A medical degradable zinc alloy, a manufacturing method and an application thereof

Abstract

This invention relates to a medical biodegradable zinc alloy, its manufacturing method, and its applications. The method involves selecting zinc-based alloy powder materials and a binder. A layer of the powder material is deposited on a substrate of a printing platform. Based on the constructed model, the binder is selectively sprayed onto the surface of the powder layer to solidify the cross-sectional pattern of the constructed model. The printing platform then descends by the thickness of one powder layer, and another layer of powder material is deposited. This process is repeated until the constructed model is printed. After printing, the entire substrate supporting the printed model is removed and placed in a vacuum oven for a certain time to enhance the curing strength of the binder. After curing, excess powder is removed to obtain a green blank. The green blank is then degreased and sintered to obtain the medical biodegradable zinc alloy. The medical biodegradable zinc alloy prepared by binder spray additive manufacturing possesses certain mechanical properties, along with an appropriate degradation rate and good biocompatibility, and is expected to be further applied in clinical orthopedic and vascular stent implantation.

Description

Technical Field

[0001] This invention belongs to the field of additive manufacturing technology, specifically relating to a medical biodegradable zinc alloy, its manufacturing method, and its application. Background Technology

[0002] Compared to traditional manufacturing methods, additive manufacturing technology is based on a discrete accumulation forming concept, a "bottom-up" material accumulation method widely used in aerospace, military, automotive, and medical fields. Binder jetting (BJ) is a type of metal additive manufacturing technology. The specific process involves laying a powder bed, selectively spraying a binder into the powder bed to create adhesion between powder particles while the remaining particles remain loose, repeating this process layer by layer, printing, and then curing in an oven. After completion, a complete green preform can be removed, and finally, appropriate post-processing methods can be selected to obtain the desired part. Binder jetting technology enables product personalization, rapid prototyping, and even mass production of end parts.

[0003] Zinc (Zn) is an essential trace element for the human body, playing a crucial role in enzyme and protein synthesis and cell signal transduction. Due to its good biocompatibility and suitable degradation rate, zinc holds promise as a next-generation biodegradable metallic material for biomedical applications. Traditional processes for preparing biodegradable metal implants involve melting, casting, rolling, extrusion, or drawing, followed by a series of complex procedures such as turning, machining, planing, grinding, and welding, making it difficult to produce intricate and complex geometries. Therefore, the traditional process for preparing zinc alloys is relatively complex, difficult to control, and costly. The rapid development of additive manufacturing technology provides a more direct and effective means for preparing intricate and complex biodegradable metal geometries. Laser powder bed fusion (L-PBF) is an additive manufacturing technology suitable for preparing biodegradable zinc alloys. While it can produce personalized parts with excellent mechanical properties and complex microstructures, its expensive equipment and demanding working environment limit its ability to rapidly and mass-produce parts.

[0004] Existing technology 1 (CN110205505A) discloses a method for preparing a room-temperature high-ductility zinc alloy. The method comprises the following steps: first, the zinc alloy components are batched according to their weight percentages (wt.%): manganese 0.1-2, aluminum 0-1, tin 0-2, with the remainder being zinc; the alloy is then heated and melted in a resistance furnace, and the molten zinc alloy is poured into a water-cooled iron mold; subsequently, the zinc alloy casting billet is heat-treated and machined into a disc shape; finally, the disc-shaped zinc alloy is subjected to high-pressure torsion. This method is cumbersome and difficult to meet the requirements of customized medical implant devices. Summary of the Invention

[0005] In order to overcome the above-mentioned problems in the prior art, the present invention provides a medical biodegradable zinc alloy, a manufacturing method and an application, to solve the above-mentioned problems in the prior art.

[0006] A method for manufacturing a biodegradable zinc alloy for medical use, the method comprising the following steps:

[0007] S1. After drying the zinc-based alloy powder material, place it in a powder spreader and select a binder corresponding to the powder material;

[0008] S2: A layer of the powder material is laid on the substrate of the printing platform. According to the constructed model, the binder is selectively sprayed on the surface of the powder layer formed by the powder material to solidify the cross-sectional pattern of the constructed model. Then the printing platform is lowered by the thickness of one powder layer, and another layer of powder material is laid. The above process is repeated until the constructed model is printed.

