A high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function and its preparation method

Abstract

The present invention discloses a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function and a preparation method thereof. The method comprises: ① using an anodic oxidation process to introduce a primary titanium nanotube (TNT) array structure on the surface of a titanium / titanium alloy substrate; ② combining a vacuum electroplating process to cleverly break the surface tension limitation, and efficiently introduce metal antibacterial components such as copper and silver into the TNT to form a secondary inlaid interlocking composite coating structure; ③ removing the metal coating that exceeds the height of the TNT array through free abrasive processing, and achieving polishing of the product surface; ④ after air flow flushing, multiple cleanings, packaging and irradiation sterilization, the desired high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function is obtained. The above-mentioned coating exhibits excellent bonding strength and wear resistance thanks to the protection of the TNT array structure; at the same time, the metal coating can exert long-lasting and efficient antibacterial properties. The product can be used for the prevention and treatment of postoperative infections in orthopedics and dentistry.

Description

Technical Field

[0001] The present invention relates to the technical field of preparation of medical devices, and in particular to a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function and a preparation method thereof. Background Art

[0002] Postoperative infection after implantation has long been a significant problem for clinicians and patients. Studies show that the overall incidence of infection after orthopedic fracture surgery ranges from 0.4% to 16%, with infection rates of approximately 1.5% after open fractures and 1.2% to 2.2% after knee and hip replacements, with mortality rates ranging from 2.7% to 18%. The infection rate after pelvic and tibial tumor reconstruction surgery is as high as 15% to 43%. Furthermore, with the development of industries like transportation and construction, and the aging population, the number of surgical procedures is expected to increase annually, indirectly leading to a rise in the number of infections. Therefore, infection prevention and control is urgent.

[0003] In recent years, antimicrobial coating technology has gradually gained favor among researchers and physicians due to its convenience and high efficiency. However, despite the continuous development of antimicrobial coating technology and the gradual development and promotion of various antimicrobial coating products, problems still exist in the bonding strength between the coating and the substrate, the coating's scratch resistance, and the antimicrobial duration, necessitating an urgent technological upgrade.

[0004] Therefore, to address the above problems, the present invention introduces a primary TNT (titanium nanotube) array structure on the surface of titanium / titanium alloy materials through anodizing technology. Simultaneously, vacuum plating technology is used to overcome the surface tension problem of the TNT tube mouth, achieving the efficient introduction of a metal antibacterial coating such as silver and copper within the TNT array. The coating and the TNT array form a secondary inlaid interlocking composite coating structure, resulting in a high-efficiency vacuum-loaded silver bone implant device with high bonding strength and long-lasting antibacterial properties. Leveraging the properties of TNT, the device is endowed with high coating bonding strength and high wear resistance, while achieving long-term anti-infection. Summary of the Invention

[0005] The purpose of the present invention is to address the deficiencies in the prior art and provide a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function and a preparation method thereof; the implant device is composed of metal antibacterial components such as titanium / titanium alloy, silver / copper, and is manufactured by combining processes such as anodizing, vacuum electroplating, free abrasive processing, multiple cleanings and airflow flushing, and has the advantages of high bonding strength and long-lasting antibacterial function.

[0006] A method for preparing a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function comprises the following steps:

[0007] 1) Mechanically polishing the titanium / titanium alloy material, and ultrasonically cleaning the material using acetone, ethanol, and deionized water in sequence; anodizing the sample using an anodizing device to form a primary TNT array structure on its surface;

[0008] 2) The anodized titanium / titanium alloy material is placed in a vacuum furnace for vacuum treatment and maintained under ultra-high vacuum conditions. Antibacterial metal materials such as silver and copper are in situ injected into the TNT array using a vacuum electroplating process to form a secondary inlaid interlocking composite coating structure;

[0009] 3) subjecting the sample to free abrasive processing to remove the antibacterial metal material exceeding the height of the TNT array and to polish the sample surface;

[0010] 4) The samples are subjected to multiple cleaning, air flow flushing, packaging and irradiation sterilization to obtain the desired high-efficiency vacuum-loaded silver bone implant device with high bonding strength and long-lasting antibacterial function.

