CN114732944B

CN114732944B - Zinc-based bar with composite structure and preparation method thereof

Info

Publication number: CN114732944B
Application number: CN202210362839.4A
Authority: CN
Inventors: 郑玉峰; 朱冬晖; 杜绍康; 苏颖超; 夏丹丹
Original assignee: Peking University
Current assignee: Peking University
Priority date: 2022-04-07
Filing date: 2022-04-07
Publication date: 2023-01-13
Anticipated expiration: 2042-04-07
Also published as: CN114732944A

Abstract

The invention discloses a zinc-based bar with a composite structure and a preparation method thereof, wherein the zinc-based bar comprises zinc elements and alloy elements; the alloy element is alum or chromium, the mass percent of the alloy element is 0-1%, but not 0, and the balance is zinc element; the structure is that more than two arc grooves are uniformly arranged on the side surface of the bar, and hydroxyapatite is filled in the arc grooves. The invention has simple structure, perfect functions, excellent mechanical property, proper degradation rate, corresponding biological function, simple processing technology and easy production.

Description

Zinc-based bar with composite structure and preparation method thereof

Technical Field

The invention belongs to the field of medical metal materials, and particularly relates to a zinc-based bar with a composite structure and a preparation method thereof.

Background

Biodegradable implants are intended to provide temporary mechanical support to injured tissue and to degrade properly in vivo to avoid injury from secondary removal procedures. Compared with the bioabsorbable metals magnesium (Mg) and iron (Fe), zinc (Zn) is a new type of bioabsorbable metal, and the biodegradation rate of the zinc (Zn) is more consistent with the clinical requirement. Zinc is the second most abundant microelement in human body, and plays a key role in maintaining cardiac function, promoting bone formation and mineralization. Therefore, zn has great potential as a new generation of cardiovascular stents, orthopedic implants and wound closure devices.

However, pure zinc lacks sufficient mechanical strength for cardiovascular stents and weight bearing orthopedic implants. Furthermore, in previous studies pure zinc showed local degradation, which could lead to a high risk of sudden implant failure. The alloying can improve the mechanical property of the alloy and weaken the non-uniform corrosion condition of the alloy. In recent years, many researchers have been dedicated to develop multifunctional composite materials, for example, patent (CN 111227996B) discloses a degradable medical titanium-based composite bar with osteoinductive and osteoinductive activities and its preparation method, a method of compounding three alloys of titanium, zinc and magnesium, and filling the inside with osteoinductive active substances; however, the composite bar is composed of at least three layers of metals with different components, the problem of galvanic corrosion caused by contact of two different alloys exists, and the used magnesium alloy has the condition of excessively high corrosion rate, which can cause early failure and serious pitting corrosion.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide the zinc-based bar with the composite structure and the preparation method thereof, and the zinc-based bar has excellent mechanical properties, proper degradation rate, corresponding biological functions, simple processing technology and easy production.

The purpose of the invention is realized by the following technical scheme:

a zinc-based bar with a composite structure comprises zinc elements and alloy elements; the alloy element is vanadium (V) or chromium (Cr), the mass percent of the alloy element is 0-1%, but not 0, and the balance is zinc element.

The following table is an exemplary composition of the composite structural zinc-based bar (including but not limited to the following ingredients):

preferably, the zinc-based bar with the composite structure has a structure that more than two arc grooves are uniformly arranged on the side surface of the bar, and six arc grooves are preferably selected; the circle center of the arc of the groove is on the section circle of the bar, and the diameter of the arc contour of the groove is 1/8-1/5 times of the diameter of the bar; hydroxyapatite is filled in the arc groove.

Preferably, the outer layer of the zinc-based bar material with the composite structure is coated with a functional medicine-carrying coating; the coating comprises a degradable high polymer coating, a ceramic coating or a drug coating.

The preparation method of the zinc-based bar with the composite structure comprises the following steps:

(1) Mixing: pure Zn, pure Cr or pure V are taken as raw materials and mixed according to a proportion to obtain a mixture;

(2) Smelting: firstly, pumping the vacuum degree to 4 multiplied by 10 ^-4 ～3×10 ^-3 Pa, filling argon to 4X 10 ³ Pa, the temperature for smelting the mixture is 450-600 ℃, and then casting and cooling are carried out to obtain an ingot;

(3) Extruding: extruding the cast ingot at 150-300 deg.c and extruding rate of 10-40 at 0.1-10 mm/s to form rod;

(4) Annealing: annealing at 200-300 deg.c for 50-100 min to obtain rough bar blank;

(5) Processing a groove: and calibrating the cutting point of the arc groove, and processing by adopting a milling cutter, a linear cutting method or a laser etching method to obtain the zinc-based bar with the composite structure and the arc groove.

