Synergistic 3D printed metal implant and method of making same

Abstract

The application discloses a synergistic 3D printing metal implant and a preparation method thereof. The implant is prepared by the following steps: forming a nano-cone needle structure on the surface of a 3D printing porous metal implant body through micro-arc oxidation treatment and surface etching, and then sequentially immersing the implant in a solution containing antibacterial ions, heat treatment, suspension liquid containing composite functions and heat treatment. The 3D printing metal implant prepared by the application has stable and long-acting antibacterial performance, excellent biocompatibility and bone integration promotion effect. The preparation method is simple, low in cost and suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to a 3D printed implant, in particular to a synergistic 3D printed metal implant, and a preparation method thereof, and belongs to the technical field of surface treatment. BACKGROUND

[0002] In clinical surgery, according to the clinical treatment plan, the bone implant is implanted into the fracture or the part to be repaired of the human body in the sterile environment of the operating room. After the implant contacts with the bone tissue, the classic theory considers that it mainly includes three stages: acute inflammation period, neutrophils and macrophages are infiltrated due to surgical trauma, necrotic tissue is removed and potential bacterial infection is resisted, a temporary interface layer rich in fibrin is formed to provide a microenvironment for subsequent bone integration; then bone integration is started, osteoblasts are recruited to the implant surface through physical-chemical signals, osteoblasts secrete type I collagen and calcium salt, bone matrix deposition is formed, the fibrous layer is gradually replaced, and early bone-implant anchoring is established; finally, the new bone is remodeled through the Havens system to achieve mechanical adaptation, and the implant-bone interface achieves structure-function integration. During the whole process, the bone implant not only needs to provide mechanical support function, but also needs to have good bone integration and antibacterial function, especially in the case of large open wounds or poor recovery environment, poor bone healing or bacterial infection of the implant will lead to failure of the bone implant. During bone healing, once bacteria form a biofilm on the surface of the implant, the resistance to antibacterial agents and the immune system is greatly enhanced, the sensitivity to antibacterial drugs is reduced, and the biofilm structure itself also hinders drug penetration, so that antibacterial is crucial to the implant in the early, middle and late stages.

[0003] Titanium and titanium alloy is the first choice for joint replacement, fracture fixation and other surgeries in clinical application due to its good biocompatibility. However, the problem is that titanium and titanium alloy material itself is bioinert and has no osteogenic activity and antibacterial property. 3D printed implants are increasingly being researched and applied, which can customize the macroscopic morphology and microscopic three-dimensional porous structure according to the needs of patients, and the surface roughness and specific surface area of the processed surface are beneficial to the adhesion of osteoblasts, and the prepared macroscopic three-dimensional porous structure is more conducive to bone ingrowth, so in the case of meeting the mechanical requirements, the demand for 3D printed implants and modification of 3D printed implants is very strong. The Chinese patent with publication number CN119279865A discloses a personalized 3D printed porous composite hydroxyapatite coated skull repair body, which mainly uses 3D printing to form a bionic trabecular structure in the porous area, and the bionic trabecular structure and the small hole and microporous structure on the truss structure, and the porous structure of the bionic trabecular structure in the porous area is sprayed with a composite coating of hydroxyapatite and titanium, so that it has high individualization, biocompatibility, osteoinductive ability and bone ingrowth effect. It needs to be particularly noted that the three-dimensional porous morphology has a stronger demand for antibacterial property. Since the material itself does not have antibacterial property, bacteria can slightly contaminate the implant in the surgical environment or open wound environment, and the three-dimensional porous structure is more likely to hide dirt. Once the bacteria form a biofilm on the internal porous surface of the three-dimensional porous structure, it will be very difficult to remove, and the bacterial infected implant needs to be replaced with a new implant.

[0004] Therefore, it is of great significance to develop an implant that can meet the requirements of mechanical support performance and bone ingrowth, and has stable and efficient antibacterial property and osteogenic effect after implantation. SUMMARY

[0005] In view of the problems existing in the prior art, the first object of the present application is to provide a 3D printed metal implant with synergistic effect. The implant not only has good biocompatibility, osteoinductive ability and bone ingrowth effect, but also has stable and long-acting antibacterial property.

