Method for preparing a phosphating coating of a medical zinc alloy surface doped with divalent metal functional ions

Abstract

This invention relates to a method for preparing a phosphating coating doped with divalent metal functional ions on the surface of medical zinc alloys. The invention involves introducing an oxidant and a nucleation modifier into a phosphating solution containing divalent metal functional ions. Through a two-step liquid-phase transformation method, the oxidant first accelerates the reaction, improving the uniformity and density of the underlying phase to form a dense underlying phase. Then, the nucleation modifier refines the grain size of the upper phase through adsorption, forming a particulate upper phase. Finally, a biphase composite phosphating coating doped with different divalent metal functional ions is obtained. The phosphating coating obtained by this method is dense and uniform, has strong adhesion, and can degrade slowly. It effectively reduces the initial degradation rate of zinc alloys and Zn. 2+ It releases and reduces cytotoxicity; at the same time, it can continuously release divalent metal functional ions with good biological activity over a longer period of time, which significantly improves the biocompatibility of zinc alloys in two aspects.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials technology and relates to a method for preparing a phosphating coating on the surface of a medical zinc alloy doped with divalent metal functional ions. Background Technology

[0002] With advancements in research, zinc alloys, as a novel biodegradable medical metal material, have demonstrated unique advantages in fields such as orthopedic implants, cardiovascular interventions, and nerve repair. Zinc is the second most essential trace element for the human body after iron, and it serves as a cofactor for over 300 enzymes in the human body, playing a crucial role in the development of the immune and nervous systems, as well as bone growth and mineralization. In orthopedic applications, Zn... 2+ It can precisely regulate the expression of bone-related genes such as alkaline phosphatase and type I collagen, effectively promoting osteoblast adhesion, proliferation, and differentiation. Simultaneously, zinc alloys possess a moderate degradation rate, a uniform corrosion pattern, and good mechanical properties, enabling them to maintain structural integrity during the critical period of fracture healing and provide reliable support in harsh service environments such as the medullary cavity. This overcomes the premature failure problems of magnesium alloys caused by excessively rapid degradation, localized corrosion, and hydrogen production during degradation. Furthermore, the inherent broad-spectrum antibacterial properties of zinc alloys help reduce the risk of infection at the implantation site during orthopedic implantation surgery.

[0003] However, the human body's response to Zn 2+ Its tolerance is less than that of Mg 2+ For zinc alloy implants, Zn 2+ The rapid initial release and excessively high local concentrations of zinc can lead to cytotoxicity, severely limiting the clinical application of medical zinc alloys in tissue repair. To address this issue, surface modification has become a highly effective method to improve the biocompatibility of zinc alloys. Currently, surface coatings for zinc and zinc alloy implants can be mainly classified into inorganic coatings, organic coatings, and composite coatings. Surface modification methods mainly include chemical conversion, anodic oxidation, micro-arc oxidation, electrochemical deposition, and magnetron sputtering. Although some research has focused on the surface modification of zinc and zinc alloys, there are still many shortcomings. For example, some coatings formed by micro-arc oxidation and magnetron sputtering can form galvanic corrosion with the substrate, thus accelerating zinc degradation and reducing its biocompatibility. 2+ The initial release of these substances did not decrease but increased, causing more serious cytotoxicity. For example, some coatings in the current research are non-degradable, such as DLC, Ti and ZrO2 coatings. During service, as the zinc substrate corrodes and degrades, the coating may peel off and remain in the body. The human body cannot excrete it through metabolism, which may lead to long-term inflammation and other problems.

[0004] Patent CN111218677A discloses a method for preparing a bioactive calcium-phosphorus coating on the surface of a biodegradable medical zinc alloy, which forms the calcium-phosphorus coating on the zinc alloy surface through liquid phase deposition. This method does not require specialized equipment and allows for control of the coating thickness and zinc ion release rate. However, the problem lies in the fact that the bond between the calcium-phosphorus coating and the zinc alloy substrate is mainly physical, based on van der Waals forces. The significant differences in their coefficients of thermal expansion and crystal structures result in weak coating adhesion, making it prone to peeling or cracking during implantation or service. Furthermore, the coating has a high roughness, making it difficult to achieve sub-micron level precision control.

[0005] Patent CN115779142A discloses a biodegradable drug-loaded coating for the surface of zinc alloy implants and its preparation method. The drug-loaded coating is prepared on the zinc alloy surface through the synthesis of photosensitive biodegradable polycarbonate, macromolecular self-assembly, and ultraviolet curing. This coating exhibits strong adhesion, can uniformly and sustainably release drugs, and inhibits the burst release of zinc ions. However, the problem lies in the possibility that ultraviolet curing may affect the activity of heat-sensitive drugs, and the polymer degradation products are acidic, potentially causing local inflammation.

[0006] Patent CN121006497A discloses a method for preparing a toughened zinc-based medical material with osteogenic, time-degradable, and antibacterial properties. This patent constructs a zinc phosphate coating on the surface of pure zinc powder through chemical deposition, and uses it as the outer layer of the composite material to achieve Zn… 2+ The initial slow release of ZnP allows for the initial slow degradation of the entire composite material, thereby enhancing osteogenic function. However, patent examples show that this single ZnP coating has a significant impact on ZnP content. 2+ The initial release of the coating has limited regulatory power and cannot achieve long-term effective regulation. In addition, the coating will undergo high-temperature heat treatment in subsequent thermal processing (pre-sintering, hot extrusion), which may cause the zinc phosphate coating to undergo phase transformation, decomposition or interdiffusion with the substrate, thereby changing its structure, composition and interface properties or even causing failure. In other words, this surface modification method is largely subject to subsequent steps.

[0007] Patent CN110448728A discloses a method for preparing a magnesium-phosphorus biocompatible coating on the surface of a medical zinc-based material and its application. The method involves pre-treating the surface of zinc and zinc alloys, followed by constant-temperature immersion in a phosphate solution to generate the magnesium-phosphorus coating. This coating can slow down the initial release rate of zinc ions, a degradation product, while simultaneously releasing an appropriate amount of bioactive magnesium. 2+ However, the problem lies in the presence of large-sized magnesium hydrogen phosphate particles in the coating, which reduces the overall uniformity of the coating, and Mg... 2+ The release duration is short, with significant release only in the first 7 days rather than long-term sustained release, thus failing to achieve long-term sustained bone-promoting effects.

[0008] In summary, while some current surface modification methods and coatings can solve some problems, they have certain limitations. Therefore, there is an urgent need to develop a simple, easy-to-implement, non-toxic, uniform, dense coating with multifunctional bioactivity to effectively enhance the application of biodegradable medical zinc alloys in clinical implants for hard tissue repair in orthopedics, dentistry, and other fields. Summary of the Invention

[0009] To address the aforementioned technical problems, this invention provides a method for preparing a phosphating coating doped with divalent metal functional ions on the surface of medical zinc alloys. This invention introduces an oxidant and a nucleation regulator into a phosphating solution containing divalent metal functional ions. Through a two-step liquid-phase transformation method, the oxidant first accelerates the reaction, improving the uniformity and density of the underlying phase to form a dense underlying phase. Then, the nucleation regulator refines the grain size of the upper phase through adsorption, forming a particulate upper phase. Finally, a biphase composite phosphating coating doped with different divalent metal functional ions is obtained. The phosphating coating obtained by this method is dense and uniform, has strong adhesion, and can degrade slowly. It effectively reduces the initial degradation rate of zinc alloys and Zn. 2+ It releases and reduces cytotoxicity; at the same time, it can continuously release divalent metal functional ions with good biological activity over a longer period of time, which significantly improves the biocompatibility of zinc alloys in two aspects.

