A long-lasting intelligent composite antibacterial coating with dual pH response function and its preparation method

Abstract

The present invention discloses a long-lasting intelligent composite antibacterial coating with dual pH response function and its preparation method, including: 1) constructing a nanotube structure on the surface of a pretreated titanium alloy substrate by a surface anodizing process; 2) combining a cyclic vacuum infusion + low-temperature micro-airflow process, infusing a povidone-iodine mixed solution into the nanotube pores on the titanium alloy surface; 3) after the titanium alloy surface is washed with water, a surface silanization treatment is performed to introduce a silane preparation with a double bond; 4) combining a surface cyclic light curing process, NAC-ChiMA is introduced into the substrate surface by a double bond addition reaction between the silane preparation and chitosan (NAC-ChiMA) modified with MA and NAC, to achieve the preparation of a composite antibacterial coating. The composite coating realizes the sequential release and slow release of NAC and povidone-iodine through the characteristics of vacuum drug loading and dual pH response, first destroying the extracellular polymeric substances of the bacterial biofilm, and then killing the bacteria in the biofilm, thereby achieving effective treatment of orthopedic implant infection.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical material preparation, and relates to an antibacterial coating and a preparation method thereof, and in particular to a long-lasting intelligent composite antibacterial coating with dual pH response function and a preparation method thereof. Background Art

[0002] Orthopedic implant infections have long been a clinical challenge for orthopedic surgeons. Current clinical approaches to address this issue primarily include debridement and systemic and topical antibiotic therapy. However, these approaches suffer from drawbacks such as the development of antibiotic resistance, incomplete debridement, the impact of debridement surgery on tissue regeneration, and biofilms blocking antibiotics. Antimicrobial coating technology, with its advantages of ease of use, stable performance, and outstanding bactericidal efficacy, has become a research hotspot in this field in recent years.

[0003] However, most of the existing antibacterial coating technologies focus on the antibacterial effect on bacteria, and the presence of biofilm makes it difficult for antibacterial drugs to reach the bacterial body, resulting in low sterilization efficiency. Bacterial biofilm refers to a large number of bacterial aggregation membranes formed by bacteria adhering to the contact surface, secreting polysaccharide matrix, fibrin, lipid protein, etc., and wrapping themselves in it. Among them, extracellular polymeric substances have a barrier effect on antibacterial drugs (such as antibiotics, etc.), greatly reducing the effectiveness of antibacterial drugs. Therefore, how to break through the biofilm barrier is the key to antibacterial.

[0004] To address this issue, disrupting the bacterial biofilm first, freeing the bacteria within it, and then releasing active antimicrobial components to kill the free bacteria can significantly improve the effectiveness of infection treatment. Therefore, the present invention utilizes this antimicrobial strategy to design a novel composite antimicrobial coating material to address the challenge of orthopedic implant infection. Summary of the Invention

[0005] The purpose of the present invention is to provide a long-lasting intelligent composite antibacterial coating with dual pH response function and a preparation method thereof in view of the shortcomings of the existing technology and combining the advantages of various materials and processes.

[0006] The present invention addresses the challenge of orthopedic implant infection through the careful selection and combination of raw materials and the ingenious design of the composite coating structure. Using titanium alloy, povidone-iodine, sodium alginate, chitosan, methacrylic anhydride (MA), N-acetylcysteine ​​(NAC), silane preparations with double bonds, and photoinitiators as raw materials, and employing a combination of processes including anodization, vacuum infusion, surface silanization, grafting modification, and surface photocuring, a long-lasting, intelligent composite antibacterial coating with dual pH-responsiveness is successfully prepared. This composite coating, through its dual pH-responsiveness, nanotube drug loading, and hydrogel swelling properties and structure, enables the sequential and slow release of NAC and povidone-iodine, first destroying the extracellular polymeric substances (EPS) of the bacterial biofilm and then killing the bacteria within the biofilm, effectively treating orthopedic implant infection.

