Preparation method of medical degradable zinc alloy GBR membrane, GBR membrane and application thereof

Abstract

The application discloses a preparation method of a medical degradable zinc alloy GBR membrane, the GBR membrane and application of the GBR membrane. The preparation method comprises the following steps: providing a zinc-based implant as a substrate; preparing a reaction solution containing a molybdenum source solution and a phosphorus source solution; and performing chemical conversion reaction on the substrate in the molybdenum source solution and the phosphorus source solution respectively, so as to form a molybdenum and phosphorus loaded composite coating on the surface of the substrate. The GBR membrane prepared by the application not only retains the excellent mechanical supporting performance and biodegradability of the zinc alloy substrate, and effectively prevents the risk of secondary surgery removal; and further forms a molybdenum and phosphorus loaded composite coating by a chemical conversion method, utilizes the synergistic effect of molybdenum and phosphorus elements, and endows the implant with excellent functions of promoting bone formation, resisting infection and promoting blood vessel growth, so that the application has a wide application prospect in the field of directional guided bone regeneration such as oral implantation and maxillofacial reconstruction.

Description

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a method for preparing a medical biodegradable zinc alloy GBR membrane, the GBR membrane itself, and its applications. Background Technology

[0002] Bone defects are a common pathological condition in clinical orthopedics and oral and maxillofacial surgery. During the repair of bone defects, bone tissue grows more slowly than surrounding soft tissues (such as fibroblasts and epithelial cells), often resulting in the bone regeneration space being squeezed and encroached upon by surrounding soft tissues. To address this issue, guided bone regeneration (GBR) technology has emerged. The core of this technology lies in using a barrier membrane (GBR membrane) to prevent soft tissue cells from entering the bone defect area, thereby providing a relatively closed and stable space for bone regeneration and repair.

[0003] Currently, biodegradable zinc (Zn) and its alloys are attracting significant attention as potential GBR membrane materials. Zinc not only possesses excellent biocompatibility and mechanical properties, but its greatest advantage lies in its biodegradability, which avoids the risk of requiring a second surgery to remove the implant and significantly reduces patient suffering. Furthermore, zinc is an essential trace element for the human body. 2+ It not only participates in regulating DNA replication and enzyme activity, but also exerts broad-spectrum antibacterial effects by inducing the production of reactive oxygen species (ROS) or binding to bacterial cell membranes.

[0004] Despite the aforementioned advantages of zinc alloys, single zinc-based materials still face challenges in the complex in vivo environment. For example, how to further enhance their surface bioactivity to accelerate osteointegration, and how to obtain more durable and efficient antibacterial and anti-inflammatory capabilities. Current improvement methods mainly include alloying (such as Zn-Cu, Zn-Ag, etc.) and surface modification (such as preparing calcium phosphate coatings, zinc oxide coatings, etc.). However, simple alloying or single-component coatings often fail to simultaneously address the multiple needs of promoting bone growth, preventing infection, and promoting angiogenesis. Summary of the Invention

[0005] This invention aims to at least partially solve one of the technical problems in related technologies. Therefore, the objective of this invention is to provide a method for preparing a medical biodegradable zinc alloy GBR film, the GBR film itself, and its applications.

[0006] To achieve the above objectives, according to a first aspect of the present invention, a method for preparing a medical biodegradable zinc alloy GBR membrane includes: Provide zinc-based implants as the matrix; Prepare a reaction solution, wherein the reaction solution comprises a molybdenum source solution and a phosphorus source solution; The substrate is immersed in the reaction solution to carry out a chemical transformation reaction, so as to form a molybdenum- and phosphorus-loaded composite coating on the surface of the substrate.

[0007] According to one embodiment of the present invention, the step of providing a zinc-based implant as a matrix includes: The zinc material is heated to 500-700℃ to melt and then cast into zinc ingots. The zinc ingot is homogenized at 250–350°C for 24–72 hours and then cooled. The treated zinc ingots are held at 250℃~270℃ for 1 to 3 hours, and then hot-extruded at an extrusion ratio of 16:1-40:1 and an extrusion speed of 0.5 to 1.5 mm / s to obtain zinc rods. The zinc rod is cut into zinc sample sheets of a predetermined thickness.

[0008] According to one embodiment of the present invention, before immersing the matrix in the reaction solution, the method further includes: The substrate surface is polished using 1500 to 2000 grit sandpaper; The polished substrate was then subjected to ultrasonic cleaning in acetone, ethanol, and ultrapure water in sequence.

