Preparation method of intravascular bioabsorbable pure magnesium stent

Abstract

The invention discloses a preparation method of an intravascular bio-absorbable pure magnesium stent. The preparation method comprises the following processing steps on a pure magnesium material: step 1, carrying out equal channel angular pressure (ECAP) treatment; 2, high-pressure torsion extrusion (HPTE) treatment is carried out; 3, drawing the thin-walled tube; 4, designing a bracket; 5, laser engraving is conducted; sixthly, polishing, cleaning and surface treatment are conducted; and 7, plasma chemical vapor phase TiO2 surface deposition is carried out. The pure magnesium stent prepared by the preparation method of the technical scheme has excellent physical and mechanical properties and good biocompatibility and corrosion resistance, completely meets the performance index requirements of clinical absorbable stent implantation, has good compliance and control performance, is easy to pass through stenosis and distortion lesions, and has good application prospects. The absorbable pure magnesium stent can be used for stent implantation of cardiovascular vessels, cerebrovascular vessels, peripheral blood vessels, hollow organs and the like, will become absorbable pure magnesium stents which clinicians like to use, and will also bring good news to vast patients.

Description

Technical Field

[0001] The invention relates to the technical field of absorbable stents, in particular to a method for preparing an intravascular bioabsorbable pure magnesium stent. Background Art

[0002] The performance of biodegradable pure magnesium and its alloy implants is related to their tissue compatibility, corrosion type and corrosion rate, physical properties and reliability of use. Remodeling deformation (SPD) technologies such as high pressure torsion (HPT) and equal channel angular pressing (ECAP), especially the twisted channel angular pressing (TCAP) method based on equal channel angular pressing (ECAP), can improve the performance of pure magnesium and its alloy-based implants by affecting the grain refinement and homogenization of the pure magnesium structure. At present, there are no pure magnesium material intravascular absorbable stents in the world because the physical properties of pure magnesium material are insufficient. However, after repeated research, we have developed an intravascular bioabsorbable stent made of pure magnesium metal. The relevant research and development background technology is briefly described below.

[0003] Grain refinement introduced by SPD processing may also soften magnesium. Pure magnesium exhibits the opposite Hall-Petch behavior at room temperature, so grain refinement below a certain level reduces its strength, and the reduction in strength of ultrafine-grained pure magnesium is associated with a significant increase in ductility. We found that this SPD technique produced an average grain size of only 0.32μm but an elongation of up to 360% by HPT-processing pure magnesium tensile samples and testing them at room temperature. This exceptional elongation is attributed to the occurrence of fine-grained grain boundary sliding in pure magnesium. We found that for grain sizes greater than 4μm, deformation is twin-controlled and the data follow the Hall-Petch relationship. However, for grain sizes less than 4μm, there is a break in the flow stress relationship (σ, with grain size d), and the data follow the relationship predicted by the grain boundary sliding mechanism, called slip control. Since HPT processing is usually performed at room temperature, grain growth can be prevented and the final grain size is smaller than that in ECAP. For example, in pure magnesium processed by ECAP at high temperature, the final grain size is greater than 10 μm, while in pure magnesium processed by HPT at room temperature, the grain size is less than 1 μm.

[0004] In the twin-controlled regime (coarse grains), the ductility decreases with increasing grain size, while the opposite trend is observed in the slip-controlled regime (fine and ultrafine grains), where the ductility decreases with decreasing grain size. A ductility peak is observed within a range of grain sizes.

[0005] Pure magnesium is an exception to this trend, as these materials exhibit higher ductility with reduced grain size in the slip-controlled regime. Data from samples processed by HPT show an improvement in overall properties. Higher strength and lower corrosion rates can be achieved. This improvement in properties of pure magnesium and its alloys processed by HPT is attributed to the significant grain refinement and structural homogenization that HPT promotes.

[0006] Processing by HPT is more effective in grain refinement and structural homogenization than other processing techniques. We found that the mechanical properties of magnesium and its alloys were significantly improved by grain refinement. High strength and excellent ductility were observed in fine-grained and ultrafine-grained magnesium processed by SPD. Corrosion resistance improved after SPD treatment with the reduction of grain size in magnesium and its alloys. Biocompatibility testing and in vivo studies showed that SPD processing had no adverse effects on the biological response of magnesium. High-pressure torsion can also be used to produce magnesium-based composites with higher strength and incorporation of bioactive particles. In summary, SPD processing is used to obtain a homogeneous structure with ultrafine grains in magnesium.