[0006] The second object of the present application is to provide a preparation method of a 3D printed metal implant with synergistic effect. The method is simple, short in process flow and low in cost, and is suitable for industrial production.

[0007] In order to achieve the above technical purposes, the present application provides a preparation method of a 3D printed metal implant with synergistic effect, which comprises the following steps: subjecting a 3D printed porous metal implant body to micro-arc oxidation treatment and surface etching to form a nano-cone needle structure on the surface, then sequentially immersing the body in a solution containing antibacterial ions, heat treating I, immersing the body in a suspension containing a composite functional substance, and heat treating II, to obtain the 3D printed metal implant with synergistic effect. The composite functional substance comprises a bioactive ceramic component, an antibacterial metal oxide and a water-soluble metal salt.

[0008] The present application makes the 3D printed metal implant have macroscopic porous pore structure of millimeter scale, surface microscopic hole of micron scale and nano-cone needle structure with antibacterial and osteogenic effects by the above-mentioned surface treatment, and the surface structure can realize specific acoustic absorption, efficient acoustic heat conversion and ion release functions. Among them, the porous honeycomb titanium oxide sound heat conversion layer is formed by using 3D printing porous technology and micro-arc oxidation technology, and the deep penetration ability of ultrasonic makes it realize local acoustic heat conversion and temperature rise under low-frequency ultrasonic in the surface layer and the inner porous layer. Through the macroscopic porous structure of 3D printing, the surface nano-cone needle and the nano-scale thickness coating, the cross-scale bone integration and antibacterial synergistic effect is realized. Among them, the inner layer is always in a sustained antibacterial state through the physical and chemical synergistic effect of the nano-cone needle and the antibacterial ion doping on the surface of the nano-cone needle, and when the bacterial infection is more serious, the ultrasonic response starts the acoustic heat conversion effect of the nano-cone needle, accelerates the ion release and the tip heat effect of the nano-cone needle, pierces the attached bacterial cell membrane and realizes the antibacterial ion injection, so as to achieve the purpose of sterilization and prevent the occurrence of infection in the early and late stages of implantation and reduce the risk of postoperative complications; the nano-cone needle surface also has an osteogenic outer layer, which contains salt components (alkali metal chloride and / or alkaline earth metal chloride), bioactive ceramics and oxides (antibacterial metal oxides), which can dissolve and release in the body fluid environment, and based on the local rapid heating of the responsive acoustic response and acoustic heat conversion characteristics, the rapid disintegration and release of the mixed coating of the recrystallized salt component, calcium phosphate or biological glass and oxide formed by the heat treatment of the outer layer are accelerated, which is beneficial to the recruitment of osteoblasts in the early stage of the implant to promote bone integration and the rapid release of antibacterial ions to achieve short-term antibacterial effect.

[0009] In addition, the antibacterial ion salt attached to the nano-cone needle makes the surface obtain a local "pinning" effect to facilitate the attachment of the osteogenic coating on the surface of the cone needle, and the pinned ion salt regulates the nucleation and growth of the osteogenic bioactive ceramic component on the surface of the cone needle in the subsequent heat treatment, forming a uniform and oriented dissolution and slow-release osteogenic outer layer on the surface of the cone needle. The micro-rough surface and "pinned" ion salt also significantly improve the adhesion of the cone needle surface and the osteogenic outer layer, preventing the soluble calcium phosphate mixed coating of the outer layer from falling off due to insufficient adhesion during the implantation process, thereby affecting the short-term antibacterial and osteogenic effects.

[0010] As a preferred scheme, the 3D printed porous metal implant base is designed based on the defect site of the patient, the shape and shape of the metal implant are designed, the solid porous structure is constructed, and then the implant is printed and formed by using a laser 3D printing equipment.

[0011] As a preferred scheme, the porosity of the 3D printed porous metal implant base is 20%~80%.

[0012] As a preferred solution, the micro-arc oxidation treatment is performed under the following conditions: the electrolyte comprises at least one of trisodium citrate, sodium phosphate, ethylenediaminetetraacetic acid, manganese sulfate, manganous sulfate, zinc sulfate, zinc acetate, tungsten silicate, sodium tungstate, sodium borate, ammonium molybdate, calcium acetate, sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide; the total concentration of the electrolyte is not more than 20 g / L, and the concentration of any one of the solute components in the electrolyte is 2-8 g / L; the voltage is 200-400 V, the duty cycle is 5%-15%, and the frequency is 1000-2000 Hz.

