A biomedical degradable Mn-based alloy and its preparation method and application

Abstract

This invention discloses a biodegradable Mn-based alloy for biomedical use, its preparation method, and its application, belonging to the field of materials technology for surgical supplies. The process includes the following steps: (1) alloy raw materials Mn, Fe, and Cu are vacuum induction melted to obtain an MnFeCu alloy ingot; (2) the MnFeCu alloy ingot is homogenized to obtain a homogenized MnFeCu alloy; (3) the homogenized MnFeCu alloy is rolled and annealed to obtain an annealed MnFeCu alloy; (4) the oxide layer on the surface of the annealed MnFeCu alloy is removed to obtain the biodegradable Mn-based alloy for biomedical use. The biodegradable Mn-based alloy of this invention exhibits excellent mechanical and degradation properties and good biocompatibility, making it suitable for the manufacture of medical implants such as bone nails, bone plates, vascular stents, and intestinal stents.

Description

Technical Field

[0001] This invention relates to the field of materials technology for surgical supplies, and in particular to a biodegradable Mn-based alloy for biomedical use, its preparation method, and its application. Background Technology

[0002] Common non-degradable biomedical metals such as 316L stainless steel, cobalt-chromium alloys, and titanium alloys often cause numerous adverse events after implantation due to their non-degradable nature. For example, after implantation of 316L stainless steel stents into a patient's blood vessels, complications such as in-stent restenosis, in-stent thrombosis, and late-stage lumen loss during angiography are common. Degradable biomedical metals, on the other hand, are biodegradable. After implantation, they provide temporary mechanical support and gradually degrade as they assist in the recovery of damaged tissues, avoiding long-term retention of the implant and the resulting adverse effects.

[0003] Common biodegradable biomedical metals include Mg alloys, Zn alloys, and Fe alloys. Mg is an essential trace element for the human body; Mg ions can inhibit abnormal nerve excitation and reduce the incidence of atherosclerosis. However, Mg alloys have poor plasticity, high brittleness, and degrade unevenly and rapidly. Implants made from Mg are prone to premature cracking and collapse in the body, thus losing their supporting function prematurely. Zn is also an essential trace element for the human body, playing an important role in cell proliferation and bone repair. Zn alloy vascular stents can maintain mechanical integrity for 6 months after implantation and completely degrade within 12 months. Before and after complete stent degradation, there is no significant thrombosis, intimal hyperplasia, or tissue inflammation in the blood vessels. However, Zn alloys have low tensile strength, and implants made from them often cannot provide sufficient mechanical support; furthermore, high concentrations of Zn ions can inhibit the proliferation and migration of vascular smooth muscle cells. Fe is an essential element for the human body with excellent biocompatibility. In the body, it does not cause excessive release of H ions or a significant increase in pH, and it has minimal impact on the local microenvironment. Fe-based alloys have appropriate elastic modulus, radial support strength, and ductility, good formability, and are easy to forge into various special shapes.

[0004] For example, Chinese patent CN108677099A provides a medical biodegradable Fe-Mn-Ag alloy material and its preparation and application. The chemical composition of the various components, by weight percentage, is: Mn: 30%, Ag: 2-10%, and the remainder is iron. This invention utilizes the biodegradability of Fe30Mn alloy through corrosion in the human body environment. A positively charged antibacterial element, Ag, is added to the alloy, and a novel biodegradable iron-based alloy is prepared using vacuum arc melting and rapid solidification in a copper mold. This significantly improves the degradation rate of the alloy, which is beneficial for shortening the degradation time after implantation, reducing the irritation of the implant to the body, and allowing for subsequent degradation through Ag degradation. +The release of the material gives the implant certain antibacterial properties, improving the therapeutic effect of the medical device. This invention proposes a material with good mechanical properties and biocompatibility, and with superior nuclear magnetic resonance compatibility.

[0005] Chinese patent CN109811265A discloses an Fe-Mn-Cu-C alloy and its medical applications. The alloy composition and weight percentages are: Mn 10-35 wt.%, Cu 0.2-5.0 wt.%, C 0.2-1.5 wt.%, with the balance being Fe. This invention utilizes the biodegradable and corrosive properties of Fe in the human body environment. By adding appropriate amounts of Mn, Cu, and C elements to Fe, a Fe-Mn-Cu-C alloy is prepared through melting, casting, and forging. Through the synergistic effect of the alloying elements, the mechanical properties and corrosion rate in the biological environment are improved, and the material possesses various beneficial biological functions. The Fe-Mn-Cu-C alloy, possessing mechanical properties, degradation resistance, and bioactivity, is suitable for implantable device materials in the medical field.