[0009] S3. After printing, remove the entire substrate that supports the printed model and place it in a vacuum oven. Keep it warm for a certain time to strengthen the curing strength of the adhesive. After curing, remove excess powder to obtain the green blank.

[0010] S4. The green blank is degreased and sintered to obtain a sintered component of medical biodegradable zinc alloy.

[0011] In addition to the aspects described above and any possible implementations, a further implementation is provided in which the particle size of the zinc-based alloy powder material is 5-50 μm.

[0012] In addition to the aspects described above and any possible implementation, a further implementation is provided in which the drying temperature in step S1 is 60-100°C and the time is 8-12 hours.

[0013] In addition to the aspects and any possible implementations described above, a further implementation is provided in which the number of powder layers is multi-layered, the thickness of each layer is 30-50 μm, the powder spreading speed is 30-60 pps, the binder saturation of the piezoelectric nozzle is 60-90%, the X-axis printing speed of the nozzle is 300-500 pps, and the Y-axis printing speed is 50-150 pps.

[0014] In addition to the aspects and any possible implementations described above, a further implementation is provided in which a vacuum oven is used for curing in S3, the curing temperature is 150-250°C, and the holding time is 120-300 min.

[0015] In addition to the aspects described above and any possible implementation, a further implementation is provided in which the degreasing temperature in S4 is 200-350°C, the holding time is 60-300 min, and the heating rate is 2-5°C / min.

[0016] In addition to the aspects described above and any possible implementation, a further implementation is provided in which the sintering temperature in S4 is 420-480℃, the holding time is 240-500min, and the heating rate is 1-3℃ / min.

[0017] The present invention also provides a medical biodegradable zinc alloy, which is manufactured by the method described above. Its surface has a controllable hierarchical porous structure or a dense structure, a compressive strength of 22-145 MPa, a hardness of 12-84 HV, and an in vitro degradation rate of 0.11-0.73 mm / year after 28 days.

[0018] The present invention also provides an application of the aforementioned biodegradable zinc alloy in clinical medical implant devices.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) This invention employs binder jet additive manufacturing to prepare a biodegradable zinc alloy for medical use. Compared to traditional manufacturing processes, this invention is unrestricted in producing porous parts with diverse shapes and complex structures. Furthermore, compared to other laser and electron beam additive manufacturing technologies, the binder jet additive manufacturing used in this invention is lower in cost and faster in preparation speed. Unlike laser powder bed fusion and other additive manufacturing technologies, the forming process of binder jet additive manufacturing in this invention is carried out at room temperature and atmospheric conditions, avoiding problems related to oxidation, residual stress, elemental segregation, and phase transformation. Loose powder in the powder bed can be highly recovered. In addition, binder jet additive manufacturing does not require expensive sealed chambers for vacuuming or inerting; therefore, compared to other additive manufacturing technologies, the build volume of the binder jet equipment is the largest (up to 2200×1200×600mm).

[0021] (2) The biodegradable zinc alloy for medical use prepared by binder spraying additive manufacturing in this invention possesses certain mechanical properties that meet the basic mechanical performance requirements of trabecular bone and vascular stents. Furthermore, the degradation rate of the binder-sprayed zinc alloy is faster than other processes, and while matching the bone healing and repair rate, it also exhibits good biocompatibility.

[0022] (3) The biodegradable zinc alloy for medical use prepared in this invention can produce parts with dual-mode pores by controlling the binder spraying additive manufacturing printing process and the sintering process. This is similar to powder metallurgy, where designed pores (microchannels) and pores generated by the process itself (pores within the microstructure) are left after the original blank is sintered. These pores, with their microchannels and microstructure pores, can regulate the degradation rate and promote bone adhesion and inward cell growth.

