Preparation method and application of a highly adhesive biomimetic mineralized hydrogel coating

Abstract

This invention discloses a method for preparing and applying a highly adhesive biomimetic mineralized hydrogel coating, relating to the field of bone implant surface modification technology. The method includes immersing a pre-treated bone implant in a polyvinyl alcohol solution, followed by a single freeze-thaw cycle and annealing; then alternately immersing the annealed bone implant in calcium-containing and phosphorus-containing solutions for surface mineralization; subsequently inducing the surface mineralization product to form hydroxyapatite; thus obtaining a highly adhesive biomimetic mineralized hydrogel coating on the bone implant surface. This invention uses a dip-coating method to coat the bone implant surface with a highly adhesive hydrogel coating. By adjusting the number of dip-coating cycles, the coating thickness and surface smoothness can be controlled.

Description

Technical Field

[0001] This invention relates to the field of bone implant surface modification technology, specifically to a method for preparing and applying a highly adhesive biomimetic mineralized hydrogel coating. Background Technology

[0002] Currently, orthopedic implant materials mainly include ceramics, polymers, metals, and composites. Among them, biomedical metallic materials are the most widely used bone implant materials due to their excellent mechanical properties and machinability. Traditional medical stainless steel is low in cost, has superior mechanical properties, and good corrosion resistance, but localized corrosion can easily release harmful metal ions or fragments, posing a potential hazard to the human body, requiring surface protection. Titanium and its alloys possess high strength, good corrosion resistance, and excellent biocompatibility, and are widely used in orthopedic and dental implants. However, its high elastic modulus can easily lead to stress shielding effects, causing implant loosening and increasing the risk of infection. The bioinertness of titanium alloys also limits the improvement of their osseointegration and antibacterial properties. Second-generation bone implant materials, such as polyetheretherketone (PEEK), have become emerging bone implant materials because their elastic modulus is close to that of cortical bone, and they possess excellent wear resistance, radiation permeability, and biocompatibility. However, the bioinertness of PEEK hinders its effective integration with bone tissue, limiting its clinical application. Current research primarily focuses on surface modification and the addition of active materials to enhance the bioactivity and biocompatibility of PEEK. While existing technologies have improved the performance of metallic and polymeric implant materials to some extent, achieving stronger bioactivity and antibacterial effects while maintaining excellent mechanical properties remains a major challenge in bone implant material research. Therefore, developing biomimetic mineralization coatings with stronger adhesion and bioactivity to improve the interfacial bonding between bone implant materials and bone tissue has become a key technological direction for promoting clinical applications in this field.

[0003] Hydrogels, due to their unique tunable mechanical properties and excellent biocompatibility, have broad application prospects in the field of tissue engineering. By introducing inorganic minerals such as calcium phosphate compounds or calcium carbonate, the prepared hydrogels can maintain their mechanical properties while also possessing good osteoinductive capabilities, thus significantly enhancing their application value in bone tissue engineering. Currently, the main methods for preparing mineralized hydrogels include immersion methods and in-situ mineralization methods, but these methods have some limitations. For example, Chinese patent (CN107778416A) describes an immersion method in which acrylonitrile / vinylimidazole hydrogel is first immersed in a mixed solution of calcium chloride and sodium dihydrogen phosphate, allowing calcium and phosphate ions to diffuse into the gel matrix. Then, ammonia is used to adjust the pH value to promote the mineralization reaction, forming a mineralized hydrogel. However, this method requires a long mineralization time of 24 to 48 hours, resulting in low coating preparation efficiency. Chinese patent (CN112625158A) uses a polyacrylamide hydrogel containing alkaline phosphatase to carry out a mineralization reaction in a triethanolamine solution of calcium glycerophosphate. This process relies on a photoinitiator, the calcification solution is complex to prepare, and the calcification time is as long as 3 to 10 days. In addition, Chinese patent (CN114432275A) mixes hydrogel material, a crosslinking polymer initiator, and the crosslinking polymer initiator to prepare a prepolymer, which is then vacuum-treated and dried in an oven to obtain a highly adhesive analgesic hydrogel microneedle patch. However, this method is complex, has many limitations on hydrogel materials, has narrow applicability, and the complex preparation process affects the flexibility of subsequent drug loading.

[0004] In summary, existing hydrogel coating modification technologies for bone implant surfaces face challenges such as complex preparation processes, long cycle times, and insufficient adhesion between the coating and the substrate. Therefore, developing a hydrogel coating that is simple to prepare, has strong adhesion, and possesses biomimetic mineralization properties is of great significance for enhancing the clinical application potential of bone implants. Summary of the Invention

[0005] To address the shortcomings of the aforementioned background technology, this invention primarily solves the problems of poor surface bioactivity of existing bone implants, weak adhesion of modified coatings, and poor osteogenic performance. This invention provides a method for preparing and applying a strongly adhesive biomimetic mineralized hydrogel coating. The composite coating prepared by this method can form a strong adhesion with the substrate material, significantly improving the stability of the coating, and provides a simple biomimetic mineralization method that shortens the mineralization time, forming a uniformly deposited hydroxyapatite coating on the surface of the bone implant.

[0006] The first objective of this invention is to provide a method for preparing a strongly adhesive biomimetic mineralized hydrogel coating, comprising the following steps:

[0007] After the surface-pretreated bone implant is immersed in a polyvinyl alcohol solution, it undergoes a single freeze-thaw cycle and is then annealed.

[0008] The annealed bone implants were alternately immersed in calcium-containing and phosphorus-containing solutions for surface mineralization treatment; then the surface mineralization products were induced to become hydroxyapatite; that is, a highly adhesive biomimetic mineralized hydrogel coating was obtained on the surface of the bone implants.

[0009] Preferably, the surface mineralization treatment includes:

[0010] After annealing, the bone implant is immersed in a phosphorus-containing solution for 2-4 minutes, then rinsed in deionized water for 10-15 seconds, then immersed in a calcium-containing solution for 2-4 minutes, and rinsed in deionized water for 10-15 seconds. This cycle is repeated 3-6 times.

[0011] Preferably, the phosphorus-containing solution is a dipotassium hydrogen phosphate solution with a concentration of 200-400 mM;

[0012] The calcium-containing solution is a calcium chloride solution with a concentration of 300~600mM.