[0011] Furthermore, the mechanical polishing used in step 1) includes rough polishing, semi-finishing polishing, and finishing polishing in sequence, so that the substrate roughness is less than 0.5 microns; the ultrasonic cleaning time of acetone, ethanol, and deionized water is 10 minutes, and the ultrasonic power is 60-80W. The anodizing solution formula is: ammonium fluoride (1-2wt%), calcium dihydrogen phosphate (0.5-1wt%), Sr(OH)2·8H2O (0.1-0.25wt%) dissolved in 50 (v / v)% glycerol aqueous solution; the anode is the sample, the cathode is a titanium alloy, the distance between the anode and the cathode is 20-30 cm, the voltage is 40-60V, the reaction time is 1-3 hours, and the TNT pore size is 80-110nm;

[0012] Furthermore, the vacuuming condition in step 2) is vacuuming for 5-15 minutes, and the vacuum degree in the chamber is higher than 0.05 Pa; the vacuum plating process is one of physical vapor deposition, laser pulse deposition, vacuum sputtering coating, electron beam evaporation coating, etc., preferably physical vapor deposition, and the relevant process parameters of physical vapor deposition are: the target material is a silver target material or a copper target material with a purity greater than 99.99%, and the background vacuum reaches 5.5×10 -3 Pa, target power density is 1-5W / cm 2 , target current is 5-20A, and temperature is 400-500℃.

[0013] Furthermore, the process parameters of free abrasive processing in step 3) are as follows: the sample is fixed in the abrasive box, the depth is 1 / 3 of the position above the bottom of the abrasive box, the abrasive is one or more of Al2O3, Si3N4, and ZrO2, and the particle size is controlled to be 0.3-0.6um. During processing, the abrasive box revolves, and the sample rotates in the abrasive box. The revolution rate is 80-120r / min, the rotation rate is 40-60r / min, the processing time is 15-30min, and Ra is not greater than 0.1um; multiple cleaning is ultrasonic cleaning using ultrapure water, ethanol, and ultrapure water in sequence, the ultrasonic power is 60-80W, and the cleaning time is 15min / time; the gas used for air flow flushing is nitrogen, the air flow rate is 15-35m / s, and the time is 3-10min.

[0014] Furthermore, in step 4), multiple cleaning is carried out by ultrasonic cleaning with ultrapure water, ethanol, and ultrapure water in sequence, with an ultrasonic power of 60-80W and a cleaning time of 15 minutes per time; the gas used for air flow flushing is nitrogen, with an air flow rate of 15-35m / s and a time of 3-10 minutes. The packaging is vacuum packaging. The irradiation sterilization process is to use Co 60 Irradiation sterilization, irradiation dose 10-15kGy.

[0015] Compared with the prior art, the present invention has the following advantages:

[0016] 1) The present invention addresses the problems of low bonding strength between traditional antibacterial coatings and substrates, the coating's poor scratch resistance, and short antibacterial duration. Using titanium / titanium alloys, silver / copper antibacterial active components, and other raw materials, and employing a combination of processes including anodizing, vacuum plating, free abrasive processing, multiple cleanings, and airflow flushing, the present invention produces a high-efficiency vacuum-loaded silver bone implant with high bonding strength and long-lasting antibacterial function. This is an original invention of the present invention.