[0007] The technical solutions of the present invention are as follows:

[0008] A method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function comprises the following steps:

[0009] 1) Pretreatment: remove the oxide film on the surface of titanium alloy and perform ultrasonic cleaning;

[0010] 2) Anodizing: Anodizing the pre-treated titanium alloy to construct a nanotube structure on its surface;

[0011] 3) Cyclic vacuum loading of antimicrobial drugs: The anodized titanium alloy is placed in a mixed solution of povidone iodine / sodium alginate / glycerol, ultrasonically dispersed, and then transferred to a vacuum environment to achieve vacuum infusion of the solution. The pressure is maintained for a period of time, and the mixture is dried. The above vacuum loading process is repeated several times to obtain a titanium alloy substrate loaded with antimicrobial drugs;

[0012] 4) Surface silanization: The surface of the titanium alloy substrate loaded with the antibacterial drug is rinsed with deionized water and then immersed in an ethanol / water solution of a silane preparation with double bonds and allowed to react for a period of time;

[0013] 5) Surface cyclic photocuring: After rinsing the surface silanized sample with deionized water, immerse it in a PBS solution containing NAC-ChiMA and a photoinitiator under light-proof conditions for a period of time. After taking it out, use a UV light source for photocuring. The above immersion and photocuring process is repeated several times to obtain a long-lasting intelligent composite antibacterial coating with dual pH response function.

[0014] Furthermore, in step 1), the ultrasonic cleaning is to use acetone, ethanol, and deionized water in sequence to clean the titanium alloy under ultrasonic conditions for 15-20 minutes to remove impurities such as oil on the surface.

[0015] Furthermore, in step 2), the anodizing treatment step includes: placing the cleaned titanium alloy in an electrolytic cell for anodizing treatment, wherein the electrolyte in the electrolytic cell is composed of 78.5-94.4wt% glycerol, 5-20wt% deionized water, 0.1-0.5wt% ammonium fluoride and 0.5-1wt% sodium lauryl sulfate; the voltage is 25-50V, the distance between the anode titanium alloy and the cathode is 15-25cm, and the reaction time is 1-8 hours.

[0016] Furthermore, in step 3), the povidone iodine / sodium alginate / glycerol mixed solution is composed of 59.5-90 wt% povidone iodine, 0.25-0.75 wt% sodium alginate and 9.25-39.75 wt% glycerol, and the viscosity of the sodium alginate is ≥0.002 Pas.

[0017] Furthermore, in step 3), the ultrasonic dispersion time is 10-30 min, the vacuum degree of the vacuum infusion is 1-30 Pa, and the vacuuming time is 0.1-2 hours; the pressure holding time is 1-3 hours; the drying is micro-airflow drying at a temperature of 20-25°C for 1-6 hours; the number of cycles of the vacuum infusion + low-temperature micro-airflow process is regulated according to factors such as the structure of the nanotubes on the titanium alloy surface and the iodine loading, and the number of cycles is approximately 5-15 times.

[0018] Furthermore, in step 4), the solvent in the ethanol / water solution of the silane preparation with a double bond is a mixed solution of ethanol and water in a volume ratio of 1:1, and the solute silane preparation with a double bond is one or more of γ-(methacryloyloxy)propyltrimethoxysilane (KH570), vinyltri(β-methoxyethoxy)silane (KH-172), vinyltrimethoxysilane (KH-171), and vinyltriethoxysilane (KH-151), with a concentration of 2.5-7.5 wt%.

[0019] Furthermore, in step 5), the NAC-ChiMA is prepared by double-modifying chitosan using methacrylic anhydride MA and N-acetylcysteine ​​NAC, and the specific steps include:

[0020] ① Dissolve chitosan in 2wt% acetic acid solution to prepare a 2-5wt% chitosan solution, transfer the solution to a 60-80°C water bath, slowly add 10-20wt% methacrylic anhydride dropwise under stirring, react for a period of time, add an equal volume of deionized water to terminate the reaction, transfer the resulting product to a dialysis bag, dialyze for 3-7 days, and then freeze-dry to obtain ChiMA;

[0021] ② Take 1-2wt% ChiMA and dissolve it in deionized water at a temperature of 60-80°C, then add 0.25-2.5wt% NAC and react under stirring conditions for 2-4 hours. The resulting product is transferred to a dialysis bag and dialyzed for 3-7 days and then freeze-dried to obtain NAC-ChiMA.