[0013] Preferably, the product after surface mineralization treatment is induced to become hydroxyapatite, including:

[0014] The surface-mineralized bone implants were immersed in calcium chloride solution for 24-36 hours to induce the surface-mineralized products to become hydroxyapatite.

[0015] The calcium-to-phosphorus ratio in hydroxyapatite is 1.60–1.75, and the particle size is 300–500 nm.

[0016] Preferably, prior to surface mineralization treatment, the procedure further includes immersing the annealed bone implants in a 1 M Tris buffer solution with pH=9 for 12 to 24 hours.

[0017] Preferably, when immersing the surface-pretreated bone implant into the polyvinyl alcohol solution, the process includes at least one immersion in the polyvinyl alcohol solution; wherein, each immersion process involves immersing the surface-pretreated bone implant into the polyvinyl alcohol solution, ensuring that no bubbles are generated on the surface, and then removing it and placing it in an oven to dry for 10 to 15 minutes.

[0018] After the surface-pretreated bone implant is immersed in a polyvinyl alcohol solution, it is left to stand at room temperature for 0.5 to 1 hour; wherein the concentration of the polyvinyl alcohol solution is 10 to 12 wt%.

[0019] Preferably, a single freeze-thaw cycle includes: immersing the surface-pretreated bone implant in a polyvinyl alcohol solution, freezing it at -20 to -18°C for 8 to 10 hours, and then thawing it at room temperature for 2 to 4 hours.

[0020] Preferably, the annealing temperature is 100~110℃ and the annealing time is 90~120 minutes.

[0021] The second objective of this invention is to provide a highly adhesive biomimetic mineralized hydrogel coating, prepared by the method described above, wherein the highly adhesive biomimetic mineralized hydrogel coating has a thickness of 15-23 μm and an interfacial toughness of up to 208.54 J / m. 2 .

[0022] The third objective of this invention is to provide an application of a strongly adhesive biomimetic mineralized hydrogel coating in bone implants.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] This invention provides a method for preparing and applying a biomimetic mineralized hydrogel coating with strong adhesion. By annealing, the generation of ordered nanocrystalline domains inside the hydrogel and surface hydrogen bonds is induced, which improves the adhesion performance of the coating. The hydroxyapatite on the surface after biomimetic mineralization is conducive to the proliferation and adhesion of osteoblasts on the surface, thereby promoting the repair of bone tissue.

[0025] This invention uses annealing treatment to increase the crosslinking degree of the hydrogel, resulting in a smooth coating appearance and excellent adhesion.

[0026] This invention provides a method for preparing a mineralized hydrogel coating. The process is simple, the raw materials are inexpensive, and the preparation time is short. A uniform hydroxyapatite coating is formed on the surface of the hydrogel. This method is applicable to a variety of bone implant materials and is conducive to industrial production.

[0027] This invention employs a dip-coating method to coat the surface of a bone implant with a highly adhesive hydrogel coating. By adjusting the number of dip-coating cycles, the thickness and surface smoothness of the coating can be controlled.

[0028] This invention regulates the soaking time of the mineralization solution, thereby controlling the thickness and distribution of the mineralization coating and thus adjusting the biological properties of the bone implant.

[0029] This invention employs plasma treatment or sulfonation treatment to pretreat bone implant materials, thereby increasing the surface active groups of the bone implant and improving the material modification effect. Attached Figure Description

[0030] Figure 1 The image shows a scanning electron microscope (SEM) image of the surface coating morphology of the strongly adherent biomimetic mineralized PEEK implant at different mineralization times as described in Example 2.

[0031] Figure 2 The images are scanning electron microscope (SEM) images of the surfaces of the SPEEK implant, PVA-SPEEK implant, and HA-PVA-SPEEK implant described in Example 5.

[0032] Figure 3 This is a cross-sectional scanning electron microscope image of the strongly adhesive hydrogel coating described in Example 5.

[0033] Figure 4 This is a water contact angle test experiment on the surface of the SPEEK implant, PVA-SPEEK implant, and HA-PVA-SPEEK implant described in Example 5.

[0034] Figure 5 This is a 90° peel test experiment of the strong adhesion hydrogel coating described in Example 5.

[0035] Figure 6 The results are the biocompatibility test results of the SPEEK implant, PVA-SPEEK implant and HA-PVA-SPEEK implant surface described in Example 5.

[0036] Figure 7 The image shows scanning electron micrographs of cell morphology on the surface of the SPEEK implant, PVA-SPEEK implant, and HA-PVA-SPEEK implant described in Example 5. Detailed Implementation

[0037] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below in conjunction with specific embodiments and accompanying drawings. However, the embodiments described are not intended to limit the present invention.

[0038] The main objective of this invention is to address the problems of poor surface bioactivity, weak adhesion of modified coatings, and unsatisfactory osteogenic properties in existing bone implants. It provides a simple, stable, and quick method for preparing a strongly adhesive biomimetic mineralized hydrogel coating. Annealing enhances the cross-linking properties within the hydrogel, forming nanocrystalline domains and hydrogen bonds, thereby improving the adhesion of the hydrogel coating. A biomimetic mineralization method using calcium and phosphorus solutions is employed to generate uniform hydroxyapatite on the surface of the hydrogel-coated bone implant.

[0039] The bone implants used in the following embodiments include titanium alloy, polyetheretherketone (PEEK), magnesium alloy, zinc alloy, or stainless steel.

[0040] To achieve the above objectives, the first aspect of the present invention provides a method for preparing a strongly adhesive biomimetic mineralized hydrogel coating, comprising the following steps:

[0041] The surface-pretreated bone implant is immersed in a polyvinyl alcohol (PVA) solution and then subjected to a single freeze-thaw cycle, followed by annealing. The surface pretreatment of the bone implant includes grinding and surface activation.

[0042] Annealed bone implants were alternately immersed in calcium-containing and phosphorus-containing solutions for surface mineralization. The mineralized product was then induced to form hydroxyapatite (HA), resulting in a strongly adhesive biomimetic mineralized hydrogel coating on the bone implant surface. The prepared hydrogel coating had a smooth and uniform surface.