[0017] 2) The present invention cleverly combines anodization and vacuum plating techniques, creating a new application for an established process. First, anodization is used to introduce a primary TNT array structure onto the surface of a titanium / titanium alloy. Titanium / titanium alloys are inherently susceptible to oxidation reactions, forming an oxide layer. This creates a bottleneck in improving the bond strength between the metal antibacterial coating and the substrate. Therefore, the present invention reverses this process by directly performing the reverse anodization process. This not only addresses oxidation concerns but also creates a large number of drug-loading sites for future use. However, while TNTs have always been ideal drug-loading sites, the significant surface tension at the tube openings prevents efficient drug loading in TNTs using traditional solution electroplating techniques. Therefore, the present invention addresses this surface tension issue by further integrating vacuum plating technology. By leveraging the high vacuum conditions during vacuum plating to form the coating, the gas inside the TNTs is expelled, fundamentally and cleverly resolving the surface tension issue. Furthermore, the vacuum plating process and the silver (or copper) plating are integrated, requiring no additional steps to simultaneously achieve efficient loading of metallic antimicrobial active components, such as silver and copper, within the TNT tube, resulting in a single-element silver / copper antimicrobial coating (this coating is a single metal, significantly different from other nano-antimicrobial coatings). Furthermore, upon entering the TNT, the silver and copper metallic antimicrobial active components form a secondary interlocking composite coating structure with the TNT. This structure not only ensures a secure interlocking bond between the metallic antimicrobial components and the substrate, increasing the bonding strength between the coating and the substrate through physical and mechanical interlocking. Furthermore, the three-sided TNT wrapping creates a highly effective physical barrier, extending the release cycle and antimicrobial efficacy of the antimicrobial components. Furthermore, the TNT array also serves as a physical protective framework, ensuring that the softer metallic antimicrobial coating, such as silver and copper, is not damaged by friction and scratches during use. This TNT array framework, thanks to the high hardness of titanium / titanium alloy oxide, withstands mechanical wear and damage.

[0018] 3) The present invention constructs a controllable TNT array structure and introduces a secondary inlaid interlocking composite metal antibacterial coating structure into it. On the one hand, the metal coating can achieve the purpose of anti-infection through direct contact and continuous long-term release. On the other hand, since the TNT array structure covered by the metal antibacterial coating is exposed through free abrasive processing, the TNT structure has an osteogenesis effect. Therefore, this implant device has the dual effects of anti-infection and osteogenesis.

[0019] 4) The present invention innovatively uses free abrasive processing to reduce and polish instruments after vacuum plating. Free abrasive processing can perform surface treatment on various special-shaped materials. Medical instruments have different shapes, and even 3D-printed products. Therefore, free abrasive processing can solve the problem of instrument shape and effectively polish every corner of the instrument. At the same time, free abrasive processing removes the metal antibacterial coating on the surface that exceeds the height of the TNT, exposing the TNT to play the role of wear resistance and bone promotion. It also makes the coating bonding strength not entirely borne by the metal antibacterial coating, but transfers part of the bonding strength to the secondary inlaid interlocking composite structure of the TNT and the coating.

[0020] 5) The bone implant device of the present invention has the functions of high bonding strength, high biocompatibility, high wear resistance, and long-term antibacterial properties, and can address the problem of preventing and treating short-term / long-term postoperative infections of various orthopedic and dental implants. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a SEM image of a TNT array (corresponding to Example 1);

[0022] Figure 2 Photos of a TNT sample and a high-efficiency vacuum-loaded silver bone implant device sample with high bonding strength and long-lasting antibacterial function (the left side is the TNT sample of Comparative Example 2, and the right side is the vacuum-loaded silver bone implant device sample of Example 1);

[0023] Figure 3 The results of the coating bonding strength of the high-efficiency vacuum silver-loaded bone implant device sample with high bonding strength and long-lasting antibacterial function (corresponding to Example 1 and Example 1);

[0024] Figure 4 The ion release curve of a high-efficiency vacuum silver-loaded bone implant device sample (taking the silver coating as an example) with high binding strength and long-lasting antibacterial function (corresponding to Example 1); DETAILED DESCRIPTION

[0025] The technical solutions and effects of the present invention are further described below with reference to specific drawings and specific examples.

[0026] Comparative Example 1

[0027] 1) Mechanically polish the TC4 titanium alloy sample to a base roughness of less than 0.5 μm, and then ultrasonically clean the material using acetone, ethanol, and deionized water in sequence;

[0028] 2) The obtained TC4 titanium alloy sample was coated with a silver coating using physical vapor deposition technology, wherein the target material was a silver target with a purity greater than 99.99%, and the background vacuum reached 5.5×10 -3 Pa, target power density is 3W / cm 2, target current is 10A, temperature is 450℃;

[0029] 3) The samples were ultrasonically cleaned for 15 min using ultrapure water, ethanol, and ultrapure water, followed by cleaning using a 30 m / s nitrogen flow, and finally packaged and sterilized by irradiation.

