CN106606801A - Zn-ZnO zinc alloy and its preparation method and application - Google Patents

Abstract

The invention discloses a Zn-ZnO series zinc alloy, a preparation method and application thereof. The zinc alloy of the present invention includes Zn and ZnO, and the mass percentage of ZnO in the zinc alloy is 0-10%, but 0 is not included. The zinc alloy also includes trace elements, which are at least one of silicon, phosphorus, lithium, silver, tin and rare earth elements; the mass percentage of the trace elements is 0-3%, but not Include 0. The mechanical properties of the Zn-ZnO series zinc alloy of the present invention meet the requirements of the strength and toughness of medical implant materials, have no cytotoxicity to endothelial cells and osteoblasts, can inhibit the proliferation of smooth muscle cells, and have good tissue compatibility and blood Compatibility, and at the same time, it can control the degradation by body fluids, and the dissolved metal ions can be absorbed and utilized by organisms or metabolized and excreted from the body. It also has excellent antibacterial properties and can be applied to the preparation of medical implants.

Description

A kind of Zn-ZnO system zinc alloy and its preparation method and application

technical field

The invention belongs to the technical field of preparation of medical metal materials, and relates to a Zn-ZnO series zinc alloy and its preparation method and application, in particular to a Zn-ZnO series zinc alloy and its preparation method and its use in the preparation of body fluid degradable medical implants in the application.

Background technique

Biomedical materials are materials used to diagnose, treat, repair or replace diseased tissues and organs of living organisms or enhance their functions. It is the basis for the study of artificial organs and medical devices, and can be divided into repair materials, cardiovascular system materials, medical membrane materials, drug release carrier materials, biosensor materials, dental materials, etc. according to their uses. According to the composition and properties, there are mainly biomedical metal materials, bioceramics, biomedical polymers, biomedical composite materials and bio-derived materials. Biomedical metal materials have high mechanical strength and fatigue resistance, and are the most widely used load-bearing implant materials in clinical practice, and their applications cover hard tissues, soft tissues, artificial organs and shell auxiliary equipment. At present, the metal materials used in clinical application mainly include pure titanium, tantalum, niobium, zirconium, stainless steel, cobalt-based alloys and titanium-based alloys, etc., and most of them are inert materials. These materials are non-degradable in the human body and are permanently implanted. When the implant expires in the human body, it must be removed through a second operation, thereby causing unnecessary physical pain and economic burden to the patient.

A biomedical degradable metal is a metal material that can be slowly degraded in the body, and its degradation products have a benign reaction with the tissues and organs of the body, and can be absorbed by the body without residue after helping the tissues to fully recover. In this way, the long-term impact of the material on the body can be minimized. The material is gradually absorbed by the body during the process of helping the body recover, and its degradation products can be absorbed or excreted through metabolism, and no secondary surgery is required after tissue recovery. Because the design of degradable metal materials is more humanized and functional, it has become a research hotspot in the field of international materials.

Degradable medical magnesium alloys have been a research hotspot for several years. Different alloy systems and new structures and surface modifications are emerging, such as Mg-Ca, Mg-Sr, Mg-Zn and improvements to industrial alloys AZ31 and WE43. And new porous, nanocrystalline and amorphous structures make magnesium alloys more and more close to application. Although magnesium alloys have a series of advantages, rapid degradation and excessive hydrogen evolution have always been a bottleneck that magnesium alloys cannot overcome. Compared with magnesium alloys, iron-based alloys have a stable but slow degradation rate, and their corrosion products can cause inflammation. Therefore, it is a demand to develop a degradable metal material with a suitable degradation rate and a benign reaction with tissues. .

From the perspective of corrosion, zinc and its alloys have a more positive corrosion potential than magnesium, and are more active than iron, so they can be used as sacrificial anode materials. Therefore, its corrosion rate should be between the two, and it may have a more suitable degradation rate in vivo. From the perspective of the effect of zinc on the human body, zinc is an element necessary for normal growth, reproduction and life extension of humans and animals. It participates in the synthesis of many enzymes and plays a regulatory role. An adult needs 10-15mg of zinc per day. Lactating women Daily needs 30-40mg of zinc, normal adult human body contains 2-4g of zinc, of which 60% exists in muscle and 30% exists in bone. There are about 100 zinc-containing enzymes related to the human body, including alcohol dehydrogenase, alkaline phosphatase, carbonic anhydrase, procarboxypeptidase and cytosolic superoxide dismutase. Zinc is involved in the control of protein synthesis and the growth and development of the body. Zinc is closely related to nucleic acid, amino acid metabolism and protein synthesis. Experiments have proved that zinc deficiency leads to enhanced oxidation of amino acids, reduced binding of methionine to tissue protein, reduced participation of cystine in skin protein synthesis, and caused glycine and proline to synthesize glue. Quality disorders can also cause increased liver arginase activity. Zinc participates in the metabolism of protein and nucleic acid, and regulates the synthesis and function of cells. Zinc is the most effective and least toxic trace element among the essential trace elements. It is an element necessary for the formation of various protein molecules. 98% of zinc is distributed in cells. The content of zinc in cells is higher than that of other trace elements. The zinc content in the brain is 5 times that of copper and 8 times that of manganese. Zinc is also involved in the formation of many biological membranes, has the effect of reducing lipid peroxidation, can improve the nutritional metabolism and resistance of mucosal epithelium, and stabilize and protect cell membranes. Zinc plays an important role in insulin production and is also closely related to growth hormone and sex hormones. Zinc plays an important role in maintaining the immune function of the human body. It plays an important role in cell division and activation of enzymes, maintaining the proliferation and differentiation of T cells, and promoting antibody production. Whether it is human or animal, the reduction of zinc content in the body can cause the decline of cellular immune function and increase the susceptibility to disease. Zinc can produce antiviral effects by interfering with and inhibiting the replication of viral DNA. Bones contain a large amount of zinc in the human body, and the zinc in bones is mainly concentrated in the calcified osteoid layer. Slow bone growth is a common symptom of zinc deficiency in the daily diet. The study found that zinc can promote osteogenic bone repair and mineralization, and zinc can stimulate the gene expression of transcription factor Runx2, which is related to osteoblast differentiation. Zinc also inhibits osteoclastic resorption by inhibiting the differentiation of osteoclast-like cells from bone marrow stem cells and promoting the apoptosis of mature osteoclasts. Zinc also has an inhibitory effect on osteoclastogenesis induced by osteoclast differentiation factors. Zinc transporters are expressed in both osteoblasts and osteoclasts, and dietary zinc intake is beneficial to bone mass growth. Zinc's important impact on cardiovascular health is determined by its role in various proteins and enzymes in the body. Zinc plays an important role in intracellular redox signaling pathways, and ischemia and infarction trigger the release of zinc from proteins leading to cardiomyopathy. Zinc supplementation can enhance myocardial function and prevent coronary artery disease and cardiomyopathy. Sufficient zinc supplementation can protect cardiomyocytes from oxidative stress and prevent the inflammatory response that occurs when the myocardium is damaged. Zinc has a healing effect, which is beneficial to promote the survival of cardiac stem cells that play a healing role during cardiac recovery. Pathological manifestations of zinc deficiency include slow growth, labor difficulties, neuropathy, cyclic anorexia, diarrhea, dermatitis, alopecia, blood loss, hypotension and hypothermia. Zinc deficiency also affects the epidermis, gut, central nervous system, immune system, bones and reproductive system. Zinc deficiency can reduce the activity of osteoblasts, affect the synthesis of collagen and proteoglycan and the activity of alkaline phosphatase. So zinc has good biocompatibility and suitable degradation performance.