[0022] Furthermore, in step ①, the number average molecular weight of the chitosan is 300,000-800,000, and the degree of deacetylation is 60-80%; the dropping time is 1-2 hours, and the reaction time is 2-6 hours.

[0023] Furthermore, in step 5), the photoinitiator is one or more of LAP photoinitiator, 127 photoinitiator, and I2959 ultraviolet photoinitiator, with a concentration of 0.25-0.5wt%; the immersion time is 5-30min; the ultraviolet light wavelength is 408nm, and the photocuring time is 30s-10min; and the number of cycles is 3-5 times.

[0024] Compared with the prior art, the present invention has the following advantages:

[0025] 1) The composite antibacterial coating uses titanium alloy, povidone iodine, sodium alginate, chitosan, MA, NAC, a silane preparation with double bonds, a photoinitiator, and the like as raw materials, and successfully prepares a long-lasting intelligent composite antibacterial coating with dual pH-responsiveness using a combination of processes including anodic oxidation, vacuum infusion, surface silanization, grafting modification, and surface photocuring. The selection of these raw materials and combined processes are designed based on the sample preparation requirements of the present invention and are original to the present invention.

[0026] 2) The antibacterial coating has a multi-level composite structure: the first level is nanotube structure + povidone iodine / sodium alginate, the second level is a silane coupling agent layer, and the third level is NAC-ChiMA. The primary structure plays the role of efficient drug loading; the secondary structure provides surface grafting / cross-linking sites for the tertiary structure; the tertiary structure realizes the encapsulation of the TNT tube mouth to achieve the purpose of sustained release and pH-responsive release of antibacterial drugs. The above-mentioned multi-level structures arranged in sequence achieve efficient drug loading and intelligent controlled release through mutual cooperation.

[0027] 3) The composite antibacterial coating is produced by a combination of processes including anodizing, cyclic vacuum infusion + low-temperature micro-airflow process, acid etching, surface silanization, and surface photocuring. The various processes work together to give the coating material excellent antibacterial properties: titanium alloy is used as a substrate, and a nanotube structure is constructed on the surface in combination with the anodizing process, which can serve as a site for loading povidone iodine. The cyclic vacuum infusion process can achieve efficient loading of povidone iodine in titanium nanotubes. Compared with other simple impregnation, ultrasound, electrophoresis and other processes, the loading capacity is increased exponentially. The mixed solution used in the vacuum infusion process is innovatively designed by the present invention for vacuum conditions. Povidone iodine is the antibacterial active ingredient, and sodium alginate is used as a viscosity-enhancing component to effectively prevent the solution from boiling under high vacuum conditions. Sodium alginate also has excellent biocompatibility. The addition of glycerol can effectively ensure that the solution does not solidify under high vacuum conditions, ensuring that the solution can smoothly enter the interior of the nanotubes. MA and NAC double-modify chitosan, giving it double bonds and NAC molecules capable of destroying EPS. The surface silanization and surface photocuring processes perfectly match the characteristics of in-situ encapsulation of the coating. The conditions are mild and no impurities are introduced. NAC-ChiMA can effectively encapsulate the openings of titanium nanotubes, achieving long-term (sustained) and intelligent controlled release of active ingredients.

[0028] 4) The composite antibacterial coating is specifically designed based on the structural characteristics of bacterial biofilms. Once an orthopedic implant is infected, the surrounding microenvironment becomes weakly acidic (pH = about 5.5-6.0). The NAC-ChiMA on the surface of the composite antibacterial coating will undergo ester bond hydrolysis under weakly acidic conditions (first pH response), thereby releasing NAC to destroy the EPS of the biofilm; then the amino groups on the chitosan main chain in the NAC-ChiMA will be protonated, making the polymer network structure loose (second pH response), thereby releasing the povidone-iodine in the nanotubes on the surface of the titanium alloy substrate, killing the exposed bacteria after the EPS is destroyed. At the same time, sodium alginate and povidone-iodine co-exist in the nanotube pores, acting as a binder, making the release cycle of povidone-iodine more effective. This design cleverly breaks the bacterial biofilm's barrier ability to drugs and achieves the purpose of efficient anti-infection.