[0010] The objective of this invention can be achieved through the following methods:

[0011] In a first aspect, the present invention provides a method for preparing a phosphating coating on the surface of a medical zinc alloy doped with divalent metal functional ions, wherein the divalent metal functional ions include Mg 2+ 、Sr 2+ Ca 2+ Mn 2+ One or more of the above, wherein the preparation method includes the following steps: S1. Prepare a phosphating solution containing divalent metal salt, dihydrogen phosphate, and oxidant. Immerse the zinc alloy material in the phosphating solution to form a dense bottom phase of the phosphating coating. S2. After the bottom dense phase of the phosphate coating is formed, a nucleation regulator is added to the phosphate treatment solution and the soaking continues to form the upper particulate phase of the phosphate coating.

[0012] The phosphating coating prepared by the method of this invention is a two-phase composite coating. The bottom phase is a composite phosphate (zinc magnesium phosphate / strontium / calcium / manganese), with a thickness of 2-5 μm, petal-shaped, tightly bonded to the substrate, and dense and uniform. The upper phase is a hydrogen phosphate (magnesium hydrogen phosphate / strontium / calcium / manganese), with a size of 5-15 μm, equiaxed small particles, uniformly distributed on the bottom phase. The ratio of doped divalent metal functional ions to zinc ions in the bottom phase composite phosphate is 1:1-1:2.

[0013] Further, in step S1, the thickness of the bottom dense phase is 2-5 μm, wherein the molar ratio of the doped divalent metal functional ions to zinc ions is 1:1-1:2. In step S2, the size of the upper particulate phase is 5-15 μm.

[0014] Further, in step S1, the zinc alloy material is a pretreated zinc alloy material; the pretreatment is as follows: mechanically grinding or electrochemically polishing the surface of the zinc alloy material to remove the surface oxide layer, then placing the zinc alloy material in anhydrous ethanol for ultrasonic cleaning to remove grinding debris and other impurity particles, taking it out and drying it with cold air, and then using an ultraviolet ozone generator for cleaning treatment.

[0015] Furthermore, the zinc alloy material includes one of the following Zn-based alloys: pure Zn, Zn-Al, Zn-Ag, Zn-Cu, Zn-Ca, Zn-Li, Zn-Mg, Zn-Fe, Zn-Mn, and Zn-Re.

[0016] Further, in step S1, the divalent metal salt includes at least one selected from magnesium, strontium, calcium, and manganese salts; the concentration of the divalent metal salt in the phosphating solution is 0.05-0.3 mol / L; wherein the concentration of magnesium salt is 0.1-0.3 mol / L, and / or the concentration of strontium salt is 0.05-0.1 mol / L, and / or the concentration of calcium salt is 0.1-0.2 mol / L, and / or the concentration of manganese salt is 0.1-0.2 mol / L. This concentration varies slightly depending on the Ksp of the hydrogen phosphate of each divalent ion.

[0017] Furthermore, the divalent metal salt is selected from at least one of magnesium chloride, magnesium nitrate, magnesium sulfate, strontium chloride, strontium nitrate, calcium chloride, calcium nitrate, manganese chloride, manganese nitrate, and manganese sulfate.

[0018] Further, in step S1, the dihydrogen phosphate salt is selected from at least one of sodium dihydrogen phosphate, potassium dihydrogen phosphate, and ammonium dihydrogen phosphate.

[0019] Further, in step S1, the concentration of dihydrogen phosphate in the phosphating solution is 0.1-0.5 mol / L, and the molar ratio of divalent metal salt to dihydrogen phosphate is 1:1-1:2. The divalent metal salt and dihydrogen phosphate are the basic substrates of this phosphating solution, providing divalent functional ions and phosphorus sources, respectively, for the phosphating coating. If the concentrations of divalent metal salt and dihydrogen phosphate are too low, the coating reaction will be insufficient, failing to form a dense and uniform coating, and the coating thickness will be reduced, significantly decreasing the protective and uniform properties of the phosphating coating. If the concentrations of divalent metal salt and dihydrogen phosphate are too high, a supersaturated solution will form, making the solution prone to turbidity. Suspended particles formed in the solution will adhere to the sample surface, leading to a decrease in coating adhesion and hindering coating preparation. If the ratio of divalent metal salt to dihydrogen phosphate is too low, the content of divalent functional ions in the coating will decrease (for example, if the ratio of magnesium salt to dihydrogen phosphate is too low, the magnesium content in the underlying zinc magnesium phosphate phase will decrease, making it a mixture of zinc phosphate and zinc magnesium phosphate, and the content of the upper magnesium hydrogen phosphate phase will also decrease). This will reduce the efficiency of the coating in releasing divalent functional ions and will not effectively suppress the initial release of zinc ions. If the ratio of divalent metal salt to dihydrogen phosphate is too high, it will lead to the rapid formation and growth of hydrogen phosphate particles on the coating surface, which is not conducive to the uniformity of the coating.

[0020] Further, in step S1, the oxidant is selected from at least one of hydrogen peroxide, sodium nitrate, and potassium nitrate. This oxidant is used to accelerate the substrate reaction, refine the coating grains, and improve adhesion.

[0021] Further, in step S1, the concentration of the oxidant in the phosphating solution is 0.05-0.2 mol / L.

[0022] In this invention, the specific mechanism of action of the oxidant is as follows: the oxidant (e.g., nitrate) has a certain mild oxidizing effect under slightly acidic conditions, which can accelerate the reaction between the substrate and the solution, that is, accelerate the dissolution of zinc ions from the surface of the zinc alloy substrate, and rapidly combine with divalent functional ions and phosphate ions in the solution, chemically co-depositing on the zinc alloy surface to form a composite phosphate (zinc magnesium / strontium / calcium / manganese phosphate) in the coating. The addition of this oxidant significantly accelerates the nucleation rate of the composite phosphate and greatly increases the number of nucleation sites, thereby achieving the refinement and densification of the underlying flower-like phase, thus improving the uniformity and density of the coating and its adhesion to the substrate. If the concentration of the oxidant (nitrate) is too low, the texture cannot be refined, and the flower-like structure remains relatively coarse, which is detrimental to the uniformity of the texture and the density of the coating, and cannot effectively reduce the initial release concentration of zinc ions. If the concentration of the oxidant (nitrate) is too high, the chemical co-deposition reaction is too fast, which will promote the primary dissociation of dihydrogen phosphate in the solution too quickly, and react rapidly with a large number of divalent functional ions in the solution to generate larger particulate hydrogen phosphate (magnesium hydrogen phosphate / strontium hydrogen phosphate / calcium / manganese), which adhere to the coating, which is also detrimental to the overall uniformity and adhesion of the coating.

[0023] Furthermore, in step S2, the nucleation regulator is selected from at least one of sodium phosphate and potassium phosphate.

[0024] Further, in step S2, the concentration of the nucleation regulator in the phosphating solution is 0.1-0.4 mol / L, and the pH value of the solution is adjusted to 4.5-5.5.