As zinc oxide, zinc oxide has certain antibacterial and anti-inflammatory effects. At the same time, by compounding different contents of zinc oxide, it can also adjust the corrosion rate and improve biocompatibility, tissue compatibility and blood compatibility.

At present, Lepu (Beijing) Medical Devices Co., Ltd. has a patent on degradable new base alloy stents, and Xi'an Advance Medical Technology Co., Ltd. has a patent on the preparation method of medical biodegradable zinc alloy capillary tubes and corrosion-resistant high-strength zinc alloys. Patents for alloy implant materials. There are no documents and patents at home and abroad to report the preparation and properties of Zn-ZnO zinc alloys, and it is proposed to use Zn-ZnO zinc alloys as biodegradable biomedical materials.

Contents of the invention

The object of the present invention is to provide a Zn-ZnO series zinc alloy and its preparation method and application. The Zn-ZnO zinc alloy prepared by the invention has suitable mechanical properties, adjustable corrosion rate, good cell compatibility and blood compatibility, and excellent antibacterial performance, and can be used for the preparation of biomedical implants.

The Zn-ZnO series zinc alloy provided by the present invention includes Zn and ZnO;

The mass percentage of ZnO in the Zn-ZnO series zinc alloy is 0-10%, but excluding 0%.

In the above-mentioned Zn-ZnO zinc alloy, trace elements can also be included, and the trace elements are at least one of silicon, phosphorus, lithium, silver, tin and rare earth elements; the mass percentage of the trace elements is 0～ 3%, but not including 0.

The surface of the above-mentioned Zn-ZnO zinc alloy can also be coated with a degradable polymer coating, a ceramic coating or a drug coating;

The thicknesses of the degradable polymer coating, the ceramic coating and the drug coating are all 0.01-5 mm.

The preparation material of the degradable polymer coating can be at least one of the following 1) and 2):

1) Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), L-polylactic acid (PLLA), polycyanoacrylate (PACA), polyanhydride, polyphosphazene, polypara Any of dioxanone, poly-hydroxybutyrate or polyhydroxyvalerate;

2) Polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), L-polylactic acid (PLLA), polycyanoacrylate (PACA), and polydioxanone Copolymers of at least two of them; Further, polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), L-polylactic acid (PLLA), polycyanoacrylate (PACA ) and any two copolymers of polydioxanone, the ratio of any two can be proportioned according to the specific needs in the preparation process, such as: the mass ratio of PLLA and PCL can be (1 -9):1.

The preparation material of the ceramic coating can be at least one of hydroxyapatite, tricalcium phosphate and tetracalcium oxyphosphate;

The drug coating can be at least one of rapamycin and its derivative coating, paclitaxel coating, everolimus coating, sirolimus coating, mitomycin coating and antibacterial coating kind.

The Zn-ZnO series zinc alloy provided by the present invention is specifically any one of the following 1)-6), which is the percentage by weight:

1) Composed of 90-99% Zn and 1%-10% ZnO;

2) Composed of 99.75% Zn and 0.25% ZnO;

3) Composed of 99.5% Zn and 0.5% ZnO;

4) Composed of 99% Zn and 1% ZnO;

5) Composed of 95% Zn and 5% ZnO;

6) Composed of 90% Zn and 10% ZnO.

The Zn-ZnO series zinc alloy provided by the invention has adjustable degradation speed, good biocompatibility, blood compatibility and excellent antibacterial performance, and is a reliable biomedical implant material.

The present invention further provides a method for preparing the above-mentioned Zn-ZnO zinc alloy, comprising the following steps:

Zn, ZnO and the trace elements are mixed according to any one of the following 1) and 2) (in powder form) to obtain a (homogeneous) mixture;

1) Zn and ZnO;

2) Zn, ZnO and trace elements;

According to the steps of a) or b) below, the Zn-ZnO zinc alloy is obtained;

a) Sintering the homogeneous mixture under vacuum or an inert atmosphere, and obtaining the Zn-ZnO zinc alloy after cooling;

b) Under vacuum or an inert atmosphere, sinter the homogeneous mixture, and coat the degradable polymer coating, the ceramic coating or the drug coating after cooling to obtain the Zn-ZnO system zinc alloy.