[0043] The surface mineralization treatment includes:

[0044] After annealing, the bone implant is immersed in a phosphorus-containing solution for 2-4 minutes, then rinsed in deionized water for 10-15 seconds, then immersed in a calcium-containing solution for 2-4 minutes, and rinsed in deionized water for 10-15 seconds. This cycle is repeated 3-6 times.

[0045] The phosphorus-containing solution is a dipotassium hydrogen phosphate solution with a concentration of 200-400 mM, preferably 300 mM; the calcium-containing solution is a calcium chloride solution with a concentration of 300-600 mM, preferably 500 mM.

[0046] Before surface mineralization treatment, the following steps are also included: immersing the annealed bone implants in a 1 M pH=9 Tris buffer solution for 12-24 hours to adjust the pH inside the surface polyvinyl alcohol hydrogel to the pH=9 most suitable for hydroxyapatite growth.

[0047] It should be noted that phosphorus is provided by dipotassium hydrogen phosphate solution (300 mM) and calcium is provided by calcium chloride solution (500 mM), which induces a diffusion reaction on the surface of the hydrogel coating to generate a mineralized HA coating.

[0048] Specifically, the product after surface mineralization treatment is induced to become hydroxyapatite, including:

[0049] The surface-mineralized bone implant is immersed in calcium chloride solution for 24-36 hours to induce the surface-mineralized product to become hydroxyapatite. The main process involves stabilizing the implant in calcium chloride solution at pH 11 for 24 hours to obtain a uniformly distributed hydroxyapatite coating that is not affected by liquid disturbance.

[0050] The calcium-to-phosphorus ratio in hydroxyapatite is 1.60–1.75, and the particle size is 300–500 nm.

[0051] According to the present invention, when immersing the surface-pretreated bone implant into a polyvinyl alcohol solution, the process includes at least one immersion in the polyvinyl alcohol solution; wherein, each immersion process involves immersing the surface-pretreated bone implant into the polyvinyl alcohol solution, ensuring that no bubbles are generated on the surface, and then removing it and placing it in an oven to dry for 10 to 15 minutes.

[0052] After the surface-pretreated bone implant is immersed in a polyvinyl alcohol solution, it is left to stand at room temperature for 0.5 to 1 hour.

[0053] The concentration of the polyvinyl alcohol solution is 10-12 wt%.

[0054] A single freeze-thaw cycle includes: immersing the surface-pretreated bone implant in a polyvinyl alcohol solution, freezing it at -20 to -18°C for 8 to 10 hours, and then thawing it at room temperature for 2 to 4 hours.

[0055] The annealing temperature is 100~110℃ and the annealing time is 90~120 minutes; during the annealing process, the heating rate is 2℃ / min, and after holding at the temperature, it is cooled in the furnace.

[0056] In one embodiment, the specific preparation method of the PVA aqueous solution is as follows:

[0057] 1.1) Weigh 10 g of PVA powder (molecular weight 27.04522) at room temperature and dissolve it in 90 mL of deionized water. Stir the solution magnetically at 100 °C for 5 hours until a transparent and homogeneous PVA aqueous solution is obtained.

[0058] 1.2) Centrifuge the prepared PVA aqueous solution at 5000 rpm for 20 minutes to eliminate residual bubbles in the solution.

[0059] In one embodiment, the specific preparation method of the strongly adhesive PVA hydrogel coating is as follows:

[0060] 2.1) Immerse the pretreated bone implant in the prepared PVA solution, ensuring no air bubbles form on the surface. Remove the bone implant and dry it in an oven for 15 minutes. Repeat the immersion process and allow it to stand for 0.5 hours. Then, freeze the bone implant coated with hydrogel at -20 °C for 8 hours, thaw it at room temperature for 3 hours, and air dry it for 8 hours to obtain a smooth PVA hydrogel-coated bone implant.

[0061] 2.2) The bone implant prepared above was annealed at 100 °C for 1.5 hours. The specific annealing process parameters were: heating rate 2 °C / min, holding time 90 minutes, and cooling in the furnace.

[0062] In one embodiment, the specific preparation method of the strongly adhesive biomimetic mineralized hydrogel coating is as follows:

[0063] 3.1) The bone implant with strong adhesion hydrogel coating was immersed in 1 M Tris buffer solution at pH=9 for 24 hours to adjust the pH value inside the hydrogel.

[0064] 3.2) The bone implant was sequentially immersed in a 300 mM dipotassium hydrogen phosphate solution for 2 minutes, in deionized water for 10 seconds, in a 500 mM calcium chloride solution for 2 minutes, and then in deionized water for 10 seconds. This cycle was repeated 5 times to control the thickness of the mineralization coating.

[0065] 3.3) The mineralized hydrogel-coated bone implant was immersed in a 500 mM calcium chloride solution at pH=11 for 24 hours to allow the mineralized calcium phosphate to mature into hydroxyapatite.

[0066] 3.4) Remove the mineralized hydrogel-coated bone implant from the solution and rinse it three times with deionized water to remove residual calcium chloride from the surface.

[0067] The bone implant was immersed in a dipotassium hydrogen phosphate solution, and phosphate ions were evenly distributed on the surface and inside the hydrogel through diffusion. After immersion in a calcium chloride solution, the diffused calcium ions and the phosphate ions distributed in the hydrogel attracted each other under electrostatic attraction, and a chemical reaction occurred to form calcium phosphate precipitate, which was subsequently matured into HA under pH=11 conditions.

[0068] The second aspect of this invention provides a highly adhesive biomimetic mineralized hydrogel coating, prepared by the method described above. The highly adhesive biomimetic mineralized hydrogel coating has a thickness of 15-23 μm and an interfacial toughness of up to 208.54 J / m. 2 .

[0069] The third aspect of this invention provides the application of a highly adhesive biomimetic mineralized hydrogel coating in bone implants.

[0070] It should be noted that, unless otherwise specified, the experimental methods used in this invention are all conventional methods; and the reagents and materials used, unless otherwise specified, are all commercially available.