[0025] In this invention, the specific mechanism of action of the nucleation regulator is as follows: after the bottom dense phase has been fully formed, the nucleation of the upper phase hydrogen phosphate (magnesium / strontium / calcium / manganese phosphate) is promoted by supplementing the phosphorus source and increasing the pH. Furthermore, the anisotropic growth of the hydrogen phosphate block particles is inhibited by adsorption onto the high-energy crystal faces of the hydrogen phosphate grains, thereby achieving grain refinement. If sodium hydroxide is used to adjust the pH instead of phosphate, this grain refinement effect will not be achieved. If the adjusted pH is too low, the primary dissociation of dihydrogen phosphate in the solution will be insufficient, failing to form the effective component of the hydrogen phosphate phase. This will significantly reduce the effect of the coating in releasing divalent functional ions, thus decreasing its bone-promoting and angiogenic efficacy. If the adjusted pH is too high, the primary dissociation of dihydrogen phosphate in the solution will be too rapid, causing the rapidly formed hydrogen phosphate particles to aggregate or grow, which is detrimental to the uniformity of the coating and will also adversely affect the morphology of the bottom flower-like composite phosphate phase, reducing its density.

[0026] Further, in step S1 or S2, the immersion temperature is 40-60 ℃; the immersion time in step S1 is 1-2 h, and the immersion time in step S2 is 1-3 h. If the immersion temperature is too low, the coating reaction is too slow, resulting in low preparation efficiency; if the immersion temperature is too high, it will accelerate Ostwald ripening, and the small grains with high curvature are more likely to redissolve under the energy provided by the high temperature. The dissolved ions migrate and deposit on the surface of the large grains with low curvature, resulting in coarse coating grains. If the immersion time in step S1 is too short, a uniform and dense bottom phase cannot be formed in the coating, and the zinc substrate cannot be completely covered and protected. In subsequent service, local corrosion is likely to occur, leading to rapid failure. If the immersion time in step S2 is too short, the number of hydrogen phosphate particles in the formed upper phase will be small, and a sufficient concentration of divalent functional ions cannot be released during service, which will significantly reduce the promoting effect on cell growth and biological repair.

[0027] One of the innovative ideas behind this invention for preparing phosphating coatings doped with divalent metal functional ions on zinc alloy surfaces is the construction of a customizable bioactive interface through the controllable doping of diverse divalent metal ions. Unlike existing technologies (such as CN110448728A) that rely solely on a single magnesium ion to achieve basic biocompatibility, this invention abandons the single-function ion strategy and innovatively proposes the introduction of a flexibly selectable library of divalent metal ions into the phosphating coating for controllable doping. This ion library not only includes conventional magnesium ions but also encompasses strontium ions, manganese ions, calcium ions, and other ions with unique and irreplaceable biological functions. The breakthrough of this design lies in its transformation, for the first time, of a zinc-based phosphating coating from a passive barrier with a fixed composition into an active platform with programmable functionality. By selecting different doping ions, coatings can precisely achieve differentiated clinical goals: for example, strontium doping enables the coating to acquire a clear local therapeutic function of "anti-osteoporosis," manganese doping endows it with the efficacy of "powerfully initiating cellular integrins to accelerate bone integration," while calcium doping can serve as a "core template for guiding in-situ biomineralization." This can solve the inherent problem of existing coating technologies having a single functional dimension and being unable to adapt to complex clinical needs (such as osteoporotic bone beds and wounds at risk of infection). The innovative idea behind this is that it provides a universal functional design principle and implementation method, enabling coatings to carry different functional ions according to different application scenarios, thereby realizing the leap from "general-purpose" to "customized" biomedical coatings.

[0028] The second innovative idea of ​​this invention for preparing a phosphating coating doped with divalent metal functional ions on a zinc alloy surface is based on a two-step liquid-phase transformation mechanism of "preferential nucleation of the dense underlying phase followed by the subsequent growth of the upper particulate phase," thereby achieving a structure-function correlation design for the coating. This invention abandons the previous design approach of homogenized coatings and creatively reveals and utilizes a step-by-step controllable liquid-phase transformation deposition mechanism. Its innovative idea lies in: by controlling the chemical composition, pH value, and reaction interface kinetics of the phosphating solution, a dense, continuous, flower-like underlying phase, mainly composed of composite phosphate, is induced to form on the zinc alloy substrate first. This underlying phase serves as the main framework of the coating, and its main function is to provide excellent substrate adhesion and basic barrier protection. Subsequently, under specific changes in the interfacial microenvironment (increased hydrogen phosphate ion concentration and increased pH), the metal functional ions in the solution are driven to combine with hydrogen phosphate, resulting in the in-situ epitaxial growth of a blocky or particulate upper phase of hydrogen phosphate on top of the underlying phase. The upper particulate phase serves as a "reservoir" for functional ions, and its morphology, size, and distribution can be independently controlled, thereby achieving independent optimization of the functional ion release kinetics. This structural innovation enables the phosphating coating to simultaneously possess strong adhesion, uniform corrosion mechanical properties, and controllable and durable biological functions.

[0029] The third innovative aspect of this invention for preparing phosphating coatings doped with divalent metal functional ions on zinc alloy surfaces is the synergistic introduction of oxidants and nucleation modifiers to jointly control the entire coating deposition process from nanocrystalline nuclei to micron-sized structures. The oxidant gently adjusts the oxidation state of the metal substrate surface, forming a more uniform and dense bottom phase. The nucleation modifier, by adsorbing onto the high-energy crystal faces of the grains, inhibits the anisotropic growth of bulk particles, resulting in a fine and uniformly distributed upper phase. Under the coupled regulatory effect of these two, both phases in the phosphating coating undergo significant structural changes: the petal structure of the bottom phase becomes finer, greatly increasing the coating's density; while the particle size of the upper phase is significantly reduced, its distribution is more uniform, and its bond with the underlying zinc-magnesium phosphate layer is stronger, further increasing the overall uniformity of the coating. Ultimately, the adhesion between the coating and the substrate is also significantly improved. Compared to coatings prepared without the introduction of oxidants and nucleation modifiers, the coating prepared using this method can achieve a lower initial release concentration of zinc ions and a longer inhibition time, while simultaneously increasing the release concentration of divalent metal functional ions and extending their release time. In addition, the oxidant and nucleation regulator used are homologous soluble substances in the formulation of the phosphating solution. The introduction of the two will not introduce new impurities into the phosphating coating. That is, when optimizing the structure of the coating, it will not affect the effective components of the coating, nor will it affect the bioactivity and good biocompatibility of the coating.

[0030] The fourth innovative idea of ​​this invention for preparing a phosphating coating doped with divalent metal functional ions on the surface of zinc alloys is the chemical co-deposition of divalent metal functional ions, phosphate ions, hydrogen phosphate ions in solution, and zinc ions generated by the substrate reaction to form a dense phosphating coating in situ on the zinc alloy substrate surface. The bonding method is chemical bonding, which provides stronger adhesion compared to physical bonding methods such as coating or magnetron sputtering, and is not limited by the sample shape and size (coating and magnetron sputtering have certain requirements on sample shape and structure; for example, samples with deep holes or complex shapes cannot obtain a complete film in three-dimensional space). Furthermore, using this liquid-phase conversion method, only the phosphating solution needs to be prepared before immersion, and reagents only need to be added once during the process. The process is simple, easy to implement, environmentally friendly, and low-cost, making it suitable for the actual engineering production of various complex-shaped implantable devices.

[0031] Secondly, the present invention provides a phosphating coating on the surface of a medical zinc alloy doped with divalent metal functional ions, obtained by the preparation method described above.