In the above preparation method, the mixing is specifically adding Zn, ZnO and the trace elements into a vacuum ball milling tank under an argon protective atmosphere, and the ball milling speed is 180-250rpm, the ball-to-material ratio (10-20): 1 (such as : 10:1 or 20:1) ball milled for 15-60 minutes to obtain a homogeneous mixture, which was stored in argon to prevent oxidation.

And/or, the sintering is specifically spark plasma sintering (Spark Plasma Sintering).

And/or, specifically, the spark plasma sintering is to add the mixture into a graphite grinding tool, axially pressurize and vacuum sinter, the specific parameters of the spark plasma sintering are controlled as follows: initial sintering pressure 1MPa, heat preservation sintering The pressure is 30-60MPa, the temperature is first raised to 150-300°C at 100°C/min, then to 200-350°C at 50°C/min, and finally to 250-400°C at 25°C/min, and the holding time is 3-6min. The temperature is cooled in the furnace to obtain the Zn-ZnO zinc alloy.

In order to meet different clinical needs, the preparation method of the above-mentioned Zn-ZnO series zinc alloy also includes the step of coating.

The method for coating the biodegradable polymer coating is to pickle the Zn-ZnO zinc alloy, and then dissolve it in the preparation material of the biodegradable polymer coating in trichloroethane. After dipping in the colloid for 10 to 30 minutes, pull out at a uniform speed and perform centrifugation to obtain a Zn-ZnO zinc alloy coated with a biodegradable polymer coating;

The method for applying the ceramic coating can be any one of plasma spraying, electrophoretic deposition, anodic oxidation or hydrothermal synthesis;

The plasma gas main gas used in the plasma spraying is Ar, the flow rate is 30-100 scfh, the plasma gas secondary gas is _H2 , the flow rate is 5-20 scfh, the spraying current is 400-800A, the spraying voltage is 40-80V, and the spraying distance 100-500mm;

The method of electrodepositing the degradable ceramic coating is to use Zn-ZnO zinc alloy as the cathode in the electrolyte solution containing calcium and phosphorus salts, and the current density is 2-10 mA/cm ² , after 10-60 minutes of treatment, wash and dry obtaining the Zn-ZnO zinc alloy;

The method of combining anodic oxidation and hydrothermal synthesis is to put the Zn-ZnO zinc alloy in an electrolyte solution containing 0.01-0.5 mol/L β-sodium glycerophosphate and 0.1-2 mol/L calcium acetate at 200-500V Oxidation at low temperature for 10-30 minutes, and then treating the Zn-ZnO-based zinc alloy at 200-400° C. for 1-4 hours.

The method for applying the drug coating is a physical and chemical method;

The physical method coating process mainly adopts soaking and spraying methods; the chemical method mainly uses the principle of electrochemistry for electroplating;

The soaking method is to prepare the active drug and the controlled-release carrier (or a separate active drug) into a solution, the specific concentration may vary due to the solution viscosity and the required drug dose, and then soak the medical implant into the solution , and then go through the necessary post-treatment process, such as cross-linking, drying, curing and other steps, to make a drug coating;

The spraying method is to prepare the active drug and the controlled-release carrier (or a separate active drug) into a solution, and then apply the solution evenly on the surface of the medical implant through a spraying tool or special spraying equipment, and then dry and solidify the solution. After the post-processing step, the drug coating is produced;

The chemical method is to use active drugs and (or) controlled-release carriers to undergo electro-oxidation-reduction reactions on the electrodes made of the medical implants, so that a stable chemically bonded drug coating is formed on the surface of the medical implants.

The invention utilizes the Zn-ZnO series zinc alloy to control the degradation speed and biological functionality. Zn is an essential trace element for the human body, which can promote the proliferation and differentiation of osteoblasts and inhibit the growth of osteoclasts. Zinc also plays an important role in cardiovascular health. It can protect cardiomyocytes and prevent inflammation, and ZnO is a commonly used chemical additive widely used in food processing, and it also has antibacterial and anti-inflammatory effects. The Zn-ZnO series zinc alloy is selected as the degradable medical implant. The compressive strength of the Zn-ZnO series zinc alloy of the present invention meets the strength requirements of medical implant materials, and at the same time, it can also have sufficient toughness, the degradation rate in the body can be adjusted, it is non-toxic to endothelial cells and osteoblasts, and can inhibit smooth muscle cells Proliferation, good and adjustable blood compatibility, and excellent antibacterial properties, so the Zn-ZnO series zinc alloy is a medical implant with excellent comprehensive properties.

The Zn-ZnO series zinc alloy provided by the present invention can be applied to the preparation of the following medical implants: bone repair instruments, dental repair instruments;

The bone repair instrument can be a bone tissue repair bracket, a bone adapter, a fixation wire, a fixation screw, a fixation rivet, a fixation pin, a bone splint, an intramedullary nail or a bone sleeve;

The dental restoration device may be an endodontic needle or a tooth filling material.

Further, the Zn-ZnO zinc alloy can be applied to the preparation of medical implants with any of the following properties in 1)-6):

1) the mechanical properties of the Zn-ZnO series zinc alloy;

2) The adjustable degradation performance of the Zn-ZnO zinc alloy

3) blood compatibility of the Zn-ZnO series zinc alloy;

4) the cytocompatibility of the Zn-ZnO series zinc alloy;

5) the antibacterial properties of the Zn-ZnO series zinc alloy;

6) The Zn-ZnO zinc alloy inhibits smooth muscle cell proliferation.