[0013] As a preferred solution, the surface etching is performed by at least one of an alkaline solution etching and a plasma etching.

[0014] As a preferred solution, the alkaline solution comprises at least one of sodium hydroxide solution, potassium hydroxide solution, calcium hydroxide solution, sodium carbonate solution, and potassium carbonate solution. The mass concentration of the alkaline solution is 1-20%. The etching temperature is 60-250°C, and the etching time is 30 min-24 h.

[0015] As a preferred solution, the antibacterial ions comprise at least one of magnesium ions, zinc ions, copper ions, and silver ions.

[0016] As a preferred solution, the concentration of the antibacterial ions is 0.0001 mol / L-0.015 mol / L.

[0017] As a preferred solution, the solution containing the antibacterial ions is immersed under the following conditions: the temperature is 20-50°C, and the time is 10-60 min. Before the immersion treatment, the vacuum and pressure relief are performed for multiple times.

[0018] As a preferred solution, the bioactive ceramic component comprises at least one of calcium phosphate and bioactive glass.

[0019] As a preferred solution, the antibacterial metal oxide comprises at least one of silver oxide, copper oxide, zinc oxide, magnesium oxide, and calcium oxide.

[0020] As a preferred solution, the calcium phosphate comprises at least one of hydroxyapatite, tricalcium phosphate, and amorphous calcium phosphate.

[0021] As a preferred solution, the tricalcium phosphate comprises at least one of β-TCP and α-TCP.

[0022] As a preferred solution, the bioactive glass comprises at least one of 45S5, S53P4, 58S, and 13-93.

[0023] As a preferred solution, the solid content of the suspension is 0.01-1 wt%.

[0024] As a preferred solution, the mass concentration of the water-soluble metal salt in the suspension is 0.5-5%.

[0025] As a preferred solution, the water-soluble metal salt comprises an alkali metal salt and / or a water-soluble alkaline earth metal salt. The water-soluble metal salt is more preferably a metal chloride.

[0026] As a preferred solution, the conditions for the impregnation of the suspension containing the composite functional substance are: temperature 20-50℃, time 10-60 min. Before the impregnation treatment, multiple vacuum and pressure relief treatments are performed.

[0027] As a preferred solution, the conditions for the heat treatment I and the heat treatment II are: temperature 200-700℃, time 60-300 min.

[0028] As a preferred solution, after the end of the heat treatment II, a cleaning and sterilization treatment is performed.

[0029] The application also provides a 3D-printed metal implant with synergistic effects, which is prepared by the above method. The implant obtained by the application has a composite coating on the surface, and can realize specific sound absorption, efficient sound-heat conversion and ion release functions. The micron-scale pore layer constructed by micro-arc oxidation has sound response and sound-heat conversion properties. The nano-cone needle structure layer is formed in situ on the sound response layer by etching treatment. The surface of the cone needle is loaded with zinc, copper, silver, magnesium ion salt or oxide to form a long-acting antibacterial substance. At the same time, a nanoscale osteoconductive outer layer with antibacterial properties is also covered.

[0030] As a preferred solution, the porosity of the surface coating of the 3D-printed metal implant is 30%-70%, and the diameter of the inner nano-cone needle is 50-100 nm.

[0031] Compared with the prior art, the application has the following beneficial effects:

[0032] (1) The 3D-printed metal implant with a composite coating on the surface is prepared by micro-arc oxidation and surface etching to obtain a nano-cone needle structure surface layer, and then by multiple impregnation-heat treatment. Based on the synergistic effect of the porous honeycomb titanium oxide sound-heat conversion layer, the nano-cone needle inner layer and the antibacterial osteoconductive outer layer, the 3D-printed metal implant has stable and long-acting antibacterial properties and bone integration (osteogenic) effect.