[0009] According to one embodiment of the present invention, the molybdenum source solution is selected from solution 1 or solution 4, and the phosphorus source solution is selected from solution 2 or solution 3; the solutions 1 to 4 are configured as follows: Solution 1: A mixed solution containing 0.1–0.5 mol / L sodium molybdate and 0.10–0.30 mol / L H₂O₂, with a pH of 4.0–6.0; Solution 2: A mixed solution containing 0.05–0.10 mol / L zinc nitrate and 0.10–0.20 mol / L H3PO4, with a pH of 2.0–3.0; Solution 3: An aqueous solution of sodium dihydrogen phosphate containing 0.10–0.20 mol / L phosphate; Solution 4: A mixed solution containing 0.1–0.5 mol / L sodium molybdate and 0.10–0.20 mol / L sodium nitrate, with a pH of 4.0–6.0.

[0010] According to one embodiment of the present invention, the step of forming the molybdenum-phosphorus composite coating adopts a "molybdenum first, then phosphorus" process, specifically including: The substrate is immersed in solution 1 for reaction, then removed and dried to form a molybdenum coating on the substrate surface; The substrate with the molybdenum coating is immersed in the solution 3 for reaction, then removed and dried to obtain a zinc alloy GBR film with a molybdenum coating first and then a phosphate coating.

[0011] According to one embodiment of the present invention, the reaction time of the matrix in solution 1 is 15 to 30 minutes; the reaction time of the matrix in solution 3 is 20 to 40 minutes; and the drying conditions are all drying in a drying oven at 50 to 70°C for 2 to 6 hours.

[0012] According to one embodiment of the present invention, the step of forming the molybdenum-phosphorus composite coating adopts a "phosphorus first, molybdenum later" process, specifically including: The substrate is immersed in solution 2, subjected to ultrasonic vibration and reaction, and then removed and dried to form a phosphate coating on the substrate surface; The substrate with the phosphate coating is immersed in the solution 4 for reaction. During the reaction, the solution 4 is replaced with a new one periodically. After the reaction is completed, the substrate is removed and dried to obtain a zinc alloy GBR film with a phosphate coating first and then a molybdenum coating.

[0013] According to one embodiment of the present invention, the matrix is ​​ultrasonically vibrated in solution 2 for 3 to 8 minutes, and then allowed to stand for 15 to 30 minutes; the reaction time of the matrix in solution 4 is 18 to 30 hours, and solution 4 is replaced every 6 to 10 hours.

[0014] According to a second aspect of the present invention, the medical biodegradable zinc alloy GBR membrane provided by the present invention is prepared by the preparation method described above; The GBR membrane includes a zinc-based implant matrix and a molybdenum- and phosphorus-loaded composite coating covering the surface of the matrix; the molybdenum- and phosphorus-loaded composite coating is attached to the surface of the matrix by chemical bonding and has functions of promoting bone growth, resisting infection and promoting angiogenesis.

[0015] According to a third aspect of the present invention, the present invention proposes the application of the medical biodegradable zinc alloy GBR membrane as described above in the preparation of medical devices for guiding bone regeneration, dental implantation or maxillofacial reconstruction to repair bone defects.

[0016] This invention utilizes a chemical conversion method to form a molybdenum- and phosphorus-loaded composite coating on the surface of a zinc substrate. This not only preserves the excellent mechanical support properties and biodegradability of the zinc alloy substrate but also addresses the problem of insufficient bioactivity in traditional materials by leveraging the synergistic effect of molybdenum and phosphorus. Specifically, the introduced molybdenum ions significantly enhance osteogenic differentiation, inhibit osteoclasts, and provide a broad-spectrum antibacterial and anti-inflammatory environment by activating signaling pathways such as JAK / STAT3. The phosphate component effectively improves the wettability and roughness of the implant surface, accelerating cell adhesion and bone mineral deposition. This composite coating endows the GBR membrane with excellent multiple functions including osteopromoting, anti-infection, and angiogenesis promotion, establishing a dynamic balance between degradation, tissue regeneration, and immune regulation within the bone defect repair microenvironment, thus possessing extremely high clinical application value.

[0017] Other features and advantages of the present invention will be described in detail in the following detailed description section. Attached Figure Description

[0018] Figure 1 The images show macroscopic views of the pure Zn sample and its coatings in the examples.

[0019] Figure 2 The SEM surface morphology of the pure Zn untreated group sample in the example is shown.