[0032] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention modifies the formulation of the treatment solution to separately react Mg 2+ 、Sr 2+ Ca 2+ Mn 2+ Different divalent metal functional ions were successfully incorporated into the phosphating coating, achieving customized multifunctionality. Furthermore, the introduction of oxidants and nucleation modifiers, along with a two-step liquid-phase transformation method, resulted in a dense, uniform, and strongly bonded phosphating coating. This effectively reduces the initial degradation rate of zinc alloys and slows down the degradation of Zn. 2+ It can release the initial ions and also continuously release bioactive divalent metal functional ions over a longer period of time, which significantly improves the biocompatibility of zinc alloys in two ways.

[0033] 2. The phosphating coating obtained by the method of this invention can effectively reduce the initial degradation rate of zinc alloys and slow down the initial release of zinc ions. This effect is significant within 28 days, maintaining a concentration below 5 ppm for the first 14 days and below 15 ppm from days 14 to 28, both within a concentration range favorable to osteoblasts. Simultaneously, it can continuously release bioactive divalent metal functional ions for a longer period. For example, the magnesium-doped phosphating coating still releases more than 50 ppm of magnesium ions after 28 days, and the strontium-doped phosphating coating still releases more than 5 ppm of strontium ions after 28 days, both within a concentration range favorable to osteoblast proliferation and differentiation. The phosphating coating obtained by the method of this invention significantly improves the biocompatibility of zinc alloys by controlling excessive zinc ion release and increasing beneficial functional ions.

[0034] 3. The process of this invention is simple and easy to implement, environmentally friendly, low in cost, and high in production efficiency, making it suitable for practical engineering production and clinical applications. Furthermore, the coating of this invention is chemically grown in situ; the coating can be formed wherever the treatment solution can reach, thus it is not limited by the shape of the device. It is applicable not only to bone screws and plates but also to various complex-shaped zinc alloy intraosseous implants. Attached Figure Description

[0035] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings: Figure 1 A scanning electron microscope image of the magnesium-doped phosphate coating on the zinc alloy surface prepared in Example 1; Figure 2 Scanning electron microscope (SEM) images of the phosphate coatings on the zinc alloy surfaces prepared in comparative examples 1-6; Figure 3 Fluorescent micrographs of live / dead staining of MC3T3-E1 osteoblasts adhering to the coating prepared in Example 1, the coating prepared in Comparative Example 1, the bare zinc alloy, and the negative control group (well plate). Detailed Implementation

[0036] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. The following examples are implemented under the premise of the technical solution of the present invention, providing detailed implementation methods and specific operating procedures, which will help those skilled in the art to further understand the present invention. It should be noted that the scope of protection of the present invention is not limited to the following embodiments; any adjustments and improvements made under the concept of the present invention are all within the scope of protection of the present invention.

[0037] Example 1 The zinc alloy matrix in this embodiment is Zn. A 2Cu-0.8Li alloy disc, in extruded state, has dimensions of Φ12×2 mm. The desired coating is a magnesium-doped phosphating coating.

[0038] The surface of the zinc alloy small discs was mechanically polished sequentially using 320#, 1200#, and 3000# SiC sandpaper to remove the oxide layer until a bright silver-white finish was achieved. Then, they were ultrasonically cleaned in anhydrous ethanol for 10 minutes, removed, and dried with cold air. Next, they were cleaned using a UV ozone generator for 15 minutes on each side. A phosphating solution was prepared with the following formula: 0.2 mol / L MgSO4·7H2O + 0.3 mol / L NaH2PO4·2H2O + 0.1 mol / L NaNO3. After adding ultrapure water, the pretreated zinc alloy small discs were placed in the solution and immersed in a 50 ℃ water bath for 1.5 hours. After the dense zinc-magnesium phosphate bottom phase has formed, Na3PO4·12H2O reagent is slowly added to the treatment solution to adjust the pH to 5.0. At this point, the Na3PO4 concentration in the treatment solution is approximately 0.2 mol / L. The solution is then soaked in a 50 ℃ water bath for 1.5 h to form the upper particulate phase of magnesium hydrogen phosphate. After soaking, the sample is collected and rinsed sequentially with ultrapure water and anhydrous ethanol, then dried to obtain small disc samples coated with the magnesium-doped phosphate coating.

[0039] The obtained magnesium-doped phosphate coating has a two-phase structure of zinc magnesium phosphate and magnesium hydrogen phosphate, and its microstructure is as follows: Figure 1 As shown. The zinc-magnesium phosphate layer is located at the bottom layer, tightly bonded to the substrate, and is flower-shaped, dense, and uniform, with a thickness of 2-5 μm. The magnesium hydrogen phosphate layer consists of equiaxed small particles, uniformly distributed on the zinc-magnesium phosphate layer, with a thickness (particle size) of 5-15 μm. The overall roughness Ra of the coating is 4.5 μm. The adhesion between the coating and the substrate is 12.4 MPa.

[0040] The coating samples prepared by this process were immersed in a culture medium for 28 days, and the Zn content was measured. 2+ The release concentration remained below 5 ppm for the first 14 days and below 10 ppm from days 14 to 28, which were less than 20% and 50% of those of uncoated bare metal discs, respectively; simultaneously, it was able to continuously release bioactive Mg for 28 days. 2+ For the first 14 days, the concentration of Mg remained above 100 ppm, and even on day 28, it was still above 50 ppm. 2+ Release (all within concentration ranges favorable for osteoblast proliferation and differentiation). Cells were cultured using 100% concentration extract of the coated samples for 1 day and 3 days to verify indirect cell viability. Cell viability was measured to be above 120%, superior to the culture medium control group, indicating a significant positive promoting effect on osteoblasts; while the cell viability of the 100% concentration extract of bare metal was below 20%, showing significant cytotoxicity. MC3T3-E1 cells were directly seeded onto the sample surface to verify direct cell viability. After 3 days of co-culture, fluorescence micrographs showing cell viability and death staining are shown below. Figure 3As shown in the figure (green dots represent live cells; dead cells are not representative and are not analyzed because they are removed during rinsing and other experimental procedures). The results show that cells can hardly adhere to bare metal. Figure 3 (c)), while cells on the coated sample were able to adhere normally ( Figure 3 (a) The number of live cells increased significantly, with a live cell density of 116 cells / mm². 2 The growth was good. Direct cell experiments also demonstrated that the coating prepared by this process has excellent biocompatibility. In addition, the dense and uniform magnesium-doped phosphate coating on the zinc alloy surface prepared by the process of Example 1 greatly improved the cell compatibility of the bare zinc alloy, and the cell adhesion rate and survival rate were significantly higher than those of the process of Comparative Example 1.

[0041] Example 2 The zinc alloy matrix in this embodiment is Zn. The 2Cu-1Mg alloy intramedullary nail is in the extruded state and has dimensions of Φ2×30 mm. A strontium-doped phosphating coating is desired.

[0042] The zinc alloy intramedullary nail was electrochemically polished using a phosphoric acid-ethylene glycol-acetic acid polishing solution to remove the surface oxide layer until it was bright silvery-white. It was then ultrasonically cleaned in anhydrous ethanol for 10 min, removed, and dried with cold air. Following this, it was cleaned using a UV ozone generator for 15 min. A phosphating solution was prepared with the following formula: 0.1 mol / L Sr(NO3)2·4H2O + 0.15 mol / L NaH2PO4·2H2O + 0.05 mol / L KNO3. After adding ultrapure water, the pretreated zinc alloy intramedullary nail was placed in the solution and immersed in a 55 ℃ water bath for 2 h. Once the dense zinc phosphate bottom phase had formed, Na3PO4·12H2O was slowly added to the solution to adjust the pH to 4.8. At this point, the Na3PO4 concentration in the solution was approximately 0.16 mol / L. The solution was then immersed in a 50 ℃ water bath for another 1 h to form the upper strontium hydrogen phosphate particulate phase. After soaking, the sample was collected and rinsed with ultrapure water and anhydrous ethanol in sequence, and then dried to obtain the intramedullary nail sample coated with the strontium-doped phosphating coating.

