Preparation method of osteogenesis, sequential degradation and antibacterial strengthening and toughening zinc-based medical material

Abstract

The invention provides a preparation method of an osteogenesis, sequential degradation and antibacterial strengthening and toughening zinc-based medical material, and belongs to the technical field of biomedical metal. The preparation method of the strengthened and toughened zinc-based medical material comprises the following steps: (1) performing chemical deposition treatment on pure zinc to obtain pure zinc with a zinc phosphate coating deposited on the surface; (2) the cylindrical device is placed in a mold, an iron wire is placed on the inner layer of the cylindrical device, and Zn-X alloy is filled to be flush with the iron wire; (3) the outer layer of the cylindrical device is filled with the pure zinc with the zinc phosphate coating deposited on the surface obtained in the step (1), the cylindrical device is drawn out, cold press molding is conducted, and a green body is obtained; and (4) pre-sintering the green body obtained in the step (3), and performing hot extrusion to obtain the strengthened and toughened zinc-based medical material. The strengthened and toughened zinc-based medical material has a time sequence degradation mode, and meanwhile has excellent tensile and compression performance and good antibacterial and corrosion-resistant performance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical metals, and particularly relates to a preparation method of a strong and tough zinc-based medical material with osteogenesis, time sequence degradation and antibiosis. BACKGROUND

[0002] The degradable metal bone implant is mainly used for fracture fixation, bone defect repair and bone tissue regeneration. It needs to provide sufficient support strength in the early stage of implantation to avoid fixation failure. At the same time, the degradation rate should match the bone healing process (usually maintaining mechanical properties for 3-6 months and completely degrading for 12-24 months); in addition, it also needs to have the properties of promoting osteogenesis, antibiosis, anti-inflammatory and the like to avoid complications such as infection and nonunion.

[0003] Zinc is a new degradable metal, and its degradation rate is between that of magnesium and iron. Moreover, zinc ions have natural antibacterial properties and osteogenesis promotion effect, and are regarded as an ideal candidate material. However, the existing pure zinc and its alloy have a slow degradation rate (0.1-0.2 mm / y), and the deposition of corrosion products will hinder the further degradation of the implant, so that the residual implant after the late stage of bone healing (>6 months) may cause stress shielding and hinder new bone growth. At the same time, the degradation rate of the implant made of pure zinc and its alloy is uncontrollable (too fast in the early stage to cause mechanical failure, and too slow in the later stage to hinder bone healing), and it cannot match the needs of different stages of bone healing (slow degradation in the early stage to maintain mechanical properties, and accelerated degradation in the later stage to avoid stress shielding). More importantly, the in-vivo osteoblasts are very sensitive to the concentration of zinc ions (low zinc ion concentration promotes proliferation, high zinc ion concentration inhibits proliferation and even kills cells), and slow degradation in the early stage of implantation can better promote the proliferation, differentiation and mineralization of osteoblasts, thereby promoting new bone formation. Therefore, the current single-material zinc-based medical material cannot meet the needs of strong and tough support in the early stage and osteogenesis in the long term at the same time. Therefore, developing a zinc-based composite material with time sequence degradation of "external slow release and internal rapid release" is an effective method to solve the above problems.

[0004] As an effective means, the powder metallurgy and galvanic corrosion method can effectively accelerate the degradation of the medical zinc-based material. However, the mechanical properties of the powder metallurgy sample are low, especially the elongation. Moreover, although the additional reinforcing phase can form a galvanic corrosion structure to accelerate the degradation, it will increase the ball milling and powder mixing process, and will further reduce the elongation due to uneven dispersion and local stress concentration.

[0005] At present, there is no report on the preparation of a strong and tough zinc-based medical material with osteogenesis, time sequence degradation and antibiosis and the corresponding performance research in the domestic and foreign literature. SUMMARY

[0006] The application aims to provide a preparation method of an osteogenic, time-degradable and antibacterial toughened zinc-based medical material.

[0007] In order to achieve the above-mentioned application purposes, the application provides the following technical solutions. The application provides a preparation method of an osteogenic, time-degradable and antibacterial toughened zinc-based medical material, comprising the following steps. (1) performing chemical deposition treatment on pure zinc to obtain pure zinc with a zinc phosphate coating deposited on the surface; (2) placing a cylindrical device in a mold, placing a wire in the inner layer of the cylindrical device, and filling Zn-X alloy to the level of the wire; (3) filling the pure zinc with the zinc phosphate coating deposited on the surface obtained in step (1) to the outer layer of the cylindrical device, extracting the cylindrical device, and cold pressing to obtain a blank; (4) pre-sintering the blank obtained in step (3) and hot extruding to obtain the toughened zinc-based medical material.

[0008] Preferably, the chemical deposition treatment in step (1) is performed using a phosphating solution; the temperature of the chemical deposition is 50-80 DEG C, and the time of the chemical deposition is 5-60 min.

[0009] Further preferably, the phosphating solution contains 5-15 g / L of phosphoric acid, 10-30 g / L of zinc nitrate hexahydrate and 0.1-3 g / L of graphene oxide, and the rest is water.

[0010] Preferably, the diameter of the wire in step (2) is 0.05-0.5 mm, the length of the wire is 35-45 mm, and the Zn-X alloy comprises one of Zn-Mg, Zn-Cu, Zn-Ca, Zn-Sr, Zn-Se, Zn-RE, Zn-Mn, Zn-Ge, Zn-Li, Zn-Fe and Zn-Ga alloy.

[0011] Preferably, the filling height in step (3) is 35-45 mm, the pressure of the cold pressing is 10-50 MPa, and the pressure is kept for 2-30 min after the cold pressing.

[0012] Preferably, the temperature of the pre-sintering in step (4) is 200-380 DEG C, the time of the pre-sintering is 0.5-3 h, and the rate of the hot extrusion is 0.2-100 mm / s.

[0013] The application further provides the application of the toughened zinc-based medical material prepared by the preparation method in the preparation of bone fixation materials or bone repair materials.

[0014] Preferably, the bone fixation material comprises a bone plate, and the bone repair material comprises a guided bone regeneration membrane.

[0015] Preferably, the prepared material is pre-processed to obtain a toughened zinc-based medical material, and then hot-rolled to obtain the bone fixation material or the bone repair material.

[0016] Further preferably, the pre-processing temperature is 280-360℃, the pre-processing time is 0.5-1h, the hot-rolling deformation is 3-10% reduction per pass, and the hot-rolling time is determined according to the total reduction of 70-99% of the bone fixation material or the bone repair material.

[0017] Compared with the prior art, the present application has the following beneficial effects: The present application provides a preparation method of a toughened zinc-based medical material with osteogenesis, time-dependent degradation and antibacterial properties, which is suitable for the preparation of orthopedic fixation devices (such as bone screws and bone plates) and bone repair devices (guided bone regeneration membranes). The toughened zinc-based medical material has a time-dependent degradation mode, excellent tensile and compressive properties, good antibacterial and corrosion resistance, and good blood compatibility, cell compatibility, and osteogenic differentiation and mineralization ability.