[0020] Figure 3a The SEM surface morphology of the pure Zn-plated molybdenum group samples in the examples is shown. Figure 3b Elemental analysis of the pure Zn-plated molybdenum group samples in the examples; Figure 4a The SEM surface morphology of the pure Zn sample first coated with molybdenum and then coated with phosphate coating in the example is shown. Figure 4b Elemental analysis of the pure Zn sample first plated with molybdenum and then with phosphate coating in the examples; Figure 5 The SEM surface morphology of the pure Zn-plated phosphate coating group samples in the examples; Figure 6a The SEM surface morphology of the pure Zn sample coated with phosphorus first and then molybdenum in the example is shown. Figure 6b Elemental analysis of the pure Zn sample coated with phosphorus first and then molybdenum in the examples; Figure 7a The image shows the SEM surface morphology of the pure Zn sample coated with phosphorus first and then molybdenum in the example; the "Spectrum 2" markings in the image indicate the sampling points for energy dispersive spectroscopy analysis. Figure 7b for Figure 7a The EDS spectrum corresponding to the marked point position shows the characteristic peaks of oxygen (O), phosphorus (P), zinc (Zn) and molybdenum (Mo); Figure 7c for Figure 7b The corresponding elemental composition quantitative analysis table lists the weight percentage and atomic percentage of each element; Figure 8 The results of the CCK-8 assay for MC3E3-T1 cells cultured in 50% extract of each group of samples for 72 h are shown in the examples (P < 0.01).

[0021] Figure 9 The following are the fluorescence staining results of MC3E3-T1 cells cultured in 25% extract of each group of samples for 24h and 72h. It can be seen that with the increase of culture time, the cells are in good extension state and the cell density increases. Detailed Implementation

[0022] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0023] This invention is based on the inventor's following discoveries and research.

[0024] The inventors discovered that during bone defect repair, fibroblasts or epithelial cells in surrounding soft tissues typically grow faster, while bone tissue grows relatively slowly. This results in limited space for bone growth and restricted nutrient supply, thus affecting bone tissue growth. Currently, novel biodegradable zinc alloys for bone repair, such as Zn-Cu, Zn-Ag, and Zn-Mg-Cu, developed through alloying methods, have demonstrated good osteogenic and antibacterial effects in both in vitro and in vivo animal experiments. Furthermore, surface modification can be used to impart specific physicochemical properties to the material surface to meet desired clinical requirements. For example, zinc phosphate coatings, calcium phosphate coatings, zinc oxide coatings, and collagen coatings have been successfully prepared on zinc alloy surfaces.

[0025] Bioactive polymer coating design is a novel design concept that can generate a more favorable interfacial microenvironment, thereby achieving a dynamic balance between degradation, vascular remodeling and anti-infection on the surface of bone implants.

[0026] The method for preparing a biodegradable zinc alloy GBR film for medical use according to embodiments of the present invention includes: 1) Provide zinc-based implants as a matrix.

[0027] Zinc or zinc alloy materials with good biocompatibility and mechanical properties are selected as materials and processed into a membrane structure suitable for clinical guided bone regeneration (GBR) applications. This zinc matrix not only provides an adhesion surface for subsequent coatings, but also serves as a support part of the implant. Utilizing the biodegradable properties of zinc metal itself, the risk of patients having to undergo a second surgery to remove the implant after bone defect repair can be avoided, thereby reducing patient suffering.

[0028] 2) Prepare a reaction solution, wherein the reaction solution contains a molybdenum source solution and a phosphorus source solution.

[0029] The molybdenum source solution provides sufficient active molybdenum components to the reaction system. These components exert biological effects in the subsequently deposited coating, mainly by promoting osteogenic differentiation and inhibiting osteoclast activity through activation of signaling pathways such as JAK / STAT3, as well as endowing the material surface with broad-spectrum antibacterial and anti-inflammatory capabilities. The phosphorus source solution, on the other hand, provides active phosphate components. The main function of these components is to optimize the interfacial properties of the coating. By significantly improving the hydrophilicity and micro-roughness of the zinc matrix surface, it provides physical anchors for early cell adhesion and spreading, and serves as a nucleation site for biomineralization to accelerate the bone integration process.

[0030] 3) The substrate is immersed in the reaction solution to carry out a chemical transformation reaction to form a molybdenum- and phosphorus-loaded composite coating on the surface of the substrate.