[0023] (4) Given the complexity of the geometry of clinical orthopedic and vascular stents, binder jet additive manufacturing can use software such as CATIA, CAD, and SOLIDWORKS to construct models of various complex geometries of biodegradable implants (bone screws, bone plates, etc.), and set corresponding printing parameters for printing, thereby achieving personalized customization of implants. The biodegradable zinc alloy prepared by the additive manufacturing method provided by this invention has excellent mechanical properties, a moderate degradation rate, and good biocompatibility, and can be used in medical implant devices including vascular stents, vascular anastomoses, bone screws, bone plates, bone filling materials, etc. Attached Figure Description

[0024] Figure 1 A schematic diagram of the pure zinc powder used in Example 1;

[0025] Figure 2 This is a schematic diagram of the microstructure and elemental analysis of the pure zinc sample manufactured by binder spraying additive manufacturing in Example 1.

[0026] Figure 3 This is a schematic diagram of the stress-strain curve of a pure zinc sample manufactured by binder spraying additive manufacturing in Example 1.

[0027] Figure 4 This is a schematic diagram showing the weight loss and degradation rate of the pure zinc sample manufactured by binder spraying additive manufacturing in Example 1 at different times.

[0028] Figure 5 This is a schematic diagram illustrating the biocompatibility of the MC3T3 cell sample, a pure zinc sample manufactured by binder spraying additive manufacturing in Example 1.

[0029] Figure 6 This is a photograph of the live / dead cells of MC3T3 cells in the pure zinc sample manufactured by binder spraying additive manufacturing in Example 1.

[0030] Figure 7 This is a flowchart of the method of the present invention. Detailed Implementation

[0031] To better understand the technical solution of this invention, the content of this invention includes, but is not limited to, the specific embodiments described below. Similar technologies and methods should be considered within the scope of protection of this invention. To make the technical problems to be solved, the technical solutions, and advantages of this invention clearer, a detailed description will be provided below in conjunction with the accompanying drawings and specific embodiments.

[0032] It should be understood that the embodiments described in this invention are merely some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention.

[0033] The terminology used in the embodiments of this invention is for the purpose of describing particular embodiments only and is not intended to limit the invention. The singular forms “a,” “the,” and “the” as used in the embodiments of this invention and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise.

[0034] like Figure 7 As shown, the present invention provides a method for manufacturing a medical biodegradable zinc alloy, the method comprising the following steps:

[0035] S1: Prepare raw materials. Take zinc-based alloy powder material prepared by gas atomization, dry it in a vacuum drying oven, and then place it in a powder spreader. Select an appropriate water-based binder according to the powder material;

[0036] S2: Printing the model. A layer of the powder material is laid on the substrate of the printing platform. Then, the nozzle selectively sprays the binder onto the powder layer surface according to the model slices to solidify the cross-sectional pattern of the model. The platform then descends by the thickness of one powder layer, and a new powder layer is laid. The nozzle repeats the above process until the model is printed. The entire printing process can be carried out at room temperature and in air without the protection of an inert chamber.

[0037] S3: High-temperature curing. After printing, immediately remove the entire substrate that carries the printing powder bed and place it in a vacuum oven. Keep it at a certain temperature for a certain time to strengthen the curing strength of the adhesive. After curing, remove excess powder to obtain the green blank.

[0038] S4: Debinding and sintering. The debinding process is integrated into the front stage of sintering. Through segmented heating or heat preservation debinding, volatile molecules in the binder are removed. After this process is completed, the heating stage is immediately started to begin high-temperature sintering in order to obtain a dense final part.

[0039] Preferably, the zinc-based alloy powder material has a particle size range of 5-50 μm, which allows for better flowability of the powder when spread by the powder spreader of the adhesive jet printer.

[0040] Preferably, the drying conditions are: 60-100℃, time 8-12h, and powder oxygen content less than 100ppm. Under these drying conditions, the powder has low adhesion and good flowability, which is more conducive to the powder spreading process.