[0007] Additionally, many studies of materials processed by ECAP have failed to produce grains with ultrafine (less than 1 μm) size. Therefore, most studies report that SPD worsens corrosion resistance. This proves that they used samples whose grain structure was not ultrafine. Our study shows that reducing the grain size can reduce the corrosion rate. This observation supports the theory that during the corrosion process, the interior of the grain acts as the cathode and the grain boundary acts as the anode, and a reduction in the ratio between the cathode and anode area fractions can reduce the corrosion rate. It is also obvious that samples produced by HPT show smaller grain sizes and lower corrosion rates. This is attributed to the lower temperatures at which HPT is usually carried out and the larger strain amounts applied. The former reduces the grain size, and the latter increases the structure.

[0008] The study showed that the data for samples processed via ECAP were not significantly different from the untreated material. The data range indicated a slight increase in strength, but also a slight increase in corrosion rate uniformity. One notable trend was that the data for samples processed via HPT showed an improvement in overall performance. The data range for these samples expanded to higher strength and lower corrosion rates. This improvement in performance of magnesium and its alloys processed via HPT is attributed to the ability of HPT to promote significant grain refinement and structural homogenization.

[0009] The present invention further processes pure magnesium using SPD, especially HPT, to obtain the required pure magnesium thin-walled tube, and produces a bioabsorbable pure magnesium stent by laser engraving. It has good physical properties, biocompatibility and corrosion resistance, and can be used in the fields of cardiovascular and cerebrovascular, hollow organs, and can also be used in industrial fields such as electronics and aerospace. Summary of the invention

[0010] The purpose of the present invention is to solve the above problems and to design a method for preparing an intravascular bioabsorbable pure magnesium stent.

[0011] To achieve the above-mentioned purpose, the technical solution of the present invention is a method for preparing an intravascular bioabsorbable pure magnesium stent, comprising the following processing steps of the pure magnesium material:

[0012] Step 1: Perform equal channel angular pressure (ECAP) treatment;

[0013] Step 2: High pressure torsional extrusion (HPTE) treatment;

[0014] Step 3: Drawing the thin-walled tube;

[0015] Step 4: Bracket design;

[0016] Step 5: Laser engraving;

[0017] Step 6: Polishing, cleaning and surface treatment;

[0018] Step 7: Plasma chemical vapor TiO2 surface deposition.

[0019] As a further description of the present technical solution, in the step one, the pure magnesium material is 99.9%-99.99999% pure and is made into a 10-50mmX100-500mm rod. The pure magnesium is first subjected to ECAP processing, treated at 250-300°C for 1-5 times, and treated at 200-250°C for 1-10 times. The mold used for ECAP treatment has two channels, which intersect at an angle of 102-120°, respectively, and are twisted with an outer curvature arc at an angle of 15-25°. The entire mold is uniformly heated by a heater along the vertical channel, and the temperature is monitored at the intersection of the channels. Before each new pass, the sample is always rotated 90° in the same direction along the longitudinal axis to perform all multiple pressings, and the sample is pressed into the ECAP mold at a speed of 10-30mm / min.

[0020] As a further description of the present technical solution, in the step 2, the pure magnesium material is subjected to high pressure torsional extrusion (HPTE) treatment, the magnesium material is annealed at 300-500°C for 30 minutes, and then cooled in a furnace; after annealing, the sample is extruded at 150-200°C with an extrusion ratio of 3:1.

[0021] As a further description of the technical solution, in the step 2, after extrusion, HPTE treatment is performed at 180-200° C. with a translation speed of 6-12 mm / min (v6) and a rotation speed of 0.6-1.2 rpm, and the number of treatment cycles is 1-10 cycles.

[0022] As a further description of the present technical solution, in the step three, the pure magnesium material is annealed at 280-300°C for 30 minutes, then cooled in a furnace, and then extruded and drawn at 200°C with an extrusion ratio of 3:1 to obtain a thin-walled tube with a diameter of 0.1-0.15mm and a length of 2 meters, and the tube wall thickness error is <5 microns.

[0023] As a further description of the present technical solution, in step four, the pure magnesium material is used to design a stent pattern, which attempts to increase the flexibility and compliance of the stent, so that the stent can easily pass through narrow and twisted calcified lesions, and is convenient for clinical use.

[0024] As a further description of the technical solution, in the step five, the pure magnesium thin-walled tube is laser engraved according to the above-mentioned design pattern.