In the step (3), before extrusion, the bar is homogenized and is kept at the temperature of 200-300 ℃ for 18-24 h.

In the step (5), before the groove is machined, the bar is turned, the geometric shape of the bar is normalized, and the oxide layer on the surface of the bar is removed.

Furthermore, the composite structure zinc-based bar with the arc groove is filled with fillers in the arc groove by adopting a hydroxyapatite powder sintering method.

The filling method is characterized in that hydroxyapatite Dan Gutai powder is used as a raw material, the raw material is filled in a graphite mold, and the graphite mold is fixed by a spark plasma sintering technology, and the filling method specifically comprises the following steps:

(1) Designing a cylindrical graphite die with the length equivalent to that of the bar to be processed, wherein the inner diameter is the diameter of the processed bar;

(2) Putting the bar into a mould, filling hydroxyapatite powder into the concave part of the arc groove, and compacting;

(3) And (3) placing the die into a discharge plasma sintering furnace, sintering for 5-10 min at the sintering temperature of 350-500 ℃ under the protection of argon, and cooling to room temperature along with the furnace after the sintering is finished to obtain the zinc-based bar material with the composite structure and filled with the hydroxyapatite.

Further, a functional coating capable of carrying medicines is coated on the surface of the composite structure zinc-based bar filled with the hydroxyapatite. The coating comprises a degradable high polymer coating, a ceramic coating or a medicine coating, and the thickness is 0.01-5 mm.

The degradable high polymer coating is any one of polycaprolactone, polylactic acid, chitosan, collagen, polyglycolic acid, L-polylactic acid, polyanhydride, poly-p-dioxanone or poly-hydroxybutyrate; the ceramic coating is at least one of hydroxyapatite, tricalcium phosphate or tetracalcium phosphate; the drug coating is at least one of everolimus coating, sirolimus coating, mitomycin coating or antibacterial coating.

The application of the zinc-based bar material with the composite structure is used for preparing intramedullary nails, bone pins, spinal fixation equipment or bone repair supports.

Compared with the prior art, the invention has the following advantages and effects:

(1) The invention adopts Cr or V as alloy element to prepare zinc alloy. Cr and V are in the fourth transition subgroup, belong to transition metal elements, and have good mechanical and chemical properties, so that the method has a wide application prospect in the field of biomedicine. Firstly, they have properties similar to those of zinc, which are beneficial to the improvement of metallurgical process and mechanical properties. Through the first principle research on the influence of the transition metal on the basal plane fault energy of the zinc alloy, the transition metal and Zn are found to possibly form strong local atomic bonds. In addition, cr is a micronutrient in mammals and plays an important biological role in carbohydrate and lipid metabolism; the tolerable upper limit intake of V is lower and is 1.8mg/d, but plays an important role in cardiovascular and neural functions; the zinc-based bar material has excellent mechanical property and proper degradation rate, can meet the service time requirements of different parts in vivo by regulating and controlling the difference of element types and components, and has the characteristic of adjustable degradation rate. Moreover, the invention only uses a single zinc alloy, and solves the problem of galvanic corrosion caused by contact of two different alloys.

(2) The bar material is innovative in structure, and the six circular arc grooves are uniformly distributed on the side surface of the bar material, so that not only can osteoinductive osteointegrative substances be filled, but also the effect of increasing the strength can be realized in the structure; hydroxyapatite is filled in the arc groove, so that the bonding capability of the bar and the bone can be enhanced, and the novel bone induction potential is achieved.

(3) The coating is applied to the surface containing hydroxyapatite and zinc alloy, and after the thin coating is degraded in a short time, the material can be induced to be combined with a bone interface, so that a time adaptation function exists; the coating is a functional carrier, active groups on the surface of the coating can carry various medicines, and the coating can directly play a biological and medicinal function according to different coatings.