[0030] The TC4 silver coating sample was obtained by the above process, and the silver coating bonding strength was 20.3 MPa (such as Figure 3 The silver coating was partially torn off during the bonding strength test. Live-dead cell fluorescence staining of the sample extract revealed a live cell ratio of 85.2%. An inhibition zone test revealed an inhibition zone diameter of 2.7±0.4cm. The sample was placed in 5ml of PBS solution, and after 30 days, the silver ion release was 34.38±5.24ug / ml. The sample was used in a rabbit femoral defect infection model, and HE staining revealed a mild local inflammatory reaction, less new bone formation, and Gram staining revealed a low local bacterial load.

[0031] Comparative Example 2

[0032] 1) Mechanically polishing the titanium / titanium alloy to a substrate roughness of less than 0.5 μm, followed by ultrasonic cleaning of the material using acetone, ethanol, and deionized water in sequence; anodizing the sample using an anodizing apparatus to form a primary TNT array structure on its surface, wherein the electrolyte formula is ammonium fluoride (1 wt%), calcium dihydrogen phosphate (1 wt%), and Sr(OH)2·8H2O (0.1 wt%) dissolved in 50 (v / v)% glycerol aqueous solution, with the sample as the anode and the titanium alloy as the cathode, the inter-electrode spacing is 20 cm, the voltage is 40 V, and the reaction time is 2 h;

[0033] 2) The anodized titanium / titanium alloy material was placed in a vacuum furnace and evacuated for 10 minutes until the vacuum in the chamber was higher than 0.05 Pa, and the pressure was maintained for 10 minutes. Then, silver was in situ injected into the TNT array using physical vapor deposition technology to form a two-level mosaic interlocking composite coating structure. The target material was a silver target with a purity greater than 99.99%, and the background vacuum reached 5.5×10 - 3 Pa, target power density is 3W / cm 2 , target current is 10A, temperature is 450℃;

[0034] 3) The silver-loaded bone implant device is obtained by subjecting the above sample to multiple cleaning, air flow flushing, packaging and irradiation sterilization.

[0035] Compared with Comparative Example 1, an anodizing step was added to form TNT nanotubes on the surface. The diameter of the TNT tubes on the surface of the sample obtained in this comparative example was 80-90 nm, and the bonding strength of the silver coating was 38.5 MPa. The sample extract was taken for live and dead cell fluorescence staining experiments, and the proportion of live cells was 88.6%. The inhibition zone experiment showed that the diameter of the inhibition zone was 2.5±0.6 cm. The sample was placed in 5 ml of PBS solution, and after 30 days, the silver ion release amount was 29.65±4.20 ug / ml. The sample was used in a rabbit femoral defect infection model. Compared with Comparative Example 1, HE staining showed that the local inflammatory reaction was milder, Masson trichrome staining showed more new bone formation, and Gram staining showed that the local bacterial amount was less.

[0036] Example 1

[0037] 1) The titanium / titanium alloy was mechanically polished to a substrate roughness of less than 0.5 μm, and then the material was ultrasonically cleaned using acetone, ethanol, and deionized water in sequence; the sample was anodized using an anodizing device to form a primary TNT array structure on its surface, wherein the electrolyte formula was ammonium fluoride (1 wt%), calcium dihydrogen phosphate (1 wt%), and Sr(OH)2·8H2O (0.1 wt%) dissolved in 50 (v / v)% glycerol aqueous solution, the anode was the sample, the cathode was the titanium alloy, the inter-electrode spacing was 20 cm, the voltage was 40 V, and the reaction time was 2 h; the SEM image of the TNT array is shown as follows Figure 1 As shown;