[0025] As a further description of the present technical solution, in step six, the pure magnesium stent is polished, cleaned and surface treated, polished in the polishing liquid of an automated polishing machine for 10 minutes, rinsed, and then ultrasonically cleaned in acetone and ethanol for 10 minutes each, ultrasonically cleaned in deionized double distilled water for 10 minutes, and dried at 60°C in argon for later use.

[0026] As a further description of the present technical solution, in the step seven, radio frequency plasma enhanced chemical vapor titanium deposition is performed on the surface of the pure magnesium bracket, and a titanium coating is deposited on the surface of the pure magnesium alloy bracket using a radio frequency plasma enhanced chemical vapor deposition method. Under a negative self-bias voltage of 400V, a 10-17% titanium content working atmosphere is formed in a 20Pa mixed methane and titanium isopropoxide control chamber. Before deposition, the pure magnesium alloy bracket is ultrasonically cleaned in an acetone bath for 10 minutes, then cleaned in an anhydrous ethanol bath for 10 minutes, and then dried for 10 minutes after three-distilled deionized water cleaning; then immediately transferred to the chamber of the PECVD system, the deposition process includes loading, plasma cleaning, plasma deposition and unloading steps; the system is connected to an RFX-13.56 radio frequency generator with a frequency of 600MHz, and the deposition chamber is evacuated to a base pressure of 10-8Torr, and plasma cleaning is performed for 10 minutes using argon and oxygen with mass flow rates of 90SCCM and 50SCCM, respectively.

[0027] As a further description of the present technical solution, in step seven, in the cleaning step, the peak voltage is 400±10V, the RF power is 80±10W, and the DC bias is -140±10V; then 1.6-3SCCM titanium isopropoxide and 90SCCM methane are used to deposit the Ti coating; the deposition time is 40-60 minutes, the voltage is 300±10V, the RF power is 120±10W, and the DC bias is -400±10V; during the cleaning and deposition steps, the total pressure is maintained at 20Pa, which is monitored and measured by a Baratron pressure gauge.

[0028] Pure magnesium materials were plasma treated at different treatment powers and times, and an island-like nanostructured TiO2 layer and a pit-like nanostructured TiO2 layer were generated on the surface of the plasma-oxidized samples. We found that the plasma-deposited oxidized samples with rough oxide layers formed higher wettability and exhibited excellent blood compatibility. These findings indicate that TiO2 plasma modification is a practical method to promote the blood compatibility of biomedical pure magnesium surfaces.

[0029] The beneficial effect is that the pure magnesium stent prepared by the preparation method of the technical solution has excellent physical and mechanical properties, good biocompatibility and corrosion resistance, fully meets the performance index requirements of clinical absorbable stent implantation, has good compliance and controllability, is easy to pass through narrow and tortuous lesions, and can be used for stent implantation needs in cardiovascular, cerebrovascular, peripheral blood vessels and hollow organs. It will become an absorbable pure magnesium stent that clinicians like to use, and will also bring good news to patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 In the figure, A is the microstructure of pure Mg starting material; B is the microstructure of pure Mg sample after ECAP; C is the relationship between the number of ECAP circles and grain diameter; D is the relationship between the number of ECAP circles and microhardness.

[0031] Figure 2 This is the evolution of the pure magnesium grain structure during HPT processing; A: P = 5 GPa, 0.5 RPM at room temperature (RT); B: P = 5 GPa, RT, 1 RPM; C: P = 5 GPa, RT, 10 RPM. The high-angle boundary is represented by black lines, and the low-angle boundary is represented by red.

[0032] Figure 3 It is a graph showing the change of tensile properties of pureMg and ZK60 alloys with sample conditions, including pMg-ECAP, pMg-ECAP+EX; ZK-ECAP, ZK-ECAP+EX; YS: tensile yield strength; UTS: ultimate tensile strength; FE: elongation at break.

[0033] Figure 4 This is the appearance of a pure magnesium specimen that was processed by HPT and pulled to failure at room temperature;

[0034] Figure 5 Orientation image mapping (OIM) of longitudinal cross-sections of samples; A: pMg-an (pMg: Pure pMagnesium; an: anneal), B: pMg-180, C: ZK60-ex (ex: extrusion) and D: ZK60-150.

[0035] Figure 6 Surface optical images of different samples before and after HPTE processing after being immersed in PBS: (a) pMg-an and (b) pMg-180 show surface corrosion and crevice corrosion, (c) ZK60-ex and (d) ZK60-250 show pitting holes.