[0018] The present application effectively realizes initial slow degradation and improves osteogenic function by using zinc-based powder with a load functional coating as the outer layer, and effectively realizes late-stage fast degradation and toughening function by using pure iron wire toughened zinc-based powder as the inner layer. At the same time, the present application can solve the problem of coating peeling and falling off during the fixation of the implant in the bone and subsequent in-vivo friction, and cannot effectively control the degradation. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0020] Figure 1 Flow chart for preparing hot-extruded time-dependent degradation composite material; Figure 2 Experimental results of Test Example 1, wherein, Figure 2 A in the above formula is the X-ray diffraction (XRD) spectrum of pure zinc (ZnP@Zn) powder with a surface coated with ZnP coating and the XRD spectrum of the hot-extruded time-dependent degradation composite material, Figure 2 B in the above formula is a photograph of the cross section and longitudinal section of the hot-extruded time-dependent degradation composite material, Figure 2C is the low-magnification optical microstructure (OM) image of the interface between the inner and outer layers of the hot-extruded time-degradation composite material, Figure 2 C1 is the high-magnification OM image of the interface between the inner and outer layers of the hot-extruded time-degradation composite material, Figure 2 D is the low-magnification OM image of the interface between the inner and outer layers of the hot-extruded time-degradation composite material, Figure 2 D1 is the high-magnification OM image of the inner layer of the hot-extruded time-degradation composite material; Figure 3 is a scanning electron microscope (SEM) low-magnification image of the longitudinal section of the hot-extruded time-degradation composite material, wherein 1 is the interface between the inner and outer layers, 2 is the ZnP@Zn outer layer, and 3 is the pure iron wire toughened Zn-Cu composite material inner layer; Figure 4 is an X-ray energy spectrum (EDS) area scan image of the hot-extruded time-degradation composite material; Figure 5 is an EDS line scan image of the hot-extruded time-degradation composite material; Figure 6 is a SEM high-magnification image of the hot-extruded time-degradation composite material, wherein 1 is the interface between the inner and outer layers, 2 is the ZnP@Zn outer layer, and 3 is the pure iron wire toughened Zn-Cu composite material inner layer; Figure 7 is the EDS point scanning result of the hot-extruded time-degradation composite material, from left to right, spot1~4; Figure 8 is the chemical composition analysis result of the hot-extruded time-degradation composite material; Figure 9 is a comparison chart of the degradation rate and zinc ion concentration of the hot-extruded ZnP@Zn, pure iron wire toughened Zn-Cu composite material, and time-degradation composite material in Hanks' solution; Figure 10 is a comparison chart of the alkaline phosphatase (ALP) and alizarin red S (ARS) staining quantitative analysis of the hot-extruded ZnP@Zn, pure iron wire toughened Zn-Cu composite material, and time-degradation composite material on MC-3T3 cells; Figure 11 is a chart of the inhibition zone diameter (IZD) and colony forming unit (CFU) of the hot-extruded ZnP@Zn, pure iron wire toughened Zn-Cu composite material, and time-degradation composite material on Staphylococcus aureus. DETAILED DESCRIPTION

[0021] The various exemplary embodiments of the present application will now be described in detail, which should not be considered as limiting the present application, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present application.

[0022] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. Additionally, for a range of values of, for example, the upper limit and lower limit of a range of values are included in the disclosure as if both are expressly written herein. Every intermediate value of the range, as well as every sub-range between any intermediate values, is included in the disclosure. The upper and lower limits of these smaller ranges can be independently included or excluded from the ranges.

[0023] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned herein are incorporated by reference to disclose and describe in full the methods and / or materials which are described therein. In the case of conflict between the present specification and any document incorporated herein by reference, the present specification will control.

[0024] Many modifications and variations of the present application described in the specification are possible without departing from the scope or spirit of the application. Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application disclosed herein. The specification and examples are illustrative only.

[0025] As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", or variations thereof, are intended to be open-ended terms that mean including, but not limited to.

[0026] The present application provides a method for preparing an osteogenic, time-degradable, antibacterial and toughened zinc-based medical material, comprising the following steps: (1) performing chemical deposition treatment on pure zinc to obtain pure zinc with a zinc phosphate coating deposited on the surface of the pure zinc; (2) placing a cylindrical device in a mold, placing a wire in the inner layer of the cylindrical device, and filling the cylindrical device with Zn-X alloy to the level of the wire; (3) filling the pure zinc with a zinc phosphate coating deposited on the surface of the pure zinc obtained in step (1) to the outer layer of the cylindrical device, extracting the cylindrical device, and cold pressing to form a blank; (4) pre-sintering the blank obtained in step (3) and hot extruding to obtain the toughened zinc-based medical material.

[0027] In the present application, the particle size of the pure zinc in step (1) is preferably 0.5-10 µm, further preferably 1-8 µm, more further preferably 3-6 µm, and still further preferably 5 µm; the chemical deposition treatment is preferably carried out using a phosphating solution; the temperature of the chemical deposition is preferably 50-80 °C, further preferably 60-70 °C, and more further preferably 65 °C; the time of the chemical deposition is preferably 5-60 min, further preferably 10-50 min, more further preferably 20-40 min, and still further preferably 30 min; the phosphating solution preferably contains 5-15 g / L phosphoric acid, 10-30 g / L zinc nitrate hexahydrate, and 0.1-3 g / L graphene oxide or MXene, with the balance being water, further preferably 8-12 g / L phosphoric acid, 15-25 g / L zinc nitrate hexahydrate, and 0.5-2 g / L graphene oxide or MXene, with the balance being water, and more further preferably 10 g / L phosphoric acid, 20 g / L zinc nitrate hexahydrate, and 1 g / L graphene oxide or MXene, with the balance being water; the pH of the phosphating solution is 2-4; after the chemical deposition treatment, the metal powder is preferably removed, washed with deionized water and alcohol, and dried to obtain the pure zinc with a zinc phosphate (ZnP) coating on the surface; the number of washes is preferably 1-3, and further preferably 2; the drying method is preferably hot air drying, the drying temperature is preferably 40-80 °C, further preferably 50-70 °C, and more further preferably 60 °C; and the drying time is preferably 10-60 min, further preferably 20-50 min, more further preferably 30-40 min, and still further preferably 35 min.