[0033] (2) For the internal shielding problem of 3D printing three-dimensional porous, the present application utilizes the fluidity of the solution and the bypassing of the three-dimensional porous, adopts chemical etching and solution immersion method, realizes uniform covering of 3D printing three-dimensional porous matrix with antibacterial and osteogenesis promoting coating;

[0034] (3) The present application overcomes the limitation that the existing 3D printing forming needs to be immediately heat treated at high temperature to adjust the crystal organization and thermal stress after 3D printing forming treatment to meet the mechanical properties of the implant, at the same time, since the metal is oxidized after heat treatment, the 3D printing surface is oxidized to form an oxide skin, which needs to be treated to remove the oxide skin before other coating treatment, the whole process is complicated and the removal of the oxide skin in the printing hole is poor, the present application directly performs alkali etching and deposition coating treatment, forms and obtains inorganic matter in the highest oxidation state, and then performs post-heat treatment, constructs a composite coating, realizes the composite function of 3D printing matrix mechanical properties, antibacterial and osteogenesis promoting coating, reduces the process complexity, prevents the generation of process oxide skin and the removal of complicated and poor effect problems, the preparation method is simple, the cost is low, and it is suitable for industrial production. BRIEF DESCRIPTION OF DRAWINGS

[0035] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced below. Obviously, the drawings in the following description are only embodiments of the present application, and those skilled in the art can obtain other drawings according to the provided drawings without creating any creative labor.

[0036] Figure 1 It is a schematic diagram of the surface composite coating of the 3D printing metal implant of the present application.

[0037] Figure 2 It is a surface electron microscope graph of the 3D printing metal implant prepared in Example 1 of the present application.

[0038] Figure 3 It is a surface electron microscope graph of the 3D printing metal implant prepared in Example 2 of the present application.

[0039] Figure 4 It is a surface electron microscope graph of the 3D printing metal implant prepared in Example 2 of the present application.

[0040] Figure 5 It is a surface electron microscope graph of the 3D printing metal implant prepared in Example 2 of the present application.

[0041] Figure 6 It is a surface electron microscope graph of the 3D printing metal implant prepared in Comparative Example 1 of the present application.

[0042] Figure 7SEM of the surface of the 3D-printed metal implant prepared for Invention Comparative Example 2. DETAILED DESCRIPTION

[0043] The technical solutions of the present application will be described clearly and completely below in combination with the embodiments of the present application and the accompanying drawings. Obviously, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0044] Example 1

[0045] (1) Based on the defect site of the patient, the macro implant morphology and shape are designed, and the solid porous microstructure is constructed; the laser 3D printing equipment is used to print the implant according to the predetermined morphology, shape and microstructure, wherein the pore size of the 3D printed implant is controlled to be 150-500 μm, the macro porosity is 60%, and after printing, the unformed powder is removed by sandblasting and pickling post-processing, and a 3D printed titanium alloy implant body is obtained.

[0046] (2) The above 3D printed titanium alloy implant body is suspended on a hanger and immersed in a micro-arc oxidation solution, and the sample is anode for micro-arc oxidation treatment at room temperature, the solution is prepared by using 2 g / L trisodium citrate, 5 g / L calcium acetate and 2 g / L zinc sulfate, the voltage is set to 200V with 15% duty cycle and 1000Hz frequency for 2min, 300V with 5% duty cycle and 1000Hz frequency for 2min, 400V with 5% duty cycle and 2000Hz frequency for 5min, and the formed surface micro-pore porosity is 30%.

[0047] (3) After the micro-arc oxidation treated 3D printed implant is rinsed and dried, it is immersed in a solution containing 10% sodium hydroxide for chemical corrosion treatment, the corrosion temperature is 230°C, the corrosion time is 30min, after the corrosion is completed, the implant is rinsed with purified water and dried to constant weight, then the implant is placed in a plasma treatment cavity for cleaning, Ar and O2 mixed gas is used, the Ar gas flow is set to 5mL / min, the O2 gas flow is set to 30mL / min, the cleaning power is 300W, and the cleaning time is 60min.