[0036] Figure 7 is the corrosion potential of pure Mg in PBS at 37°C over time.

[0037] Figure 8 These are the surface field emission scanning electron microscope (FE-SEM) images of the untreated group of pure magnesium materials and the group treated with plasma chemical vapor TiO2 surface deposition: A: untreated sample of pure magnesium; B: sample of the pure magnesium treated group was oxidized by plasma TiO2 deposition at 150W for 30 minutes; C: sample of the pure magnesium treated group was oxidized by plasma TiO2 deposition at 300W for 30 minutes.

[0038] Fig. 9 The bracket pattern design drawing is made of pure magnesium material. DETAILED DESCRIPTION

[0039] The present invention is described in detail below in conjunction with the accompanying drawings. A method for preparing an intravascular bioabsorbable pure magnesium stent includes the following processing steps for the pure magnesium material:

[0040] Step 1: performing equal channel angular pressing (ECAP) treatment; in the step 1, the pure magnesium material has a purity of 99.9%-99.99999% and is made into a rod of 10-50mmX100-500mm. First, the pure magnesium is subjected to ECAP processing, treated at 250-300°C for 1-5 times, and treated at 200-250°C for 1-10 times. The mold used for ECAP treatment has two channels, which intersect at an angle of 102-120°, respectively, and are twisted with an outer curvature arc at an angle of 15-25°. The entire mold is uniformly heated by a heater along a vertical channel, and the temperature is monitored at the intersection of the channels. Before each new pass, the sample is always rotated 90° in the same direction along the longitudinal axis to perform all multiple pressings. The sample is pressed into the ECAP mold at a speed of 10-30mm / min.

[0041] Step 2: performing high pressure torsional extrusion (HPTE) treatment; in the step 2, the pure magnesium material is subjected to high pressure torsional extrusion (HPTE) treatment, the magnesium material is annealed at 300-500°C for 30 minutes, and then cooled in a furnace; after annealing, the sample is extruded at 150-200°C with an extrusion ratio of 3:1, and after extrusion, at 180-200°C with a translation speed of 6-12mm / min (v6) and a rotation speed of 0.6-1.2rpm, through HPTE treatment, the number of treatment cycles is 1-10 cycles.

[0042] Step three: drawing a thin-walled tube; in step three, the pure magnesium material is annealed at 280-300°C for 30 minutes, then cooled in a furnace, and then extruded and drawn at 200°C with an extrusion ratio of 3:1 to obtain a thin-walled tube with a diameter of 0.1-0.15mm and a length of 2 meters, and the tube wall thickness error is <5 microns.

[0043] Step 4: Bracket design; In step 4, the pure magnesium material is subjected to bracket pattern design, such as Fig. 9 As shown, the design attempts to increase the flexibility and compliance of the stent, making it easier for the stent to pass through narrow and tortuous calcified lesions, making it easier for clinical use.

[0044] Step 5: Laser engraving: In step 5, the pure magnesium thin-walled tube is laser engraved according to the above-mentioned design pattern.

[0045] Step six: polishing, cleaning and surface treatment; in step six, the pure magnesium stent is polished, cleaned and surface treated, polished in the polishing liquid of an automated polishing machine for 10 minutes, rinsed, ultrasonically cleaned in acetone and ethanol for 10 minutes each, ultrasonically cleaned in deionized double distilled water for 10 minutes, and dried at 60°C in argon for later use.

[0046] Step seven: plasma chemical vapor TiO2 surface deposition. In step seven, radio frequency plasma enhanced chemical vapor titanium deposition is performed on the surface of the pure magnesium bracket. A titanium coating is deposited on the surface of the pure magnesium alloy bracket using a radio frequency plasma enhanced chemical vapor deposition method. Under a negative self-bias voltage of 400V, a 10-17% titanium content working atmosphere is formed in a 20Pa mixed methane and titanium isopropoxide control chamber. Before deposition, the pure magnesium alloy bracket is ultrasonically cleaned in an acetone bath for 10 minutes, then cleaned in an anhydrous ethanol bath for 10 minutes, and then dried for 10 minutes after three-distilled deionized water cleaning; then immediately transferred to the chamber of the PECVD system, the deposition process includes loading, plasma cleaning, plasma deposition and unloading steps; the system is connected to an RFX-13.56 radio frequency generator with a frequency of 600MHz, the deposition chamber is evacuated to a base pressure of 10-8Torr, and plasma cleaning is performed for 10 minutes using argon and oxygen with mass flow rates of 90SCCM and 50SCCM, respectively.