[0029] 5) The composite antibacterial coating preparation technology involved in the present invention is universally applicable to medical devices in infectious disease scenarios. It is a platform technology that can be widely promoted to various fields such as orthopedics and dental antibacterial implants. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 Schematic diagram of the structure of the long-lasting intelligent composite antibacterial coating with dual pH response function in the present invention.

[0031] Figure 2 These are SEM images of TNT and a long-lasting intelligent composite antibacterial coating with dual pH response function in an embodiment of the present invention (TNT sample on the left and composite antibacterial coating sample on the right).

[0032] Figure 3 Schematic diagram of the antibacterial effect of the long-lasting intelligent composite antibacterial coating with dual pH response function in Example 1 of the present invention.

[0033] Figure 4 This is the release curve of the antibacterial active ingredient of the long-lasting intelligent composite antibacterial coating with dual pH response function in an embodiment of the present invention (a 1cm*1cm*0.2cm TC4 metal sheet was placed in a 3ml PBS solution, and the extracts at different time points were diluted to 1 / 1000 with deionized water and then detected using an ICP-MS device to obtain the data; the control sample was a blank iodine-loaded TNT without a silane coupling agent and a NAC-ChiMA coating layer).

[0034] Figure 5 This is the release curve of the antibacterial active ingredient of the long-lasting intelligent composite antibacterial coating with dual pH response function in an acidic environment in Example 1 of the present invention (a 1cm*1cm*0.2cm TC4 metal sheet was placed in an aqueous solution with a pH value of 4.5 for 9 hours, and the extracts at different time points were diluted to 1 / 1000 with deionized water and then detected using an ICP-MS device to obtain the data). DETAILED DESCRIPTION

[0035] The technical solution of the present invention is described clearly and in detail below with reference to specific examples and accompanying drawings.

[0036] The structural diagram of the long-lasting intelligent composite antibacterial coating with dual pH response function of the present invention is as follows Figure 1 As shown, the antibacterial coating has a multi-level composite structure: the first level is nanotube structure + povidone iodine / sodium alginate, the second level is a silane coupling agent layer, and the third level is NAC-ChiMA.

[0037] Example 1:

[0038] 1) Pretreatment: First, the titanium alloy was polished and sandblasted to remove the oxide film on its surface. Then, the titanium alloy was cleaned in acetone, ethanol, and deionized water under ultrasonic conditions for 15 minutes to remove impurities such as oil on the surface.

[0039] 2) Anodization: The titanium alloy substrate after the above pretreatment was anodized, wherein the electrolyte formula was 80wt% glycerol, 19wt% deionized water, 0.5wt% ammonium fluoride, and 0.5wt% sodium lauryl sulfate; the voltage was 25V, the distance between the sample and the electrode was 20cm, and the reaction time was 4 hours; the SEM image of the obtained structure is shown in FIG. Figure 2 Shown on the left;

[0040] 3) Cyclic vacuum loading of antimicrobial drugs: The titanium alloy treated in step 2) is placed in a mixed solution of povidone iodine / sodium alginate / glycerol, wherein the mixed solution formula is 60wt% povidone iodine / 0.5wt% sodium alginate / 39.5wt% glycerol, wherein the viscosity of sodium alginate is ≥0.002Pas; ultrasonication is performed for 10 minutes to uniformly disperse the above solution, and then the solution is transferred to a vacuum environment with a vacuum degree of less than 30Pa for vacuum infusion; after maintaining the pressure for 1 hour, the sample is removed and dried in a micro-airflow at 25°C for 1 hour; the above vacuum iodine loading process is repeated 10 times.