[0028] In the present application, the cylindrical device in step (2) is preferably a cylindrical plastic tube; the outer diameter of the cylindrical plastic tube is preferably 10-35 mm, further preferably 15-30 mm, and more preferably 20 mm; the wall thickness of the cylindrical plastic tube is preferably 0.4-0.6 mm, further preferably 0.5 mm; the height of the cylindrical plastic tube is preferably 55-65 mm, further preferably 60 mm; the diameter of the mold is preferably 35-45 mm, further preferably 40 mm; the diameter of the iron wire is preferably 0.05-0.5 mm, further preferably 0.1-0.4 mm, and more preferably 0.2-0.3 mm; the length of the iron wire is preferably 35-45 mm, further preferably 38-42 mm, and more preferably 40 mm; the iron wire is pure iron or Fe-Mn metal wire; the Zn-X alloy preferably includes one of Zn-Mg, Zn-Cu, Zn-Ca, Zn-Sr, Zn-Se, Zn-RE, Zn-Mn, Zn-Ge, Zn-Li, Zn-Fe, and Zn-Ga alloy; the particle size of the Zn-X alloy is preferably 1-20 µm, further preferably 5-15 µm, and more preferably 10 µm; and the mass ratio of the Zn-X alloy to the iron wire is preferably 10-100:1, further preferably 20-80:1, more preferably 40-60:1, and more preferably 50:1.

[0029] In the present application, the height of the filling in step (3) is preferably 35-45 mm, further preferably 38-42 mm, and more preferably 40 mm; the cylindrical device is preferably subjected to electromagnetic vibration treatment after being extracted, the frequency of the electromagnetic vibration is preferably 10-300 Hz, further preferably 50-250 Hz, more preferably 100-200 Hz, and more preferably 150 Hz; the amplitude of the electromagnetic vibration is preferably 2-4 mm, further preferably 3 mm; the time of the electromagnetic vibration is preferably 5-30 min, further preferably 10-25 min, and more preferably 20 min; the pressure of the cold pressure forming is preferably 10-50 MPa, further preferably 20-40 MPa, and more preferably 30 MPa; and the pressure is preferably maintained for 2-30 min after the cold pressure forming, further preferably 5-20 min, and more preferably 10 min.

[0030] In the present application, the temperature of the pre-sintering in step (4) is preferably 200-380℃, further preferably 250-350℃, and more preferably 300℃; the time of the pre-sintering is preferably 0.5-3h, further preferably 1-2h, and more preferably 1.5h; the pre-sintering is preferably performed in a muffle furnace; the pre-sintering treatment preferably obtains a metallurgical piece; the rate of the hot extrusion is preferably 0.2-100mm / s, further preferably 10-80mm / s, more preferably 20-60mm / s, again more preferably 30-50mm / s, and yet more preferably 40mm / s; the method of the hot extrusion is preferably heating the metallurgical piece to 280-360℃, keeping the temperature for 0.5-1h, placing the piece in an extrusion barrel with a diameter of 35-45mm, and extruding to obtain the strong and toughened zinc-based medical material; further preferably, the method is heating the metallurgical piece to 300-350℃, keeping the temperature for 0.6-0.8h, placing the piece in an extrusion barrel with a diameter of 38-42mm, and extruding to obtain the strong and toughened zinc-based medical material; more preferably, the method is heating the metallurgical piece to 320-340℃, keeping the temperature for 0.7h, placing the piece in an extrusion barrel with a diameter of 40mm, and extruding to obtain the strong and toughened zinc-based medical material; again more preferably, the method is heating the metallurgical piece to 330℃, keeping the temperature for 0.7h, placing the piece in an extrusion barrel with a diameter of 40mm, and extruding to obtain the strong and toughened zinc-based medical material; the diameter of the strong and toughened zinc-based medical material is preferably 8-12mm, and further preferably 10mm.

[0031] The present application also provides the use of the strong and toughened zinc-based medical material prepared by the preparation method in the preparation of bone fixation materials or bone repair materials.

[0032] In the present application, the bone fixation material preferably comprises a bone plate, and the bone repair material preferably comprises a guided bone regeneration membrane; the strong and toughened zinc-based medical material prepared by the preparation method is pretreated and hot-rolled to obtain the bone fixation material or the bone repair material.

[0033] In the present application, the temperature of the pre-treatment is preferably 280-360℃, further preferably 300-350℃, more preferably 320-340℃, and even more preferably 330℃; the time of the pre-treatment is preferably 0.5-1h, further preferably 0.6-0.8h, more preferably 0.7h; the pre-treatment is preferably performed in a muffle furnace; the deformation of the hot rolling is preferably 3-10% reduction per pass, further preferably 5-8% reduction per pass, and more preferably 7% reduction per pass; the time of the hot rolling is preferably adjusted to obtain a total reduction of 70-99% of the bone fixation material or bone repair material, further preferably 80-95%, and more preferably 90%; the holding time before each pass of the hot rolling is preferably 2-5min, further preferably 3-4min, and more preferably 3.5min.

[0034] Example 1 A method for preparing an osteogenic, time-degradable, antibacterial and strong and toughened zinc-based medical material, comprising the following steps: (1) immerse pure zinc powder with a particle size of 1 µm in a phosphating solution (containing 10 g / L phosphoric acid, 15 g / L zinc nitrate hexahydrate, 0.2 g / L graphene oxide, and the rest is water, and the pH is adjusted to 2.5 with dilute hydrochloric acid) heated to 60℃, and mechanically stir at 1500 r / min for 30 min, then take out the metal powder, wash it with deionized water and alcohol for 2 times respectively, and dry it at 50℃ for 20 min to obtain pure zinc powder with a zinc phosphate (ZnP) coating deposited on the surface; (2) place a cylindrical plastic tube with an outer diameter of 24 mm, a wall thickness of 0.5 mm, and a height of 60 mm in a mold with a diameter of 40 mm, place a iron wire with a diameter of 0.1 mm and a length of 40 mm in the inner layer of the cylindrical plastic tube, and fill a Zn-Cu alloy with a particle size of 3 µm to the same level as the upper surface of the iron wire, and the mass ratio of the Zn-Cu alloy to the iron wire is 40:1; (3) fill the pure zinc powder with a zinc phosphate (ZnP) coating deposited on the surface obtained in step (1) between the cylindrical plastic tube and the cold pressing mold, and the filling height is 40 mm, then take out the cylindrical plastic tube, and perform electromagnetic vibration at 60 Hz and a vibration amplitude of 3 mm for 10 min to ensure that the powder is fully filled in the mold and uniformly overflows in the inner and outer layers, and then cold press the powder into a tablet at 40 MPa, and hold for 2 min to obtain a green body; (4) pre-sinter the green body obtained above in a muffle furnace at 340℃ for 2 h to obtain a metallurgical part, then heat the metallurgical part to 340℃ and hold for 0.5 h, quickly place it in an extrusion barrel with a diameter of 40 mm, and extrude it at a speed of 40 mm / s to obtain a strong and toughened zinc-based medical material with a diameter of 10 mm, which is named as a hot extruded state time-degradable composite material.