[0041] Preferably, the powder spreading roller rotates during the powder spreading process. During printing, when the powder spreading roller stops rotating, the powder diffusion becomes noticeably uneven because the powder adheres to the static roller during spreading. The powder spreading roller plays a crucial role in compacting the powder and increasing the green body density.

[0042] Preferably, the powder layer is multi-layered, with each layer having a thickness of 30-50μm, a powder spreading speed of 30-60pps, a binder saturation of 60-90% sprayed by the piezoelectric nozzle, a print speed of 300-500pps on the X-axis, and a print speed of 50-150pps on the Y-axis. By using this layer thickness and powder spreading speed, as well as the corresponding binder saturation and print speed, a green body with dimensions that better match the design, lower surface roughness, and higher density can be obtained.

[0043] Preferably, the curing temperature in a vacuum oven is 150-250℃ and the holding time is 120-300min. Under this temperature and holding time, the strength of the green body is better, which is beneficial to subsequent experiments.

[0044] Preferably, the degreasing temperature is 200-350℃, the holding time is 60-300min, and the heating rate is 2-5℃ / min. At this temperature and holding time, there will be less degreasing residue.

[0045] Preferably, the sintering temperature is 420-480℃, the holding time is 240-500min, and the heating rate is 1-3℃ / min. Samples obtained at this temperature and holding time are more dense and have higher mechanical properties.

[0046] The preparation method provided by this invention uses an aqueous binder, which fills the gaps between powder materials during the printing process and provides temporary adhesion, ensuring the structural integrity of the green body. It is then removed in subsequent processes, leaving less than 3% residue.

[0047] The preparation method provided by this invention is lower in cost and faster in preparation speed compared to other laser and electron beam additive manufacturing technologies. For example, to print the same 120mm×120mm×10mm zinc alloy part, laser powder bed melting requires the protection of an inert chamber and takes more than 8 hours to print, while binder jet additive manufacturing can be carried out in air, and the nozzle moves faster, eliminating the need for preheating the substrate and air exchange, and can be completed in only about 2-3 hours.

[0048] The preparation method provided by this invention, due to the support of loose powder in the powder bed, can construct a corresponding three-dimensional model according to the shape requirements of the actual medical implant, and set corresponding process parameters such as adhesive saturation and printing speed for printing. It has the characteristics of precise manufacturing and personalized customization, and can obtain devices of any shape to realize personalized customization of implants.

[0049] In the sintering process described in step S4, the sintering temperature exceeds the melting point of zinc. Theoretically, when the liquid phase volume is too high, the liquid phase expands out of the surface, causing the sample to deform and lose its original shape. However, due to the residue of the binder components and the binding of the oxide film, the liquid phase does not expand outward, allowing the sample to maintain high dimensional accuracy and retain its shape during liquid phase migration.

[0050] Mechanical property testing revealed that the zinc-based alloy prepared by this invention exhibits a compressive strength of 22-145 MPa and a hardness of 12-84 HV. In simulated body fluid degradation tests, the zinc-based alloy showed a moderate and significantly improved degradation rate, with a 28-day degradation rate of 0.11-0.73 mm / year, better matching the degradation rate requirements of bone and vascular implants. In contrast, existing zinc-based alloys produced using laser powder bed fusion printing showed a 28-day degradation rate of only 0.04-0.15 mm / year. Biocompatibility evaluation of the zinc-based alloy extract of this invention, diluted 10-fold according to ISO 10993 standards, showed that MC3T3 cell viability was greater than 90% after 3-5 days of culture. Live / dead staining results showed that the cells exhibited spindle-shaped and filopodia, indicating good cell condition and demonstrating the good biocompatibility of the zinc alloy described in this invention.

[0051] The preparation method provided by this invention can obtain a controllable hierarchical porous structure or a dense bulk on the surface of a zinc-based alloy by controlling one or more of the following conditions: binder saturation, printing speed, sintering temperature, and time. The porosity of this hierarchical structure facilitates cell adhesion and growth, improving the biocompatibility of binder-jet printed zinc-based alloys.