[0041] 4) Surface silanization: After rinsing the sample surface obtained in step 3) with deionized water, immerse it in a 1:1 ethanol / water solution containing 5 wt% KH570 and react for 4 hours;

[0042] 5) Surface cyclic photocuring: After the sample obtained in step 5) was rinsed with deionized water, it was immersed in a 0.25wt% LAP / PBS solution containing 0.5wt% NAC-ChiMA under light-proof conditions and reacted for 15 minutes. After being taken out, it was photocured using a 408nm wavelength ultraviolet light source for 5 minutes. The above immersion and photocuring reaction were repeated 3 times to obtain the desired composite antibacterial coating material. The SEM image of the obtained structure is shown in FIG. Figure 2 As shown on the right, the antibacterial effect diagram is as follows Figure 3 The release curve of its active ingredient in acidic environment is shown as Figure 5 shown.

[0043] 6) The iodide ion release cycle of the sample was 28 days. The sample extract (the sample was placed in 3 ml of culture medium / PBS and shaken at 37°C for 24 hours; 10% FBS was added to the culture medium for the CCK-8 test, and PBS was used for the antibacterial test) was subjected to a CCK-8 test and an antibacterial test, respectively. The relative cell activity was 90%, and the antibacterial rate was 96%.

[0044] Example 2:

[0045] 1) Pretreatment: First, the titanium alloy was polished and sandblasted to remove the oxide film on its surface. Then, the titanium alloy was cleaned in acetone, ethanol, and deionized water under ultrasonic conditions for 15 minutes to remove impurities such as oil on the surface.

[0046] 2) Anodization: The titanium alloy substrate after the above pretreatment was subjected to anodization treatment, wherein the electrolyte formula was 80 wt% glycerol, 19 wt% deionized water, 0.5 wt% ammonium fluoride, and 0.5 wt% sodium lauryl sulfate; the voltage was 25 V, the distance between the sample and the electrode was 20 cm, and the reaction time was 4 hours;

[0047] 3) Cyclic vacuum loading of antimicrobial drugs: The titanium alloy treated in step 2) is placed in a mixed solution of povidone iodine / sodium alginate / glycerol, wherein the mixed solution formula is 60wt% povidone iodine / 0.5wt% sodium alginate / 39.5wt% glycerol, wherein the viscosity of sodium alginate is ≥0.002Pas; ultrasonication is performed for 10 minutes to uniformly disperse the above solution, and then the solution is transferred to a vacuum environment with a vacuum degree of less than 30Pa for vacuum infusion; after maintaining the pressure for 1 hour, the sample is removed and dried in a micro-airflow at 25°C for 1 hour; the above vacuum iodine loading process is repeated 15 times.

[0048] 4) Surface silanization: After rinsing the sample surface obtained in step 3) with deionized water, immerse it in a 1:1 ethanol / water solution containing 5 wt% KH570 and react for 4 hours;

[0049] 5) Surface cyclic photocuring: After rinsing the sample obtained in step 5) with deionized water, immerse it in a 0.25wt% LAP / PBS solution containing 0.5wt% NAC-ChiMA under light-proof conditions, react for 15 minutes, and then take it out and use a 408nm wavelength ultraviolet light source for photocuring for 5 minutes; the above immersion and photocuring reaction are repeated 3 times to obtain the desired composite antibacterial coating material.

[0050] 6) Compared with Example 1, the number of repeated loading of the antimicrobial drug was increased, and the amount of antimicrobial drug released increased by 23% compared with the control group; the release time was correspondingly extended, and the iodine release period of this sample was approximately 35 days; the extract of the sample from Example 2 was subjected to CCK-8 test and antibacterial test, and the relative cell activity was 88%, and the antibacterial rate was >99%.

[0051] Example 3:

[0052] 1) Pretreatment: First, the titanium alloy was polished and sandblasted to remove the oxide film on its surface. Then, the titanium alloy was cleaned in acetone, ethanol, and deionized water under ultrasonic conditions for 15 minutes to remove impurities such as oil on the surface.