The present invention has the following advantages:

(1) The mechanical properties of the Zn-ZnO series zinc alloy prepared by the present invention meet the requirements of the strength and toughness of medical implant materials, and can be degraded in vivo at the same time, and have the characteristics of "degradable and absorbable in vivo" and "can provide effective mechanical support" characteristic.

(2) When the Zn-ZnO zinc alloy of the present invention is used for degradable medical implants, its degradation rate in vivo can be adjusted by adding different contents of hydroxyapatite, so as to achieve different implant degradation rates for different parts of the body. Requirements to achieve the purpose of adjustable corrosion rate.

(3) The degradable medical implant provided by the present invention has no toxicity to endothelial cells and osteoblasts and can inhibit the proliferation of smooth muscle cells, has good biocompatibility, has good cell compatibility and blood compatibility and excellent Antibacterial ability, at the same time, the biological functionality (cytocompatibility, blood compatibility, antibacterial ability) of Zn-ZnO zinc alloy can be adjusted by adding different components to achieve the purpose of designing its biological functionality.

(4) The Zn-ZnO series zinc alloy prepared by the present invention has the constituent element Zn which is an essential trace element for the human body, and has the functions of promoting osteogenesis and inhibiting osteoclastoabsorption, and ZnO has the functions of antibacterial and anti-inflammatory.

Description of drawings

Fig. 1 is the metallographic phase of the Zn-ZnO series zinc alloy in Example 3.

Fig. 2 is the X-ray diffraction analysis chart of the Zn-ZnO series zinc alloy in Example 3.

Fig. 3 is the compression curve of the Zn-ZnO series zinc alloy in Example 4.

Fig. 4 is the macrocorrosion surface of the Zn-ZnO series zinc alloy immersed in Hank's simulated body fluid for 3 months in Example 5.

FIG. 5 is a scanning electron microscope image of the Zn-ZnO zinc alloy immersion corrosion surface in Example 5. FIG.

FIG. 6 is an EDS energy spectrum elemental analysis diagram of Zn-ZnO zinc alloy immersion corrosion products in Example 5. FIG.

Fig. 7 is the pH change diagram of the Zn-ZnO series zinc alloy in Example 5 immersed in Hank's simulated body fluid for 3 months.

Figure 8 shows the weight loss corrosion rate and solution ion concentration of the Zn-ZnO zinc alloy in Example 5 soaked in Hank's simulated body fluid for 3 months (*p<0.05).

Fig. 9 is the electrochemical corrosion polarization curve of the Zn-ZnO zinc alloy in Example 5 in Hank's simulated body fluid.

Fig. 10 is the hemolysis rate of the Zn-ZnO zinc alloy in Example 6 (*p<0.05).

Figure 11 shows the morphology and number of platelets adhered to the surface of the Zn-ZnO zinc alloy in Example 6 (*p<0.05).

Fig. 12 is the concentration of Zn ions in the platelet-poor plasma of the Zn-ZnO zinc alloy in Example 6 (*p<0.05).

Fig. 13 is the contact angle of the Zn-ZnO zinc alloy in Example 7 (*p<0.05).

Figure 14 is the cell survival rate of the Zn-ZnO zinc alloy in Example 7 (*p<0.05).

Fig. 15 is the zinc ion concentration of the Zn-ZnO system zinc alloy leaching solution in Example 7 (*p<0.05).

Figure 16 is the antibacterial rate of the Zn-ZnO zinc alloy in Example 8 (*p<0.05).

Figure 17 shows the Zn ion concentration and pH value of the Zn-ZnO zinc alloy in the bacterial suspension in Example 8 (*p<0.05).

detailed description

The present invention will be described below through specific examples, but the present invention is not limited thereto.

The experimental methods described in the following examples, unless otherwise specified, are conventional methods; the reagents and materials, unless otherwise specified, can be obtained from commercial sources.

The percentages used in the following examples are all mass percentages unless otherwise specified.

Embodiment 1, preparation Zn-ZnO series zinc alloy:

1) Using pure Zn powder (purity 99.9%, particle size 45-109 μm) (purchased from Alfa Aesar), ZnO powder (purity 99.9%, particle size <5 μm) (purchased from Sigma-Aldrich) as raw materials, according to different mass ratios (The mass ratio of Zn to ZnO is 99.75:0.25, 99.5:0.5, 99:1, 95:5, 90:10) in a vacuum glove box, put into a vacuum ball mill jar under the protection of argon, and pass through a planetary ball mill Mix evenly, ball milling speed 200rpm, ball to material ratio 20:1, ball milling time 60min, get a uniform mixture with different mass ratios of Zn and ZnO, store in an argon protective atmosphere to prevent oxidation;

2) Put the homogeneous mixture in step 1) into the graphite abrasive tool, pressurize axially and sinter by spark plasma vacuum: the initial sintering pressure is 1MPa, the heat preservation sintering pressure is 60MPa, firstly the temperature is raised to 250℃ at 100℃/min, and then The temperature was raised to 350°C at 50°C/min, and finally to 380°C at 25°C/min, and the holding time was 6 minutes to obtain Zn-ZnO-based zinc alloys with different mass ratios of Zn to ZnO. Among them, the mass ratio of Zn to ZnO was 99.75: 0.25 named Zn/0.25ZnO; Zn to ZnO mass ratio of 99.5: 0.5 named Zn/0.5ZnO; Zn to ZnO mass ratio of 99:1 named Zn/1ZnO; Zn to ZnO mass ratio of 99:5 named Zn/5ZnO; the mass ratio of Zn to ZnO is 99:10, named Zn/10ZnO.