[0071] Example 1

[0072] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a PEEK implant includes the following steps:

[0073] Step 1: PEEK surface pretreatment: Use sandpaper to polish the surface of the PEEK sample, put the polished PEEK sample into deionized water and ultrasonically clean it for 5 minutes to remove residual impurities; immerse the cleaned PEEK sample in concentrated sulfuric acid for 1 minute to perform surface sulfonation treatment; quickly put the sulfonated PEEK sample into ice water for 1 minute to terminate the sulfonation reaction.

[0074] The sulfonated PEEK sample was immersed in a 3 wt% sodium hydroxide solution for 2 hours to further neutralize the residual sulfuric acid on the surface; it was then ultrasonically cleaned with deionized water for 15 minutes to remove residual sodium hydroxide and other impurities from the sample surface.

[0075] Step 2: Preparation of strong adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water; stir magnetically at 100 ℃ for 5 hours until a transparent and homogeneous PVA aqueous solution is formed; centrifuge the prepared PVA aqueous solution at 5000 rpm for 20 minutes to eliminate residual bubbles in the solution; immerse the pretreated sulfonated PEEK sample in the PVA solution, ensuring that no bubbles are generated on the surface, remove the coated sulfonated PEEK sample, and divide the sample into 3 groups for different treatments.

[0076] Group 1: Take out the coated sulfonated PEEK samples and let them stand at room temperature for 0.5 hours;

[0077] Group 2: Take out the coated sulfonated PEEK sample, dry it in an oven for 15 minutes, immerse the sample in PVA solution again, and let it stand for 0.5 hours;

[0078] Group 3: Take out the coated sulfonated PEEK sample, dry it in an oven for 15 minutes, perform the second impregnation operation, dry the sample in an oven for 15 minutes again, perform the third impregnation operation, and let it stand for 0.5 hours.

[0079] The three groups of sulfonated PEEK samples were frozen at -20℃ for 8 hours after standing, then thawed at room temperature for 3 hours, and then air-dried for 8 hours to obtain PVA hydrogel coatings with smooth surfaces.

[0080] Step 3: Annealing treatment: Anneal the three groups of coated hydrogel coatings at 100 ℃ for 1.5 hours respectively. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace.

[0081] Step 4: Biomimetic Mineralization Treatment: The three groups of annealed, strongly adhesive hydrogel PEEK samples were immersed in 1M Tris buffer solution (pH=9) for 24 hours to adjust the pH inside the hydrogel. The samples were then sequentially immersed in 300 mM dipotassium hydrogen phosphate solution for 2 minutes, deionized water for 10 seconds, 500 mM calcium chloride solution for 2 minutes, and then in deionized water for 10 seconds. This cycle was repeated 5 times to control the thickness of the mineralized coating. The mineralized strongly adhesive hydrogel PEEK samples were then immersed in 500 mM calcium chloride solution (pH=11) for 24 hours to allow the amorphous calcium phosphate formed during mineralization to mature into HA.

[0082] That is, a strongly adherent biomimetic mineralized hydrogel coating was obtained on the surface of the three groups of PEEK.

[0083] Example 1 investigates the effect of the number of times PVA solution is soaked on the coating thickness of the biomimetic mineralized hydrogel with strong adhesion on the surface of PEEK bone implants using a single variable method.

[0084] Example 2

[0085] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a PEEK implant includes the following steps:

[0086] Step 1: PEEK Surface Pretreatment: Use sandpaper to polish the surface of the PEEK sample. Place the polished PEEK sample in deionized water and ultrasonically clean for 5 minutes to remove residual impurities. Immerse the cleaned PEEK sample in concentrated sulfuric acid for 1 minute for surface sulfonation treatment. Immediately place the sulfonated PEEK sample in ice water for 1 minute to terminate the sulfonation reaction. Immerse the sulfonated PEEK sample in a 3 wt% sodium hydroxide solution for alkali washing for 2 hours to further neutralize the residual sulfuric acid on the surface. Ultrasonically clean with deionized water for 15 minutes to remove residual sodium hydroxide and other impurities from the sample surface.

[0087] Step 2: Preparation of a strong-adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water; stir magnetically at 100 ℃ for 5 hours until a transparent and homogeneous PVA aqueous solution is formed; centrifuge the prepared PVA aqueous solution at 5000 rpm for 20 minutes to eliminate residual bubbles in the solution; immerse the pretreated sulfonated PEEK sample in the PVA solution, ensuring that no bubbles are generated on the surface; remove the coated sulfonated PEEK sample, dry it in an oven for 15 minutes, immerse it again, and let it stand for 0.5 hours. Freeze the sulfonated PEEK sample at -20 ℃ for 8 hours, then thaw it at room temperature for 3 hours, and then air dry it for 8 hours to obtain a smooth PVA hydrogel coating.

[0088] Step 3: Annealing treatment: Anneal the above-coated hydrogel coating at 100 ℃ for 1.5 hours. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace.

[0089] Step 4: Biomimetic mineralization treatment: The annealed PEEK hydrogel sample was immersed in 1 M Tris buffer solution at pH=9 for 24 hours to adjust the pH inside the hydrogel.

[0090] After pH adjustment, the PEEK samples were subjected to the following soaking steps in sequence:

[0091] Potassium hydrogen phosphate solution immersion: PEEK samples were divided into four groups and immersed in 300 mM potassium hydrogen phosphate solution for 30 seconds, 1 minute, 2 minutes and 3 minutes respectively to control the amount of phosphate diffusion in the early stage of mineralization.

[0092] Deionized water cleaning: After soaking in dipotassium hydrogen phosphate solution, the four groups of samples were soaked in deionized water for 10 seconds to remove unreacted ions and residual solution.

[0093] Immersion in calcium chloride solution: The above four groups of samples were immersed in 500 mM calcium chloride solution for 30 seconds, 1 minute, 2 minutes and 3 minutes respectively to promote the diffusion and reaction of calcium ions on the surface of hydrogel.

[0094] Deionized water rinsing: After soaking in calcium chloride solution, immerse the four groups of samples in deionized water for 10 seconds each to ensure the removal of excess calcium ions and solution residue;

[0095] Cyclic repetition: The above soaking operations of dipotassium hydrogen phosphate, calcium chloride and deionized water were repeated 4 times for each group according to different soaking times, so as to gradually control the thickness and uniformity of the mineralized coating.