[0047] During the cleaning step, the peak voltage was 400±10V, the RF power was 80±10W, and the DC bias was -140±10V; the Ti coating was then deposited using 1.6-3SCCM titanium isopropoxide and 90SCCM of methane; the deposition time was 40-60 minutes, the voltage was 300±10V, the RF power was 120±10W, and the DC bias was -400±10V; during the cleaning and deposition steps, the total pressure was maintained at 20Pa, which was monitored and measured by a Baratron pressure gauge.

[0048] Pure magnesium materials were plasma treated at different treatment powers and times, and an island-like nanostructured TiO2 layer and a pit-like nanostructured TiO2 layer were generated on the surface of the plasma-oxidized samples. We found that the plasma-deposited oxidized samples with rough oxide layers formed higher wettability and exhibited excellent blood compatibility. These findings indicate that TiO2 plasma modification is a practical method to promote the blood compatibility of biomedical pure magnesium surfaces.

[0049] The present invention utilizes severe plastic deformation (SPD) method, namely twisted channel angle pressing (TCAP) and high pressure torsion extrusion (HPTE) method, to greatly refine pure magnesium grains, thereby significantly enhancing the physical properties of pure magnesium materials. And by extrusion and drawing into thin-walled tubes, further optimizing the design and laser engraving and plasma chemical vapor TiO2 surface deposition treatment, an intravascular bioabsorbable pure magnesium metal stent is obtained. Some specific processing methods and characterization results are as follows.

[0050] like Figure 1 Shown

[0051] The microstructure of the received blank is as follows Figure 1 As can be seen in Figure 1, the sample has a rather coarse grain structure with an average grain size of about 250 μm. In order to refine the grains of the pure magnesium billet without generating any cracks during the ECAP process, the initial processing temperature of the billet was increased to 275-300°C and 200-250°C, respectively. Our previous research work has demonstrated that by increasing the initial temperature, the formability of the material is significantly improved without affecting the grain refinement effect. That is, the strategy of performing the first set of ECAP at a relatively high temperature aims to first achieve a large reduction in grain size, and then complete the refinement to the desired state through subsequent multiple ECAPs at lower temperatures.

[0052] Figure 1 B shows that the original coarse-grained structure of pure magnesium has been significantly refined (compared to Figure 1 A), in the ECAP treated sample, twinning is also evident in the coarser grains. After 4 passes at 200-250 °C, this prevents the realization of a finer structure. Finally, an equiaxed structure with a grain size of 22 μm was achieved in the extruded sample by ECAP.

[0053] like Figure 2 Shown

[0054] The evolution of the grain structure of pure magnesium at different stages of HPT processing observed using EBSD is shown. High-angle boundaries are represented by black lines and low-angle boundaries are represented by red. Coarse grains surrounded by fine grains are observed at low turns, and a uniform distribution of ultrafine grains is observed after multiple turns. Since HPT processing is usually performed at room temperature, grain growth can be prevented and the final grain size is smaller than that in ECAP. For example, in pure magnesium processed by ECAP at high temperature, the final grain size is larger than 10μm, while in pure magnesium processed by HPT at room temperature, the grain size is less than 1μm.

[0055] In contrast, processing of coarse-grained magnesium results in an uneven distribution of grain sizes if ECAP processing is performed at low temperatures and a uniform distribution of medium-sized grains if processing is performed at high temperatures. Combining thermomechanical processing operations can improve the initial structure of the material and lead to the development of a uniform distribution of fine grains. The amount of strain applied during HPT is usually much larger than that in ECAP. Therefore, although some heterogeneity in the grain size distribution is observed in the initial stages of processing, the grain structure usually evolves to a uniform distribution of ultrafine grains.

[0056] like Figure 3 The improvement in tensile properties is shown

[0057] The tensile stress of the received sample and the ECAP treated sample is shown in Figure 3 , including 0.2% yield stress (YS), ultimate tensile strength (UTS) and elongation at break (FE). For pure Mg, the yield stress did not change significantly after ECAP, while UTS increased from 285MPa to 326MPa, and the elongation at break also increased significantly, from 8.1% of the initial value to 18.3%.