Embodiment 2, preparation is coated with the Zn-ZnO series zinc alloy of ceramic coating:

1) Using pure Zn powder (purity 99.9%, particle size 45-109 μm) (purchased from Alfa Aesar), ZnO powder (purity 99.9%, particle size <5 μm) (purchased from Sigma-Aldrich) as raw materials, according to different mass ratios (The mass ratio of Zn to ZnO is 99.75:0.25, 99.5:0.5, 99:1, 95:5, 90:10) in a vacuum glove box, put into a vacuum ball mill jar under the protection of argon, and pass through a planetary ball mill Mix evenly, ball milling speed 200rpm, ball to material ratio 20:1, ball milling time 60min, get a uniform mixture with different mass ratios of Zn and ZnO, store in an argon protective atmosphere to prevent oxidation;

2) Put the homogeneous mixture in step 1) into the graphite abrasive tool, pressurize axially and sinter by spark plasma vacuum: the initial sintering pressure is 1MPa, the heat preservation sintering pressure is 60MPa, firstly the temperature is raised to 250℃ at 100℃/min, and then The temperature was raised to 350°C at 50°C/min, and finally to 380°C at 25°C/min, and the holding time was 6 minutes to obtain Zn-ZnO zinc alloys with different mass ratios of Zn and ZnO.

3) The surface of the Zn-ZnO series zinc alloy obtained in step 2) is coated with a ceramic coating-tricalcium phosphate, and the specific steps are as follows: use plasma spraying, the main gas of the plasma gas used is Ar, the flow rate is 60scfh, and the plasma gas The secondary gas is H ₂ , the flow rate is 15scfh, the spraying current is 600A, the spraying voltage is 60V, and the spraying distance is 250mm; the Zn-ZnO series zinc alloy with a ceramic coating of 0.59mm is obtained by spraying.

Embodiment 3, Zn-ZnO system zinc alloy microstructural analysis:

The Zn-ZnO series zinc alloy in Example 1 was prepared by wire cutting to prepare a 10×10×1mm sample, which was sequentially ground and polished by 400#, 800#, 1200# and 2000# SiC sandpaper series. After ultrasonic cleaning in acetone, absolute ethanol and deionized water for 15 min, dry at 25 °C. The sample was subjected to X-ray diffraction analysis, etched with 4% nitric acid alcohol for 5-30 seconds, washed with deionized water, dried, observed under a metallographic microscope, and tested for density by a densitometer.

Figure 1 shows the metallographic phase of Zn-ZnO zinc alloy. It can be seen from Figure 1 that ZnO is evenly distributed on the boundary of pure Zn particles. With the increase of ZnO content, ZnO on the boundary begins to aggregate, splitting the pure zinc particles combination between.

Figure 2 is an X-ray diffraction analysis diagram of Zn-ZnO zinc alloy, and only elemental zinc and zinc oxide are found in X-ray diffraction analysis.

Table 1 shows the density of Zn-ZnO zinc alloys. The density decreases with the increase of ZnO content, and the agglomeration of ZnO increases the porosity of the material.

Table 1. Density of Zn-ZnO zinc alloy

Embodiment 4, Zn-ZnO zinc alloy mechanical property test:

With the Zn-ZnO series zinc alloy prepared according to the method of Example 1, samples were prepared according to the ASTM-E9-89a compression test standard and the ASTM-E10-01 hardness test standard respectively, and were successively passed through 400#, 800#, 1200# and 2000# #SiC sandpaper series for grinding and polishing. After ultrasonic cleaning in acetone, absolute ethanol and deionized water for 15 minutes, the test was carried out at room temperature using a microhardness tester and a universal material mechanics testing machine, with a load of 0.1kN, a pressure hold of 15s, and a compression speed of 0.2mm/min.

Figure 3 is the compression curve of the Zn-ZnO series zinc alloy. It can be seen from the curve that when the ZnO content is below 1wt.%, it has no effect on the compression plasticity of the composite material, and then with the increase of the ZnO content, the brittleness of the material increases, and the composite material The compressive plasticity decreases with the increase of ZnO content.

The room temperature mechanical properties of Zn-ZnO series zinc alloy samples are shown in Table 2. Among them, it can be seen from Table 2 that with the increase of ZnO content, the material strength decreases slightly before the 1wt.% ZnO content, and then decreases significantly, but The hardness is slightly reduced. Since the addition of ZnO splits the bonding strength of the matrix, and the second phase itself has no strengthening effect, the compressive strength decreases with the increase of the second phase content.

Table 2. Mechanical experiment results of Zn-ZnO series zinc alloy

Embodiment 5, Zn-ZnO series zinc alloy corrosion performance test:

The Zn-ZnO series zinc alloy in Example 1 was prepared by wire cutting to immerse a sample of φ6x1mm, which was sequentially ground and polished by 400#, 800#, 1200# and 2000# SiC sandpaper series. After ultrasonic cleaning in acetone, absolute ethanol and deionized water for 15 min, dry at 25 °C. After soaking in Hank's simulated body fluid (NaCl 8.0g, CaCl ₂ 0.14g, KCl 0.4g, NaHCO ₃ 0.35g, glucose 1.0g, MgCl ₂ 6H ₂ O 0.1g, Na ₂ HPO ₄ 2H ₂ O 0.06g, KH ₂ PO ₄ 0.06g, MgSO ₄ 7H ₂ O 0.06g were dissolved in 1L deionized water), soaked for different time intervals and tested the pH value of the solution at corresponding time points, but after three months, the samples were taken out and washed with deionized water, Dry in the air, observe the surface of the sample through a 2.5-dimensional imager and a scanning electron microscope (S-4800, Hitachi, Japan), and detect the composition of corrosion products by an energy dispersive spectrometer. The soaked Hank's simulated body fluid was used to test the concentration of ions in the solution by an inductively coupled plasma emission spectrometer. Finally, the corrosion products were cleaned with glycine cleaning solution (250g/1000ml) and the corrosion rate was calculated by weight loss method.