[0043] The obtained strontium-doped phosphating coating has a dense and uniform two-phase structure of strontium zinc phosphate and strontium hydrogen phosphate, with a thickness of ~10 μm. The overall roughness Ra of the coating is 4.7 μm. The adhesion between the coating and the substrate is 13.8 MPa.

[0044] The coated intramedullary nail samples prepared by this process were immersed in a culture medium for 28 days, and the Zn content was measured. 2+The release concentration remained below 3 ppm for the first 14 days and below 8 ppm from days 14 to 28, which are less than 20% and 40% of those of uncoated bare metal intramedullary nails, respectively; it also continuously released Sr with good bioactivity. 2+ 28 days Sr 2+ The release concentrations were all above 20 ppm (all within the concentration range favorable for osteoblast proliferation and differentiation). Cells were cultured using 100% concentration extracts of the coated intramedullary nail samples after 1 and 3 days to verify indirect cell viability. Cell viability was measured to be above 110%, indicating a significant positive promoting effect on osteoblasts. Direct cell viability was verified by directly seeding MC3T3-E1 cells onto the sample surface. Results showed a significant increase in the number of viable cells on the surface of the coated intramedullary nail samples, with a viable cell density reaching 10⁹ cells / mm² after 3 days of culture. 2 Furthermore, the cells exhibited good growth morphology, with pseudopodia adhering and growing along the annular wall of the intramedullary nail. This strontium-doped phosphating coating significantly promoted the proliferation, spread, and adhesion of osteoblasts, thereby substantially improving the biocompatibility of the zinc alloy intramedullary nail.

[0045] Example 3 The zinc alloy matrix in this embodiment is Zn. The 3Cu alloy plate is in the cast state, measuring 6 × 20 mm, with 4 mm chamfered corners and three 2 mm circular holes in the center. A calcium-doped phosphating coating is desired.

[0046] The zinc alloy bone plate was electrochemically polished using a phosphoric acid-ethylene glycol-acetic acid polishing solution to remove the surface oxide layer until it was bright silver-white. It was then ultrasonically cleaned in anhydrous ethanol for 10 min, removed, and dried with cold air. Following this, it was cleaned using a UV ozone generator for 15 min. A phosphating solution was prepared with the following formula: 0.15 mol / L CaCl2·2H2O + 0.2 mol / L NaH2PO4·2H2O + 0.06 mol / L NaNO3. After adding ultrapure water, the pretreated zinc alloy bone plate was placed in the solution and immersed in a 50 ℃ water bath for 2 h. Once the dense zinc-calcium phosphate bottom phase had formed, Na3PO4·12H2O was slowly added to the solution to adjust the pH to 5.5. At this point, the Na3PO4 concentration in the solution was approximately 0.25 mol / L. The solution was then immersed in a 50 ℃ water bath for another 1.5 h to form the upper granular phase of calcium hydrogen phosphate. After soaking, the sample was collected and rinsed with ultrapure water and anhydrous ethanol in sequence, and then dried to obtain the bone plate sample coated with the calcium-doped phosphate coating.

[0047] The obtained calcium-doped phosphate coating has a dense and uniform two-phase structure of zinc calcium phosphate and dicalcium hydrogen phosphate, with a thickness of ~20 μm. The overall roughness Ra of the coating is 5.3 μm. The adhesion between the coating and the substrate is 10.6 MPa.

[0048] The coated bone plate samples prepared by this process were immersed in a culture medium for 28 days, and the Zn content was measured. 2+ The release concentration remained below 5 ppm for the first 14 days and below 10 ppm from days 14 to 28, which were less than 15% and 30% of those of uncoated bare metal plates, respectively; it also continuously released bioactive Ca. 2+ 28-day Ca 2+ The release concentrations were all between 100-200 ppm (within the concentration range favorable for osteoblast proliferation and differentiation). Cells were cultured using 100% concentration extract of the coated bone plate samples after 1 and 3 days to verify indirect cell viability. Cell viability was measured to be above 120%, indicating a significant positive promoting effect on osteoblasts. Direct cell viability was verified by directly seeding MC3T3-E1 cells onto the sample surface. Results showed a significant increase in the number of viable cells on the surface of the coated bone plate samples, with a viable cell density reaching 114 cells / mm² after 3 days of co-culture. 2 Furthermore, the cells exhibited good growth morphology, with pseudopodia spreading along the surface of the bone plate. Both direct and indirect cell experiments demonstrated the good biocompatibility of the coating.

[0049] Example 4 The zinc alloy matrix in this embodiment is Zn. A porous 2Mg alloy bone tissue engineering scaffold, formed by 3D printing LPBF technology, measures Φ10×5 mm, has a porosity of 75%, and an average pore size of 700 μm. A manganese-doped phosphating coating is to be prepared.

[0050] The zinc alloy porous bone tissue engineering scaffold was electrochemically polished using a phosphoric acid-ethylene glycol-acetic acid polishing solution to remove the surface oxide layer until it reached a bright silver-white color. It was then ultrasonically cleaned in anhydrous ethanol for 10 min, removed, and dried with cold air, followed by cleaning with a UV ozone generator for 30 min. A phosphating solution was prepared with the following formula: 0.2 mol / L MnCl2·4H2O + 0.35 mol / L NaH2PO4·2H2O + 0.05 mol / L KNO3. After adding ultrapure water, the pretreated zinc alloy scaffold was placed in the solution and immersed in a 40 ℃ water bath for 2 h. Once the dense zinc manganese phosphate bottom phase had formed, Na3PO4·12H2O was slowly added to the solution to adjust the pH to 4.5. At this point, the Na3PO4 concentration in the solution was approximately 0.12 mol / L. Immersion in a 40 ℃ water bath continued for 1 h to form the upper manganese hydrogen phosphate granular phase. After soaking, the sample was collected and rinsed with ultrapure water and anhydrous ethanol in sequence, and then dried to obtain a porous bone tissue engineering scaffold sample coated with the manganese-doped phosphating coating.

[0051] The obtained manganese-doped phosphate coating has a dense and uniform two-phase structure of zinc manganese phosphate and hydrogen manganese phosphate, with a thickness of ~5 μm. The overall roughness Ra of the coating is 4.2 μm. The adhesion between the coating and the substrate is 13.6 MPa.

[0052] The coated porous bone tissue engineering scaffold samples prepared by this process were immersed in culture medium for 28 days, and the Zn content was measured. 2+ The release concentration remained below 5 ppm for the first 14 days and below 15 ppm from days 14 to 28, which were less than 10% and 20% of the uncoated bare metal scaffold, respectively; simultaneously, it was able to continuously release bioactive Mn. 2+ 28 days Mn 2+ The release concentrations were all between 1-3 ppm (within the concentration range favorable for osteoblast proliferation and differentiation, and promoting endothelial cell adhesion and migration). Cells were cultured using 100% concentration extract of the coated scaffold samples for 1 day and 3 days to verify indirect cell viability. Cell viability was measured to be above 115%, indicating a significant positive promoting effect on osteoblasts. MC3T3-E1 osteoblasts and HUVEC endothelial cells were directly seeded onto the scaffold to verify direct cell viability. Results showed that both cell types not only grew normally on the coating surface but also entered the porous structure, adhering and growing along the porous curved surface. After 7 days of culture, the cell penetration rate reached over 80%. MC3T3-E1 osteoblasts showed good spreading morphology, and the viable cell density reached 10⁶ cells / mm² after 3 days of co-culture. 2The coating exhibited excellent osteogenic activity; simultaneously, HUVEC endothelial cells formed a continuous monolayer, uniformly ascended, and crossed cross-linking nodes, demonstrating superior endothelialization ability. This coating significantly improved the biocompatibility of the zinc alloy porous bone tissue engineering scaffold, reducing its cytotoxicity from grade 3 (uncoated) to grade 0, and demonstrating significant positive effects on both osteogenic and endothelialization promotion. Furthermore, the porous zinc alloy scaffold maintained its three-dimensional interconnected pore structure after coating, retaining structural integrity even after 28 days of immersion, without significant pore blockage.