[0035] Example 2 A method for preparing an osteogenic, time-degradable, antibacterial and toughened zinc-based medical material, the steps are as follows: (1) Immerse pure zinc powder with a particle size of 3 µm into a phosphating solution (containing 10 g / L phosphoric acid, 15 g / L zinc nitrate hexahydrate, 0.2 g / L graphene oxide, and the rest is water, adjust pH to 2.5 with dilute hydrochloric acid) heated to 60°C, mechanically stir at 1000 r / min for 30 min, take out the metal powder, wash it with deionized water and alcohol for 2 times respectively, dry at 50°C for 20 min, obtain pure zinc powder with zinc phosphate coating deposited on the surface; (2) Place a cylindrical plastic tube with an outer diameter of 20 mm, a wall thickness of 0.5 mm, and a height of 60 mm into a mold with a diameter of 40 mm, place a iron wire with a diameter of 0.2 mm and a length of 40 mm in the inner layer of the cylindrical plastic tube, fill the Zn-Li alloy with a particle size of 5 µm to the same level as the upper surface of the iron wire, the mass ratio of the Zn-Cu alloy to the iron wire is 20:1; (3) Fill the pure zinc powder with zinc phosphate (ZnP) coating deposited on the surface obtained in step (1) between the cylindrical plastic tube and the cold pressing mold, the filling height is 40 mm, extract the cylindrical plastic tube, 100 Hz, 3 mm amplitude electromagnetic vibration for 10 min, ensure that the powder is fully filled and uniformly overfilled in the mold and the inner and outer layers, cold pressing at 30 MPa after powder tabletting machine, keep pressure for 5 min, obtain a green body; (4) In a muffle furnace, pre-sinter the obtained green body at 340°C for 2h, obtain a metallurgical part, heat the metallurgical part to 340°C, keep it for 0.5h, quickly place it in an extrusion barrel with a diameter of 40 mm, extrude at 20 mm / s to obtain a toughened zinc-based medical material with a diameter of 10 mm.

[0036] Example 3 A method for preparing an osteogenic, time-degradable, antibacterial and toughened zinc-based medical material, the steps are as follows: (1) Immerse pure zinc powder with a particle size of 0.5 µm into a phosphating solution (containing 5 g / L phosphoric acid, 30 g / L zinc nitrate hexahydrate, 0.1 g / L graphene oxide, and the rest is water, adjust pH to 2 with dilute hydrochloric acid) heated to 50°C, mechanically stir at 1500 r / min for 60 min, take out the metal powder, wash it with deionized water and alcohol for 2 times respectively, dry at 50°C for 10 min, obtain pure zinc powder with zinc phosphate coating deposited on the surface; (2) Place a cylindrical plastic tube with an outer diameter of 10 mm, a wall thickness of 0.4 mm, and a height of 55 mm into a mold with a diameter of 35 mm, place a iron wire with a diameter of 0.05 mm and a length of 35 mm in the inner layer of the cylindrical plastic tube, fill the Zn-X alloy with a particle size of 1 µm to the same level as the upper surface of the iron wire, the mass ratio of the Zn-Cu alloy to the iron wire is 10:1; (3) The pure zinc powder with zinc phosphate (ZnP) coating on the surface obtained in step (1) is filled between the cylindrical plastic tube and the cold pressing mold, the filling height is 35 mm, the cylindrical plastic tube is extracted, electromagnetic vibration is performed at 10 Hz and 2 mm amplitude for 30 min, the powder is ensured to fully fill the mold and the inner and outer layers are uniformly overfilled, cold pressing is performed at 10 MPa by using a powder tablet press, and the pressure is maintained for 10 min after molding to obtain a blank; (4) The blank obtained above is pre-sintered in a muffle furnace at 200 ℃ for 3 h to obtain a metallurgical piece, the metallurgical piece is heated to 280 ℃ and kept for 1 h, and then quickly placed in an extrusion barrel with a diameter of 35 mm, and extruded at 0.2 mm / s to obtain a strong and tough zinc-based medical material with a diameter of 8 mm.

[0037] Example 4 A preparation method of a strong and tough zinc-based medical material with osteogenic, time-degrading and antibacterial properties, the steps are as follows: (1) The pure zinc powder with a particle size of 10 µm is immersed in a phosphating solution (containing 15 g / L phosphoric acid, 10 g / L zinc nitrate hexahydrate, 3 g / L graphene oxide, and the rest is water, and the pH is adjusted to 4 with dilute hydrochloric acid) heated to 80 ℃, and mechanical stirring is performed at 1000 r / min for 5 min, the metal powder is taken out, and then washed with deionized water and alcohol for 2 times respectively, and dried at 50 ℃ for 30 min to obtain pure zinc powder with zinc phosphate coating on the surface; (2) A cylindrical plastic tube with an outer diameter of 35 mm, a wall thickness of 0.6 mm, and a height of 65 mm is placed in a mold with a diameter of 45 mm, a wire with a diameter of 0.5 mm and a length of 45 mm is placed in the inner layer of the cylindrical plastic tube, and Zn-X alloy with a particle size of 20 µm is filled to the same level as the upper surface of the wire, and the mass ratio of the Zn-Cu alloy to the wire is 100:1; (3) The pure zinc powder with zinc phosphate (ZnP) coating on the surface obtained in step (1) is filled between the cylindrical plastic tube and the cold pressing mold, the filling height is 45 mm, the cylindrical plastic tube is extracted, electromagnetic vibration is performed at 300 Hz and 4 mm amplitude for 5 min, the powder is ensured to fully fill the mold and the inner and outer layers are uniformly overfilled, cold pressing is performed at 50 MPa by using a powder tablet press, and the pressure is maintained for 2 min after molding to obtain a blank; (4) The blank obtained above is pre-sintered in a muffle furnace at 380 ℃ for 0.5 h to obtain a metallurgical piece, the metallurgical piece is heated to 360 ℃ and kept for 0.5 h, and then quickly placed in an extrusion barrel with a diameter of 45 mm, and extruded at 100 mm / s to obtain a strong and tough zinc-based medical material with a diameter of 12 mm.

[0038] Example 5 A preparation method of a bone repair material, the steps are as follows: The toughened zinc-based medical material prepared in Example 1 was placed in a muffle furnace heated to 280°C and kept for 1 h, and then quickly taken out. Hot rolling was performed at a reduction of 3% per pass, and then the material was kept for 5 min before each pass of hot rolling. A bone repair material with a total reduction of 99% and a thickness of 0.1 mm was obtained.

[0039] Example 6 A method for preparing a bone fixation material, comprising the following steps: The toughened zinc-based medical material prepared in Example 2 was placed in a muffle furnace heated to 340°C and kept for 0.5 h, and then quickly taken out. Hot rolling was performed at a reduction of 5% per pass, and then the material was kept for 5 min before each pass of hot rolling. A bone fixation material with a total reduction of 90% and a thickness of 1 mm was obtained.

[0040] Example 7 A method for preparing a bone repair material, comprising the following steps: The toughened zinc-based medical material prepared in Example 3 was placed in a muffle furnace heated to 360°C and kept for 0.5 h, and then quickly taken out. Hot rolling was performed at a reduction of 5% per pass, and then the material was kept for 2 min before each pass of hot rolling. A bone repair material with a total reduction of 95% and a thickness of 0.4 mm was obtained.