[0052] As an embodiment of this invention, the present invention also discloses the application of a biodegradable zinc alloy in clinical medical implantable devices. The clinical medical implantable devices include vascular stents, vascular anastomoses, bone screws, bone plates, bone filling materials, etc. Because the zinc-based alloy sample possesses certain mechanical properties, a moderate degradation rate, and good biocompatibility, it can be used in medical implantable devices.

[0053] The following examples and comparative models are used for illustration.

[0054] Example 1

[0055] (1) Take about 3 kg of pure zinc powder with a particle size of 5-30 μm and put it into a vacuum drying oven. Set the drying temperature to 80℃ and the time to 10 h.

[0056] (2) Use Magics software to build a printing model, import it into the operating software of the adhesive jet printer, and set the printing process parameters, including layer thickness of 40μm, powder spreading speed of 50pps, X-axis printing speed of 350pps, Y-axis printing speed of 110pps, and adhesive saturation of 80%.

[0057] (3) After printing, place the entire substrate in a vacuum drying oven for curing. Set the temperature to 180℃ and the time to 180min. After curing, wait for it to cool to room temperature before removing it for powder cleaning to obtain a pure zinc green blank.

[0058] (4) The green blank was placed in a crucible for degreasing and sintering. The temperature was raised from room temperature to 200℃ and held for 30 min, then raised to 380℃ and held for 120 min; then the temperature was raised to the sintering temperature of 450℃ and held for 360 min; finally, the temperature was lowered to below 100℃ in the furnace and the blank was removed to obtain a sintered sample of pure zinc. Its microstructure was observed, such as... Figure 2 As shown, sintering necks are formed between some powder particles. The density of these particles was statistically analyzed using ImageJ software, indicating that the structure is dense.

[0059] (5) In accordance with the requirements of the national standard GB / T 7314-2017 "Metallic Materials - Compression Test at Room Temperature", the sintered compression specimens were cleaned with alcohol and deionized water and then their strength was verified according to the study. The verified compressive properties (stress-strain curves) are as follows: Figure 3 As shown in Table 1. Meanwhile, in accordance with GB / T 4340.1-2009 "Metallic materials - Vickers hardness test - Part 1: Test method", the hardness of the polished sample was verified, and the verified strength results are shown in Table 1.

[0060] (6) Perform an in vitro immersion test on pure zinc samples using simulated body fluids. Figure 4 The results showed that the degradation rate of the sample was 0.67 mm / year after 28 days, which meets the requirements for material degradation rate for bone implants and vascular implants.

[0061] (7) Biocompatibility was evaluated after diluting the pure zinc sample extract 10-fold and 4-fold according to ISO 10993 standard. After 1 day of MC3T3 cell culture, the cell viability was 90% and 22%, respectively. Figure 5 As shown. Live and dead staining results are as follows. Figure 6 The cells exhibited a spindle-shaped structure and filopodia, were in good condition, and showed good biocompatibility.

[0062] Example 2

[0063] The operation method in this embodiment is exactly the same as that in Example 1. The only difference is that the sintering temperature is 420℃. The mechanical property test results of the prepared pure zinc sample are shown in Table 1, which shows certain mechanical characteristics.

[0064] Example 3

[0065] The operation method in this embodiment is exactly the same as that in Example 1. The only difference is that the temperature used in the sintering process is 480℃. The mechanical property test results of the prepared pure zinc sample are shown in Table 1.

[0066] Table 1: Comparison of mechanical property test results of the above three embodiments with the performance data (pure zinc samples prepared by casting and hot rolling) recorded in the literature.

[0067]

[0068]

[0069] The microstructure of the pure zinc powder used in Example 1 is as follows: Figure 1 As shown, the powder has good sphericity, uniform distribution, some satellite powder, and good flowability, meeting the requirements of binder jet printing.

[0070] Figure 2 This document presents the microstructure and elemental analysis of the pure zinc sample prepared by binder spraying in Example 1. It shows that after sintering, sintered necks formed between some powder particles, resulting in a dense microstructure. Energy dispersive spectroscopy (EDS) analysis revealed that oxygen (O) was enriched at the particle edges, while the particle centers contained pure zinc. No carbon (C) was observed. Since the liquid phase could not fill all the internal space of the sample, some interconnected and unconnected pores remained. These pores were also preserved after sintering when designing samples with a certain degree of porosity (microchannels).