[0031] During this process, a chemical reaction occurs between the zinc substrate surface and active ions in the solution. Through nucleation and growth, a tightly bonded and structurally stable molybdenum- and phosphorus-loaded composite coating is formed in situ on the zinc substrate surface. This chemical transformation process achieves the bonding between the coating and the substrate through chemical bonding and other methods, thereby obtaining the medical biodegradable zinc alloy GBR film coated with the molybdenum- and phosphorus-loaded coating described in this embodiment.

[0032] This invention utilizes a chemical conversion method to form a molybdenum- and phosphorus-loaded composite coating on the surface of a zinc substrate. This not only preserves the excellent mechanical support properties and biodegradability of the zinc alloy substrate but also addresses the problem of insufficient bioactivity in traditional materials by leveraging the synergistic effect of molybdenum and phosphorus. Specifically, the introduced molybdenum ions significantly enhance osteogenic differentiation, inhibit osteoclasts, and provide a broad-spectrum antibacterial and anti-inflammatory environment by activating signaling pathways such as JAK / STAT3. The phosphate component effectively improves the wettability and roughness of the implant surface, accelerating cell adhesion and bone mineral deposition. This composite coating endows the GBR membrane with excellent multiple functions including osteopromoting, anti-infection, and angiogenesis promotion, establishing a dynamic balance between degradation, tissue regeneration, and immune regulation within the bone defect repair microenvironment, thus possessing extremely high clinical application value.

[0033] In one embodiment of the present invention, the step of providing a zinc-based implant as a matrix includes: First, the zinc material is heated to 500–700°C to melt and cast into zinc ingots. Within this temperature range, the zinc material can fully melt and maintain good fluidity. After the melt is homogeneous, it is poured into a mold to cool and solidify, thus obtaining the initial zinc ingot.

[0034] Next, the zinc ingot is homogenized at 250–350°C for 24–72 hours and then cooled. In this step, in order to eliminate dendritic segregation generated during the casting process and homogenize the internal structure, the zinc ingot is placed in a heat treatment furnace and homogenized for a long time at a temperature range of 250–350°C for 24–72 hours. After the treatment, it is cooled in the furnace or air-cooled to room temperature.

[0035] Furthermore, the treated zinc ingot is held at 250℃~270℃ for 1 to 3 hours, and then hot-extruded under extrusion ratios of 16:1-40:1 and extrusion speeds of 0.5 to 1.5 mm / s to obtain zinc rods. In other words, the homogenized zinc ingot undergoes hot extrusion deformation processing. The specific steps are as follows: first, the ingot is heated to 250℃~270℃ and held for 1 to 3 hours to bring the material to a suitable hot working state for plastic deformation; then, hot extrusion is performed under process parameters of an extrusion ratio set at 16:1-40:1 and an extrusion speed controlled at 0.5 to 1.5 mm / s, and the ingot is processed into a dense zinc rod through intense plastic deformation.

[0036] Finally, the zinc rod is cut into zinc sample sheets of a predetermined thickness. For example, the zinc rod can be transversely cut into zinc sample sheets of a predetermined thickness (e.g., 0.8 to 1.5 mm) using processing methods such as wire cutting or mechanical cutting, according to the size requirements of the GBR membrane for clinical applications, as a substrate for subsequent chemical conversion treatment.

[0037] The aforementioned preparation process involves strict control of various parameters during smelting, homogenization heat treatment, and hot extrusion. The prolonged homogenization treatment effectively reduces casting defects and compositional segregation. Furthermore, the combination of a high extrusion ratio and low-speed extrusion promotes sufficient dynamic recrystallization of the zinc matrix, refining the grain size and reducing internal porosity and other defects. This fine-grained structure improves the tensile strength and ductility of the zinc-based implant, enabling it to meet the mechanical support requirements for maintaining space within the GBR membrane.

[0038] In one embodiment of the present invention, before immersing the substrate in the reaction solution, the method further includes: The substrate surface is polished using 1500 to 2000 grit sandpaper. This process removes natural oxide scale, oil stains, rust spots, and physical scratches generated during the initial heat treatment and cutting process, thereby exposing a fresh metal substrate surface with uniform color, smoothness, and high chemical reactivity.

[0039] The polished substrate was sequentially ultrasonically cleaned in acetone, ethanol, and ultrapure water. This process removes residual abrasive debris and adsorbed microparticles from the surface. Specifically, the zinc substrate was immersed sequentially in containers filled with acetone, anhydrous ethanol, and ultrapure water, and ultrasonically cleaned for a certain period of time in each. Utilizing the cavitation effect generated by ultrasound in the liquid, organic impurities and inorganic particles adhering to tiny crevices can be deeply exfoliated. After cleaning, the substrate was removed and dried for subsequent reactions.