[0041] Comparative Example 1 A method for preparing a single hot-extruded ZnP@Zn material, comprising the following steps: (1) Pure zinc powder with a particle size of 1 µm was immersed in a phosphating solution (containing 10 g / L phosphoric acid, 15 g / L zinc nitrate hexahydrate, 0.2 g / L graphene oxide, and the rest being water, with dilute hydrochloric acid being used to adjust the pH to 2.5) heated to 60°C, and mechanically stirred at 1500 r / min for 30 min. The metal powder was then taken out and washed twice with deionized water and alcohol, and dried at 50°C for 20 min to obtain pure zinc powder with a ZnP coating deposited on the surface; (2) The pure zinc powder with a ZnP coating deposited on the surface obtained in step (1) was filled into a cold pressing mold with a diameter of 40 mm, and the filling height was 40 mm. The powder was subjected to electromagnetic vibration at 60 Hz and a vibration amplitude of 3 mm for 10 min to ensure that the powder was fully filled in the mold. The powder was then cold pressed at 40 MPa for 2 min to obtain a green body; (4) The green body obtained above was pre-sintered in a muffle furnace at 340°C for 2 h to obtain a metallurgical part. The metallurgical part was then heated to 340°C and kept for 0.5 h, and then quickly placed in an extrusion barrel with a diameter of 40 mm. The material was extruded at a speed of 10 mm / s to obtain a toughened zinc-based medical material with a diameter of 10 mm, which was named as hot-extruded ZnP@Zn.

[0042] Comparative Example 2 A method for preparing a single hot-extruded pure iron wire toughened Zn-Cu composite material, comprising the following steps: (1) Iron wires with a diameter of 0.1 mm and a length of 40 mm are uniformly placed in a cold pressing mold with a diameter of 40 mm, and a Zn-Cu alloy with a particle size of 3 µm is filled to the same level as the upper surface of the iron wires, and the mass ratio of the Zn-Cu alloy to the iron wires is 40:1; (2) Electromagnetic vibration is performed at 60 Hz and a 3 mm amplitude for 10 min to ensure that the powder is fully filled in the mold, and a powder tablet press is used to cold-press form at 40 MPa, and pressure is maintained for 2 min to obtain a green body; (3) The green body obtained above is pre-sintered in a muffle furnace at 340℃ for 2 h to obtain a metallurgical part, the metallurgical part is heated to 340℃ and kept for 0.5 h, and then quickly placed in an extrusion barrel with a diameter of 40 mm, and extruded at a speed of 10 mm / s to obtain a strong and tough zinc-based medical material with a diameter of 10 mm, which is named as a hot-extruded pure iron wire toughened Zn-Cu composite material.

[0043] Test Example 1 XRD analysis The pure zinc powder (ZnP@Zn powder) with a zinc phosphate (ZnP) coating deposited on the surface prepared in Example 1 and the hot-extruded time-degradation composite material prepared in Example 1 are subjected to XRD analysis. The specific operation is as follows: The cross section of the hot-extruded time-degradation composite material prepared in Example 1 is cut by a wire cutting device to obtain a round piece with a diameter of 10 mm and a thickness of 1 mm, the outer surface of which is polished with 800# SiC sandpaper, and then ultrasonically cleaned with absolute ethyl alcohol and deionized water for 15 min, respectively, and dried.

[0044] The XRD test of the ZnP@Zn powder and the hot-extruded time-degradation composite material after the above treatment is performed by an X-ray diffractometer at a test speed of 2° / min and a test step of 0.02° / s, at a 2θ diffraction angle of 30-70°, a Cu-Kα target radiation source and room temperature. The test results are shown as A in Figure 2 .

[0045] As shown by A in Figure 2 , the ZnP@Zn powder contains α-Zn phase and significant ZnP diffraction peaks, compared with which, in addition to containing α-Zn and ZnP diffraction peaks, the hot-extruded time-degradation composite material also contains α-Fe and CuZn4 phases, indicating that the hot-extruded time-degradation composite material contains inner and outer layer structures.

[0046] As shown by B in Figure 2 , the outer layer and the inner layer of the hot-extruded time-degradation composite material have obvious layering phenomenon, and the outer layer mainly contains black structure while the inner layer contains long strip-shaped fiber structure.

[0047] As shown byFigure 2 C and Figure 2 As can be seen from C1, there is a clear boundary between the inner and outer layers of the hot-extruded time-degrading composite material. The outer layer is composed of a uniformly distributed black second phase, while the inner layer is composed of an irregular reinforcing phase. No obvious cracks were observed.

[0048] Depend on Figure 2 D and Figure 2 As shown in D1, the hot-extruded sequentially degradable composite material has a fiber structure along the extrusion direction, and the iron wire is parallel to the extrusion direction, exhibiting typical fiber reinforcement characteristics. The diameter of the iron wire is approximately 43.6 ± 4.1 μm.

[0049] Experimental Example 2: Metallographic Structure Analysis by OM, SEM and EDS The cross-section of the hot-extruded time-degradable composite material prepared in Example 1 was cut using a wire cutting device to obtain a circular piece with a diameter of 10 mm and a thickness of 1 mm; at the same time, it was cut in half along the axis of the hot-extruded time-degradable composite material to obtain a longitudinal section.

[0050] To avoid zinc alloy recovery and recrystallization during hot mounting, acrylic powder and epoxy resin (volume ratio 5:4) were poured into a mold for cold mounting to obtain metallographic samples. The metallographic samples were then polished to a mirror finish using silicon carbide sandpaper to 2000 grit and then polished with 0.5 μm diamond polishing fluid. The samples were etched with 0.5 vol.% nitric acid alcohol for a certain period until a clear microstructure appeared. Simultaneously, the microstructure of the metal samples was observed using a scanning electron microscope (SEM), and the corresponding phases were analyzed using an attached energy dispersive spectroscopy (EDS) instrument. SEM and EDS analyses were performed using the same sample surface conditions and test locations as those observed by optical microscopy (OM). The SEM test voltage was 15 kV, and the scanning light source mode was backscattered electrons. The results are as follows: Figures 3 to 8 As shown.

[0051] Depend on Figure 3 and Figure 4 It can be seen that the irregular curved surface around the iron wire can increase its bonding performance with Zn-Cu powder. From the SEM low-magnification image and EDS surface scan image of the longitudinal section morphology, it can be seen that the outer layer of the hot-extruded sequentially degradable composite material mainly contains Zn, O, and P elements, while the inner layer contains Zn, Cu, and Fe elements. This corresponds to the ZnP@Zn powder and the iron wire-strengthened Zn-Cu powder added to the two layers, respectively.

[0052] It can be seen from the longitudinal section EDS line scan image (such as...) Figure 5 As shown in the figure, the element content in the two layers of the hot-extruded time-degradable composite material changes alternately, and no obvious diffusion cross-section layer is observed.