[0006] Mn exhibits a moderate degradation rate, low magnetic susceptibility, and lower electrode potential than Fe. FeMn-based alloys, made by adding an appropriate amount of Mn to Fe-based alloys, show rapid degradation, low magnetic susceptibility, and good magnetic resonance imaging (MRI) performance. However, compared to other matrix metal alloys, Fe-based alloys still have relatively weaker MRI capabilities and slower degradation rates. Corrosion products are also more robust and often encapsulated by newly formed intima, easily leading to chronic inflammation and inhibiting tissue regeneration. Furthermore, while carbon in existing Fe-based alloys can optimize hardness, strength, and wear resistance, high carbon content can reduce ductility and toughness; simultaneously, excessively high carbon content can cause the alloy to become brittle and even crack.

[0007] Compared to Fe-based alloys, the Mn-based alloys of this invention have been less studied in the field. Mn-based alloys exhibit excellent mechanical properties and their microstructure is an austenitic phase with extremely low magnetic susceptibility at room temperature. Mn is an essential trace element for the human body, playing a crucial role in promoting bone growth and development, maintaining normal fat metabolism, and brain function; furthermore, it has been reported that appropriate amounts of Mn are non-toxic to the cardiovascular system. Cu is also an essential trace element for the human body, participating in the metabolism of glucose, amino acids, and cholesterol, as well as various catalytic reactions, playing an important role in human growth and development; copper-containing biomaterials demonstrate good performance in protecting the cardiovascular system, exerting antibacterial effects, and promoting fracture healing. Summary of the Invention

[0008] In view of the above-mentioned deficiencies of the prior art, in a first aspect of the present invention, a method for preparing biodegradable Mn-based alloys for biomedical applications that is simple in process and suitable for large-scale production is provided, comprising the following steps:

[0009] (1) The alloy raw materials Mn, Fe and Cu are vacuum induction melted to obtain MnFeCu alloy ingots;

[0010] (2) The MnFeCu alloy ingot is homogenized to obtain a homogenized MnFeCu alloy;

[0011] (3) The homogenized MnFeCu alloy is rolled and annealed to obtain an annealed MnFeCu alloy;

[0012] (4) Remove the oxide layer on the surface of the annealed MnFeCu alloy to obtain a biodegradable Mn-based alloy for biomedical use.

[0013] Preferably, in step (1), the composition ratio of the alloy raw material by mass percentage is as follows: 50% to 70% Mn, 27% to 49% Fe, and 1% to 3% Cu.

[0014] Preferably, in step (1), during the vacuum induction melting process, the environment of the alloy raw material is first evacuated to a pressure ≤ 1×10⁻⁶. -4 Pa, then an inert gas is introduced to ensure that the ingot is not oxidized during smelting and to inhibit the boiling of the molten metal.

[0015] Inert gases are gases that do not react with any component in the alloy raw materials.

[0016] Preferably, in step (1), during the vacuum induction melting, the minimum duration for which the alloy raw material is continuously heated after melting to keep it in a liquid state is 5 minutes, so that the ingot composition is uniform.

[0017] Preferably, in step (2), the homogenization treatment temperature is 900-1100℃ and the treatment time is 1-6h.

[0018] Preferably, in step (3), the rolling process includes hot rolling or cold rolling.

[0019] More preferably, the hot rolling temperature is 900–1100°C, and the rolling deformation in the vertical direction is 55%–75%.

[0020] More preferably, the cold rolling temperature is room temperature, and the rolling deformation in the vertical direction is 55% to 75%.

[0021] Preferably, in step (3), the annealing temperature is 800-1000℃ and the treatment time is 0.5-1.5h.

[0022] In a second aspect of the present invention, a biodegradable Mn-based alloy for biomedicine with excellent mechanical properties, low magnetic susceptibility, and good magnetic resonance imaging performance is provided, which is prepared by the method of the first aspect of the present invention.

[0023] In a third aspect of the invention, the application of the biodegradable Mn-based alloy of the second aspect of the invention is provided, specifically its application as a biodegradable medical implant material in the preparation of implantable devices.

[0024] Preferably, the implantable device includes a bone screw, a bone plate, a vascular stent, or an intestinal stent.