The electrochemical test is to pass the above-mentioned treated samples through the Autolab electrochemical workstation, and perform electrochemical tests in Hank's simulated body fluid.

Figure 4 shows the macro-corrosion surface of Zn-ZnO zinc alloy immersed in Hank's simulated body fluid for 3 months. The results show that with the increase of ZnO content, the corrosion of the material is gradually aggravated, and the corrosion pits and white corrosion products on the surface of the material also increase with the increase of ZnO content. The content increases and increases, and the edge corrosion of the material is more serious.

Figure 5 is a scanning electron microscope image of the Zn-ZnO series zinc alloy soaked corrosion surface. The microscopic corrosion morphology is consistent with the macroscopic corrosion morphology. With the increase of ZnO content, the corrosion products on the surface of the material increase, and the corrosion microcracks gradually increase and expand. , the surface of Zn/0.25ZnO material has only a small amount of spherical corrosion products and cracks, while the surface of Zn/10ZnO material is completely covered by corrosion products, the corrosion cracks expand, and the material surface peels off.

Fig. 6 is an EDS energy spectrum elemental analysis diagram of Zn-ZnO zinc alloy immersion corrosion products. It can be seen that the corrosion products contain Zn, O, C, Ca, P, Mg, which may be composite corrosion products of calcium phosphorus salt and Zn, Mg carbonate.

Figure 7 is the pH change diagram of Zn-ZnO zinc alloy immersed in Hank's solution for 3 months. It can be seen from the figure that the composite material has a higher pH value than pure zinc and Hank's solution, Zn/0.25 The pH change of ZnO is close to that of pure zinc. With the increase of ZnO content, the overall pH value of the composite material at different time points is in line with Zn/10ZnO>Zn/5ZnO>Zn/1ZnO>Zn/0.5ZnO>Zn/0.25ZnO, overall It is said that with the increase of ZnO content, the pH value also increases, and the degradation of the composite material is accelerated. The overall pH change trend of the composite material is similar to the change trend of Hank's solution itself, so the change trend is not caused by the material itself, and the pH value change trend of the material itself is relatively stable, so the corrosion layer of the Zn-ZnO zinc alloy can prevent further corrosion. The role of corrosion.

Figure 8 shows the corrosion rate and the ion concentration in the solution calculated according to the weight loss after the Zn-ZnO series zinc alloy was soaked in Hank's solution for 3 months. From the perspective of corrosion rate, the corrosion rate of Zn/0.25ZnO and Zn/0.5ZnO and The corrosion rate of the composite material is significantly accelerated with the increase of ZnO content, and the degradation rate of Zn/10ZnO is about 9 times that of pure zinc. The ion concentration shows that the zinc ion concentration of Zn/0.25ZnO and Zn/0.5ZnO is close to that of pure zinc. After adding 1wt.% and above ZnO, although the corrosion rate is accelerated, the zinc content of the matrix is reduced, and the effect of the latter is greater than that of the former. effect, so the concentration of zinc ions decreases.

Figure 9 is the electrochemical corrosion polarization curve of Zn-ZnO zinc alloy in Hank's solution, and Table 3 is the electrochemical corrosion rate of Zn-ZnO zinc alloy in Hank's solution. It can be seen from Table 3 that the composite material The electrochemical corrosion rate of ZnO increases with the increase of ZnO content, which is consistent with the results of weight loss. ZnO particles gather at the boundary, resulting in a large number of defects and vacancies, which accelerates the corrosion of materials.

Table 3. Electrochemical corrosion rate of Zn-ZnO zinc alloy

The standard deviation is in brackets, * means p<0.05 compared with pure zinc

Embodiment 6, Zn-ZnO zinc alloy blood compatibility test:

The Zn-ZnO series zinc alloy in Example 1 was prepared by wire cutting to prepare a φ10x1mm sample piece, which was polished by 400#, 800#, 1200# and 2000# SiC sandpaper series. After ultrasonic cleaning in acetone, absolute ethanol and deionized water for 15 min, dry at 25 °C. Fresh blood was collected from healthy volunteers and stored in an anticoagulant tube containing 3.8 wt.% sodium citrate as an anticoagulant. Dilute blood samples with 0.9% normal saline at a ratio of 4:5. Soak the sample in 10mL of normal saline, keep warm at 37±0.5°C for 30min, add 0.2mL of diluted blood sample, and keep warm at 37±0.5°C for 60min. 10 mL of normal saline was used as a negative control group, and 10 mL of deionized water was used as a positive control group. After centrifugation at 3000rpm for 5 minutes, the supernatant was taken to measure the absorbance OD value with a Unic-7200 ultraviolet-visible spectrophotometer at 545nm, and three groups of parallel samples were set up for statistical analysis.

Calculate the hemolysis rate with the following formula:

Hemolysis rate=(OD value of experimental group-OD value of negative group)/(OD value of positive group-OD value of negative group)×100%.