[0048] (4) The 3D printed implant treated in step (3) is immersed in a prepared solution containing 0.015 mol / L copper acetate, placed in a vacuum oven, and set to a temperature of 30°C and a vacuum degree of 30 KPa, and then vacuumized and depressurized for 3 times, and then immersed at constant temperature for 10 min, and dried to remove water; then the immersed implant is placed in a high-temperature sintering furnace for high-temperature heat treatment, in an atmospheric environment, at a treatment temperature of 200°C, and a treatment time of 60 min, and then cooled to room temperature after the treatment is completed.

[0049] (5) The implant after the above heat treatment is immersed in a 5% concentration of sodium chloride salt solution containing 0.1% nano-hydroxyapatite and 0.1% nano-copper oxide, and an ultrasonic blending suspension solution is formed, and then vacuumized and depressurized for 3 times, and then ultrasonic treated for 10 min, and then dried to constant weight; then the immersed implant is again subjected to high-temperature heat treatment, at a treatment temperature of 600°C and a vacuum degree of 99 KPa, and a heat treatment time of 300 min.

[0050] (6) The product after the above treatment is washed, packed in an inner bag, and subjected to gamma ray irradiation sterilization, and a sterilization dose of 25-40 KGy is obtained to obtain the final product.

[0051] The surface coating structure of the 3D printed implant prepared under the conditions of this embodiment is analyzed, as shown in FIG. 1, wherein (a) is the coating microstructure under a magnification scale of 1 mm, (b) is the coating microstructure under a magnification scale of 20 μm, and (c) is the coating microstructure under a magnification scale of 5 μm, and it can be seen from the figures that the implant has a macro-porous pore structure and a micron-scale surface micro-porous hole obtained by 3D printing, and the magnified figure shows that the micro-surface presents a porous morphology similar to a volcano, indicating that the micro-arc oxidation has no effect on the macrostructure, and the further magnified figure shows that the surface presents a state of nano-cone needle spreading. Figure 2 Figure 2 According to the in-vitro hydroxyapatite deposition test method of YY / T 0964 "Surgical implants - Bioactive glass and glass-ceramic materials", after immersion in a simulated body fluid, the sample is subjected to ultrasonic treatment by using an ultrasonic generator, and the appearance change after mineralization is observed by 3D, as shown in FIG. 2, and particles are generated on the surface, indicating that the 3D printed metal implant prepared by the present application has good biological mineralization activity.

[0052] According to the in-vitro hydroxyapatite deposition test method of YY / T 0964 "Surgical implants - Bioactive glass and glass-ceramic materials", after immersion in a simulated body fluid, the sample is subjected to ultrasonic treatment by using an ultrasonic generator, and the appearance change after mineralization is observed by 3D, as shown in FIG. 2, and particles are generated on the surface, indicating that the 3D printed metal implant prepared by the present application has good biological mineralization activity. Figure 3

[0053] ​​According to the test method in JIS Z2801 "Test and Evaluation of Antibacterial Performance of Antimicrobial Products", Escherichia coli and Staphylococcus aureus are used for antibacterial rate test, after the sample is added, ultrasonic treatment is carried out for 15 min by using an ultrasonic generator, then according to the test method, culture and calculation of antibacterial rate are carried out, then the sample is soaked in Tris-HCl buffer solution at 37℃ for 7 days, 21 days and 60 days respectively, and then Escherichia coli and Staphylococcus aureus are used for antibacterial rate test, after the sample is added, ultrasonic treatment is carried out for 15 min by using an ultrasonic generator, then according to the test method, culture and calculation of antibacterial rate are carried out, and the results are shown in Table 1. Among them, the preparation process of the Tris-HCl buffer solution used in the application is as follows: 800 mL of deionized water is placed in a beaker, placed on a magnetic stirrer, 35 mL of 1 mol / L hydrochloric acid solution is added, and tris(hydroxymethyl) aminomethane is added under stirring to adjust the pH to 7.25, and finally the solution is transferred to a 1000 mL volumetric flask and diluted to volume to prepare the Tris buffer solution.

[0054] ;

[0055] From the results in Table 1, it can be seen that the 3D printed metal implant prepared by the application has long-acting antibacterial performance, and the antibacterial rate is stable at more than 99%.