[0053] As can be seen from the SEM high magnification images and EDS point scanning and chemical composition results (as shown in Figures 6 to 8 Fig. 2), there is no obvious delamination fracture at the interface between the inner and outer layers of the hot extruded time-degraded composite material. The matrix phase in the outer layer is mainly composed of Zn and O elements (spot 1), while the black phase region contains a higher content of P, O and Zn elements (spot 2). In comparison, the matrix phase in the inner layer is mainly composed of Zn, Cu and O elements (spot 3), while the iron wire contains a large amount of Fe and O elements (spot 4).

[0054] Test Example 3: Tensile and compressive property test According to the standard test method for tensile testing of metallic materials (ASTM-E8-04), the hot extruded ZnP@Zn prepared in Comparative Example 1, the hot extruded pure iron wire toughened Zn-Cu composite material prepared in Comparative Example 2, the hot extruded time-degraded composite material prepared in Example 1 and the bone fixation material prepared in Example 6 were subjected to tensile test.

[0055] The hot extruded materials were cut by a wire cutting device to prepare tensile samples with a length of 6 mm and a diameter of 10 mm, and the outer surface of the samples was polished with 800# SiC sandpaper. The tensile test was performed at room temperature using a universal material mechanics testing machine at a tensile speed of 1 mm / min.

[0056] Meanwhile, the hot extruded time-degraded composite material was compressed into a cylindrical compression sample with a diameter of 10 mm and a height of 15 mm by a wire cutting device, and the outer surface of the sample was polished with 800# SiC sandpaper. The compression test was performed at room temperature using a universal material mechanics testing machine at a compression speed of 1 mm / min. The results are shown in Table 1.

[0057]

[0058] As can be seen from Table 1, the hot extruded time-degraded composite material has the highest tensile strength (416 MPa), yield strength (333 MPa), compressive yield strength (446 MPa), elongation (30.7%) and no differentiated compression strain (≥70%).

[0059] The tensile strength of the bone fixation material is 473 MPa, the yield strength is 357 MPa, and the elongation is 26.7%.

[0060] Test Example 4: Polarization property test The hot extruded ZnP@Zn prepared in Comparative Example 1, the hot extruded pure iron wire toughened Zn-Cu composite material prepared in Comparative Example 2, the hot extruded time-degraded composite material prepared in Example 1 and the bone fixation material prepared in Example 6 were subjected to polarization curve test using an electrochemical workstation equipped with a three-electrode system.

[0061] The electrochemical corrosion test was performed in a beaker containing 150 mL of solution, and the temperature of the solution was controlled to 37.0 ± 0.5 °C using a constant temperature water bath. The sample was cut into a round metal test piece (10 mm in diameter and 1.5 mm in height) using a wire cutting machine, embedded with cold inlay, then polished to 2000 mesh using diamond sandpaper, and finally polished using diamond polishing liquid with a particle size of 1 µm. The metal test piece, saturated calomel electrode, and pure platinum sheet electrode were used as the working electrode, reference electrode, and auxiliary electrode, respectively.

[0062] The open circuit potential test was performed before the electrochemical corrosion test, and the test time was 30 min until the open circuit potential was stable. The potential was set to -0.3 V to 0.6 V relative to the open circuit potential, and the scan rate was 1 mV / s. The corrosion potential and corrosion current density of the sample were obtained by selecting the intersection of the cathode Tafel curve and the horizontal extension line of the corrosion potential. The corrosion rate of the sample was tested and calculated according to “ASTM G102-23 Calculation of Corrosion Rates and Related Information from Electrochemical Measurements”. The results are shown in Table 2.

[0063]

[0064] As shown in Table 2, the cross-section sample of the hot extruded time degradation composite material has a moderate corrosion potential (-1.12 V), corrosion current density (38.3 µA / cm 2 ), and corrosion rate (558 µm / y) between the ZnP@Zn alloy and the pure iron wire toughened Zn-Cu composite material. The corrosion potential, corrosion current density, and corrosion rate of the bone fixation material are -1.07 V, 41.5 µA / cm 2 , and 605 µm / y, respectively.

[0065] Test Example 5: Immersion corrosion test The immersion test was used to evaluate the degradation behavior of the hot extruded ZnP@Zn prepared in Comparative Example 1, the hot extruded pure iron wire toughened Zn-Cu composite material prepared in Comparative Example 2, the hot extruded time degradation composite material prepared in Example 1, and the bone fixation material prepared in Example 6 in Hanks’ solution.

[0066] The sample was cut using a wire cutting machine to prepare a round metal test piece of the same size as the electrochemical corrosion test, and polished to 2000 mesh using diamond sandpaper. According to “ASTM G31-21 Standard Guide for Laboratory Immersion Corrosion Testing of Metals”, the test piece was placed in Hank’s solution at 37.0 ± 0.5 °C in a constant temperature water bath for 0.5-90 d, and the exposure ratio of the surface area of the test piece to the volume of the solution was 1 cm 2 / 20 mL.

[0067] After the immersion test, the inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to analyze the chemical composition of the zinc ion concentration in the solution after the immersion test.

[0068] Meanwhile, the immersion sample was placed in a mixed solution of CrO3 with a concentration of 200 g / L and AgNO3 with a concentration of 10 g / L for ultrasonic cleaning for 5 min to fully remove the surface corrosion products. Before immersion and after removing the corrosion products, the sample weight was measured using an electronic balance (accuracy of 0.1 mg), and the degradation rate was calculated according to the “ASTM G31-21 Standard Guide for Laboratory Immersion Corrosion Testing of Metals”. The results are shown in Figure 9

[0069] As can be seen from Figure 9 , after immersion in Hanks’ solution for 0.5-90 d, both the hot-extruded ZnP@Zn alloy and the pure iron wire toughened Zn-Cu composite material showed an increase in degradation rate and zinc ion concentration, which eventually stabilized, indicating that the above two samples were typical uniform degradation modes. In comparison, the hot-extruded time-degradation composite material showed a slow increase in degradation rate and zinc ion concentration in a short time (0.5-14 d) and was close to the ZnP@Zn alloy, showing a slow short-term degradation characteristic, while in the long-term degradation process (30-90 d), its degradation rate and zinc ion concentration increased linearly, showing a fast long-term degradation characteristic. The above results show that the hot-extruded time-degradation composite material has a time-degradation mode.

[0070] After immersion in Hanks’ solution for 0.5-90 d, the degradation rate of the bone fixation material in a short time (0.5-14 d) was 26.9-31.2 μm / y and the zinc ion concentration was 13.5-14.6 μg / ml / d, while in the long-term degradation process (30-90 d), the degradation rate and zinc ion concentration increased linearly, and the degradation rate and zinc ion concentration were 33.4-43.5 μm / y and 20.5-38.7 μg / ml / d, respectively, showing a time-degradation mode.