[0025] Based on the above technical solutions, the inventive concept of this invention lies in using vacuum induction melting technology to introduce an appropriate amount of Fe and a small amount of Cu into Mn to prepare a biomedical biodegradable Mn-based alloy. Mn and Fe primarily serve to ensure the alloy possesses excellent mechanical properties, degradation performance, processability, and biocompatibility; Cu primarily serves to ensure the alloy has strong antibacterial properties and provides solid solution strengthening.

[0026] On the one hand, regarding the elemental composition of the Mn-based alloy, it contains fewer elements, only three essential elements for the human body: Mn, Fe, and Cu. The Mn content is dominant (50-70 wt.%), the Fe content is moderate (27-49 wt.%), and the Cu content is low (1-3 wt.%). The alloy has the superior mechanical properties, low magnetic susceptibility, work hardening ability, magnetic resonance imaging performance, and cell compatibility of Mn-based alloys compared to Fe-based alloys, and also has a shape memory effect. At the same time, it also has the advantages of Fe in terms of biocompatibility and formability, and Cu in terms of protecting the cardiovascular system, antibacterial properties, and promoting fracture healing.

[0027] On the other hand, in the preparation of this invention, the MnFeCu alloy ingot is homogenized to dissolve and disperse oxide particles in the microstructure, and to homogenize the microstructure composition. Then, it is rolled, and the shape is changed from a coarse rod to a thin plate or thin rod by hot rolling or cold rolling. Then, it is annealed to eliminate the residual stress generated by hot rolling or cold rolling and to promote the recrystallization of deformed grains to become equiaxed grains. Finally, the oxide layer and defects on the surface of the annealed MnFeCu alloy in the thin plate or thin rod shape are machined or ground by lathe or grinding machine to complete the preparation. The entire process, through controlled casting, rolling, and heat treatment, ensures a more uniform alloy composition and microstructure. The microstructure consists of fine equiaxed crystals, and the phase is a single austenitic phase with extremely low magnetic susceptibility at room temperature. It exhibits excellent mechanical and degradation properties, good biocompatibility, and good magnetic resonance imaging performance. Its comprehensive performance meets the service requirements of most biodegradable medical implants such as bone screws, bone plates, vascular stents, and intestinal stents. Furthermore, the equipment involved in the process includes vacuum induction melting furnaces, box-type resistance furnaces, small rolling mills, lathes, and grinding machines, making the materials readily available and widely applicable.

[0028] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0029] This invention provides a method for preparing biodegradable Mn-based alloys for biomedical use. The process is simple, the equipment used in the process is readily available, and it is suitable for large-scale production and widespread application.

[0030] This invention provides a biodegradable Mn-based alloy for biomedical use. The alloy contains fewer elements, has a uniform composition and microstructure, and consists of a single austenitic phase with extremely low magnetic susceptibility at room temperature. It exhibits excellent mechanical properties, low magnetic susceptibility, good magnetic resonance imaging performance, excellent biocompatibility and formability, and moderate and uniform degradation rate.

[0031] This invention provides the application of biodegradable Mn-based alloys in biomedicine. When made into medical implants, they can provide sufficient support during the treatment period. After treatment, they can gradually and uniformly degrade and be completely absorbed by the human body within a controllable time, avoiding the physical and economic burden on patients caused by long-term rejection reactions and secondary surgeries. Attached Figure Description

[0032] Figure 1 In the image, (a), (b), and (c) are scanning electron microscope (SEM) images of the as-cast alloys labeled Mn50, Mn60, and Mn70 prepared in Test Examples 1 to 3, respectively, at a magnification of 200.

[0033] Figure 2 In the image, (a), (b), and (c) are scanning electron microscope (SEM) images of the biomedical biodegradable Mn-based alloys prepared in Test Examples 1 to 3 at a magnification of 500, respectively.

[0034] Figure 3 The tensile engineering strain-stress curves of the biomedical biodegradable Mn-based alloys in Examples 1-3 are shown.

[0035] Figure 4 Electrochemical polarization curves of biodegradable Mn-based alloys for biomedical applications in Examples 4-6;

[0036] Figure 5 The results of the cytotoxicity test of the biodegradable Mn-based alloy in Example 2 are shown.

[0037] Figure 6 The results of animal experiments on the biodegradable Mn-based alloy for biomedical use in Example 2 are shown (HE staining images of various organs and tissues). Detailed Implementation

[0038] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0039] In the following embodiments:

[0040] Mn powder, Fe powder, and Cu powder were purchased from the market, and their purity was 99.99%.