[0053] Example 5 The zinc alloy matrix in this embodiment is Zn. The 1Ag alloy alveolar mesh, formed by 3D printing LPBF technology, has macroscopic dimensions of 20×10×10 mm. The desired coating is a magnesium- and strontium-doped phosphating coating.

[0054] The zinc alloy alveolar mesh was electrochemically polished using a phosphoric acid-ethylene glycol-acetic acid polishing solution to remove the surface oxide layer until it reached a bright silver-white color. It was then ultrasonically cleaned in anhydrous ethanol for 10 min, removed, and dried with cold air. Following this, it underwent ultraviolet ozone treatment for 15 min. A phosphating solution was prepared with the following formula: 0.1 mol / L MgSO4·7H2O + 0.1 mol / L Sr(NO3)2·4H2O + 0.3 mol / L NaH2PO4·2H2O + 0.1 mol / L NaNO3. After adding ultrapure water, the pretreated zinc alloy alveolar mesh was placed in the solution and immersed in a 55 ℃ water bath for 2 h. After the dense zinc magnesium phosphate (MgFe) strontium-doped bottom phase has formed, Na3PO4·12H2O reagent is slowly added to the treatment solution to adjust the pH to 4.8. At this point, the Na3PO4 concentration in the treatment solution is approximately 0.16 mol / L. The solution is then soaked in a 50 °C water bath for 1.5 h to form the magnesium hydrogen phosphate-strontium hydrogen phosphate upper particulate phase. After soaking, the sample is collected and rinsed sequentially with ultrapure water and anhydrous ethanol, then dried to obtain the alveolar mesh sample coated with the magnesium-doped strontium phosphate coating.

[0055] The obtained magnesium-doped, strontium-phosphated coating is a dense and uniform bilayer structure of zinc phosphate ((Mg,Sr,Zn)3(PO4)2)-hydrogen phosphate (containing MgHPO4 and SrHPO4), with a thickness of ~15 μm. The overall roughness Ra of the coating is 5.0 μm. The adhesion between the coating and the substrate is 13.3 MPa.

[0056] The coated alveolar mesh sample prepared by this process was immersed in a culture medium for 28 days, and the Zn content was measured. 2+The release concentration remained below 5 ppm for the first 14 days and below 15 ppm from days 14 to 28, which are respectively 15% and 30% lower than those of uncoated bare metal alveolar mesh; it also continuously releases Mg with good bioactivity. 2+ and Sr 2+ 28 days Mg 2+ The release concentrations were all above 50 ppm, Sr 2+ The release concentrations were all above 20 ppm (all within the concentration range favorable for osteoblast proliferation and differentiation). Cells were cultured using 100% concentration extracts of the coated alveolar mesh samples after 1 and 3 days to verify indirect cell viability. Cell viability was measured to be above 120%, indicating a significant positive promoting effect on osteoblasts. MC3T3-E1 osteoblasts and HGF fibroblasts were directly seeded onto the sample surface to verify direct cell viability. Results showed that both cell types exhibited good growth morphology, with cell pseudopodia adhering and growing along the mesh structure of the alveolar mesh. The viable cell density of MC3T3-E1 cells reached 121 cells / mm² after 3 days of co-culture. 2 After 7 days of HGF cell culture, the cell coverage of the mesh exceeded 95%. This magnesium-doped, strontium-phosphating coating significantly promoted the proliferation, spreading, and adhesion of osteoblasts and fibroblasts, and significantly improved the biocompatibility of the zinc alloy alveolar mesh.

[0057] Comparative Example 1 The preparation method of this comparative example is basically the same as that of Example 1, except that the phosphating solution does not contain an oxidant (NaNO3) and no nucleation regulator (Na3PO4) is added later. The specific formula is: 0.2 mol / L MgSO4·7H2O + 0.3 mol / L NaH2PO4·2H2O. After adding ultrapure water to prepare the solution, 2 mol / L NaOH is slowly added to adjust the pH of the solution to 5.0. The pretreated zinc alloy discs are placed in the solution and immersed in a 50 ℃ water bath for 3 h before the samples are collected.

[0058] The resulting phosphate coating still retains the two-phase structure of zinc magnesium phosphate and magnesium hydrogen phosphate, but the flower-like zinc magnesium phosphate has a coarser structure with a thickness of 2-5 μm; the blocky magnesium hydrogen phosphate is larger in volume and dispersed on the zinc magnesium phosphate layer, with a thickness (particle size) of 50-80 μm. Its microstructure is as follows: Figure 2 As shown in (a), the overall roughness Ra of the coating is 10.3 μm. The adhesion between the coating and the substrate is 6.4 MPa.

[0059] The coating samples prepared by this process were immersed in a culture medium for 28 days, and the Zn content was measured. 2+ The release concentration will exceed 15 ppm in the later stages of soaking (14-28 days); at the same time, Mg 2+The release of Mg is only effective in the early stage (1-14 days), and in the later stage of soaking (14-28 days). 2+ The release was below 5 ppm. MC3T3-E1 cells were directly seeded onto the sample surface to verify direct cell viability. Fluorescence micrographs showing cell viability and death staining were obtained, as shown in the figures. Figure 3 As shown in (b), the live cell density on the coated sample under this process is 78 cells / mm². 2 .

[0060] In summary, without the addition of oxidants and nucleation modifiers, the physical properties (uniformity, density, adhesion) and chemical properties (Zn inhibition) of the coating will be significantly affected. 2+ Release and increase Mg 2+ Both release and biocompatibility decreased significantly.

[0061] Comparative Example 2 The preparation method of this comparative example is basically the same as that of Example 1, except that the phosphating solution does not contain oxidant (NaNO3). The specific formula is: 0.2mol / L MgSO4·7H2O + 0.3mol / L NaH2PO4·2H2O. After adding ultrapure water to prepare the solution, the pretreated zinc alloy discs are placed in it and soaked in a water bath at 50 ℃ for 1.5 h. Then, Na3PO4·12H2O reagent is slowly added to the solution to adjust the pH to 5.0, and the solution is soaked in a water bath at 50 ℃ for another 1.5 h before the sample is collected.

[0062] The resulting phosphate coating still retains the two-phase structure of zinc magnesium phosphate and magnesium hydrogen phosphate, but the flower-like zinc magnesium phosphate has a coarser structure with a thickness of 2-5 μm; the blocky magnesium hydrogen phosphate is larger in volume and dispersed on the zinc magnesium phosphate layer, with a thickness (particle size) of 20-40 μm. Its microstructure is as follows: Figure 2 As shown in (b), the overall roughness Ra of the coating is 9.1 μm. The adhesion between the coating and the substrate is 5.9 MPa.