[0058] The grain size is greatly reduced by performing ECAP. However, this grain size dependence is not the only factor affecting the yield strength and elongation at break properties of Mg alloys. According to our previous studies, the mechanical behavior of ECAP-treated Mg is also related to the crystallographic texture modification. In particular, when comparing the data of the ZK60 material, it can be observed that the YS and UTS after ECAP and extrusion are lower than those of the ECAP-treated alloy, despite its finer grains. The study showed that this could be related to the main texture softening effect of grain size strengthening induced during the high-temperature ECAP pass. On this basis, the elongation at failure of ZK60 increased significantly, by 100%, while the alloy still maintained a relatively high tensile strength required for stent applications.

[0059] like Figure 4 Shown

[0060] Grain refinement introduced by SPD processing may also soften magnesium. Pure magnesium exhibits an inverse Hall-Petch behavior at room temperature, so grain refinement below a certain level reduces its strength. However, we found that the reduction in strength of ultrafine-grained pure magnesium is associated with a significant increase in ductility. Figure 4 shows the appearance of a pure magnesium tensile sample processed by HPT and tested at room temperature. This SPD technique produces an average grain size of only 0.32μm. Elongations of up to 360% have been observed in this material. This exceptional elongation has been attributed to the occurrence of grain boundary sliding in this fine-grained pure magnesium. Exceptional elongations and ductility may also develop in some fine-grained magnesium alloys, including superplastic elongation in Mg-Li alloys processed by HPT. It is found that for grain sizes greater than -4μm, the deformation is twin-controlled and the data follow the Hall-Petch relationship. However, for grain sizes less than -4μm, the flow stress relationship σ breaks with the grain size d and the data follow the relationship predicted for a grain boundary sliding mechanism, also known as slip control.

[0061] like Figure 5 Shown

[0062] Orientation image maps (OIMs) mapped from longitudinal cross sections of pMg-an (A), pMg-180 (B), ZK60-ex (C), and ZK60-150 (D) samples.

[0063] The pure magnesium material was annealed at 500°C for 30 min and then cooled in the furnace. After annealing, it was extruded at 200°C with an extrusion ratio of 3:1 and then processed by HPTE at 180-200°C with a translation speed of 6-12 mm / min (v6) and a rotation speed of 0.6-1.2 rpm. Processing at lower temperatures resulted in the formation of surface cracks, and processing at higher temperatures resulted in an increase in the average grain size.

[0064] HPTE of ZK60 alloy was then studied. HPTE was performed at 300°C with an extrusion ratio of 17.4:1 (hereinafter referred to as "extrusion state") using the same translation and rotation speeds as pure magnesium, and was processed at 150°C and 250°C, respectively. HPTE of ZK60 alloy at temperatures below 150°C will cause surface cracking.

[0065] The microstructure of annealed and HPTE treated pure magnesium is shown in Figure 5 A and Figure 5B. The 15° criterion is used to distinguish low-angle boundaries (LABs) from high-angle boundaries (HABs). The grain size (D) is calculated using the equivalent diameter method. Two boundary orientation deviation thresholds (2° and 15°) are used to define grains. The corresponding average grain sizes are denoted as D2 and D15. Due to the HPTE treatment, the coarse grains in the annealed sample (average D15 of 140 ± 1 μm, D2 = 127 ± 1 μm) have been significantly refined to 1.7 ± 0.1 μm (1.4 ± 0.1 μm) after HPTE treatment.

[0066] HPTE leads to microstructural refinement of extruded ZK60 alloy. Figure 5 C and Figure 5 D. The average grain size D15 in the extruded state is 28 ± 1 μm (D2 = 19 ± 1 μm), and the grains show obvious extension along the ED axis in the longitudinal cross section of the rod, such as Figure 5 As shown in C.

[0067] We found that the grain size of ZK60 alloy after HPTE process has a strong dependence on deformation temperature: D15 = 11 μm after HPTE at 250 °C and D15 = 1.6 μm after HPTE at 150 °C. Figure 5 D shows the microstructure of ZK60 alloy after HPTE at 150 °C. The microstructure consists mainly of small particles with a size of 1 μm; however, fragments of the initially long fibers are still present in the structure. The length of these fibers is reduced to 20-50 μm.

