% against *Escherichia coli* and *Staphylococcus aureus*, while the Ag ion release rate in the antibacterial layer is 0.1-0.3 μg / (cm²·d), continuously releasing for over 30 days, meeting medical standards. The entire preparation process is performed at low temperatures, fully preserving the activity of both antibacterial and biocompatible components. The superhydrophilic layer on the surface of the antibacterial layer is only 2-4 nm thick, exhibiting no cytotoxicity and avoiding immune responses.

[0024] 2. In this invention, a SiO2 transition layer is provided between the implant substrate and the antibacterial layer. This SiO2 transition layer creates a strong interface, ensuring adhesion between the antibacterial layer and the substrate reaches ASTM level 5B. This gives the entire multifunctional coating excellent adhesion and stability. In a 90-day immersion test simulating human body fluids, there was no peeling or cracking. After 500 wipes with 75% alcohol and 20 cycles of high-pressure steam sterilization at 121°C, the antibacterial and hydrophilic properties showed no decrease.

[0025] 3. The multifunctional coated medical implant of this invention possesses superhydrophilicity and biocompatibility. When placed in the human body, the membrane water contact angle is <5°, plasma protein adsorption is reduced by more than 60%, human osteoblast adhesion rate is increased by 50%, and proliferation rate is increased by 40%. The 2-4nm thickness does not affect the adhesion and integration of the implant with bone tissue. Detailed Implementation

[0026] To further illustrate the technical means and effects adopted by the present invention to achieve the intended purpose, the following detailed description of specific embodiments based on the present invention is provided in conjunction with preferred embodiments.

[0027] Example 1

[0028] This embodiment provides a method for preparing a medical implant with a multifunctional coating, including the following steps:

[0029] Step 1: Placing the implant substrate under a protective gas atmosphere for plasma cleaning;

[0030] Specifically, this invention uses Ti-6Al-4V titanium alloy as the implant substrate, and the implant functions as an artificial joint. The substrate is placed in a plasma cleaning agent and cleaned for 5 minutes under a vacuum of 0.1 Pa and a power of 150W. During the cleaning process, an argon / oxygen mixture with a volume ratio of 4:1 is introduced. This step can thoroughly remove oxide scale, oil, and fine particles from the substrate surface, and also improve surface activity and roughness, laying a solid foundation for the subsequent adhesion of the SiO2 transition layer.

[0031] Step 2: Deposit a SiO2 transition layer onto the cleaned implant substrate using a vacuum evaporation process;

[0032] Specifically, after plasma cleaning, there is no need to transfer the substrate; the SiO2 transition layer is directly deposited within the same vacuum chamber. The SiO2 transition layer is prepared using a vacuum evaporation process, with the vacuum level ≤5×10⁻³Pa, deposition temperature controlled at 200℃, and evaporation rate at 0.1nm / s. Real-time monitoring using a crystal thickness gauge ensures precise preparation of the SiO2 transition layer. This layer strengthens the interfacial bonding between the substrate and the subsequent antibacterial layer, while SiO2 material exhibits excellent biocompatibility.

[0033] Step 3: Apply an antibacterial material to the surface of the implant substrate coated with the SiO2 transition layer to form an antibacterial layer;

[0034] Specifically, after the SiO2 transition layer is prepared, the substrate is transferred to the coating station, where an antibacterial layer is coated using a dip-coating method. In this embodiment, the antibacterial material is nano-Ag-doped hydroxyapatite (HA) liquid, with a nano-Ag doping amount of 3-5wt% and a nano-Ag particle size of 20-50nm. The dip-coating speed is 4mm / s, and the coating thickness is controlled. After coating, the antibacterial material is allowed to air dry for 5 minutes, then placed in an oven for low-temperature curing at 200℃ for 10 minutes. A trace amount of oxygen at a flow rate of 6sccm is introduced to regulate the Ag release rate.

[0035] Step 4: After coating the antibacterial layer, the implant substrate is dipped in a superhydrophilic material to form a superhydrophilic layer;

[0036] Specifically, a commercially available superhydrophilic liquid material is used. The superhydrophilic material used in the superhydrophilic layer has a hydroxyl and amino content of ≥30% on its surface and is coated onto the surface of the antibacterial layer using a high-precision dip-coating method. During the coating process, the viscosity of the superhydrophilic material is controlled at 5-8 mPa·s, the dip-coating speed is 2 mm / s, and the thickness of the superhydrophilic layer is precisely controlled to ensure that the coating is ultra-thin, uniform, free of pores and defects, and completely covers the surface of the antibacterial layer.

[0037] Step 5: After the superhydrophilic layer is coated, it is cured at low temperature to obtain a medical implant with a multifunctional coating.

[0038] Specifically, medical implants that are protected by low-temperature curing after the superhydrophilic coating are bioactive. The implant substrate is first air-dried in an ultra-clean environment at 25±5℃ and 40-60% humidity for 5-10 minutes, then placed in a constant temperature curing environment at 80-100℃ for 3-5 minutes to obtain a medical implant with a multifunctional coating. This process allows for rapid shaping without damaging the antibacterial components or the material's hydrophilic activity.

[0039] This embodiment obtains a medical implant with a multifunctional coating through the above preparation method. The multifunctional coating includes a SiO2 transition layer, an antibacterial layer and a superhydrophilic layer arranged sequentially from bottom to top, wherein the SiO2 transition layer has a thickness of 10 nm, the antibacterial layer has a thickness of 50 nm and the superhydrophilic layer has a thickness of 2 nm.