[0096] The four groups of mineralized, strongly adhesive hydrogel PEEK samples were immersed in a 500 mM calcium chloride solution at pH 11 for 24 hours to allow the amorphous calcium phosphate formed by mineralization to mature into HA. The samples immersed in dipotassium hydrogen phosphate solution and calcium chloride solution for 30 seconds, 1 minute, 2 minutes and 3 minutes were labeled as HA-PVA-SPEEK (30s), HA-PVA-SPEEK (1min), HA-PVA-SPEEK (2min) and HA-PVA-SPEEK (3min) respectively.

[0097] Example 2 investigates the effect of a single immersion time of the mineralization solution on the quality and distribution of the mineralization coating in PEEK bone implants using a single variable method.

[0098] Example 3

[0099] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a titanium alloy bone implant includes the following steps:

[0100] Step 1: Titanium alloy surface pretreatment: Use sandpaper to polish the surface of the titanium alloy sample, and ultrasonically clean it for 5 minutes to remove residual impurities; treat the cleaned titanium alloy sample with plasma for 5 minutes to increase the active groups on the surface.

[0101] Step 2: Preparation of strong adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water. Stir magnetically at 100 °C for 5 hours until a transparent and homogeneous PVA aqueous solution is formed. Centrifuge the prepared PVA aqueous solution (5000 rpm, 20 min) to eliminate residual bubbles in the solution. Immerse the pretreated titanium alloy sample in the PVA solution, ensuring that no bubbles are generated on the surface. Remove the coated titanium alloy sample and divide the sample into 3 groups for different treatments.

[0102] Group 1: Take out the coated titanium alloy sample and let it stand at room temperature for 0.5 hours;

[0103] Group 2: Take out the coated titanium alloy sample, place it in an oven to dry for 15 minutes, immerse the sample in PVA solution again, and let it stand for 0.5 hours;

[0104] Group 3: Take out the coated titanium alloy sample, first place it in the oven to dry for 15 minutes, then perform the second immersion operation, place the sample in the oven to dry for 15 minutes again, perform the third immersion operation, and let it stand for 0.5 hours.

[0105] The three groups of titanium alloy samples were frozen at -20 ℃ for 8 hours after standing, then thawed at room temperature for 3 hours and air-dried for 8 hours to obtain a smooth PVA hydrogel coating.

[0106] Step 3: Annealing treatment: Anneal the above-coated hydrogel coating at 100 ℃ for 1.5 hours. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace.

[0107] Step 4: Biomimetic Mineralization Treatment: The three groups of annealed, strongly adhesive hydrogel titanium alloy samples were immersed in a 1 M Tris buffer solution (pH=9) for 24 hours to adjust the pH inside the hydrogel. The samples were then sequentially immersed in a 300 mM dipotassium hydrogen phosphate solution for 2 minutes, deionized water for 10 seconds, a 500 mM calcium chloride solution for 2 minutes, and then in deionized water for 10 seconds. This cycle was repeated 5 times to control the thickness of the mineralized coating. The mineralized strongly adhesive hydrogel titanium alloy samples were then immersed in a 500 mM calcium chloride solution (pH=11) for 24 hours to allow the amorphous calcium phosphate formed during mineralization to mature into HA.

[0108] That is, a strongly adhered biomimetic mineralized hydrogel coating was obtained on the surface of the three groups of titanium alloys.

[0109] Example 3 investigates the effect of the number of times PVA solution is soaked on the coating thickness of the biomimetic mineralized hydrogel that adheres strongly to the surface of the titanium alloy bone implant using a single variable method.

[0110] Example 4

[0111] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a titanium alloy bone implant includes the following steps:

[0112] Step 1: Titanium alloy surface pretreatment: Use sandpaper to polish the surface of the titanium alloy sample, and ultrasonically clean it for 5 minutes to remove residual impurities; treat the cleaned titanium alloy sample with plasma for 5 minutes to increase the active groups on the surface.

[0113] Step 2: Preparation of a strong-adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water. Stir magnetically at 100 °C for 5 hours until a transparent and homogeneous PVA aqueous solution is formed. Centrifuge the prepared PVA aqueous solution (5000 rpm, 20 min) to eliminate residual bubbles in the solution. Immerse the pretreated titanium alloy sample in the PVA solution, ensuring no bubbles are generated on the surface. Remove the coated titanium alloy sample, dry it in an oven for 15 minutes, immerse it again, and let it stand for 0.5 hours. Freeze the standing titanium alloy sample at -20 °C for 8 hours, then thaw it at room temperature for 3 hours, and then air dry it for 8 hours to obtain a smooth PVA hydrogel coating.

[0114] Step 3: Annealing treatment: Anneal the above-coated hydrogel coating at 100 ℃ for 1.5 hours. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace.

[0115] Step 4: Biomimetic mineralization treatment: The strongly adhesive hydrogel titanium alloy sample was immersed in a 1 M Tris buffer solution with pH=9 for 24 hours to adjust the pH inside the hydrogel.

[0116] The pH-adjusted titanium alloy samples were then subjected to the following immersion steps:

[0117] Immersion in dipotassium hydrogen phosphate solution: The titanium alloy samples were divided into four groups and immersed in 300 mM dipotassium hydrogen phosphate solution for 30 seconds, 1 minute, 2 minutes and 3 minutes respectively, in order to control the amount of phosphate diffusion in the early stage of mineralization.

[0118] Deionized water rinsing: After soaking in dipotassium hydrogen phosphate solution, immerse the sample in deionized water for 10 seconds to remove unreacted ions and residual solution;

[0119] Immersion in calcium chloride solution: The above four groups of samples were immersed in 500 mM calcium chloride solution for 30 seconds, 1 minute, 2 minutes and 3 minutes respectively to promote the diffusion and reaction of calcium ions on the surface of hydrogel.

[0120] Deionized water rinsing: After soaking in calcium chloride solution, immerse the sample again in deionized water for 10 seconds to ensure the removal of excess calcium ions and solution residue;

[0121] Cyclic repetition: The above soaking operations of dipotassium hydrogen phosphate, calcium chloride and deionized water were repeated 4 times for each group according to different soaking times, so as to gradually control the thickness and uniformity of the mineralized coating.