[0056] Example 2

[0057] (1) Based on the defect site of the patient, the macroscopic implant shape and shape are designed, and the three-dimensional porous microstructure is constructed; the laser 3D printing equipment is used to print the implant according to the predetermined shape, shape and microstructure, the implant pore size is controlled to be 300-500 μm, the macroscopic porosity is 80%, after printing forming, the unformed powder is removed by sand blasting and pickling treatment, and the 3D printed titanium alloy implant body is obtained.

[0058] (2) The above-mentioned 3D printed titanium alloy implant body is suspended on a hanger and immersed in a micro-arc oxidation solution, and the sample is used as an anode for micro-arc oxidation treatment at room temperature, the solution is prepared by using 5 g / L sodium phosphate, 2 g / L EDTA and 2 g / L ammonium molybdate, the voltage is treated by gradient voltage, 200V, duty cycle 10%, frequency setting 1000Hz, treatment 3min, 250V, duty cycle 15%, frequency setting 1500Hz, treatment 3min, 400V, duty cycle 10%, frequency setting 2000Hz, treatment 5min, the formed surface micro-pore porosity is 35%.

[0059] (3) After the micro-arc oxidation treatment of the 3D printed implant, the implant is rinsed and dried, then immersed in a solution containing 20% sodium carbonate for chemical corrosion treatment, the corrosion temperature is 60°C, the corrosion time is 24 min, after the corrosion is completed, the implant is rinsed with purified water and dried to constant weight, then the implant is placed in a plasma treatment chamber for cleaning, Ar and O2 mixed gas is used, the Ar gas flow is set to 5 mL / min, the O2 gas flow is set to 30 mL / min, the cleaning power is 300 W, and the cleaning time is 60 min.

[0060] (4) The 3D printed implant after the above plasma cleaning is immersed in a prepared solution containing 0.008 mol / L copper acetate, and is placed in a vacuum oven, the temperature is set to 40°C, and the vacuum degree is set to 50 KPa, vacuumizing and pressure releasing are each processed for 3 times, then the implant is immersed at constant temperature for 20 min, and is dried; then the immersed implant is placed in a high temperature sintering furnace for high temperature heat treatment, the treatment temperature is 400°C, the vacuum degree is set to -10 KPa, and the treatment time is 120 min, and the implant is cooled to room temperature after the treatment is completed.

[0061] (5) The implant after the above heat treatment is immersed in a prepared 5% concentration sodium chloride salt solution containing 0.1% nano-bioglass and 0.1% nano-copper chloride, and a suspension solution is formed by ultrasonic blending, the vacuum degree is set to 30 KPa, vacuumizing and pressure releasing are each processed for 3 times, then ultrasonic treatment is performed for 10 min, and then the implant is dried to constant weight; the immersed implant is again subjected to high temperature heat treatment, the treatment temperature is 600°C, the vacuum degree is set to 80 KPa, and the heat treatment time is 180 min.

[0062] (6) The product after the above cleaning is packed in an inner bag and subjected to gamma ray irradiation sterilization, and the sterilization dose is 25-40 KGy to obtain the final product.

[0063] Figure 4 The electron microscope image of the 3D printed metal implant prepared under the conditions of the present embodiment is shown, wherein (a) is the microstructure of the coating under a magnification scale of 20 μm, and (b) is the microstructure of the coating under a magnification scale of 5 μm, it can be seen from the figure that the implant has micrometer-scale surface micro-porous holes, and further magnification shows that the surface presents a state of nano-cone needle spreading.

[0064] According to the in vitro hydroxyapatite deposition test method of YY / T 0964 "Surgical Implants - Bioactive Glass and Glass-ceramic Materials", after immersion in a simulated body fluid, the sample is subjected to ultrasonic treatment by using an ultrasonic generator, and the appearance change after mineralization is observed by 3D, as shown in FIG. 5, particles are generated on the surface, indicating that the implant has good bio-mineralization activity. Figure 5 ​

[0065] Comparative Example 1

[0066] The method of Example 1 was used to prepare a 3D-printed metal implant, except that no alkali etching was performed, and the specific steps were as follows:

[0067] (1) Based on the defect site of the patient, the macroscopic implant morphology and shape were designed, and a solid porous microstructure was constructed; a laser 3D printing device was used to print the implant according to the predetermined morphology, shape and microstructure, wherein the pore size of the 3D-printed implant was controlled to be 150-500 μm, and the macroscopic porosity was 30%; after printing, the unformed powder was removed by sandblasting and pickling post-processing, and a 3D-printed titanium alloy implant body was obtained.