[0063] The coating samples prepared by this process were immersed in a culture medium for 28 days, and the Zn content was measured. 2+ The release concentration will exceed 15 ppm in the later stages of soaking (14-28 days); at the same time, Mg 2+ The release of Mg is only effective in the early stage (1-14 days), and in the later stage of soaking (14-28 days). 2+ The release was below 5 ppm, which is the same as the phenomenon observed in Comparative Example 1, which did not add either an oxidant or a nucleation regulator. MC3T3-E1 cells were directly seeded onto the sample surface to verify direct cell viability; the viable cell density on the coated sample under this process was 82 cells / mm². 2 .

[0064] In summary, without the addition of an oxidizing agent, even with the addition of a nucleation regulator, it is still impossible to achieve uniform densification and long-term ion release regulation of the phosphating coating. The physical properties (uniformity, density, adhesion) and chemical properties (Zn inhibition) of the coating will also be affected. 2+ Release and increase Mg 2+ Both the release rate and biocompatibility were significantly reduced. A possible reason is that the oxidant not only participates in the nucleation growth of the underlying zinc magnesium phosphate layer, but also regulates the nucleation growth of magnesium hydrogen phosphate particles. Its combined action with phosphate nucleation regulators causes magnesium hydrogen phosphate particles to embed into the underlying flower-like zinc magnesium phosphate layer and be inhibited from growing.

[0065] Comparative Example 3 The preparation method of this comparative example is basically the same as that of Example 1, except that in the second step of the "two-step" method for preparing the coating, instead of adding a phosphate nucleation regulator (Na3PO4) to the phosphating solution, NaOH is used to adjust the pH of the solution. The specific formula is: 0.1mol / L NaNO3 + 0.2mol / L MgSO4·7H2O + 0.3mol / L NaH2PO4·2H2O. After adding ultrapure water to prepare the solution, the pretreated zinc alloy discs are placed in the solution and immersed in a 50 ℃ water bath for 1.5 h. Then, 2 mol / L NaOH is slowly added to the solution to adjust the pH to 5.0, and the solution is immersed in a 50 ℃ water bath for another 1.5 h before the sample is collected.

[0066] The resulting phosphate coating still exhibits a two-phase structure of zinc magnesium phosphate and magnesium hydrogen phosphate. The flower-like zinc magnesium phosphate is similar to that in Example 1, with a thickness of 2-5 μm; however, the blocky magnesium hydrogen phosphate is larger in volume, dispersed on the zinc magnesium phosphate layer, with a thickness (particle size) of 20-50 μm. Its microstructure is as follows: Figure 2 As shown in (c), the overall roughness Ra of the coating is 9.7 μm. The adhesion between the coating and the substrate is 6.1 MPa.

[0067] The coating samples prepared by this process were immersed in a culture medium for 28 days, and the Zn content was measured. 2+ The release concentration will exceed 15 ppm in the later stages of soaking (21-28 days); at the same time, Mg 2+ The release of Mg is only effective in the early stage (1-14 days), and in the later stage of soaking (14-28 days). 2+ The release was below 5 ppm, similar to the phenomenon observed in Comparative Example 1, which did not contain any oxidant or nucleation regulator. MC3T3-E1 cells were directly seeded onto the sample surface to verify direct cell viability; the viable cell density on the coated sample obtained using this process was 88 cells / mm². 2 .

[0068] In summary, if the second step of the two-step coating preparation method does not involve adding phosphate-based nucleation regulators to the treatment solution, but only adds an oxidant in the first step, it can only refine the underlying flower-like magnesium zinc phosphate layer, but cannot achieve uniform and fine particle size reduction in the upper magnesium hydrogen phosphate layer. Therefore, it still cannot achieve overall uniform density and long-term ion release regulation of the coating. The physical properties (uniformity, density, adhesion) and chemical properties (especially with increased Mg content) of the coating are also affected. 2+ Both the release rate and biocompatibility were significantly reduced. This further validates the regulatory role of phosphate nucleation regulators in the nucleation growth of the upper particulate phase.

[0069] Comparative Example 4 The preparation method of this comparative example is basically the same as that of Example 1, except that instead of the "two-step" method, an oxidant and a nucleation regulator are added simultaneously during the treatment. The specific formula is: 0.2 mol / L MgSO4·7H2O + 0.3 mol / L NaH2PO4·2H2O + 0.1 mol / L NaNO3. After adding ultrapure water to prepare a solution, Na3PO4·12H2O reagent is slowly added to adjust the pH of the solution to 5.0. The pretreated zinc alloy discs are placed in the solution and immersed in a 50 ℃ water bath for 3 h before being collected.

[0070] During the coating preparation process, the phosphating solution began to become significantly turbid after 20 minutes of water bath heating. This is because the solution contains a high concentration of both magnesium ions and hydrogen phosphate ions (derived from H2PO4). - dissociation and PO4 3- The two readily combine under conditions of pH=5.0 and heating at 50 ℃ to form magnesium hydrogen phosphate particles, which suspend in the solution and form a white turbidity, affecting the nucleation and growth of the underlying dense phase. The phosphate coating obtained after soaking for 3 h has insufficient macroscopic coverage, and while the microscopic morphology still exhibits a biphase structure of zinc magnesium phosphate and magnesium hydrogen phosphate, the structure of the flower-like zinc magnesium phosphate is significantly different from that in Example 1. The petals are clustered, with large undulations, and a thickness of 4-8 μm; the blocky magnesium hydrogen phosphate is larger in volume, dispersed on the zinc magnesium phosphate layer, and has a thickness (particle size) of 20-50 μm. Its microscopic morphology is as follows: Figure 2 As shown in (d), the overall roughness Ra of the coating is 10.2 μm. The adhesion between the coating and the substrate is 5.6 MPa.

[0071] The coating samples prepared using this process were immersed in a culture medium for 28 days, and Zn still appeared. 2+ The inhibition cycle and Mg 2+ The sustained-release effect of these treatments is relatively short (effective for only 1-14 days). To verify direct cell viability, MC3T3-E1 cells were directly seeded onto the sample surface. The viable cell density on the coated sample using this process was 86 cells / mm².2 .

[0072] In summary, without employing the two-step method and instead adding both the oxidant and the nucleation regulator simultaneously, it is impossible to achieve uniform densification and long-lasting ion release regulation in the phosphating coating. Consequently, the physical, chemical, and biocompatibility of the coating all significantly decrease. This comparative example verifies the necessity of the two-step method for preparing this coating.

[0073] Comparative Example 5 The preparation method of this comparative example is basically the same as that of Example 1, except that the oxidant in the prepared phosphating solution is at a higher concentration. The specific formula is: 0.3mol / L NaNO3 + 0.2mol / L MgSO4·7H2O + 0.3mol / L NaH2PO4·2H2O. After adding ultrapure water to prepare the solution, the pretreated zinc alloy discs are placed in the solution and soaked in a 50 ℃ water bath for 1.5 h. Then, Na3PO4·12H2O reagent is slowly added to the solution to adjust the pH to 5.0, and the solution is soaked in a 50 ℃ water bath for another 1.5 h before the sample is collected.

[0074] The obtained phosphate coating still retains the two-phase structure of zinc magnesium phosphate and magnesium hydrogen phosphate. The underlying flower-like zinc magnesium phosphate phase remains dense and uniform, with a thickness of 2-5 μm. However, the number of blocky magnesium hydrogen phosphate particles is significantly increased and their size is larger, forming agglomerates distributed on the zinc magnesium phosphate layer, with a thickness (particle size) of 50-80 μm. Its microstructure is as follows: Figure 2 As shown in (e), the overall roughness Ra of the coating is 11.7 μm. The adhesion between the coating and the substrate is 7.0 MPa.