[0040] The medical implant with the aforementioned multifunctional coating underwent performance testing. The results are as follows: water contact angle 3°, antibacterial rate against Staphylococcus aureus 99.95%, cell viability 95%, and after 20 cycles of high-pressure steam sterilization at 121°C, the coating did not peel off, and the antibacterial rate remained at 99.8%. The antibacterial rate test was conducted according to GB / T 21866-2008 standard, and the cell viability test was conducted according to ISO 10993-5 standard.

[0041] Example 2

[0042] The difference between this embodiment and Embodiment 1 is that the implant substrate is 316L medical-grade stainless steel, used for cardiovascular stents. The resulting medical implant has a multifunctional coating with a SiO2 transition layer thickness of 10 nm, an antibacterial layer thickness of 40 nm, and a superhydrophilic layer thickness of 3 nm.

[0043] The medical implant with the aforementioned multifunctional coating underwent performance testing. The results are as follows: water contact angle 4°, antibacterial rate against Escherichia coli 99.9%, cell viability 93%. After immersion in simulated body fluid for 90 days, the coating remained intact, with an Ag ion sustained-release rate of 0.2 μg / (cm²·d), conforming to ISO 10993-5 standard. The antibacterial rate test was conducted according to GB / T 21866-2008 standard, and the cell viability test was conducted according to ISO 10993-5 standard.

[0044] Example 3

[0045] The difference between this embodiment and Embodiment 1 is that the implant substrate is a cobalt-chromium alloy, used for endoscopic instruments. The resulting medical implant has a multifunctional coating with a SiO2 transition layer thickness of 10 nm, an antibacterial layer thickness of 60 nm, and a superhydrophilic layer thickness of 4 nm.

[0046] The above-mentioned medical implants with multifunctional coatings were subjected to performance tests, and the results are as follows: a water contact angle of 5°, an antibacterial rate of 99.92% against Staphylococcus aureus, and after 500 wipes with 75% alcohol, the contact angle remained at 6°, meeting the requirements for repeated disinfection and use. The antibacterial rate test was conducted according to GB / T 21866-2008 standard.

[0047] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for preparing a medical implant with a multifunctional coating, characterized in that: Includes the following steps: Step 1: Placing the implant substrate under a protective gas atmosphere for plasma cleaning; Step 2: Deposit a SiO2 transition layer onto the cleaned implant substrate using a vacuum evaporation process; Step 3: Apply an antibacterial material to the surface of the implant substrate coated with the SiO2 transition layer to form an antibacterial layer; Step 4: After coating the antibacterial layer, the implant substrate is dipped in a superhydrophilic material to form a superhydrophilic layer; Step 5: After the superhydrophilic layer is coated, it is cured at low temperature to obtain a medical implant with a multifunctional coating.

2. The method for preparing a medical implant with a multifunctional coating according to claim 1, characterized in that: In step one, the protective gas is an argon / oxygen mixture with a volume ratio of 4:1, and the total flow rate of the protective gas is 12-18 sccm; the plasma cleaning power is 100-150w, the cleaning time is 4-6min, and the cleaning vacuum degree is 0.08-0.12Pa.

3. The method for preparing a medical implant with a multifunctional coating according to claim 1, characterized in that: The vacuum evaporation process parameters in step two are: background vacuum degree ≤ 5×10⁻³Pa, deposition temperature 180-200℃, and evaporation rate 0.1-0.2nm / s.

4. The method for preparing a medical implant with a multifunctional coating according to claim 1, characterized in that: Step three includes the following steps: transferring the implant substrate to the coating station, controlling the dipping speed to 3-5 mm / s to dip in the antibacterial material, and after dipping, allowing it to air dry naturally for 5-10 minutes before transferring it to 180-200℃ for curing for 10-15 minutes. During the curing process, oxygen is introduced at a flow rate of 5-8 sccm.

5. The method for preparing a medical implant with a multifunctional coating according to claim 1, characterized in that: In step four, the viscosity of the superhydrophilic material is 5-8 mPa·s, and the dipping speed is 1-2 mm / s. Controlling the viscosity of the superhydrophilic material in this invention ensures a uniform coating.

6. The method for preparing a medical implant with a multifunctional coating according to claim 1, characterized in that: The low-temperature curing in step five includes the following steps: naturally air-drying the implant substrate in an ultra-clean environment with a temperature of 25±5℃ and a humidity of 40-60% for 5-10 minutes, and then placing it in a constant temperature curing environment of 80-100℃ for 3-5 minutes.

7. A medical implant with a multifunctional coating prepared by the preparation method according to any one of claims 1-6, characterized in that: The medical implant is any one of medical titanium alloy substrate, medical stainless steel substrate, and medical cobalt chromium alloy substrate, and the multifunctional coating includes a SiO2 transition layer, an antibacterial layer and a superhydrophilic layer arranged from bottom to top.

8. The method for preparing a medical implant with a multifunctional coating according to claim 7, characterized in that: The thickness of the SiO2 transition layer is 8-12 nm.

9. The method for preparing a medical implant with a multifunctional coating according to claim 7, characterized in that: The antibacterial layer has a thickness of 40-60 nm, and the antibacterial material used in the antibacterial layer is nano-Ag-doped hydroxyapatite liquid. The amount of nano-Ag doping in the nano-Ag-doped hydroxyapatite liquid is 3-5 wt%, and the nano-Ag particle size is 20-50 nm.

10. The method for preparing a medical implant with a multifunctional coating according to claim 7, characterized in that: The thickness of the superhydrophilic layer is 2-4 nm, and the content of hydroxyl and amino groups on the surface of the superhydrophilic material used in the superhydrophilic layer is ≥30%.