[0040] The aforementioned pretreatment process, combining physical polishing and chemical cleaning, improves the surface quality of zinc-based implants. Polishing with 1500-2000 grit sandpaper creates suitable microtexture, increasing the density of nucleation sites for chemical reactions and promoting uniform coating growth. Gradient cleaning with acetone, ethanol, and ultrapure water removes surface grease and impurities, ensuring the wetting of the reaction solution and the substrate, thereby improving the density and interfacial bonding strength of the final molybdenum- and phosphorus-loaded composite coating.

[0041] In one embodiment of the present invention, the molybdenum source solution is selected from solution 1 or solution 4, and the phosphorus source solution is selected from solution 2 or solution 3; the solutions 1 to 4 are configured as follows: Solution 1: A mixed solution containing 0.1–0.5 mol / L sodium molybdate and 0.10–0.30 mol / L H₂O₂, with a pH of 4.0–6.0; Solution 2: A mixed solution containing 0.05–0.10 mol / L zinc nitrate and 0.10–0.20 mol / L H3PO4, with a pH of 2.0–3.0; Solution 3: An aqueous solution of sodium dihydrogen phosphate containing 0.10–0.20 mol / L phosphate; Solution 4: A mixed solution containing 0.1–0.5 mol / L sodium molybdate and 0.10–0.20 mol / L sodium nitrate, with a pH of 4.0–6.0.

[0042] Specifically, solution 1 is prepared by dissolving anhydrous sodium molybdate and 30% hydrogen peroxide solution in deionized water. To ensure a balance between coating deposition rate and quality, the concentration of sodium molybdate is controlled within the range of 0.1–0.5 mol / L, preferably 0.3 mol / L; the concentration of H2O2 is controlled within the range of 0.10–0.30 mol / L, preferably 0.20 mol / L; and the pH value is precisely adjusted to between 4.0 and 6.0 using concentrated nitric acid and sodium hydroxide solution, with the optimal pH value being 5.

[0043] Solution 2 was prepared by mixing zinc nitrate hexahydrate and concentrated phosphoric acid solution to form a mixed system containing 0.05–0.10 mol / L zinc nitrate and 0.10–0.20 mol / L H3PO4. To obtain better phosphate crystal morphology, the zinc nitrate concentration was preferably 0.07 mol / L and the H3PO4 concentration was preferably 0.15 mol / L. The pH value was stabilized at 2.0–3.0 using concentrated phosphoric acid and sodium hydroxide solution, with the optimal pH value being 2.5.

[0044] Solution 3 was prepared by dissolving sodium dihydrogen phosphate in deionized water, with a phosphate concentration ranging from 0.10 to 0.20 mol / L, preferably 0.15 mol / L.

[0045] Solution 4 is prepared by combining anhydrous sodium molybdate and sodium nitrate, wherein the concentration of sodium molybdate ranges from 0.1 to 0.5 mol / L, preferably 0.3 mol / L; the concentration of sodium nitrate ranges from 0.10 to 0.20 mol / L, preferably 0.15 mol / L; and the pH is adjusted to 4.0 to 6.0, with the most preferred pH value being 5.

[0046] By employing the aforementioned precise solution control, it was ensured that the final molybdenum- and phosphorus-loaded composite coating met the requirements for clinical application of GBR membranes in terms of thickness, density, and component ratio.

[0047] In one embodiment of the present invention, the step of forming the molybdenum-phosphorus composite coating adopts a "molybdenum first, phosphorus later" process, specifically including: First, the substrate is immersed in solution 1 for reaction, then removed and dried to form a molybdenum coating on the substrate surface.

[0048] This step involves the preparation of the molybdate underlayer (i.e., the first coating). The pretreated zinc substrate is placed horizontally in a container (such as a centrifuge tube) containing a sufficient amount of molybdenum source solution (solution 1), ensuring complete immersion of the substrate. A chemical conversion reaction is carried out at room temperature for 15–30 minutes, preferably 20 minutes. During this process, bubbles are continuously generated on the substrate surface. To avoid bubble retention leading to coating defects, the container should be periodically rotated to remove attached bubbles and ensure sufficient contact between the solution and the substrate. After the reaction, the sample is removed and dried in a drying oven at 50–70°C (preferably 60°C) for 2–6 hours (preferably 4 hours). At this point, the sample surface exhibits interference colors such as red, blue, and yellow. Microscopic observation reveals irregular microcracks and pore structures distributed on the surface. If the cracks are not obvious, hot air heating or other methods can be used to induce crack propagation. These microscopic defects provide physical anchoring points for subsequent phosphate deposition.