[0041] Example 1

[0042] Preparation method of biodegradable Mn-based alloys for biomedical use:

[0043] (1) Mix Mn powder, Fe powder and Cu powder with mass fractions of 50%, 47% and 3% respectively to obtain a mixed powder; load the mixed powder into the crucible of a vacuum induction melting furnace and then evacuate the furnace to 1×10⁻⁶. -4 After vacuuming, argon gas is introduced into the melting furnace to ensure that the ingot is not oxidized during melting and to inhibit the boiling of the molten metal. After the argon gas and water cooling protection are fully activated, the mixed powder is melted by induction heating. After the mixed powder melts, it is continuously heated to keep it in a liquid state for more than 5 minutes to make the composition of the ingot uniform. After the casting is completed, the ingot is removed after it has completely cooled in the mold, and the MnFeCu alloy ingot is obtained. According to the mass fraction of each element in the cast alloy, the cast alloy is designated as Mn50 casting.

[0044] (2) In order to dissolve and disperse the oxide particles precipitated in the structure and homogenize the structure composition, the obtained MnFeCu alloy ingot was homogenized at a temperature of 1000℃ for 1h to obtain a homogenized MnFeCu alloy.

[0045] (3) After the homogenization treatment is completed, the homogenized ingot is hot rolled at a temperature of 1000℃ and the rolling deformation in the vertical direction is controlled at 65%. After the hot rolling treatment is completed, the alloy is annealed to eliminate the residual stress generated by the hot rolling treatment and promote the recrystallization behavior of the deformed grains to become equiaxed grains. The annealing temperature is 1000℃ and the annealing time is 1h to obtain the annealed MnFeCu alloy.

[0046] (4) After annealing, the oxide layer and defects on the surface of the annealed alloy can be completely removed by turning or polishing. The biomedical biodegradable Mn-based alloy is recorded as Mn50 hot rolling + annealing according to the mass fraction of each element in the alloy and the processing flow used in its preparation.

[0047] Example 2

[0048] Preparation method of biodegradable Mn-based alloys for biomedical use:

[0049] (1) Mix Mn powder, Fe powder and Cu powder with mass fractions of 60%, 37% and 3% respectively to obtain a mixed powder; load the mixed powder into the crucible of a vacuum induction melting furnace and then evacuate the furnace to 1×10⁻⁶. -4 After vacuuming, argon gas is introduced into the melting furnace to ensure that the ingot is not oxidized during melting and to inhibit the boiling of the molten metal. After the argon gas and water cooling protection are fully activated, the mixed powder is melted by induction heating. After the mixed powder melts, it is continuously heated to keep it in a liquid state for more than 5 minutes to make the composition of the ingot uniform. After the casting is completed, the ingot is removed after it has completely cooled in the mold to obtain the MnFeCu alloy ingot. According to the mass fraction of each element in the cast alloy, the cast alloy is designated as Mn60 casting.

[0050] (2) In order to dissolve and disperse the oxide particles precipitated in the structure and homogenize the structure composition, the obtained MnFeCu alloy ingot was homogenized at a temperature of 1000℃ for 1h to obtain a homogenized MnFeCu alloy.

[0051] (3) After the homogenization treatment is completed, the homogenized ingot is hot rolled at a temperature of 1000℃ and the rolling deformation in the vertical direction is controlled at 65%. After the hot rolling treatment is completed, the alloy is annealed to eliminate the residual stress generated by the hot rolling treatment and promote the recrystallization behavior of the deformed grains to become equiaxed grains. The annealing temperature is 1000℃ and the annealing time is 1h to obtain the annealed MnFeCu alloy.

[0052] (4) After annealing, the oxide layer and defects on the surface of the annealed alloy can be completely removed by turning or polishing. The biodegradable Mn-based alloy for biomedicine can be obtained. According to the mass fraction of each element in the alloy and the processing flow used in its preparation, the alloy is recorded as Mn60 hot rolling + annealing.