[0068] like Figure 6 Shown

[0069] 6A and B show the corrosion and crevice corrosion of the surface pure magnesium sample. Pure magnesium will have crevice corrosion at the boundary between the sample and the embedding material. Figure 6 As shown in C and D, ZK60 samples show different degrees of pitting corrosion in addition to surface corrosion. ZK60-ex, such as 6C, shows surface corrosion with only one pitting hole and the surrounding deposits are quite small, while for the treatment of HPTE 150℃ state, ZK60-150( Figure 6 D), multiple corrosion pits can be identified, with accumulations of larger ones protruding from the surface. Pitting not only causes holes to descend into the alloy, but also causes corrosion to spread laterally beneath the surface.

[0070] like Figure 7 Display electrochemical research

[0071] The electrochemical corrosion behavior of pure magnesium materials was studied by open circuit potential (OCP) and potentiodynamic polarization tests. A PTFE sample holder with a circular opening of 5.5 mm in diameter was used to isolate the sample body from the electrolyte and provide an electrode area of ​​23.8 mm2 in contact with the electrolyte. Phosphate buffer solution (PBS) maintained at 37 °C and pH 7.4 was selected as the electrolyte to simulate body fluid. The three-electrode setup included a platinum-coated titanium sheet as a counter electrode, Ag / AgCl, Sat.KCl, a reference electrode, and different magnesium materials as working electrodes. The experiments were carried out using a 7050AMEL constant potential / constant current instrument.

[0072] First, the OCP was measured for 15 h vs. Ag / AgCl. Then, linear polarization was performed in the potential window from –2 to –0.7 V vs. Ag / AgCl with a scan rate of 0.166 mVs–1.

[0073] From the OCP graph, it can be seen that the pure Mg sample did not establish a steady state before 12 h. In order to maintain the homogeneity of all experiments, the OCP measurements were allowed to be performed for all samples for 15 h. As shown in the figure, two different levels of OCP values ​​can be identified. More precisely, for pure Mg, a steady-state OCP is observed in the range of –1.7 V vs. Ag / AgCl. Pure Mg in both cases shows a slightly higher corrosion resistance behavior compared to extrusion after ECAP treatment.

[0074] like Figure 8 Shown

[0075] The surface field emission scanning electron microscopy (FE-SEM) images of the pure magnesium control sample and the plasma TiO2 deposition oxidation sample are shown. Obviously, the polished control sample presents a smooth and flat surface feature ( Figure 8 A). After different plasma TiO2 deposition oxidation processes, significant changes in surface morphology were observed, e.g. Figure 8 As shown in B. Island-like morphological features were found on the sample deposited and oxidized by 150W plasma TiO2 for 30 minutes. Similar morphological features can also be observed on the plasma oxidized samples at different times under 150W. As the plasma power increases to more than 200W at different times, pit-like morphological features are found on the surface layer of the plasma TiO2 deposited oxidized sample ( Figure 8 C). At 300 W for 30 min, the pit-like morphology becomes rougher.

[0076] Titanium oxide layer was formed on pure magnesium substrate by oxygen plasma TiO2 deposition oxidation modification. The morphology of TiO2 deposited oxide layer became rougher with the increase of plasma treatment power and time. The results of microstructural analysis showed that nanostructured TiO2 phase was formed on the pure magnesium surface after oxygen plasma treatment with different parameters. It also showed that the rougher oxide layer on the magnesium surface led to a hydrophilic surface. The presence of rough pit-like oxide layer with nanostructured TiO2 phase in plasma TiO2 deposition oxidation samples had better blood compatibility. It is believed that Ti implants with nanostructured TiO2 deposited oxide layer can promote stent endothelialization, improve tissue healing, and promote in vivo bone integration in bone tissue.

[0077] like Fig. 9 Shown

[0078] The new stent pattern designed for us has been repeatedly tested and has excellent compliance and flexibility. The stent is highly maneuverable and can easily pass through severe stenosis, torsion and calcified lesions, making it easy for clinicians to operate. It is a good choice for interventional treatment of complex lesions.

[0079] The pure magnesium stent prepared by the preparation method of the present technical solution has excellent physical and mechanical properties, good biocompatibility and corrosion resistance, fully meets the performance index requirements of clinical absorbable stent implantation, has good compliance and controllability, is easy to pass through narrow and tortuous lesions, and can be used for stent implantation needs in cardiovascular, cerebrovascular, peripheral blood vessels and hollow organs. It will become an absorbable pure magnesium stent that clinicians like to use, and will also bring good news to patients.

[0080] The above technical solutions only reflect the preferred technical solutions of the technical solutions of the present invention. Some changes that may be made to certain parts thereof by technicians in this technical field all reflect the principles of the present invention and fall within the protection scope of the present invention.