[0049] Subsequently, the substrate with the molybdenum coating is immersed in the solution 3 for reaction, removed and dried to obtain a zinc alloy GBR film with a molybdenum coating first and then a phosphate coating.

[0050] This step involves the preparation of the phosphate surface layer (i.e., the second coating). The dried sample coated with the molybdenum layer is horizontally immersed in a container containing a phosphorus source solution (solution 3). The reaction time is controlled between 20 and 40 minutes, preferably 30 minutes. Bubbles are generated in the initial stage of the reaction, and the container needs to be turned over promptly to remove surface bubbles. As the reaction proceeds, when no more bubbles are observed on the sample surface, the reaction has reached its endpoint. The sample is then removed and dried again under the same conditions to obtain a molybdenum-phosphorus type biodegradable zinc alloy GBR film for medical use, with a uniform molybdenum-phosphorus coating on the surface.

[0051] In another embodiment of the present invention, the step of forming the molybdenum-phosphorus composite coating adopts a "phosphorus first, molybdenum later" process, specifically including: First, the substrate is immersed in solution 2, subjected to ultrasonic vibration and reaction, and then removed and dried to form a phosphate coating on the surface of the substrate.

[0052] This step involves preparing a phosphate coating. The pretreated zinc substrate is laid flat and completely immersed in a solution containing a phosphorus source (solution 2). To promote rapid and uniform formation of phosphate crystal nuclei on the substrate surface, the immersion system is ultrasonically vibrated for 3–8 minutes (preferably 5 minutes). During this time, the substrate is flipped once to ensure uniform stress on both sides. After ultrasonication, the substrate is transferred to a centrifuge tube filled with fresh solution 2 and allowed to react horizontally for 15–30 minutes (preferably 20 minutes) under static conditions. After the reaction is complete, the sample is removed and dried in a drying oven at 50–70°C (preferably 60°C) for 2–6 hours (preferably 4 hours), thereby obtaining a uniform phosphate underlayer on the zinc substrate surface.

[0053] Subsequently, the substrate with the phosphate coating is immersed in the solution 4 for reaction. During the reaction, the solution 4 is replaced periodically. After the reaction is completed, the substrate is removed and dried to obtain a zinc alloy GBR film with a phosphate coating first and then a molybdenum coating.

[0054] This step involves a secondary conversion deposition of molybdate on the phosphate coating. The dried sample is horizontally immersed in a centrifuge tube filled with molybdenum source solution (solution 4). This step uses a long immersion method, with a total reaction time set at 18–30 hours (preferably 24 hours). To maintain the molybdenum ion concentration gradient at the reaction interface and remove reaction byproducts, fresh solution 4 is replaced every 6–10 hours (preferably 8 hours) during the reaction. Simultaneously, to ensure the uniformity of the coating thickness, it is recommended to turn the sample over every few hours. After the reaction, the sample is removed and dried and cured again under the same conditions (e.g., drying at 60°C for 4 hours), ultimately obtaining a brown zinc alloy GBR film with a phosphate coating followed by a molybdenum coating.

[0055] The medical biodegradable zinc alloy GBR membrane provided by the present invention is prepared by the preparation method described above; the GBR membrane includes a zinc-based implant substrate and a molybdenum- and phosphorus-loaded composite coating covering the surface of the substrate; the molybdenum- and phosphorus-loaded composite coating is attached to the surface of the substrate by chemical bonding and has bone-promoting, anti-infection and angiogenesis-promoting functions.

[0056] In this embodiment, the GBR forms a molybdenum- and phosphorus-loaded composite coating. The molybdenum ions released in the coating work synergistically with the phosphate components. On the one hand, it promotes osteoblast adhesion and proliferation by improving surface wettability and providing mineralization sites, thus accelerating bone defect repair. On the other hand, it utilizes the biological effects of molybdenum ions to endow the material with broad-spectrum antibacterial capabilities and inhibit inflammatory responses, while also promoting angiogenesis. This design constructs multiple functions on the zinc alloy surface, including promoting bone regeneration, anti-infection, and angiogenesis, effectively solving the problem of insufficient bioactivity in traditional zinc-based materials, and has broad clinical application prospects in the field of guided bone regeneration.

[0057] The embodiments of the present invention also propose the application of the medical biodegradable zinc alloy GBR membrane as described above in the preparation of medical devices for guiding bone regeneration, dental implants or maxillofacial reconstruction to repair bone defects.