[0075] The coating samples prepared using this process were immersed in a culture medium for 28 days, and Zn still appeared. 2+ The inhibition cycle and Mg 2+ The sustained-release effect of these treatments is generally short-lived (effective for only 1-14 days). To verify direct cell viability, MC3T3-E1 cells were directly seeded onto the sample surface. The viable cell density on the coated sample using this process was 75 cells / mm². 2 .

[0076] In summary, if the oxidant concentration is too high, the uniform densification and long-term ion release regulation of the phosphating coating cannot be achieved, resulting in a significant decrease in the coating's physical properties, chemical properties, and biocompatibility. A possible reason is that an excessively high oxidant concentration accelerates the dissolution of zinc ions and the chemical co-deposition during the coating reaction, thereby promoting the rapid primary dissociation of dihydrogen phosphate ions in the solution. This leads to a rapid reaction with the abundant magnesium ions in the solution, generating larger particles of magnesium hydrogen phosphate that adhere to the coating, negatively impacting the overall uniformity and adhesion of the coating. This comparative example verifies that the concentration of nitrate-based oxidants should be within a suitable range.

[0077] Comparative Example 6 The preparation method of this comparative example is basically the same as that of Example 1, except that a higher pH value is used in the phosphating solution. The specific formula is: 0.1 mol / L NaNO3 + 0.2 mol / L MgSO4·7H2O + 0.3 mol / L NaH2PO4·2H2O. After adding ultrapure water to prepare the solution, 2 mol / L NaOH is slowly added to adjust the pH of the solution to 6.0. The pretreated zinc alloy discs are placed in the solution and soaked in a 50 ℃ water bath for 1.5 h. At this time, the pH of the solution drops. Na3PO4·12H2O is then added to the solution to restore the pH to 6.0, and the solution is soaked in a 50 ℃ water bath for another 1.5 h before the sample is collected.

[0078] The obtained phosphate coating still possesses a two-phase structure of zinc magnesium phosphate and magnesium hydrogen phosphate, but the morphologies of both phases are significantly different from those in Example 1. The underlying flower-like zinc magnesium phosphate phase exhibits inhomogeneity and a decreased density, with a thickness of 2-4 μm. The bulk magnesium hydrogen phosphate particles have increased in size and mostly form agglomerates, distributed on the zinc magnesium phosphate layer, with a thickness (particle size) of 20-50 μm. Its microstructure is as follows: Figure 2 As shown in (f), the overall roughness Ra of the coating is 10.3 μm. The adhesion between the coating and the substrate is 7.3 MPa.

[0079] The coating samples prepared using this process were immersed in a culture medium for 28 days, and Zn still appeared. 2+ The inhibition cycle and Mg 2+ The sustained-release effect of these treatments is generally short-lived (effective for only 1-14 days). To verify direct cell viability, MC3T3-E1 cells were directly seeded onto the sample surface. The viable cell density on the coated samples obtained using this process was 80 cells / mm². 2 .

[0080] In summary, if the pH value of the phosphating solution is too high, the uniform densification and long-term ion release regulation of the phosphating coating cannot be achieved, and the physical, chemical, and biocompatibility of the coating will significantly decrease. A possible reason is that an excessively high pH value causes the primary dissociation of dihydrogen phosphate ions in the solution to be too rapid, forming more hydrogen phosphate ions. These hydrogen phosphate ions combine with magnesium ions in the solution, causing the rapidly formed magnesium hydrogen phosphate particles to aggregate or grow. They also combine with zinc ions dissolved from the matrix to directly form zinc phosphate, instead of the target phase of zinc magnesium phosphate. This has an adverse effect on both phases in the coating. This comparative example verifies that the pH value of the phosphating solution should be within a suitable range.

[0081] The properties and performance of the phosphate coatings in Examples 1-5 and Comparative Examples 1-6 are compared in Table 1.

[0082] Table 1. Comparison of the properties and performance of phosphate coatings in the examples and comparative examples

[0083] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A method for preparing a phosphating coating doped with divalent metal functional ions on the surface of a medical zinc alloy, characterized in that, The divalent metal functional ions include Mg 2+ 、Sr 2+ Ca 2+ Mn 2+ One or more of the above, wherein the preparation method includes the following steps: S1. Prepare a phosphating solution containing divalent metal salt, dihydrogen phosphate, and oxidant. Immerse the zinc alloy material in the phosphating solution to form a dense bottom phase of the phosphating coating. S2. After the bottom dense phase of the phosphate coating is formed, a nucleation regulator is added to the phosphate treatment solution and the soaking continues to form the upper particulate phase of the phosphate coating.

2. The preparation method according to claim 1, characterized in that, In step S1, the zinc alloy material includes one of pure Zn, Zn-Al, Zn-Ag, Zn-Cu, Zn-Ca, Zn-Li, Zn-Mg, Zn-Fe, Zn-Mn, and Zn-Re.

3. The preparation method according to claim 1, characterized in that, In step S1, the bottom dense phase is a composite phosphate with a thickness of 2-5 μm, wherein the molar ratio of the doped divalent metal functional ions to zinc ions is 1:1-1:

2. In step S2, the upper particulate phase is hydrogen phosphate with a size of 5-15 μm.

4. The preparation method according to claim 1, characterized in that, In step S1, the divalent metal salt includes at least one of magnesium salt, strontium salt, calcium salt, and manganese salt; in the phosphating solution, the concentration of the divalent metal salt is 0.05-0.3 mol / L; wherein the concentration of magnesium salt is 0.1-0.3 mol / L, and / or the concentration of strontium salt is 0.05-0.1 mol / L, and / or the concentration of calcium salt is 0.1-0.2 mol / L, and / or the concentration of manganese salt is 0.1-0.2 mol / L.

5. The preparation method according to claim 4, characterized in that, The divalent metal salt is selected from at least one of magnesium chloride, magnesium nitrate, magnesium sulfate, strontium chloride, strontium nitrate, calcium chloride, calcium nitrate, manganese chloride, manganese nitrate, and manganese sulfate.

6. The preparation method according to claim 1, characterized in that, In step S1, the dihydrogen phosphate is selected from at least one of sodium dihydrogen phosphate, potassium dihydrogen phosphate, and ammonium dihydrogen phosphate; in the phosphating solution, the concentration of dihydrogen phosphate is 0.1-0.5 mol / L, and the molar ratio of divalent metal salt to dihydrogen phosphate is 1:1-1:

2.

7. The preparation method according to claim 1, characterized in that, In step S1, the oxidant is selected from at least one of hydrogen peroxide, sodium nitrate, and potassium nitrate; the concentration of the oxidant in the phosphating solution is 0.05-0.2 mol / L.

8. The preparation method according to claim 1, characterized in that, In step S2, the nucleation regulator is selected from at least one of sodium phosphate and potassium phosphate; in the phosphating solution, the concentration of the nucleation regulator is 0.1-0.4 mol / L, and the pH of the solution is adjusted to 4.5-5.

5.

9. The preparation method according to claim 1, characterized in that, In steps S1 and S2, the soaking temperature is 40-60℃; the soaking time in step S1 is 1-2 h, and the soaking time in step S2 is 1-3 h.

10. A phosphating coating on the surface of a medical zinc alloy doped with divalent metal functional ions, obtained by the preparation method according to any one of claims 1-9.

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