Claims

1. A method for preparing an intravascular bioabsorbable pure magnesium stent, characterized in that: The following processing steps are involved in the processing of pure magnesium materials: Step 1: Perform equal channel angular pressure (ECAP) treatment; Step 2: High pressure torsional extrusion (HPTE) treatment; Step 3: Drawing the thin-walled tube; Step 4: Bracket design; Step 5: Laser engraving; Step 6: Polishing, cleaning and surface treatment; Step 7: Plasma chemical vapor TiO2 surface deposition.

2. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step 1, the pure magnesium material has a purity of 99.9%-99.99999% and is made into a rod of 10-50mmX100-500mm. The pure magnesium is first subjected to ECAP processing, treated at 250-300°C for 1-5 times, and treated at 200-250°C for 1-10 times. The mold used for ECAP processing has two channels, which intersect at an angle of 102-120°, respectively, and are twisted with an outer curvature arc at an angle of 15-25°. The entire mold is uniformly heated by a heater along a vertical channel, and the temperature is monitored at the intersection of the channels. Before each new pass, the sample is always rotated 90° in the same direction along the longitudinal axis to perform all multiple pressings, and the sample is pressed into the ECAP mold at a speed of 10-30mm / min.

3. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step 2, the pure magnesium material is subjected to high pressure torsional extrusion (HPTE) treatment, the magnesium material is annealed at 300-500° C. for 30 min, and then cooled in a furnace; after annealing, the sample is extruded at 150-200° C. at an extrusion ratio of 3:

1.

4. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step 2, after extrusion, the HPTE treatment is performed at 180-200° C., at a translation speed of 6-12 mm / min (v6) and a rotation speed of 0.6-1.2 rpm, and the number of treatment cycles is 1-10 cycles.

5. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step three, the pure magnesium material is annealed at 280-300°C for 30 minutes, then cooled in a furnace, and then extruded and drawn at 200°C with an extrusion ratio of 3:1 to obtain a thin-walled tube with a diameter of 0.1-0.15mm and a length of 2 meters, and the tube wall thickness error is <5 microns.

6. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step 4, the pure magnesium material is used for stent pattern design, which attempts to increase the flexibility and compliance of the stent, so that the stent can easily pass through narrow and twisted calcified lesions, and is convenient for clinical use.

7. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step five, the pure magnesium thin-walled tube is laser engraved according to the above-mentioned design pattern.

8. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In step six, the pure magnesium stent is polished, cleaned and surface treated. The stent is polished in the polishing liquid of an automatic polishing machine for 10 minutes, rinsed, ultrasonically cleaned in acetone and ethanol for 10 minutes each, ultrasonically cleaned in deionized double distilled water for 10 minutes, and dried in argon at 60°C for later use.

9. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 1, characterized in that: In the step seven, radio frequency plasma enhanced chemical vapor titanium deposition is performed on the surface of the pure magnesium bracket. A titanium coating is deposited on the surface of the pure magnesium alloy bracket using a radio frequency plasma enhanced chemical vapor deposition method. Under a negative self-bias voltage of 400 V, a 10-17% titanium content working atmosphere is formed in a 20Pa mixed methane and titanium isopropoxide control chamber. Before deposition, the pure magnesium alloy bracket is ultrasonically cleaned in an acetone bath for 10 minutes, then cleaned in an anhydrous ethanol bath for 10 minutes, and then dried for 10 minutes after three-distilled deionized water cleaning; then immediately transferred to the chamber of the PECVD system, the deposition process includes loading, plasma cleaning, plasma deposition and unloading steps; the system is connected to an RFX-13.56 radio frequency generator with a frequency of 600 MHz, the deposition chamber is evacuated to a base pressure of 10-8 Torr, and plasma cleaning is performed for 10 minutes using argon and oxygen with mass flow rates of 90 SCCM and 50 SCCM, respectively.

10. The method for preparing an intravascular bioabsorbable pure magnesium stent according to claim 9, characterized in that: In step 7, in the cleaning step, the peak voltage is 400±10V, the RF power is 80±10W, and the DC bias is -140±10V; then, the Ti coating is deposited using 1.6-3SCCM titanium isopropoxide and 90SCCM methane; the deposition time is 40-60 minutes, the voltage is 300±10V, the RF power is 120±10W, and the DC bias is -400±10V; During the cleaning and deposition steps, the total pressure was maintained at 20 Pa, as monitored by a Baratron pressure gauge.

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