[0053] 2) Anodization: The titanium alloy substrate after the above pretreatment was subjected to anodization treatment, wherein the electrolyte formula was 80 wt% glycerol, 19 wt% deionized water, 0.5 wt% ammonium fluoride, and 0.5 wt% sodium lauryl sulfate; the voltage was 25 V, the distance between the sample and the electrode was 20 cm, and the reaction time was 4 hours;

[0054] 3) Cyclic vacuum loading of antimicrobial drugs: The titanium alloy treated in step 2) is placed in a mixed solution of povidone iodine / sodium alginate / glycerol, wherein the mixed solution formula is 60wt% povidone iodine / 0.5wt% sodium alginate / 39.5wt% glycerol, wherein the viscosity of sodium alginate is ≥0.002Pas; ultrasonication is performed for 10 minutes to uniformly disperse the above solution, and then the solution is transferred to a vacuum environment with a vacuum degree of less than 30Pa for vacuum infusion; after maintaining the pressure for 1 hour, the sample is removed and dried in a micro-airflow at 25°C for 1 hour; the above vacuum iodine loading process is repeated 10 times.

[0055] 4) Compared with Example 1, the silane coupling agent and NAC-ChiMA coating were eliminated, and the release of antimicrobial drugs was significantly faster. The iodine release period of this sample was about 7 days (see Appendix). Figure 4 ); Take the sample extract of Example 3 for CCK-8 test and antibacterial test, the relative cell activity was 92% and the antibacterial rate was 90%.

[0056] Example 4:

[0057] 1) Pretreatment: First, the titanium alloy was polished and sandblasted to remove the oxide film on its surface. Then, the titanium alloy was cleaned in acetone, ethanol, and deionized water under ultrasonic conditions for 15 minutes to remove impurities such as oil on the surface.

[0058] 2) Anodization: The titanium alloy substrate after the above pretreatment was subjected to anodization treatment, wherein the electrolyte formula was 80 wt% glycerol, 19 wt% deionized water, 0.5 wt% ammonium fluoride, and 0.5 wt% sodium lauryl sulfate; the voltage was 25 V, the distance between the sample and the electrode was 20 cm, and the reaction time was 4 hours;

[0059] 3) Cyclic vacuum loading of antimicrobial drugs: The titanium alloy treated in step 2) is placed in a mixed solution of povidone iodine / sodium alginate / glycerol, wherein the mixed solution formula is 60wt% povidone iodine / 0.5wt% sodium alginate / 39.5wt% glycerol, wherein the viscosity of sodium alginate is ≥0.002Pas; ultrasonication is performed for 10 minutes to uniformly disperse the above solution, and then the solution is transferred to a vacuum environment with a vacuum degree of less than 30Pa for vacuum infusion; after maintaining the pressure for 1 hour, the sample is removed and dried in a micro-airflow at 25°C for 1 hour; the above vacuum iodine loading process is repeated 10 times.

[0060] 4) Surface silanization: After rinsing the sample surface obtained in step 3) with deionized water, immerse it in a 1:1 ethanol / water solution containing 5 wt% KH570 and react for 4 hours;

[0061] 5) Surface cyclic photocuring: After rinsing the sample obtained in step 5) with deionized water, immerse it in a 0.25wt% LAP / PBS solution containing 0.5wt% NAC-ChiMA under light-proof conditions, react for 30 minutes, and then take it out and use a 408nm wavelength ultraviolet light source for photocuring for 5 minutes; the above immersion and photocuring reaction are repeated 5 times to obtain the desired composite antibacterial coating material.

[0062] 7) Compared with Example 1, the encapsulation time and number of cycles of the NAC-ChiMA layer were increased, and its thickness was increased, thereby enhancing the destructive effect on EPS; the iodide ion release cycle of this sample was approximately 42 days; using the same method as Example 1, the extract of the sample of Example 4 was used for CCK-8 test and antibacterial test, and the relative cell activity was 91%, and the antibacterial rate was 94%.