[0038] 2) The anodized titanium / titanium alloy material was placed in a vacuum furnace and evacuated for 10 minutes until the vacuum in the chamber was higher than 0.05 Pa, and the pressure was maintained for 10 minutes. Then, silver was in situ injected into the TNT array using physical vapor deposition technology to form a two-level mosaic interlocking composite coating structure. The target material was a silver target with a purity greater than 99.99%, and the background vacuum reached 5.5×10 - 3 Pa, target power density is 3W / cm 2 , target current is 10A, temperature is 450℃;

[0039] 3) The above samples were subjected to free abrasive processing, wherein the abrasive was Al2O3 with a particle size of 0.3-0.6 μm. During processing, the abrasive box was in revolution and the sample was in rotation inside the abrasive box at a revolution rate of 120 r / min and a rotation rate of 60 r / min. The processing time was 15 min, and Ra was not greater than 0.1 μm.

[0040] 4) The samples are subjected to multiple cleaning, air flow flushing, packaging and irradiation sterilization to obtain the desired high-efficiency vacuum-loaded silver bone implant device with high bonding strength and long-lasting antibacterial function.

[0041] Compared with Comparative Example 2, the free abrasive processing step was added. The diameter of the TNT tube on the sample surface obtained in this embodiment was 80-90 nm, and the bonding strength of the silver coating was 57.2 MPa (as shown in FIG. Figure 3 The sample was treated with the medium); the live and dead cell fluorescence staining experiment was carried out on the sample extract, and the live cell ratio was 95.3%; the inhibition zone experiment showed that the diameter of the inhibition zone was 2.0±0.3cm; the sample was placed in 5ml PBS solution, and the silver ion release after 30 days was 18.26±2.59ug / ml (such as Figure 4 ); The samples were used in a rabbit femoral defect infection model. Compared with Comparative Example 2, HE staining showed no significant difference in local inflammatory response, Masson trichrome staining showed more new bone formation, and Gram staining showed no significant difference in local bacterial count.

[0042] Example 2

[0043] 1) Mechanically polishing the titanium / titanium alloy to a substrate roughness of less than 0.5 μm, followed by ultrasonic cleaning of the material using acetone, ethanol, and deionized water in sequence; anodizing the sample using an anodizing apparatus to form a primary TNT array structure on its surface, wherein the electrolyte formula is ammonium fluoride (1 wt%), calcium dihydrogen phosphate (1 wt%), and Sr(OH)2·8H2O (0.1 wt%) dissolved in 50 (v / v)% glycerol aqueous solution, with the sample as the anode and the titanium alloy as the cathode, the inter-electrode spacing is 20 cm, the voltage is 460 V, and the reaction time is 3 h;

[0044] 2) The anodized titanium / titanium alloy material was placed in a vacuum furnace and evacuated for 10 minutes until the vacuum in the chamber was higher than 0.05 Pa, and the pressure was maintained for 10 minutes. Then, silver was in situ injected into the TNT array using physical vapor deposition technology to form a two-level mosaic interlocking composite coating structure. The target material was a silver target with a purity greater than 99.99%, and the background vacuum reached 5.5×10 - 3 Pa, target power density is 3W / cm 2 , target current is 10A, temperature is 450℃;

[0045] 3) The above samples were subjected to free abrasive processing, wherein the abrasive was Al2O3 with a particle size of 0.3-0.6 μm. During processing, the abrasive box was in revolution and the sample was in rotation inside the abrasive box at a revolution rate of 120 r / min and a rotation rate of 60 r / min. The processing time was 15 min, and Ra was not greater than 0.1 μm.

[0046] 4) The samples are subjected to multiple cleaning, air flow flushing, packaging and irradiation sterilization to obtain the desired high-efficiency vacuum-loaded silver bone implant device with high bonding strength and long-lasting antibacterial function.