[0122] The four groups of mineralized, strongly adhesive hydrogel titanium alloy samples were immersed in a 500 mM calcium chloride solution at pH 11 for 24 hours to allow the amorphous calcium phosphate formed by mineralization to mature into HA.

[0123] That is, a strongly adhered biomimetic mineralized hydrogel coating was obtained on the surface of the four groups of titanium alloys.

[0124] Example 4 investigates the effect of a single immersion time of the mineralization solution on the quality and distribution of the biomimetic mineralized hydrogel that strongly adheres to the surface of the titanium alloy bone implant using a single variable method.

[0125] Example 5

[0126] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a stainless steel bone implant includes the following steps:

[0127] Step 1: Stainless steel surface pretreatment: Use sandpaper to polish the surface of the stainless steel sample, and ultrasonically clean it for 5 minutes to remove residual impurities; then treat the cleaned stainless steel sample with plasma for 5 minutes to increase the active groups on the surface.

[0128] Step 2: Preparation of strong adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water; stir magnetically at 100 ℃ for 5 h until a transparent and homogeneous PVA aqueous solution is formed; centrifuge the prepared PVA aqueous solution (5000 rpm, 20 min) to eliminate residual bubbles in the solution; immerse the pretreated stainless steel sample in the PVA solution, ensuring that no bubbles are generated on the surface; remove the coated stainless steel sample and divide the sample into 3 groups for different treatments.

[0129] Group 1: Take out the coated stainless steel samples and let them stand at room temperature for 0.5 hours;

[0130] Group 2: Take out the coated stainless steel sample, place it in an oven to dry for 15 minutes, immerse the sample in PVA solution again, and let it stand for 0.5 hours;

[0131] Group 3: Remove the coated stainless steel samples, dry them in an oven for 15 minutes, perform a second immersion operation, dry them again in an oven for 15 minutes, perform a third immersion operation, and let them stand for 0.5 hours. Freeze the three groups of stainless steel samples at -20 ℃ for 8 hours, then thaw them at room temperature for 3 hours, and then air dry them for 8 hours to obtain a smooth PVA hydrogel coating.

[0132] Step 3: Annealing treatment: Anneal the above-coated hydrogel coating at 100 ℃ for 1.5 hours. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace.

[0133] Step 4: Biomimetic Mineralization Treatment: The three groups of annealed, strongly adhesive hydrogel stainless steel samples were immersed in a 1 M Tris buffer solution (pH=9) for 24 hours to adjust the pH inside the hydrogel. The samples were then sequentially immersed in a 300 mM dipotassium hydrogen phosphate solution for 2 minutes, deionized water for 10 seconds, a 500 mM calcium chloride solution for 2 minutes, and then in deionized water for 10 seconds. This cycle was repeated 5 times to control the thickness of the mineralized coating. The mineralized strongly adhesive hydrogel stainless steel samples were then immersed in a 500 mM calcium chloride solution (pH=11) for 24 hours to allow the amorphous calcium phosphate formed during mineralization to mature into HA.

[0134] That is, a strongly adherent biomimetic mineralized hydrogel coating was obtained on the stainless steel surfaces of the three groups.

[0135] Example 5 investigates the effects of the number of times PVA solution is soaked on the coating thickness, quality, and distribution of the biomimetic mineralized hydrogel that strongly adheres to the surface of a stainless steel bone implant using a single variable method.

[0136] Example 6

[0137] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a stainless steel bone implant includes the following steps:

[0138] Step 1: Stainless steel surface pretreatment: Use sandpaper to polish the surface of the stainless steel sample, and ultrasonically clean it for 5 minutes to remove residual impurities; then treat the cleaned stainless steel sample with plasma for 5 minutes to increase the active groups on the surface.

[0139] Step 2: Preparation of a strong-adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water; stir magnetically at 100 ℃ for 5 h until a transparent and homogeneous PVA aqueous solution is formed. Centrifuge the prepared PVA aqueous solution (5000 rpm, 20 min) to eliminate residual air bubbles in the solution; take out the coated stainless steel sample, dry it in an oven for 15 minutes, impregnate it again, and let it stand for 0.5 hours. Freeze the stainless steel sample at -20 ℃ for 8 hours, then thaw it at room temperature for 3 hours, and then air dry it for 8 hours to obtain a smooth PVA hydrogel coating.

[0140] Step 3: Annealing treatment: Anneal the above-coated hydrogel coating at 100 ℃ for 1.5 hours. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace.

[0141] Step 4: Biomimetic mineralization treatment: The annealed stainless steel sample with strong adhesion hydrogel was immersed in a 1 M Tris buffer solution with pH=9 for 24 hours to adjust the pH inside the hydrogel.

[0142] The stainless steel samples, after pH adjustment, were subjected to the following immersion steps in sequence:

[0143] Immersion in dipotassium hydrogen phosphate solution: The stainless steel samples were divided into four groups and immersed in 300 mM dipotassium hydrogen phosphate solution for 30 seconds, 1 minute, 2 minutes and 3 minutes respectively, to control the amount of phosphate diffusion in the early stage of mineralization.

[0144] Deionized water rinsing: After soaking in dipotassium hydrogen phosphate solution, immerse the sample in deionized water for 10 seconds to remove unreacted ions and residual solution;

[0145] Immersion in calcium chloride solution: The above four groups of samples were immersed in 500 mM calcium chloride solution for 30 seconds, 1 minute, 2 minutes and 3 minutes respectively to promote the diffusion and reaction of calcium ions on the surface of hydrogel.

[0146] Deionized water rinsing: After each soaking in calcium chloride solution, immerse the sample in deionized water for 10 seconds to ensure the removal of excess calcium ions and solution residue;

[0147] Cyclic repetition: The above soaking operations of dipotassium hydrogen phosphate, calcium chloride and deionized water were repeated 4 times for each group according to different soaking times, so as to gradually control the thickness and uniformity of the mineralized coating.

[0148] The four groups of mineralized, strongly adhesive hydrogel stainless steel samples were immersed in a 500 mM calcium chloride solution at pH 11 for 24 hours to allow the amorphous calcium phosphate formed by mineralization to mature into HA.