[0058] In practical applications, this membrane material can be processed into barrier membranes, bone repair meshes, or guiding scaffolds that conform to clinical anatomy, covering the bone defect site and surrounding soft tissue during clinical treatment. Utilizing its excellent structural integrity, this device plays a crucial role in maintaining space and providing physical barrier, effectively preventing rapidly growing fibrous connective tissue from invading the bone defect area, thereby providing a regenerative environment for slower-growing bone tissue.

[0059] The preparation method of the present invention will be described in detail below through specific embodiments.

[0060] Example 1: Preparation of molybdenum-coated samples: Pre-treated circular pure zinc samples were immersed in 10ml centrifuge tubes filled with solution 1, placed horizontally, and allowed to react for 20 minutes. Afterward, they were dried in a 60℃ drying oven for 4 hours to obtain zinc samples with a fully molybdenum-coated surface. It is important to note that bubbles will continuously emerge from the sample surface during immersion; the centrifuge tubes must be continuously rotated to remove these bubbles. Visual observation reveals continuous color changes on the sample surface, including red, blue, and yellow, which are due to variations in the thickness of the molybdenum coating.

[0061] Example 2: Preparation of phosphate-coated samples: The pre-treated circular pure zinc sample was placed flat and completely immersed in a beaker containing solution 2. The sample was ultrasonically vibrated for 5 minutes, turning over once during the process. Then, the sample was immersed in a 10ml centrifuge tube filled with solution 2 and reacted horizontally for 20 minutes. After removal, it was dried in a 60℃ drying oven for 4 hours to obtain a zinc sample with a phosphate coating. It is important to note that the sample was turned over once during ultrasonic vibration and several times during subsequent centrifugation to ensure a uniform phosphate coating on the sample surface. Example

[0062] Preparation of samples with molybdenum coating followed by phosphate coating: Pre-treated circular pure zinc samples were immersed in 10ml centrifuge tubes filled with solution 1, placed horizontally, and allowed to react for 20 minutes. After removal, they were dried in a 60℃ drying oven for 4 hours to obtain zinc samples fully coated with molybdenum. Under a high-powered optical microscope, the sample surface was observed to be covered with air bubbles and irregular cracks. If the cracks were not obvious, they could be made more prominent by heating with a hairdryer. If the surface cracks were not obvious, it would be difficult to subsequently deposit phosphate onto the molybdenum coating. Subsequently, the zinc samples fully coated with molybdenum were immersed in 10ml centrifuge tubes filled with solution 3, placed horizontally, and allowed to react for 30 minutes. After removal, they were dried in a 60℃ drying oven for 4 hours to obtain zinc samples with molybdenum coating followed by phosphate coating. It is important to note that during the reaction in solution 3, bubbles continuously emerged from the sample surface; the centrifuge tubes needed to be rotated regularly to dislodge these bubbles. When the reaction in solution 3 is complete, visual observation shows that no more bubbles are generated on the surface of the sample, and the sample surface is uniformly covered with a phosphate coating. Example

[0063] Preparation of samples with phosphate coating followed by molybdenum coating: A pre-treated circular pure zinc sample was placed flat and completely immersed in a beaker containing solution 2. The sample was ultrasonically vibrated for 5 minutes, turning it over once during the process. Then, the sample was immersed in a 10ml centrifuge tube filled with solution 2 and reacted horizontally for 20 minutes. After removal, it was dried in a 60℃ drying oven for 4 hours to obtain a zinc sample fully coated with phosphate. Subsequently, the zinc sample fully coated with phosphate was immersed in a 10ml centrifuge tube filled with solution 4 and allowed to react horizontally for 24 hours. During the 24-hour reaction, solution 4 was replaced every 8 hours. It is important to note that the centrifuge tube was placed horizontally to ensure the sample reacts horizontally. During the 24-hour reaction, the sample was turned over every few hours to ensure a uniform coating on the sample surface. After reacting in solution 4 for 24 hours, the sample was removed and dried in a 60℃ drying oven for 4 hours to obtain a brown sample with a phosphate coating followed by a molybdenum coating.

[0064] The morphology and chemical composition of the surface coating of the samples prepared in the above embodiments were photographed and detected using scanning electron microscopy and energy dispersive spectroscopy, and successful deposition of phosphate and molybdate coatings could be observed. Fluorescence staining results of MC3E3-T1 cells at 24h and 72h showed that the cells were in a well-spread state, and the cell density increased with increasing culture time.