[0047] Compared with Example 1, the anodic oxidation voltage and time were increased. The diameter of the TNT tube on the surface of the sample obtained in this example was 100-110 nm, and the bonding strength of the silver coating was 53.6 MPa. The sample extract was subjected to a live-dead cell fluorescence staining experiment, and the proportion of live cells was 92.1%. The inhibition zone experiment showed that the diameter of the inhibition zone was 2.2±0.5 cm. The sample was placed in 5 ml of PBS solution, and the silver ion release amount after 30 days was 21.68±3.14 ug / ml. The sample was used in a rabbit femoral defect infection model. Compared with Example 1, HE staining showed no significant difference in local inflammatory response, Masson trichrome staining showed less new bone formation, and Gram staining showed no significant difference in local bacterial count.

[0048] The foregoing description is merely a partial list of preferred embodiments of the present invention, intended only to facilitate understanding of the present invention and not to limit the present invention. It should be noted that variations and improvements are possible without departing from the spirit of the present invention, and all such variations and improvements fall within the scope of protection of the present invention.

Claims

1. A method for preparing a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function, characterized by: The following steps are involved: 1) Mechanically polish the titanium / titanium alloy material and ultrasonically clean it with acetone, ethanol, and deionized water in sequence; The sample is anodized using an anodizing device to form a primary TNT array structure on its surface; 2) The anodized titanium / titanium alloy material is placed in a vacuum furnace for vacuum treatment, and the pressure is maintained under ultra-high vacuum conditions. The antibacterial metal material is in situ poured into the TNT array using a vacuum plating process to form a secondary mosaic interlocking composite coating structure; the vacuum plating process is physical vapor deposition; The relevant process parameters are: the target material is a silver target with a purity greater than 99.99%, and the background vacuum reaches 5.5×10 -3 Pa, target power density is 1-5W / cm 2 , target current is 5-20A, temperature is 400-500℃; 3) Subjecting the obtained sample to free abrasive machining to remove the antibacterial metal material that exceeds the height of the TNT array and to polish the sample surface; the process parameters for free abrasive machining are as follows: the sample is fixed in an abrasive box at a depth of 1 / 3 from the bottom of the abrasive box, the abrasive is one or more of Al2O3, Si3N4, and ZrO2, and the particle size is controlled to be 0.3-0.6μm. During machining, the abrasive box revolves and the sample rotates in the abrasive box at a revolution rate of 80-120r / min and a rotation rate of 40-60r / min. The machining time is 15-30min, and the Ra is no greater than 0.1μm. 4) The obtained sample is subjected to multiple cleaning, air flow flushing, packaging and irradiation sterilization to obtain the required high-efficiency vacuum-loaded silver bone implant device with high bonding strength and long-lasting antibacterial function.

2. The method for preparing a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function according to claim 1, characterized in that: The mechanical polishing used in step 1) includes rough polishing, semi-finishing polishing and finishing polishing in sequence, so that the substrate roughness is less than 0.5 microns; the ultrasonic cleaning time of acetone, ethanol and deionized water is 10 minutes, and the ultrasonic power is 60-80W.

3. The method for preparing a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function according to claim 1, characterized in that: The solution formula for the anodizing process in step 1) is: a glycerol aqueous solution of 1-2wt% ammonium fluoride, 0.5-1wt% calcium dihydrogen phosphate, and 0.1-0.25wt% Sr(OH)2·8H2O, with a glycerol to water volume ratio of 1:1; the anode is the sample, the cathode is a titanium alloy, the distance between the anode and the cathode is 20-30cm, the voltage is 40-60V, the reaction time is 1-3h, and the TNT pore diameter is 80-110nm.

4. The method for preparing a high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function according to claim 1, characterized in that: In step 4), multiple cleaning is performed by ultrasonic cleaning with ultrapure water, ethanol, and ultrapure water in sequence, with an ultrasonic power of 60-80W and a cleaning time of 15 minutes per time; the gas used for air flow flushing is nitrogen, with an air flow rate of 15-35m / s and a time of 3-10 minutes; the packaging is vacuum packaging, and the irradiation sterilization process is Co 60 Irradiation sterilization, irradiation dose 10-15kGy.

5. A high-efficiency vacuum silver-loaded bone implant device with high bonding strength and long-lasting antibacterial function, characterized by: The method is prepared by the method according to any one of claims 1 to 4.

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