After the whole blood was collected, a part was centrifuged at 1000rpm for 10min to prepare platelet-rich plasma. Platelet-rich plasma was dropped on the surface of the sample, and incubated at 37±0.5°C for 60 minutes, with 3 parallel samples in each group. The samples were taken out and washed 3 times with PBS buffer (pH 7.2) to remove unadhered platelets. The platelet fixation method is as follows: add 500 μL of 2.5% glutaraldehyde fixative solution to each well, fix at room temperature for two hours, then suck out the fixative solution, wash with PBS three times, and use concentrations of 50%, 60%, and 70%. 80%, 90%, 95%, and 100% alcohol were dehydrated in gradients, and each concentration gradient was dehydrated for 10 minutes. After vacuum drying, the number and shape of platelet adhesion were observed with a scanning electron microscope (S-4800, Hitachi, Japan). Ten regions were randomly selected for platelet count and statistical analysis. The other part was centrifuged at 3000rpm for 15min, and the upper layer of platelet-poor plasma was taken, and the sample was placed in a glass tube containing platelet-poor plasma at a ratio of 500ul/ ^cm2 and incubated in a water bath at 37°C for 30min, and 500ul of platelet-poor plasma after reaction was taken for coagulation Four tests. The platelet-poor plasma after reaction was taken to test the concentration of each ion in the extraction stock solution with an inductively coupled plasma emission spectrometer.

Figure 10 shows the hemolysis rate of Zn-ZnO series zinc alloy. The experimental results show that the hemolysis rate of Zn-ZnO series zinc alloy is less than 5% of the safety threshold required for clinical use. With the increase of ZnO content, the hemolysis rate rises, showing a good performance. Red blood cell and hemoglobin compatibility.

Figure 11 shows the morphology and quantity of platelets attached to the surface of Zn-ZnO zinc alloy. It can be seen from Figure 11 that most of the platelets on the surface of the composite material are polygonal and extend a small amount of pseudopodia, and the platelets on the surface of Zn/10ZnO The least foot, indicating that the platelets are in the initial stage of activation, indicating that the composite material has a certain stimulating effect on platelets. Quantitatively, with the increase of ZnO content, the number of adhered platelets reached the highest at 1wt.% ZnO, and then decreased. Compared with pure zinc, the composite can regulate the degree of platelet adhesion and activation.

Fig. 12 shows the concentration of Zn ions in the platelet-poor plasma of Zn-ZnO zinc alloy and the platelet-poor plasma (PPP) of the blank control.

Table 4 shows the four coagulation results of Zn-ZnO zinc alloy. It can be seen from Table 4 that the prothrombin time (PT) of the composite material is significantly prolonged compared with the healthy group and pure zinc and increases with the increase of ZnO content. The activated partial thromboplastin time (APTT) was also significantly prolonged compared with pure zinc, the healthy group and the reference value, and the trend was consistent with the change trend of PT. The thrombin time (TT) was significantly shortened compared with the healthy group, pure zinc, and reference values. The composite material significantly prolongs the prothrombin time (PT) and activated partial thromboplastin time (APTT), and shortens the thrombin time (TT), which is related to the increased concentration of Zn ions in platelet-poor plasma acting on the coagulation system .

Table 4. Four coagulation results of Zn-ZnO zinc alloy

* indicates significant difference with healthy control group (p<0.05); # indicates significant difference with pure zinc (p<0.05)

Example 7, Cytocompatibility experiment of Zn-ZnO series zinc alloy:

Prepare Zn-ZnO series zinc alloy according to the method of Example 1, prepare φ10x1mm sample piece by wire cutting, and grind and polish with 400#, 800#, 1200# and 2000# SiC sandpaper series. After ultrasonic cleaning in acetone, absolute ethanol and deionized water for 15 min, dry at 25 °C. Test the contact angle of the sample with deionized water. The sample is sterilized by ultraviolet rays, placed in a sterile orifice plate, and mixed with 10% serum and 1% double antibody (penicillin plus streptomycin mixed solution) according to the surface area of the sample. ) into the DMEM cell culture medium at a volume ratio of 1.25cm ² /mL, and placed in a 37°C, 95% relative humidity, 5% CO ₂ incubator for 24 hours to obtain the leached zinc matrix composite material Liquid stock solution, sealed, and stored in a refrigerator at 4°C for later use.

Extraction and cell inoculation culture and result observation: HUVEC, VSMC, cells were resuscitated and passaged, suspended in DMEM cell culture medium, seeded on 96-well culture plates, negative control group was added with DMEM cell culture medium, zinc-based complex The material extraction solution stock solution group was added with the zinc-based composite material extract solution stock solution obtained above, so that the final cell concentration was 2-5×10 ⁴ /mL. Culture in a 37°C, 5% CO ₂ incubator, take out the culture plate after 1, 2, and 4 days, observe the morphology of living cells under an inverted phase-contrast microscope, and test the cell survival rate with the CCK8 kit. The original solution of the composite material extract was tested with an inductively coupled plasma emission spectrometer to test the concentration of ions in the original solution.

Figure 13 shows the contact angle of Zn-ZnO zinc alloy. With the increase of ZnO content, the surface contact angle of the material first decreases and then increases.

Figure 14 shows the cell survival rate of Zn-ZnO series zinc alloy. The results show that: compared with pure zinc, the cell survival rate of the composite material is relatively improved, especially in the Zn/0.5ZnO and Zn/1ZnO groups. Osteoblast biocompatibility was significantly improved while smooth muscle cell proliferation was inhibited. Generally speaking, the composite material has slight toxicity to no toxicity to endothelial cells and osteoblasts, and significantly inhibits the proliferation of smooth muscle cells.

Figure 15 is the ion concentration of the Zn-ZnO zinc alloy leaching solution. From the perspective of zinc ion concentration, except for Zn/0.25ZnO, the zinc ion concentration of other composite materials decreased compared with pure zinc, and the addition of zinc oxide can improve the cell compatibility.