(4) The invention has simple structure and complete functions, comprises mechanics, osseointegration, bone induction, anti-inflammation, antibiosis, degradability and the like, and in the antibiosis performance, the Zn-0.4V alloy has the antibiosis performance of more than 60 percent on escherichia coli and the antibiosis rate of staphylococcus aureus is close to 100 percent.

Drawings

FIG. 1 is a schematic cross-sectional view of a zinc-based bar of a composite structure designed by the present invention. In the figure: 1. alloy surface grooves; 2. a functionalized coating; 3. the geometric circle center of the arc groove; 4. a zinc alloy substrate.

FIG. 2 is a schematic cross-sectional view of the grooved belt of the present invention.

FIG. 3 is a distribution histogram of mechanical properties of the zinc alloy of the present invention.

FIG. 4 shows the adhesion morphology (a) and the antibacterial rate distribution histogram (b) of the zinc alloy surface prepared by the invention after culturing Escherichia coli and Staphylococcus aureus.

FIG. 5 shows the cross-sectional scanning electron microscope appearance and in-vivo degradation rate distribution histogram of the implanted part of the zinc alloy prepared by the invention after the femoral bone tissue is implanted for 3 months and the three-dimensional reconstruction appearance of the implant. In the figure, I: implant, DP: degradation product, OS: osteoid layer, NB: new bone.

Detailed Description

In order that the invention may be readily understood, reference will now be made in detail to the specific embodiments of the invention. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that, for a person skilled in the art, many variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. The experimental procedures used in the following examples are all conventional procedures unless otherwise specified. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified. The percentages used in the following examples are by mass unless otherwise specified.

EXAMPLE 1 preparation of as-cast Zn-V alloy

Smelting by adopting a medium-frequency non-vacuum furnace, taking pure Zn (99.99%) and pure V (99.99%) as raw materials, weighing and proportioning the Zn and the alloy elements according to the mass percent, mixing the weighed powder materials together, uniformly mixing for 2 hours by using a V-shaped powder mixing machine, putting the mixture into a graphite crucible, covering the graphite crucible with salt, vacuumizing firstly, and reducing the vacuum degree to 2 multiplied by 10 ^-3 Pa, filling high-purity argon to 4 multiplied by 10 ³ And Pa or so, smelting under the protection of argon atmosphere, wherein the smelting temperature is 550 ℃, cooling to obtain Zn-0.4V cast ingots, and turning the train wagon after the detection is qualified.

EXAMPLE 2 preparation of as-cast Zn-Cr alloy

Smelting in a medium-frequency non-vacuum furnace, taking pure Zn (99.99%) and pure Cr (99.99%) as raw materials, accurately weighing and proportioning Zn and alloy elements according to mass percent, mixing weighed powder materials together, uniformly mixing for 2 hours by using a V-shaped powder mixer, putting the mixture into a graphite crucible, covering and smelting by using chaff, vacuumizing firstly, and reducing the vacuum degree to 2 multiplied by 10 ^-3 Pa, filling high-purity argon to 4 multiplied by 10 ³ And (4) about Pa, smelting under the protection of argon atmosphere, wherein the smelting temperature is 600 ℃, cooling to obtain a Zn-0.4Cr ingot, and turning the ingot after the detection is qualified.

Example 3 preparation of an extruded Zinc alloy Bar

The preparation method comprises the steps of obtaining zinc alloy cast ingots in the

embodiments

1 and 2, preparing zinc alloy bars in an extrusion mode, and performing radial extrusion, wherein the cast ingots are kept at the heat preservation temperature of 250 ℃, the extrusion temperature of 260 ℃, the extrusion ratio of 10, and the extrusion speed of 1mm/s to obtain the zinc alloy bars.

Example 4 preparation of Zinc alloy Bar containing six arc grooves

Fixing the bar subjected to annealing heat treatment on a lathe for turning, removing oxide skin generated on the surface of the bar due to heat treatment, and turning a regular cylinder with the diameter of 15 mm; dividing the cross section of the cylinder (round bar) into six equal parts by using a ruler-compass drawing method, and calibrating a groove cutting point; processing according to the position marked by figure 2 by using a wire cutting method, and cutting a groove with the radius of 1.5mm along the axis of the bar; removing processing burrs, and polishing the surface to be smooth, wherein the roughness is equal to that of 2000-mesh sand paper treatment.