[0053] Example 3

[0054] Preparation method of biodegradable Mn-based alloys for biomedical use:

[0055] (1) Mix Mn powder, Fe powder and Cu powder with mass fractions of 70%, 27% and 3% respectively to obtain a mixed powder; load the mixed powder into the crucible of a vacuum induction melting furnace and then evacuate the furnace to 1×10⁻⁶. -4After vacuuming, argon gas is introduced into the melting furnace to ensure that the ingot is not oxidized during melting and to inhibit the boiling of the molten metal. After the argon gas and water cooling protection are fully activated, the mixed powder is melted by induction heating. After the mixed powder melts, it is continuously heated to keep it in a liquid state for more than 5 minutes to make the composition of the ingot uniform. After the casting is completed, the ingot is removed after it has completely cooled in the mold, and the MnFeCu alloy ingot is obtained. According to the mass fraction of each element in the as-cast alloy, the as-cast alloy is recorded as Mn70 as-cast alloy.

[0056] (2) In order to dissolve and disperse the oxide particles precipitated in the structure and homogenize the structure composition, the obtained MnFeCu alloy ingot was homogenized at a temperature of 1000℃ for 1h to obtain a homogenized MnFeCu alloy.

[0057] (3) After the homogenization treatment is completed, the homogenized ingot is hot rolled at a temperature of 1000℃ and the rolling deformation in the vertical direction is controlled at 65%. After the hot rolling treatment is completed, the alloy is annealed to eliminate the residual stress generated by the hot rolling treatment and promote the recrystallization behavior of the deformed grains to become equiaxed grains. The annealing temperature is 1000℃ and the annealing time is 1h to obtain the annealed MnFeCu alloy.

[0058] (4) After annealing, the oxide layer and defects on the surface of the annealed alloy can be completely removed by turning or polishing. The biodegradable Mn-based alloy can be obtained by machining or polishing. According to the mass fraction of each element in the alloy and the processing flow used in its preparation, the alloy is recorded as Mn70 hot rolling + annealing.

[0059] Example 4

[0060] Preparation method of biodegradable Mn-based alloys for biomedical use:

[0061] (1) Mix Mn powder, Fe powder and Cu powder with mass fractions of 50%, 47% and 3% respectively to obtain a mixed powder; load the mixed powder into the crucible of a vacuum induction melting furnace and then evacuate the furnace to 1×10⁻⁶. -4 After vacuuming, argon gas is introduced into the melting furnace to ensure that the ingot is not oxidized during melting and to inhibit the boiling of the molten metal. After the argon gas and water cooling protection are fully activated, the mixed powder is melted by induction heating. After the mixed powder melts, it is continuously heated to keep it in a liquid state for more than 5 minutes to make the composition of the ingot uniform. After the casting is completed, the ingot is removed after it has completely cooled in the mold, and the MnFeCu alloy ingot is obtained. According to the mass fraction of each element in the cast alloy, the cast alloy is designated as Mn50 casting.

[0062] (2) In order to dissolve and disperse the oxide particles precipitated in the structure and homogenize the structure composition, the obtained MnFeCu alloy ingot was homogenized at a temperature of 1100℃ for 6 hours to obtain a homogenized MnFeCu alloy.

[0063] (3) After homogenization, the homogenized ingot is cold rolled at room temperature and the rolling deformation in the vertical direction is controlled at 65%. After cold rolling, the alloy is annealed to eliminate the residual stress generated by hot rolling and promote the recrystallization of deformed grains to become equiaxed grains. The annealing temperature is 1000℃ and the annealing time is 1h to obtain annealed MnFeCu alloy.

[0064] (4) After annealing, the oxide layer and defects on the surface of the annealed alloy can be completely removed by turning or polishing. The biodegradable Mn-based alloy for biomedicine can be obtained. According to the mass fraction of each element in the alloy and the processing flow used in its preparation, the alloy is recorded as Mn50 cold rolling + annealing.

[0065] Example 5

[0066] Preparation method of biodegradable Mn-based alloys for biomedical use:

[0067] (1) Mix Mn powder, Fe powder and Cu powder with mass fractions of 60%, 37% and 3% respectively to obtain a mixed powder; load the mixed powder into the crucible of a vacuum induction melting furnace and then evacuate the furnace to 1×10⁻⁶. -4 After vacuuming, argon gas is introduced into the melting furnace to ensure that the ingot is not oxidized during melting and to inhibit the boiling of the molten metal. After the argon gas and water cooling protection are fully activated, the mixed powder is melted by induction heating. After the mixed powder melts, it is continuously heated to keep it in a liquid state for more than 5 minutes to make the composition of the ingot uniform. After the casting is completed, the ingot is removed after it has completely cooled in the mold to obtain the MnFeCu alloy ingot. According to the mass fraction of each element in the cast alloy, the cast alloy is designated as Mn60 casting.