[0149] That is, a strongly adherent biomimetic mineralized hydrogel coating was obtained on the surface of the four groups of stainless steel.

[0150] Example 6 investigates the effect of a single immersion time of the mineralization solution on the coating quality and distribution of a biomimetic mineralized hydrogel that adheres strongly to the surface of a stainless steel bone implant using a single variable method.

[0151] Example 7

[0152] A method for preparing a strongly adhesive biomimetic mineralized hydrogel coating on the surface of a PEEK implant includes the following steps:

[0153] Step 1: PEEK Surface Pretreatment: The PEEK sample surface was sanded with sandpaper. The sanded sample was then placed in deionized water and ultrasonically cleaned for 5 minutes to remove residual impurities. The cleaned PEEK sample was then immersed in concentrated sulfuric acid for 1 minute for surface sulfonation. The sulfonated PEEK sample was immediately placed in ice water for 1 minute to terminate the sulfonation reaction. The sulfonated PEEK sample was then immersed in a 3 wt% sodium hydroxide solution for 2 hours to further neutralize any residual sulfuric acid on the surface. Finally, the sample was ultrasonically cleaned with deionized water for 15 minutes to remove residual sodium hydroxide and other impurities. The PEEK sample treated in the above manner was labeled SPEEK.

[0154] Step 2: Preparation of a strong-adhesion PVA hydrogel coating: At room temperature, weigh 10 g of PVA powder (molecular weight 27.04522) and dissolve it in 90 mL of deionized water; stir magnetically at 100 ℃ for 5 hours until a transparent and homogeneous PVA aqueous solution is formed. Centrifuge the prepared PVA aqueous solution (5000 rpm, 20 min) to eliminate residual bubbles in the solution; immerse the pretreated SPEEK sample in the PVA solution, ensuring no bubbles are generated on the surface; remove the coated SPEEK sample, dry it in an oven for 15 minutes, immerse it again, and let it stand for 0.5 hours. Freeze the SPEEK sample at -20 ℃ for 8 hours, then thaw it at room temperature for 3 hours, and then air dry it for 8 hours to obtain a smooth PVA hydrogel coating.

[0155] Step 3: Annealing treatment: Anneal the above-coated hydrogel coating at 100 ℃ for 1.5 hours. The specific annealing process parameters are set as follows: heating rate 2 ℃ / min, holding time 90 minutes, and cooling in the furnace. The sample after the above treatment is labeled as PVA-SPEEK.

[0156] Step 4: Biomimetic mineralization treatment: Immerse the strongly adhesive hydrogel PEEK sample in 1 M Tris buffer solution at pH=9 for 24 hours to adjust the pH inside the hydrogel; immerse the sample sequentially in 300 mM dipotassium hydrogen phosphate solution for 2 minutes, in deionized water for 10 seconds, in 500 mM calcium chloride solution for 2 minutes, and then in deionized water for 10 seconds; repeat the above cycle 5 times to control the thickness of the mineralization coating; immerse the mineralized strongly adhesive hydrogel PEEK sample in 500 mM calcium chloride solution at pH=11 for 24 hours to allow the amorphous calcium phosphate formed by mineralization to mature into HA, and label the sample as HA-PVA-SPEEK.

[0157] Example 7 describes the preparation of a uniform and strongly adhesive biomimetic mineralized hydrogel coating on the surface of a PEEK bone implant under optimal experimental conditions: PEEK was coated with PVA solution, dried in an oven, and re-impregnated once; the single immersion time in the mineralization solution was 2 minutes; and the coating was prepared by freeze-thaw and biomimetic mineralization.

[0158] To illustrate the relevant properties of the composite material provided by this invention, see [link to relevant documentation]. Figures 1-7 As shown, an explanation will be provided.

[0159] Figure 1 These are scanning electron microscope (SEM) images of the surface morphology of the PEEK biomimetic mineralized coating implant at different mineralization times, as described in Example 2. From... Figure 1 As can be seen, the HA content on the surface of the HA-PVA-SPEEK (30s) sample is relatively low, with nucleation and growth occurring only in a few areas; the HA content on the surface of the HA-PVA-SPEEK (1min) sample increases significantly, with some areas still showing unmineralized PVA hydrogel; the surface of the HA-PVA-SPEEK (2min) sample is uniformly covered with a layer of HA, with uniform particle size and consistent coating thickness; the surface of the HA-PVA-SPEEK (3min) sample generates a large amount of HA, forming island-like protrusions in some areas, with inconsistent coating thickness. With the addition of dipotassium hydrogen phosphate solution and chloride... calcium The hydroxyapatite content on the coating surface gradually increases with the extension of solution immersion time, indicating that controlling the mineralization time has an important influence on the structure and morphology of the coating.

[0160] Figure 2 These are scanning electron microscope (SEM) images of the surfaces of the SPEEK implant, PVA-SPEEK implant, and HA-PVA-SPEEK implant described in Example 5. From... Figure 2As can be seen, sulfonation treatment gives the SPEEK sample surface a distinct porous structure; the PVA-SPEEK sample is covered with a hydrogel coating, which makes the surface smooth and dense, enhancing the adhesion and protection of the coating; the HA-PVA-SPEEK sample coating surface is uniformly covered with hydroxyapatite, with a particle size of approximately 300-500 μm.

[0161] Figure 3 The cross-sectional scanning electron microscope image of the strongly adhesive hydrogel coating described in Example 5 shows that its thickness is between 18-25 μm, confirming the stability and controllability of the preparation process.

[0162] Figure 4 The water contact angle test was conducted on the surfaces of the SPEEK implant, PVA-SPEEK implant, and HA-PVA-SPEEK implant described in Example 5. The results showed that the SPEEK sample exhibited hydrophobic properties with a large contact angle; the PVA-SPEEK sample showed significant hydrophilicity, and the hydrogel coating significantly reduced the water contact angle; the PVA-SPEEK-MIN sample still showed significantly improved hydrophilicity compared to the SPEEK sample, which is beneficial for cell adhesion and proliferation.