[0063] The embodiments described above provide a detailed description of the technical solutions and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements and equivalent substitutions made within the scope of the principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function, characterized in that: The following steps are involved: 1) Pretreatment: remove the oxide film on the surface of titanium alloy and perform ultrasonic cleaning; 2) Anodizing: Anodize the pre-treated titanium alloy to construct a nanotube structure on its surface; 3) Cyclic vacuum loading of antimicrobial drugs: The anodized titanium alloy is placed in a mixed solution of povidone iodine / sodium alginate / glycerol, ultrasonically dispersed, and then transferred to a vacuum environment for vacuum infusion of the solution. The pressure is maintained for a period of time, and the mixture is dried. The above vacuum loading process is repeated multiple times to obtain a titanium alloy substrate loaded with antimicrobial drugs. 4) Surface silanization: The surface of the titanium alloy substrate loaded with the antimicrobial drug is rinsed with deionized water and then immersed in an ethanol / water solution of a silane preparation with double bonds and allowed to react for a period of time; 5) Surface cyclic photocuring: After rinsing the surface silanized sample with deionized water, the sample was immersed in a PBS solution containing NAC-ChiMA and a photoinitiator for a period of time under light-proof conditions. After removal, the sample was photocured using a UV light source. The above immersion and photocuring process was repeated several times to obtain a long-lasting intelligent composite antibacterial coating with dual pH response function. In step 5), the NAC-ChiMA is prepared by double-modifying chitosan using methacrylic anhydride MA and N-acetylcysteine ​​NAC, and the specific steps include: ① Dissolve chitosan in 2wt% acetic acid solution to prepare a 2-5wt% chitosan solution, transfer the solution to a 60-80°C water bath, slowly add 10-20wt% methacrylic anhydride dropwise under stirring, react for a period of time, add an equal volume of deionized water to terminate the reaction, transfer the resulting product to a dialysis bag, dialyze for 3-7 days, and then freeze-dry to obtain ChiMA; ② Dissolve 1-2 wt% ChiMA in deionized water at 60-80°C, then add 0.25-2.5 wt% NAC and react under stirring for 2-4 hours. Transfer the resulting product to a dialysis bag, dialyze for 3-7 days, and then freeze-dry to obtain NAC-ChiMA.

2. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step 1), the ultrasonic cleaning is to use acetone, ethanol and deionized water in sequence to clean the titanium alloy under ultrasonic conditions for 15-20 minutes.

3. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step 2), the anodizing treatment step includes: placing the cleaned titanium alloy in an electrolytic cell for anodizing treatment, wherein the electrolyte in the electrolytic cell is composed of 78.5-94.4wt% glycerol, 5-20wt% deionized water, 0.1-0.5wt% ammonium fluoride and 0.5-1wt% sodium lauryl sulfate; the voltage is 25-50V, the distance between the anode titanium alloy and the cathode is 15-25cm, and the reaction time is 1-8 hours.

4. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step 3), the povidone iodine / sodium alginate / glycerol mixed solution is composed of 59.5-90 wt% povidone iodine, 0.25-0.75 wt% sodium alginate and 9.25-39.75 wt% glycerol, and the viscosity of the sodium alginate is ≥0.002 Pas.

5. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step 3), the ultrasonic dispersion time is 10-30 minutes, the vacuum degree of the vacuum infusion is 1-30 Pa, and the vacuuming time is 0.1-2 hours; the pressure holding time is 1-3 hours; the drying is carried out at a temperature of 20-25°C with a micro-airflow for 1-6 hours; and the number of cycles is 5-15 times.

6. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step 4), the ethanol / water solution of the silane preparation with a double bond comprises a solvent comprising a mixed solution of ethanol and water in a volume ratio of 1:1, and the solute comprising the silane preparation with a double bond comprises one or more of γ-(methacryloyloxy)propyltrimethoxysilane, vinyltri(β-methoxyethoxy)silane, vinyltrimethoxysilane, and vinyltriethoxysilane, with a concentration of 2.5-7.5 wt%.

7. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step ①, the number average molecular weight of the chitosan is 300,000-800,000, and the degree of deacetylation is 60-80%; the dropping time is 1-2 hours, and the reaction time is 2-6 hours.

8. The method for preparing a long-lasting intelligent composite antibacterial coating with dual pH response function according to claim 1, characterized in that: In step 5), the photoinitiator is one or more of LAP photoinitiator, 127 photoinitiator, and I2959 ultraviolet photoinitiator, with a concentration of 0.25-0.5wt%; the immersion time is 5-30 min; the ultraviolet light wavelength is 408 nm, the photocuring time is 30 s-10 min; and the number of cycles is 3-5 times.

9. A long-lasting intelligent composite antibacterial coating with dual pH response function, characterized in that: Prepared by the method according to any one of claims 1 to 8.

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