[0068] (2) In order to dissolve and disperse the oxide particles precipitated in the structure and homogenize the structure composition, the obtained MnFeCu alloy ingot was homogenized at a temperature of 1100℃ for 6 hours to obtain a homogenized MnFeCu alloy.

[0069] (3) After homogenization, the homogenized ingot is cold rolled at room temperature and the rolling deformation in the vertical direction is controlled at 65%. After cold rolling, the alloy is annealed to eliminate the residual stress generated by hot rolling and promote the recrystallization of deformed grains to become equiaxed grains. The annealing temperature is 1000℃ and the annealing time is 1h to obtain annealed MnFeCu alloy.

[0070] (4) After annealing, the oxide layer and defects on the surface of the annealed alloy can be completely removed by turning or polishing. The biodegradable Mn-based alloy for biomedicine can be obtained. According to the mass fraction of each element in the alloy and the processing flow used in its preparation, the alloy is recorded as Mn60 cold rolling + annealing.

[0071] Example 6

[0072] Preparation method of biodegradable Mn-based alloys for biomedical use:

[0073] (1) Mix Mn powder, Fe powder and Cu powder with mass fractions of 70%, 27% and 3% respectively to obtain a mixed powder; load the mixed powder into the crucible of a vacuum induction melting furnace and then evacuate the furnace to 1×10⁻⁶. -4 After vacuuming, argon gas is introduced into the melting furnace to ensure that the ingot is not oxidized during melting and to inhibit the boiling of the molten metal. After the argon gas and water cooling protection are fully activated, the mixed powder is melted by induction heating. After the mixed powder melts, it is continuously heated to keep it in a liquid state for more than 5 minutes to make the composition of the ingot uniform. After the casting is completed, the ingot is removed after it has completely cooled in the mold to obtain the MnFeCu alloy ingot. According to the mass fraction of each element in the cast alloy, the cast alloy is designated as Mn70 casting.

[0074] (2) In order to dissolve and disperse the oxide particles precipitated in the structure and homogenize the structure composition, the obtained MnFeCu alloy ingot was homogenized at a temperature of 1100℃ for 6 hours to obtain a homogenized MnFeCu alloy.

[0075] (3) After homogenization, the homogenized ingot is cold rolled at room temperature and the rolling deformation in the vertical direction is controlled at 65%. After cold rolling, the alloy is annealed to eliminate the residual stress generated by hot rolling and promote the recrystallization of deformed grains to become equiaxed grains. The annealing temperature is 1000℃ and the annealing time is 1h to obtain annealed MnFeCu alloy.

[0076] (4) After annealing, the oxide layer and defects on the surface of the annealed alloy can be completely removed by turning or polishing. The biodegradable Mn-based alloy for biomedicine can be obtained. According to the mass fraction of each element in the alloy and the processing flow used in its preparation, the alloy is recorded as Mn70 cold rolling + annealing.

[0077] Test Example 1

[0078] The as-cast alloys, labeled Mn50, Mn60, and Mn70 as in Examples 1-3 of this invention, were polished and then subjected to microstructural observation using a scanning electron microscope (SEM). The SEM images are shown below. Figure 1 As shown. By Figure 1 It is known that the microstructure of the Mn50, Mn60, and Mn70 as-cast alloys consists of coarse columnar crystals with numerous large black precipitates within the grains and at the grain boundaries. The coarse columnar crystal structure and the large black precipitates deteriorate the alloy's mechanical properties. Furthermore, the large black precipitates act as a second phase, forming galvanic corrosion with the coarse columnar crystals (austenite phase), accelerating the alloy's corrosion degradation and causing uneven degradation.

[0079] Test Example 2

[0080] The alloys labeled Mn50 hot-rolled + annealed, Mn60 hot-rolled + annealed, and Mn70 hot-rolled + annealed as described in Examples 1-3 of this invention were polished and then subjected to microstructural observation using a scanning electron microscope (SEM). The SEM images are shown below. Figure 2 As shown. By Figure 2 It is known that the microstructure of the Mn50, Mn60, and Mn70 hot-rolled and annealed alloys consists of equiaxed grains with a grain size of 15–50 μm, with a small number of small black precipitates present within the grains and at the grain boundaries. The fine equiaxed grain structure exhibits excellent deformation coordination, and the black precipitates are few in number and small in size, resulting in better mechanical properties in the hot-rolled and annealed alloys compared to the cast alloys. Furthermore, the fewer small-volume black precipitates and the fine equiaxed grains form fewer galvanic corrosion pairs, resulting in a weaker ability to accelerate the non-corrosive degradation of the alloy. Therefore, the degradation of the hot-rolled and annealed alloys is more uniform than that of the cast alloys.