[0065] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details of the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0066] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable way without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0067] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A method for preparing a medical biodegradable zinc alloy GBR film, characterized in that, include: Provide zinc-based implants as the matrix; Prepare a reaction solution, wherein the reaction solution comprises a molybdenum source solution and a phosphorus source solution; The substrate is immersed in the reaction solution to carry out a chemical transformation reaction, so as to form a molybdenum- and phosphorus-loaded composite coating on the surface of the substrate.

2. According to claim 1 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， Its features are, The step of providing a zinc-based implant as a matrix includes: The zinc material is heated to 500-700℃ to melt and then cast into zinc ingots. The zinc ingot is homogenized at 250–350°C for 24–72 hours and then cooled. The treated zinc ingots are held at 250℃~270℃ for 1 to 3 hours, and then hot-extruded at an extrusion ratio of 16:1-40:1 and an extrusion speed of 0.5 to 1.5 mm / s to obtain zinc rods. The zinc rod is cut into zinc sample sheets of a predetermined thickness.

3. According to claim 1 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， Its features are, Before immersing the matrix in the reaction solution, the method further includes: The substrate surface is polished using 1500 to 2000 grit sandpaper; The polished substrate was then subjected to ultrasonic cleaning in acetone, ethanol, and ultrapure water in sequence.

4. According to claim 1 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， Its features are, The molybdenum source solution is selected from solution 1 or solution 4 below, and the phosphorus source solution is selected from solution 2 or solution 3 below; the preparation of solutions 1 to 4 is as follows: Solution 1: A mixed solution containing 0.1–0.5 mol / L sodium molybdate and 0.10–0.30 mol / L H₂O₂, with a pH of 4.0–6.0; Solution 2: A mixed solution containing 0.05–0.10 mol / L zinc nitrate and 0.10–0.20 mol / L H3PO4, with a pH of 2.0–3.0; Solution 3: An aqueous solution of sodium dihydrogen phosphate containing 0.10–0.20 mol / L phosphate; Solution 4: A mixed solution containing 0.1–0.5 mol / L sodium molybdate and 0.10–0.20 mol / L sodium nitrate, with a pH of 4.0–6.

0.

5. According to claim 4 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， Its features are, The step of forming the molybdenum-phosphorus composite coating adopts a "molybdenum first, then phosphorus" process, specifically including: The substrate is immersed in solution 1 for reaction, then removed and dried to form a molybdenum coating on the substrate surface; The substrate with the molybdenum coating is immersed in the solution 3 for reaction, then removed and dried to obtain a zinc alloy GBR film with a molybdenum coating first and then a phosphate coating.

6. According to claim 5 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， Its features are, The reaction time of the matrix in solution 1 is 15-30 minutes; the reaction time of the matrix in solution 3 is 20-40 minutes; and the drying conditions are all in a drying oven at 50-70°C for 2-6 hours.

7. According to claim 4 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， Its features are, The step of forming the molybdenum-phosphorus composite coating adopts a "phosphorus first, molybdenum later" process, specifically including: The substrate is immersed in solution 2, subjected to ultrasonic vibration and reaction, and then removed and dried to form a phosphate coating on the substrate surface; The substrate with the phosphate coating is immersed in the solution 4 for reaction. During the reaction, the solution 4 is replaced with a new one periodically. After the reaction is completed, the substrate is removed and dried to obtain a zinc alloy GBR film with a phosphate coating first and then a molybdenum coating.

8. According to claim 7 The aforementioned Preparation method of medical biodegradable zinc alloy GBR film ， The feature is that the matrix is ​​ultrasonically vibrated in solution 2 for 3 to 8 minutes, and then allowed to stand for 15 to 30 minutes; the reaction time of the matrix in solution 4 is 18 to 30 hours, and solution 4 is replaced every 6 to 10 hours.

9. A medical biodegradable zinc alloy GBR film, characterized in that, Prepared by the preparation method according to any one of claims 1 to 8; The GBR membrane includes a zinc-based implant matrix and a molybdenum- and phosphorus-loaded composite coating covering the surface of the matrix; the molybdenum- and phosphorus-loaded composite coating is attached to the surface of the matrix by chemical bonding and has functions of promoting bone growth, resisting infection and promoting angiogenesis.

10. The application of the medical biodegradable zinc alloy GBR membrane of claim 9 in the preparation of medical devices for guiding bone regeneration, dental implantation or maxillofacial reconstruction to repair bone defects.

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