Example 5 filling of hydroxyapatite

Taking 99% purity hydroxyapatite Dan Gutai powder as raw material, further grinding the powder raw material by a ball mill, wherein the rotating speed of the ball mill is 250r/min, and grinding for 45min. The treated bar is put into a cylindrical graphite die (containing a bottom) with the length equivalent to that of the bar to be processed, and the groove is filled with ground hydroxyapatite powder and compacted after filling. And (3) placing the die into a discharge plasma sintering furnace, sintering for 10min at the sintering temperature of 400 ℃ under the protection of argon, and cooling to room temperature along with the furnace after the sintering is finished. And taking out the material, and polishing the surface to prepare for coating.

Example 6 preparation of functional Chitosan (CH) coating

The treated zinc-based rods were placed in an aqueous dopamine solution (1.5 mg/ml) at 25 ℃ overnight, then rinsed with ultra-pure water to remove unattached dopamine, and dried with nitrogen. The dopamine treated surface was placed in a 3% glutaraldehyde aqueous solution at 25 ℃ and stirred overnight. Glutaraldehyde provides reactive aldehyde groups that covalently bond with dopamine and chitosan, and the substrate is rinsed with ultrapure water to remove unbound glutaraldehyde. Then, the substrate was immersed in a chitosan solution (concentration of 1.5mg/ml, dispersed in 0.1mol/L acetic acid solution) to promote the bonding between the aldehyde groups on the Zn surface and the amino groups of the chitosan molecules, resulting in a chitosan coating, and the bar shown in fig. 1 was obtained.

Test example 1 mechanical Properties of alloy

The zinc-based bars of the invention are respectively processed according to ASTM-E8/E8M-09 ⁹ Tensile test standards tensile samples, car finishes, were prepared. Ultrasonic cleaning in acetone, anhydrous ethanol and deionized water for 15min, respectively, and performing tensile test at room temperature with universal mechanics of materials tester (Instron 5969, USA) at a tensile speed of 1 × 10 ^-4 And s. The mechanical property distribution histogram is shown in fig. 3. And pureCompared with zinc, the tensile strength (UTS) of the zinc-based bar is improved to about 200MPa, the Yield Strength (YS) is between 120 and 160MPa, and the elongation is also obviously improved to 20 to 30 percent. Wherein the Zn-0.4V alloy has the best combination of mechanical strength and plasticity.

Test example 2 test of antibacterial ability of Zinc alloy surface

A test piece with the thickness of 2mm is obtained by wire-cutting the zinc-based bar material, and the cleaning method is the same as that of test example 1. Coli (E.coli, ATCC 25922,US) and Staphylococcus aureus (S.aureus, ATCC 29213,US) were cultured in Trypticase Soy Broth (TSB) at 37 ℃ and 220rpm, and the optical density at 600nm was 0.5 to 0.6. Taking 2ml of 5 × 10 ⁵ The bacterial suspension diluted in/ml TSB medium was incubated with the sample at 37 ℃ and 120rpm for 24 hours. No sample dilution suspension served as negative control. And (3) carrying out absorbance determination on the collected bacterial suspension at the wavelength of 600 nm. The inhibition rate in TSB medium was calculated using the following formula:

A _{rate of inhibition of bacteria} ＝(A _{Negative absorbance} -A _{Absorbance of the sample} )/A _{Negative absorbance}

The samples were fixed and dehydrated in the same manner as described above before being imaged by scanning electron microscopy. The adhesion of bacteria to the surface of the material and the antibacterial ratio of the material to different bacterial species are shown in fig. 4: both pure zinc and the zinc-based rods of the invention have little bacterial adhesion and no biofilm formation, indicating that the zinc-based rods have anti-adhesion performance to both strains. The pure zinc and Zn-0.4V surfaces showed much less S.aureus adhesion than the other groups. Compared with a stainless steel control group, when pure zinc and zinc alloy are cultured, the antibacterial rate to escherichia coli is remarkably improved to more than 50%, and the antibacterial rate to staphylococcus aureus is about 99%.