[0081] Test Example 3

[0082] Standard tensile tests were performed on the alloys labeled Mn50 hot-rolled + annealed, Mn60 hot-rolled + annealed, and Mn70 hot-rolled + annealed as described in Examples 1-3 of this invention, and the results were as follows: Figure 3 The strain-stress curve for tensile engineering is shown. (From...) Figure 3It can be seen that the tensile yield strengths of the Mn50 hot-rolled + annealed alloy, the Mn60 hot-rolled + annealed alloy, and the Mn70 hot-rolled + annealed alloy are 558 MPa, 522 MPa, and 470 MPa, respectively; the tensile strengths are 315 MPa, 211 MPa, and 175 MPa, respectively; and the elongations are 47%, 50%, and 57%, respectively. The Mn50 hot-rolled + annealed alloy prepared in Example 1 has the best comprehensive tensile mechanical properties.

[0083] Test Example 4

[0084] Electrochemical tests were performed on the alloys prepared in Examples 4-6 of this invention, which were labeled as Mn50 cold-rolled + annealed, Mn60 cold-rolled + annealed, and Mn70 cold-rolled + annealed, and the results were as follows: Figure 4 The polarization curves shown are from... Figure 4 It can be seen that the corrosion currents of Mn50 cold-rolled + annealed alloy, Mn60 cold-rolled + annealed alloy, and Mn70 cold-rolled + annealed alloy are 5.05 μA / cm. 2 2.29μA / cm 2 and 4.09 μA / cm 2 The theoretical corrosion rates were 0.061 mm / year, 0.027 mm / year, and 0.049 mm / year, respectively. Electrochemical tests were conducted according to ASTM G59-97 standard, and the theoretical corrosion rate (CR, mm / year) was calculated using the following formula:

[0085]

[0086] In the formula, i corr Corrosion current density, in μA / cm² 2 ρ is the alloy density, in g / cm³. 3 EW is the alloy equivalent weight.

[0087] Test Example 5

[0088] The Mn60 hot-rolled and annealed alloy prepared in Example 2 of this invention was subjected to cytotoxicity testing. The testing was conducted in accordance with ISO 10993-4:2002 and ISO 10993-5 standards. The test results are as follows: Figure 5 As shown in Table 1; the absorbance of the extract, cells, and culture medium in the experimental group is shown in Table 2; the absorbance of the extract, blank control, cells, and culture medium in the blank control group is shown in Table 3; the cell viability in the experimental group is shown in Table 4; and the cell viability in the blank control group is shown in Table 4.

[0089] The culture medium used in this test was high-glucose DMEM complete medium containing 10% fetal bovine serum and 1% penicillin-dextrose antibodies; the incubator temperature was constant at 37℃, and the atmosphere was 5% CO2; cell viability was determined by measuring cell absorbance using an ELISA reader, and the formula for calculating cell viability is as follows:

[0090] Cell viability = [(OD(experimental) - OD(control)) / (OD(control) - OD(blank))] × 100%

[0091] In the formula, OD(test) is the absorbance of cells + extract, OD(control) is the absorbance of cells + culture medium, and OD(blank) is the absorbance of culture medium.

[0092] Table 1: Absorbance of extract, cells, and culture medium

[0093]

[0094] Table 2: Absorbance of extract blank control, cells and culture medium

[0095]

[0096] Table 3: Cell viability in experimental groups

[0097]

[0098]

[0099] Table 4: Cell viability in the blank control group

[0100]

[0101] Depend on Figure 5 As shown in Tables 1, 2, 3, and 4, the effect of the leaching solution on cells is concentration-dependent; that is, high-concentration leaching solutions inhibit cell growth, while low-concentration leaching solutions promote cell growth. The 100% concentration leaching solution in the figure shows the strongest inhibitory effect on cell growth, but cell activity at this concentration is still higher than the 75% cell activity standard line, indicating that the leaching solution has no cytotoxic effect on cells. As the concentration of the leaching solution decreases, its inhibitory effect gradually decreases; the 3.125% concentration leaching solution shows the strongest promoting effect on cell growth. In summary, the hot-rolled + annealed Mn60 alloy is non-cytotoxic.