[0068] (2) The 3D-printed titanium alloy implant body was suspended on a hanger and immersed in a micro-arc oxidation solution, and a micro-arc oxidation treatment was performed at room temperature with the sample as the anode; the solution was prepared using 2 g / L trisodium citrate, 5 g / L calcium acetate and 2 g / L zinc sulfate; the voltage was set to 200 V with a duty cycle of 15% and a frequency of 1000 Hz for 2 min, 300 V with a duty cycle of 5% and a frequency of 1000 Hz for 2 min, and 400 V with a duty cycle of 5% and a frequency of 2000 Hz for 5 min.

[0069] (3) After the micro-arc oxidation treatment, the 3D-printed implant was rinsed and dried, and then placed in a plasma treatment chamber for cleaning; Ar and O2 were mixed into the gas, the Ar gas flow was set to 5 mL / min, the O2 gas flow was set to 30 mL / min, the cleaning power was 300 W, and the cleaning time was 60 min.

[0070] (4) The etched 3D-printed implant was immersed in a solution containing 0.015 mol / L copper acetate, placed in a vacuum oven, and set to a temperature of 30°C and a vacuum degree of 30 KPa; vacuum and pressure relief were each treated for 3 times, then immersed at a constant temperature for 10 min, and dried to remove water; the immersed implant was then placed in a high-temperature sintering furnace for high-temperature heat treatment; the treatment temperature was 200°C, the treatment time was 60 min, and the treatment was completed after cooling to room temperature.

[0071] (5) The implant after the above heat treatment is immersed in a prepared sodium chloride solution containing 0.1% nano-hydroxyapatite and containing 0.1% nano-copper oxide at a concentration of 5%, and a suspension solution is formed by ultrasonic blending. The vacuum degree is set to 30 KPa, and the vacuum and pressure relief are each processed for 3 times. Then, ultrasonic treatment is performed for 10 min, and then dried to a constant weight. Then, the immersed implant is subjected to high-temperature heat treatment again, the treatment temperature is 600°C, the vacuum degree is set to 99 KPa, and the heat treatment time is 300 min.

[0072] (6) The product after cleaning is packed into an inner bag and subjected to gamma ray irradiation sterilization, and the sterilization dose is 25-40 KGy to obtain the final product.

[0073] Figure 6 The electron microscope image of the 3D printed metal implant prepared under the conditions of the comparative example can be seen from the figure, and the surface presents a typical micro-arc oxidation treatment to form a porous volcano-like morphology.

[0074] According to the test method in JIS Z2801 "Test and Evaluation of Antibacterial Performance of Antibacterial Products", Escherichia coli and Staphylococcus aureus are used for antibacterial rate test. After the sample is added, ultrasonic treatment is performed for 15 min using an ultrasonic generator. Then, according to the test method, culture and calculation of the instantaneous antibacterial rate are performed. The results show that the antibacterial rate of Escherichia coli is only 5.9%, and the antibacterial rate of Staphylococcus aureus is only 13%, indicating that the antibacterial performance is poor, and it does not have long-term antibacterial performance.

[0075] Comparative Example 2

[0076] The 3D printed metal implant is prepared by the method of Example 1, except that the micro-arc oxidation treatment in step (2) is not performed, and the 3D printed titanium alloy implant substrate is directly subjected to surface etching.

[0077] Figure 7 The electron microscope image of the 3D printed metal implant prepared under the conditions of the comparative example can be seen from the figure, and the surface presents a typical micro-arc oxidation treatment to form a porous volcano-like morphology.

[0078] According to the test method in JIS Z2801 "Test and Evaluation of Antibacterial Performance of Antibacterial Products", Escherichia coli and Staphylococcus aureus are used for antibacterial rate test. After the sample is added, ultrasonic treatment is performed for 15 min using an ultrasonic generator. Then, according to the test method, culture and calculation of the instantaneous antibacterial rate are performed. The results show that the antibacterial rate of Escherichia coli is only 5.9%, and the antibacterial rate of Staphylococcus aureus is only 13%, indicating that the antibacterial performance is poor, and it does not have long-term antibacterial performance.