Test example 3 femoral implant test of Zinc alloy base Material

In vivo analysis of femoral implants was performed using male young SD (Sprague Dawley) rats (8-10 weeks, body weight = 300-325 grams, taconic Biosciences, NY), each group of samples implanted in 5 parallel rat specimens (n = 5). A 2cm incision was made longitudinally along the lateral side of the right femur. A cylindrical hole (0.3 mm diameter) was drilled in the femoral condyle perpendicular to the long axis of the femur. After the zinc and the zinc-based bar material are sterilized, the zinc and the zinc-based bar material are implanted into the columnar hole, and the incision is layered and sewed. After 3 months the rats were sacrificed and the implants and their surrounding bone tissue specimens were removed and the in vivo degradation of the silk implants was evaluated using high resolution micro CT (GE ex xpore CT-120). The implant and surrounding tissue were characterized by SEM. And calculating the degradation rate of the implant through three-dimensional reconstruction of the CT scanning image. The SEM-characterized cross-sectional topography, micro-CT three-dimensional reconstruction and material degradation rate are shown in FIG. 5. Micro-CT scanning shows that the morphology and the degradation rate (about 0.03 mm/y) of Zn and Zn-0.4V groups are similar, while the morphology of Zn-0.4Cr group is deep pit-shaped, and the degradation rate is higher (about 0.05 mm/y). SEM images show different gray values, where each letter represents a meaning: implant, DP degradation product, OS osteoid layer, NB new bone. Therefore, in an enlarged scanning electron microscope image, newly formed bone tissues and osteoid tissues around the zinc-based bar material, implants and degradation products can be observed, and the osseointegration degree is better. Therefore, the zinc-based bar material has degradability in a bone tissue environment, and the degradation rate difference caused by different alloy components is reflected; inflammation and rejection reaction do not occur, which indicates that the biocompatibility is good; the zinc-based bar material has the capability of osseointegration and is suitable for serving as an orthopedic implant material according to the inference that the surrounding newly formed osseous tissue and osteoid tissue.

The above description is only an example of the present invention, but the present invention is not limited to the above example, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention and are equivalent to each other are included in the protection scope of the present invention.

Claims

1. A zinc-based bar with a composite structure is characterized in that: including zinc and alloying elements; the alloy element is alum or chromium, the mass percent of the alloy element is 0-1%, but not 0, and the balance is zinc element; the structure is that more than two arc grooves are uniformly arranged on the side surface of the bar material, and hydroxyapatite is filled in the arc grooves; the outer layer is coated with a functional medicine-carrying coating; the coating comprises a degradable high polymer coating, a ceramic coating or a drug coating.

2. The composite structural zinc-based bar of claim 1, wherein: six arc grooves are uniformly formed in the side surface of the bar; the circle center of the arc of the groove is on the section circle of the bar, and the diameter of the arc contour of the groove is 1/8~1/5 times of the diameter of the bar.

3. A method of making the composite structural zinc-based bar of any one of claims 1~2 comprising the steps of:

(3) Extruding: extruding the bar material at the extrusion ingot casting temperature of 150-300 ℃, the extrusion ratio of 10-40 and the extrusion speed of 0.1-10 mm/s;

(5) Processing a groove: calibrating the cutting point of the arc groove, processing by adopting a milling cutter, a linear cutting or a laser etching method to obtain the zinc-based bar with the composite structure of the arc groove, and then filling the filler in the arc groove by adopting a hydroxyapatite powder sintering method.

4. A method of making a composite structural zinc-based bar according to claim 3, characterized in that: the filling is carried out by taking hydroxyapatite Dan Gutai powder as a raw material, filling in a graphite mould and fixing by a spark plasma sintering technology.

5. A method of making a composite structural zinc-based bar according to claim 3, characterized in that: coating a functional coating capable of carrying medicines on the surface of the zinc-based bar material with the composite structure filled with the hydroxyapatite; the coating comprises a degradable high polymer coating, a ceramic coating or a drug coating, and the thickness of the coating is 0.01-5 mm.

6. The method of making a composite structural zinc-based bar of claim 5, characterized in that: the degradable high polymer coating is any one of polycaprolactone, polylactic acid, chitosan, collagen, polyglycolic acid, polyanhydride, poly-p-dioxanone or poly-hydroxybutyrate; the ceramic coating is at least one of hydroxyapatite, tricalcium phosphate or tetracalcium phosphate; the drug coating is at least one of everolimus coating, sirolimus coating and mitomycin coating.