[0102] Test Example 6

[0103] Animal experiments were conducted on the Mn60 hot-rolled and annealed alloy prepared in Example 2 of this invention, and the test results are as follows: Figure 6 As shown. By Figure 6The histopathological morphology shown indicates that after subcutaneous implantation of the alloy disc in mice for 1 to 6 weeks, there was no tissue inflammation, inflammatory cell infiltration, or atypical cells in the heart, liver, spleen, and other organs of the mice. There was no significant difference between the organs and tissues of the mice in the Shame group and those of the mice in the Shame group. This proves that subcutaneous implantation of the alloy disc has no effect on the tissues of the mice and that the alloy has high biocompatibility in vivo.

[0104] The mice used in the test were normal eight-week-old male C57 mice. The alloy implant was a circular piece with a diameter of 1 cm and a thickness of 1 mm. Before implantation, it was thoroughly cleaned and disinfected sequentially with 5 wt.% tartaric acid solution, 1 mol / L NaOH solution, ultrapure water, and anhydrous ethanol. The alloy implant was implanted subcutaneously in the back of the neck of the mice. In the Shame group, the incision was sutured without placing the alloy sample, and the mice were euthanized by cervical dislocation after suturing. Mice in other groups were fed a normal diet for 1, 2, 4, 5, and 6 weeks before being euthanized by cervical dislocation. After euthanasia, the mice's hearts were perfused with physiological saline. After perfusion, tissue samples were collected and fixed from organs such as the heart, liver, and spleen. Finally, the fixed tissues were stained with hematoxylin and eosin (HE) to observe their histopathological characteristics.

[0105] The test results above show that the biodegradable Mn-based alloy prepared in this invention exhibits no obvious pores in its microstructure. The grains are mainly equiaxed crystals with a diameter of 15–50 μm, with only a small amount of precipitates present within the grains and at the grain boundaries. The phase is a single austenitic phase with extremely low magnetic susceptibility at room temperature, resulting in good magnetic resonance imaging performance. The alloy possesses excellent mechanical and degradation properties, with a tensile yield strength of 175–315 MPa, a tensile strength of 470–558 MPa, an elongation of 47–57%, and a degradation rate of 0.03–0.06 mm / year, exhibiting uniform degradation. Its comprehensive performance meets the service requirements of most biodegradable implantable devices. The alloy also demonstrates good biocompatibility in vivo, with cell experiments and animal experiments confirming its lack of biotoxicity. Therefore, the biodegradable Mn-based alloy prepared in this invention has broad application prospects as a metallic medical implant material and in the manufacture of biodegradable implantable devices.

[0106] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. A method for preparing a biodegradable Mn-based alloy for biomedical use, characterized in that, Includes the following steps: (1) The alloy raw materials Mn, Fe and Cu are vacuum induction melted to obtain MnFeCu alloy ingots; The alloy raw materials are composed of the following components by mass percentage: 50%~70% Mn, 27%~49% Fe, and 1%~3% Cu; In the aforementioned vacuum induction melting process, the environment surrounding the alloy raw materials is first evacuated to a pressure ≤1×10⁻⁶. -4 Pa, then an inert gas is introduced; the minimum duration for which the alloy raw material is heated to keep it in a liquid state after melting is 5 minutes; (2) The MnFeCu alloy ingot is homogenized to obtain a homogenized MnFeCu alloy; The homogenization treatment is performed at a temperature of 900~1100℃ for 1~6 hours. (3) The homogenized MnFeCu alloy is rolled and annealed to obtain an annealed MnFeCu alloy; The rolling process includes hot rolling or cold rolling; the hot rolling temperature is 900~1100℃, and the rolling deformation in the vertical direction is 55%~75%; the cold rolling temperature is room temperature, and the rolling deformation in the vertical direction is 55%~75%. The annealing treatment is performed at a temperature of 800~1000℃ for a time of 0.5~1.5h. (4) Remove the oxide layer on the surface of the annealed MnFeCu alloy to obtain a biodegradable Mn-based alloy for biomedical use.

2. A biodegradable Mn-based alloy for biomedical use, characterized in that: It is prepared by the method described in claim 1.

3. An application of the biodegradable Mn-based alloy for biomedical use as described in claim 2, characterized in that: Its application as a biodegradable medical implant material in the preparation of implantable devices.

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