[0071] Test Example 6 Hemolysis rate test According to the “ISO 10993-4 Biological Evaluation of Medical Devices Part 4 Selection of Tests for Interaction with Blood” standard, the hot-extruded ZnP@Zn prepared by Comparative Example 1, the hot-extruded pure iron wire toughened Zn-Cu composite material prepared by Comparative Example 2, the hot-extruded time-degradation composite material prepared by Example 1, and the bone fixation material prepared by Example 6 were subjected to hemolysis test of metal samples.

[0072] ​The above sample with a diameter of 10 mm and a height of 1.5 mm was soaked in 0.9% physiological saline at a leaching ratio of 5 g / 10 mL for 3 days to prepare an alloy sample leaching solution. The test was tested with the metal leaching solution as the experimental group, and deionized water and 0.9% sodium chloride solution were used as positive and negative control groups, respectively. To avoid blood clotting, 5 mL of heparin with a concentration of 20 g / L was added to the whole blood of 8-week-old healthy SD rats (purchased from the Experimental Animal Center of Hangzhou Medical College), and the blood was diluted with 10 mL of physiological saline. 10 mL of the test metal leaching solution and the positive and negative control group solutions were added to the centrifuge tube, and then 200 μL of the diluted anticoagulant blood was added to the centrifuge tube and incubated in a 37°C incubator for 60 min. After incubation, the centrifuge tube was centrifuged at 3000 r / min at 25°C for 5 min, 10 mL of supernatant was removed with a pipette, and the absorbance value was measured at a wavelength of 545 nm using a domestic enzyme marker.

[0073] The hemolysis rate was calculated according to Formula I: Hemolysis rate = (OD 实验组 - OD 阴性对照组 ) / (OD 阳性对照组 - OD 阴性对照组 ) x 100% Formula I.

[0074] The hemolysis rate of the hot extruded state time sequence degradation composite material in mouse blood was 2.4%, which met the requirement that the hemolysis rate of clinical medical materials should be less than 5%, and was lower than that of the hot extruded state ZnP@Zn and the hot extruded state pure iron wire toughened Zn-Cu composite material, showing good blood compatibility.

[0075] The hemolysis rate of the bone fixation material in mouse blood was 2.9%, which met the requirement that the hemolysis rate of clinical medical materials should be less than 5%, and showed good blood compatibility.

[0076] Test Example 7 Cell survival rate test L929 mouse fibroblasts (purchased from Shanghai Cell Bank) were used as a cell model, and hot extruded state ZnP@Zn prepared by Comparative Example 1, hot extruded state pure iron wire toughened Zn-Cu composite material prepared by Comparative Example 2, hot extruded state time sequence degradation composite material prepared by Example 1 and bone fixation material prepared by Example 6 were tested according to ISO 10993-5 Medical Devices-Biological Evaluation-Part 5: Cytotoxicity Test, and the specific operation was as follows: The density of the L929 mouse fibroblasts was 1 x 10 4Cell culture was performed in 48-well plates containing 10% fetal bovine serum (purchased from Thermo Fisher Scientific, USA) and double antibiotics (50 KU penicillin, 50 mg streptomycin, purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd.) in DMEM medium (purchased from Nanjing Senbeijia Biotechnology) for 1 d, and placed in a culture environment at 37℃ with 5% CO2 humidified air. At the same time, the same size and surface condition of the disc sample prepared by the soaking experiment of Test Example 5 was used for the evaluation of cell compatibility, and according to ISO 10993-12 Biological Evaluation of Medical Devices Part 12: Sample Preparation and Reference Sample, the metal sample was sterilized in a high-temperature sterilization pot at 121℃ for 30 min, and the sample surface area / solution volume ratio of 1.25 cm 2 / mL was immersed in DMEM medium without fetal bovine serum and double antibiotics for 2 d to obtain metal leaching solution. Then different concentrations of leaching solution (100%, 50% and 25%) after dilution with fresh culture medium were added to fetal bovine serum and replaced with the original cell culture medium. After 3 d of co-culture with the leaching solution under the same culture conditions, the cells were washed gently with PBS, and 200 μL of fresh culture medium containing 10% MTT solution was added to each well for 4 h for cell detection. Finally, after carefully removing the supernatant, 150 μL of dimethyl sulfoxide was added to each well, and the purple formazan crystals were dissolved and mixed by shaking bed for 10 min. Finally, 100 μL of culture medium was taken from each well and transferred to a 96-well plate, and the absorbance value was measured using an automatic enzyme marker at an absorbance wavelength of 570 nm and a reference wavelength of 650 nm. The control group used fresh culture medium without leaching solution. The calculation process of cell survival rate was performed according to ISO 10993-5 Biological Evaluation of Medical Devices Part 5: Cytotoxicity Test.

[0077] The cell survival rate was calculated according to Formula II: Cell survival rate = (OD 实验组 - OD 阴性对照组 ) / (OD 阳性对照组 - OD 阴性对照组 ) x 100% Formula II.

[0078] OD 实验组 : absorbance with cells, CCK-8 solution and leaching solution; OD 阴性对照组 : absorbance with fresh culture medium and CCK-8 solution without cells; OD 阳性对照组 : absorbance of wells with cells, CCK-8 solution without leaching solution; The results show that the cell survival rates of L929 mouse fibroblasts after being cultured in the leaching liquor of the hot-extruded time-degradation composite material at concentrations of 100%, 50% and 25% for 3 days are 63.5%, 92.4% and 106.2% respectively, which are higher than the cell survival rates of the hot-extruded ZnP@Zn (42.7%, 84.6% and 97.5%) and the hot-extruded pure iron wire toughened Zn-Cu composite material (18.9%, 60.5% and 82.3%), and the hot-extruded time-degradation composite material exhibits good blood compatibility. The cell survival rates of L929 mouse fibroblasts after being cultured in the leaching liquor of the bone fixation material at concentrations of 100%, 50% and 25% for 3 days are 54.8%, 86.7% and 97.9% respectively, indicating that the diluted leaching liquor has good cell compatibility.

[0079] Test Example 8 Alkaline phosphatase (ALP) and alizarin red (ARS) staining and activity determination The in vitro early mineralization performance of osteoblasts of the hot-extruded ZnP@Zn prepared in Comparative Example 1, the hot-extruded pure iron wire toughened Zn-Cu composite material prepared in Comparative Example 2, the hot-extruded time-degradation composite material prepared in Example 1 and the bone fixation material prepared in Example 6 was determined by ALP staining and activity test. The specific operation is as follows: MC3T3-E1 cells (purchased from Shanghai Cell Bank) with a density of 3×10 4 MC3T3-E1 cells (purchased from Shanghai Cell Bank) with a density of 3×10 Figure 10 The results are shown in Table 1.