Embodiment 8, the antibacterial test of Zn-ZnO series zinc alloy:

Prepare Zn-ZnO series zinc alloy according to the method of Example 1, prepare φ10x1mm sample piece by wire cutting, and grind and polish with 400#, 800#, 1200# and 2000# SiC sandpaper series. After ultrasonic cleaning in acetone, absolute ethanol, and deionized water for 15 min, they were dried at 25°C and sterilized under ultraviolet light. Take 1ml of frozen Staphylococcus aureus (Staphylococcus aureus) in 20ml LB liquid medium for activation at 180rpm for 12h, then take 1ml of the activated bacteria solution and continue to activate it in 40ml LB liquid medium for 1h at 200rpm, take the activated bacteria solution Add 1ml of each well into the 24-well plate with the sample, and after incubating at 37°C for 24h, take 100ul of the bacterial solution diluted ¹⁰⁵ times in PBS buffer solution, spread it on the LB solid medium, and count. Take out the sample, wash it with PBS buffer three times, gently wash away the bacteria that are not firmly adhered to the surface of the sample, put it into a centrifuge tube, add 1ml of PBS buffer, and ultrasonically shake for 10 minutes to shake the bacteria on the surface of the sample into PBS In the buffer solution, take 10ml PBS buffer solution and dilute it 1000 times, spread it on the LB solid medium, and count. Take the fine homogeneous suspension and test the concentration of zinc ions in the suspension with an inductively coupled plasma emission spectrometer, and test the pH value.

Figure 16 shows the antibacterial rate of Zn-ZnO zinc alloy relative to Ti6Al4V without antibacterial effect. The antibacterial rate in the composite material suspension has no significant difference when the ZnO content is not more than 1wt.%. With the increase of Zn/ZnO content The antibacterial rate increased, and the antibacterial rate on the surface of the material also showed the same trend, which was consistent with the ion concentration trend in the culture solution.

Figure 17 is the Zn ion concentration and pH value of the bacterial suspension of Zn-ZnO zinc alloy relative to Ti6Al4V without antibacterial effect. It can be seen from Figure 17 that the change of zinc ion concentration is consistent with the change of material antibacterial rate, while the pH The change is very small and cannot play an antibacterial effect, so the main reason is that the degraded zinc ions have a significant inhibitory effect on Staphylococcus aureus. Therefore, the Zn-ZnO-based zinc alloy has an excellent antibacterial effect.

Claims (8)

1. a kind of Zn-ZnO systems kirsite, including Zn and ZnO；

The mass percent of ZnO is 0～10% in Zn-ZnO systems kirsite, but including 0.

2. Zn-ZnO systems as claimed in claim 1 kirsite, it is characterised in that：Zn-ZnO systems kirsite In, also including trace element, the trace element is at least one in silicon, phosphorus, lithium, silver, tin and rare earth element；

In Zn-ZnO systems kirsite, the weight/mass percentage composition of the trace element is 0～3%, but including 0.

3. Zn-ZnO systems as claimed in claim 1 or 2 kirsite, it is characterised in that：Zn-ZnO systems zinc The surface of alloy is coated with degradable macromolecule coating, ceramic coating or medication coat；

The thickness of the degradable macromolecule coating, the ceramic coating and the medication coat can be 0.01～5mm.

4. Zn-ZnO systems as claimed in claim 3 kirsite, it is characterised in that：The degradable macromolecule coating Prepare material be specially it is following 1) and 2) at least one：

1) PCL, PLA, polyglycolic acid, PLLA, polybutylcyanoacrylate, condensing model, poly- Any one in phosphine nitrile, poly- para-dioxane ketone, poly- butyric ester or poly- hydroxyl valerate；

2) PLA, PCL, polyglycolic acid, PLLA, polybutylcyanoacrylate and poly- to dioxa The copolymer of at least two in hexamethylene alkanone；

The ceramic coating prepares material is specially in hydroxyapatite, tricalcium phosphate and the calcium of phosphoric acid oxygen four at least one Kind；

The medication coat is specially rapamycin and its derivative coating, taxol coating, everolimus coating, west At least one in Luo Mosi coatings, mitomycin coating and antimicrobial coating.

5. a kind of preparation method of the Zn-ZnO systems kirsite any one of claim 1-4, walks including following Suddenly：By Zn, ZnO and the trace element according to it is following 1) and 2) in any one mode carry out being mixed to get it is mixed Compound；

1) Zn and ZnO；

2) Zn, ZnO and trace element；

According to it is following a) or b) the step of obtain final product Zn-ZnO systems kirsite；

A) in a vacuum or inert atmosphere, the homogeneous mixture is sintered, the Zn-ZnO is obtained final product after cooling It is kirsite；

B) in a vacuum or inert atmosphere, the homogeneous mixture is sintered, is coated after cooling described degradable Polymeric coating layer, the ceramic coating or the medication coat obtain final product Zn-ZnO systems kirsite.

6. preparation method as claimed in claim 5, it is characterised in that：It is described to be mixed into Zn, ZnO and described Trace element, adds in vacuum ball grinder, in 180～250rpm of ball milling speed, ratio of grinding media to material under argon atmosphere (10-20)：1 time 15～60min of ball milling, obtains mixture；

It is described to be sintered to discharge plasma sintering；

The discharge plasma sintering is the mixture to be added in graphite grinding tool, axial pressure simultaneously vacuum-sintering, institute The design parameter control for stating discharge plasma sintering is as follows：Incipient sintering pressure 1MPa, heat preservation sintering pressure 30～60MPa, is first warmed up to 150～300 DEG C with 100 DEG C/min, then is warmed up to 200～350 DEG C with 50 DEG C/min, most Afterwards 250～400 DEG C are warmed up to 25 DEG C/min, 3～6min of temperature retention time, the cold cooling of stove obtains the Zn-ZnO systems Kirsite；

The mass percent of ZnO is 0～10% in Zn-ZnO systems kirsite, but including 0.

7. the Zn-ZnO systems kirsite any one of claim 1-4 can degraded by body fluid medical implant in preparation In application.

8. one kind can degraded by body fluid medical implant, its by any one of claim 1-4 Zn-ZnO systems zinc close Gold is prepared.