[0163] Figure 5 A 90° peel test was performed on the strongly adhesive hydrogel coating described in Example 5. From... Figure 5 As can be seen, in the initial stage, the peeling force is relatively small, and the displacement change is not obvious; in the middle stage, as the load increases, the hydrogel is gradually peeled off. When the unit peeling force reaches 225 N / m, the peeling force and adhesion force are balanced, and the corresponding stress value is the material's peeling force; in the later stage, under the action of the load, the displacement gradually increases until the flexible backing completely detaches from the substrate, and the test ends. The calculated results show that the interfacial toughness of the hydrogel is 208.54 J / m. 2 Therefore, this hydrogel coating exhibits high interfacial toughness and adhesion properties.

[0164] Figure 6 and Figure 7 The images show biocompatibility tests and scanning electron microscopy (SEM) images of the surfaces of the SPEEK implant, PVA-SPEEK implant, and HA-PVA-SPEEK implant described in Example 5. Figure 6 It can be seen that, within the same group, cell viability increased over time. The control group had the highest cell viability and best biocompatibility; the HA-PVA-SPEEK group was second; the PVA-SPEEK and SPEEK groups were relatively worse. Figure 7Cell morphology analysis showed that the porous structure on the surface of the SPEEK sample provided space for cell spread; the PVA-SPEEK sample became denser after annealing, and although the cell survival rate increased slightly compared with the SPEEK group, the overall biocompatibility was poor; the cells on the surface of the HA-PVA-SPEEK sample showed extensibility and longer pseudopodia, and the biocompatibility was significantly improved.

[0165] In summary, this invention provides a method for preparing and applying a highly adhesive biomimetic mineralized hydrogel coating. The method includes the following steps: First, the surface of the bone implant is pretreated to enhance the adhesion of the coating; the pretreated bone implant is immersed in a prepared polyvinyl alcohol (PVA) solution, allowed to stand, and then removed; this process is repeated. Subsequently, the resulting coating undergoes freeze-thaw cycles and annealing to obtain a highly adhesive hydrogel coating on the surface of the bone implant. Next, by repeatedly immersing the bone implant in a calcium and phosphate salt solution, a mineralization reaction is induced on the surface of the hydrogel coating, forming a uniformly distributed hydroxyapatite (HA) coating. This invention features a simple process and easy operation, achieving stable hydrogel coating adhesion on the surfaces of various bone implant materials. Furthermore, the HA nanoparticles formed through mineralization significantly improve the biocompatibility and osteogenic properties of the implant material. This coating provides a smooth and uniform appearance while exhibiting excellent adhesion strength and mineralization uniformity, offering a novel and efficient solution for the biomimetic repair of bone tissue defects.

[0166] This invention describes preferred embodiments and their effects. However, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to include both the preferred embodiments and all changes and modifications falling within the scope of this invention.

[0167] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a strong adhesion mimicked mineralized hydrogel coating, characterized in that, The method comprises the following steps: immersing the surface pretreated bone implant into a polyvinyl alcohol solution, then performing a single freeze-thaw cycle, and then performing annealing treatment; immersing the annealed bone implant alternately in a calcium-containing solution and a phosphorus-containing solution to perform surface mineralization treatment, and then inducing the product after the surface mineralization treatment into hydroxyapatite; that is, obtaining a strong adhesion biomimetic mineralized hydrogel coating on the surface of the bone implant.

2. The method of claim 1, wherein the strong-adhesion biomimetic mineralized hydrogel coating is prepared by the steps of: During the surface mineralization treatment, the following steps are included: immersing the annealed bone implant in the phosphorus-containing solution for 2-4 minutes, then rinsing in deionized water for 10-15 seconds, immersing in the calcium-containing solution for 2-4 minutes, and rinsing in deionized water for 10-15 seconds, and repeating the cycle 3-6 times.

3. The method of claim 2, wherein the strong adhesion of the biomimetic mineralized hydrogel coating is characterized by, The phosphorus-containing solution is a dipotassium hydrogen phosphate solution with a concentration of 200-400 mM; and the calcium-containing solution is a calcium chloride solution with a concentration of 300-600 mM.

4. The method of claim 1, wherein the strong adhesion of the biomimetic mineralized hydrogel coating is characterized by, The product after the surface mineralization treatment is induced into hydroxyapatite, including: immersing the bone implant after the surface mineralization treatment in the calcium chloride solution for 24-36 hours to induce the product after the surface mineralization treatment into hydroxyapatite; wherein the calcium-phosphorus ratio of the hydroxyapatite is 1.60-1.75, and the particle size is 300-500 nm.

5. The method of claim 1, wherein the strong adhesion of the biomimetic mineralized hydrogel coating is characterized by, Before the surface mineralization treatment, the annealed bone implant is also immersed in a 1 M Tris buffer solution with a pH of 9 for 12-24 hours.

6. The method of claim 1, wherein the strong adhesion of the biomimetic mineralized hydrogel coating is characterized by, When immersing the surface pretreated bone implant into the polyvinyl alcohol solution, at least one immersion into the polyvinyl alcohol solution is included; wherein each immersion process is immersing the surface pretreated bone implant into the polyvinyl alcohol solution, and after ensuring that no bubbles are generated on the surface, the bone implant is taken out and dried in an oven for 10-15 minutes; After immersing the surface pretreated bone implant into the polyvinyl alcohol solution, the bone implant is placed at room temperature for 0.5-1 hour; wherein the concentration of the polyvinyl alcohol solution is 10-12 wt%.

7. The method of claim 1, wherein the strong adhesion of the biomimetic mineralized hydrogel coating is characterized by, The single freeze-thaw cycle includes: immersing the surface pretreated bone implant into the polyvinyl alcohol solution, then placing it in a freezer at -20 to -18℃ for 8-10 hours, and then thawing it at room temperature for 2-4 hours.

8. The method of claim 1, wherein the strong adhesion of the biomimetic mineralized hydrogel coating is characterized by, The annealing treatment temperature is 100-110℃, and the annealing time is 90-120 minutes.

9. A strongly adherent biomimetic mineralized hydrogel coating, characterized in that, is prepared by the method of any one of claims 1-8, wherein the thickness of the strongly adhering biomimetic mineralized hydrogel coating is 15-23 μm, and the interfacial toughness is up to 208.54 J / m 2 .

10. Use of the strong adhesion biomimetic mineralized hydrogel coating of claim 9 in the preparation of a bone implant.

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