[0080] The results are shown in Table 1. Figure 10It can be seen that the average ALP activity and ARS activity of the 25% concentration hot extrusion state time degradation composite material leaching solution reached the maximum, which were 3.6 times and 4.3 times of the control group (annealed pure titanium, purchased from Northwest Non-ferrous Metals Research Institute), respectively, higher than that of hot extrusion state ZnP@Zn and hot extrusion state pure iron wire toughened Zn-Cu composite material, showing excellent osteogenic differentiation and mineralization capacity.

[0081] The average ALP activity and ARS activity of the 25% concentration bone fixation material leaching solution were 3.4 times and 4.0 times of the control group, respectively, showing good osteogenic differentiation and mineralization capacity.

[0082] Test Example 9: Antibacterial performance test The hot extrusion state ZnP@Zn prepared by Comparative Example 1, the hot extrusion state pure iron wire toughened Zn-Cu composite material prepared by Comparative Example 2, the hot extrusion state time degradation composite material prepared by Example 1 and the bone fixation material prepared by Example 6 were used as samples, and the antibacterial test operation procedures of “DIN EN ISO 20645 Textile fabrics. Determination of antibacterial activity. Agar diffusion wood piece test” and “ASTM F2944 Standard Test Method for Automatic Colony-Forming Unit (CFU) Testing. Image Acquisition and Analysis Method for Enumerating and Characterizing Cells and Colonies in Culture” were used to evaluate the antibacterial performance of different processing state samples on Staphylococcus aureus by using the inhibition zone diameter and colony forming unit (CFU) method. The specific operation is as follows: The same surface condition disc samples (diameter 10 mm, height 1.5 mm) prepared by the soaking experiment of Test Example 5 were used to evaluate the antibacterial performance. All samples were sterilized by the same sterilization process as the cell compatibility sample of Test Example 7.

[0083] Luria-Bertani broth powder (10 g / L peptone, 5 g / L yeast extract powder, 10 g / L sodium chloride) was added to 950 mL distilled water to completely dissolve, then distilled water was added to 1 L and the pH was adjusted to 7.0 with 0.1 mol / L NaOH solution to prepare the bacterial culture medium. S. aureus bacteria (purchased from ATCC 43300, USA) were placed in 5 mL of bacterial culture medium, and then the medium solution was diluted with PBS to a concentration of about 1×10 8 CFU / mL. Then agar powder (1.5 g / 100 mL medium) was added to the medium, heated to dissolve, and then autoclaved for 30 min. The medium solution (20 mL) cooled to 45°C was poured into a culture dish and ultraviolet sterilized for 30 min to prepare the agar culture medium plate. 500 μL of diluted bacterial suspension (1×10 6The agar medium surface was uniformly coated with 0.1 mL of the bacterial suspension (CFU / mL), and the disc sample was gently placed in the plate. Finally, after incubation at 37℃ for 1 day, the IZD value was calculated according to Formula III given in the "DIN EN ISO 20645 Textile fabrics - Determination of antibacterial activity - Agar diffusion plate test": H=(D-d) / 2 Formula III; Wherein, H is the diameter of the inhibition zone, D is the total diameter of the sample and the inhibition zone, and d is the diameter of the sample. In mm, when H is equal to or greater than 1 mm and no bacteria are present, it indicates good antibacterial performance; when H is equal to 0 mm and there is a bacterial area, the antibacterial performance is limited; when H is equal to 0 mm and there are a large number of bacteria, it does not have antibacterial performance. The results are shown in Figure 11 .

[0084] As can be seen from Figure 11 , the average size of the inhibition zone and CFU after the hot extruded time-degradable composite material was co-cultured with Staphylococcus aureus for 1 day were 4.4 mm and 6.7, respectively, showing excellent antibacterial performance between ZnP@Zn alloy and pure iron wire toughened Zn-Cu composite material. The average size of the inhibition zone and CFU after the bone fixation material was co-cultured with Staphylococcus aureus for 1 day were 3.7 mm and 10.5, respectively, showing good antibacterial performance.

[0085] As can be seen from the above examples, the present application provides a preparation method of an osteogenic, time-degradable and antibacterial strong and toughened zinc-based medical material. The strong and toughened zinc-based medical material has a time-degradable mode, excellent tensile and compressive properties, and can also play an antibacterial role.

[0086] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the art, several improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A method for preparing an osteogenic, time-degradable, and antibacterial toughened zinc-based medical material, characterized in that, Includes the following steps: (1) Pure zinc is subjected to chemical deposition treatment to obtain pure zinc with a zinc phosphate coating deposited on the surface; (2) Place the cylindrical device in the mold, place the iron wire in the inner layer of the cylindrical device, and fill it with Zn-X alloy until it is flush with the iron wire; (3) Fill the pure zinc with zinc phosphate coating on the surface obtained in step (1) into the outer layer of the cylindrical device, extract the cylindrical device, and cold press it to obtain the blank; (4) The pre-sintered blank obtained in step (3) is hot-extruded to obtain the toughened zinc-based medical material.

2. The preparation method according to claim 1, characterized in that, In step (1), a phosphating solution is used for chemical deposition. The temperature of the chemical deposition is 50-80°C, and the time of the chemical deposition is 5-60 min.

3. The preparation method according to claim 2, characterized in that, The phosphating solution contains 5-15 g / L phosphoric acid, 10-30 g / L zinc nitrate hexahydrate, and 0.1-3 g / L graphene oxide, with the remainder being water.

4. The preparation method according to claim 1, characterized in that, The diameter of the iron wire in step (2) is 0.05~0.5mm, and the length of the iron wire is 35~45mm; the Zn-X alloy includes one of Zn-Mg, Zn-Cu, Zn-Ca, Zn-Sr, Zn-Se, Zn-RE, Zn-Mn, Zn-Ge, Zn-Li, Zn-Fe, and Zn-Ga alloys.

5. The preparation method according to claim 1, characterized in that, The filling height in step (3) is 35~45mm; the pressure of cold pressing is 10~50MPa; and the pressure is maintained for 2~30min after cold pressing.

6. The preparation method according to claim 1, characterized in that, The pre-sintering temperature in step (4) is 200~380℃, the pre-sintering time is 0.5~3h, and the hot extrusion rate is 0.2~100mm / s.

7. The use of the toughened zinc-based medical material prepared by the preparation method according to any one of claims 1 to 6 in the preparation of bone fixation materials or bone repair materials.

8. The application according to claim 7, characterized in that, The bone fixation material includes a bone plate, and the bone repair material includes a guiding bone regeneration membrane.

9. The application according to claim 7, characterized in that, The toughened zinc-based medical material prepared by the preparation method according to any one of claims 1 to 6 is pretreated and then hot-rolled to obtain the bone fixation material or bone repair material.

10. The application according to claim 9, characterized in that, The pretreatment temperature is 280~360℃, and the pretreatment time is 0.5~1h; the deformation of the hot rolling is 3~10% reduction per pass, and the hot rolling time is based on obtaining bone fixation material or bone repair material with a total reduction of 70~99%.

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