[0079] ;

[0080] From the data in Table 2, it can be seen that the 3D printed metal implants prepared without the micro-arc oxidation treatment step have a decrease in antibacterial stability due to the lack of a titanium oxide sonophoresis layer. After 60 days, the antibacterial rate decreases to below 40%, which cannot meet the long-term stable antibacterial requirement.

[0081] Many modifications to these embodiments will be apparent to those of ordinary skill in the art and the foregoing description is intended to cover any and all modifications that can fall within the scope of the present application. Therefore, the above description should not be taken as limiting the scope of the application, which is defined by the metes and bounds of the appended claims.

Claims

1. A method for fabricating a synergistic 3D-printed metal implant, characterized in that: The 3D-printed porous metal implant substrate is subjected to micro-arc oxidation and surface etching to form a nano-conical needle structure on the surface. Then, it is sequentially impregnated with a solution containing antibacterial ions, heat treatment I, impregnated with a suspension containing composite functional materials, and heat treatment II to obtain the implant. The composite functional materials include bioactive ceramic components, antibacterial metal oxides, and water-soluble metal salts.

2. The method for preparing a synergistic 3D-printed metal implant according to claim 1, characterized in that: The conditions for the micro-arc oxidation treatment are as follows: the electrolyte contains at least one of the following: trisodium citrate, sodium phosphate, ethylenediaminetetraacetic acid, manganese sulfate, manganese sulfate, zinc sulfate, zinc acetate, tungsten silicate, sodium borate, sodium tungstate, ammonium molybdate, calcium acetate, sodium carbonate, potassium carbonate, potassium hydroxide, and sodium hydroxide; the total concentration of the electrolyte does not exceed 20 g / L; the voltage is 200~400V, the duty cycle is 5%~15%, and the frequency is 1000~2000Hz.

3. A method for preparing a synergistic 3D-printed metal implant according to claim 1 or 2, characterized in that: The surface etching method includes at least one of alkaline solution etching and plasma etching.

4. The method for preparing a synergistic 3D-printed metal implant according to claim 3, characterized in that: The alkaline solution includes at least one of sodium hydroxide solution, potassium hydroxide solution, calcium hydroxide solution, sodium carbonate solution, and potassium carbonate solution. The mass concentration of the alkaline solution is 1-20%; the etching temperature is 60-250℃, and the etching time is 30 min-24 h.

5. The method for preparing a synergistic 3D-printed metal implant according to claim 1, characterized in that: The antibacterial ions include at least one of magnesium ions, zinc ions, copper ions, and silver ions; The concentration of the antibacterial ions is 0.0001 mol / L to 0.015 mol / L; The conditions for immersion in a solution containing antibacterial ions are: temperature 20~50℃, time 10~60min.

6. The method for preparing a synergistic 3D-printed metal implant according to claim 1, characterized in that: The bioactive ceramic component includes at least one of calcium phosphate salt and bioactive glass. The antibacterial metal oxide includes at least one of silver oxide, copper oxide, zinc oxide, magnesium oxide, and calcium oxide.

7. The method for preparing a synergistic 3D-printed metal implant according to claim 6, characterized in that: The calcium phosphate salt includes at least one of hydroxyapatite, tricalcium phosphate, and amorphous calcium phosphate. The bioactive glass includes at least one of 45S5, S53P4, 58S, and 13-93.

8. A method for preparing a synergistic 3D-printed metal implant according to claim 1, 6, or 7, characterized in that: The solid content of the suspension is 0.01~1wt%; The water-soluble metal salt has a mass concentration of 0.5% to 5% in the suspension; The conditions for impregnating the suspension containing the complex functional material are: temperature 20~50℃, time 10~60min.

9. The method for preparing a synergistic 3D-printed metal implant according to claim 1, characterized in that: The conditions for both heat treatment I and heat treatment II are: temperature of 200~700℃ and time of 60~300min.

10. A 3D-printed metal implant with synergistic effects, characterized in that: Prepared by the method described in any one of claims 1 to 9.

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