[0071] The stress-strain curve in Example 1 is as follows: Figure 3 As shown, the sample in Example 1 has certain mechanical properties, which can meet the requirements of bone implants and vascular implants for the mechanical properties of materials.

[0072] Due to the residual porosity during sintering, the surface area of ​​the sample in contact with simulated body fluids increases, accelerating the degradation rate significantly compared to zinc-based alloys printed by laser powder bed fusion. This better matches the rate of bone regeneration and makes it suitable for implantation sites where a higher degradation rate is required. Furthermore, the surface of the binder jet-printed sample exhibits a hierarchical structure, which is absent in laser powder bed fusion or other printing methods. This hierarchical structure and porosity also facilitate cell adhesion and growth, enhancing the biocompatibility of binder jet-printed zinc-based alloys.

[0073] Combining Table 1 and Figure 4 , Figure 5 , Figure 6 The results show that the biodegradable zinc alloy for medical use prepared by the technical solution of the present invention meets the requirements for the mechanical properties of bone implants and vascular implants, while also having an appropriate degradation rate and good biocompatibility. It is expected to be further applied to the implantation of orthopedic and vascular stents in clinical practice.

[0074] The foregoing description illustrates and describes several preferred embodiments of the present invention. However, as previously stated, it should be understood that the present invention is not limited to the forms disclosed herein and should not be construed as excluding other embodiments. It can be used in various other combinations, modifications, and environments, and can be altered within the scope of the inventive concept described herein through the foregoing teachings or techniques or knowledge in related fields. Any modifications and variations made by those skilled in the art that do not depart from the spirit and scope of the present invention should be within the protection scope of the appended claims.

Claims

1. A method for manufacturing a medical biodegradable zinc alloy, characterized in that, The method includes the following steps: S1. After drying the zinc-based alloy powder material, place it in a powder spreader and select a binder corresponding to the powder material. The particle size of the zinc-based alloy powder material is 5-50 μm. S2. Lay a layer of the powder material on the substrate of the printing platform, and selectively spray the binder onto the surface of the powder layer formed by the powder material according to the constructed model to solidify the cross-sectional pattern of the constructed model; Then the printing platform descends to the thickness of one powder layer, and another layer of powder material is laid. The above process is repeated until the constructed model is printed. The number of powder layers is multi-layered, the thickness of each layer is 30-50μm, the powder laying speed is 30-60pps, the saturation of the binder sprayed by the piezoelectric nozzle is 60-90%, the X-axis printing speed of the nozzle is 300-500pps, and the Y-axis printing speed is 50-150pps. S3. After printing, remove the entire substrate that supports the printed model and place it in a vacuum oven. Keep it warm for a certain time to strengthen the curing strength of the adhesive. After curing, remove excess powder to obtain a green body. The curing temperature is 150-250℃. S4. The green blank is degreased and sintered to obtain a sintered component of medical biodegradable zinc alloy. The degreasing temperature is 200-350℃ and the sintering temperature is 420-480℃.

2. The method according to claim 1, characterized in that, The drying temperature in step S1 is 60-100℃, and the drying time is 8-12h.

3. The method according to claim 1, characterized in that, S3 is cured in a vacuum oven for 120-300 minutes.

4. The method according to claim 1, characterized in that, The holding time in S4 is 60-300 min, and the heating rate is 2-5℃ / min.

5. The method according to claim 1, characterized in that, The holding time in S4 is 240-500 min, and the heating rate is 1-3℃ / min.

6. A biodegradable zinc alloy for medical use, characterized in that, The alloy is manufactured using the method described in any one of claims 1-5, and its surface has a controllable hierarchical porous structure or a dense structure, a compressive strength of 22-145 MPa, a hardness of 12-84 HV, and an in vitro degradation rate of 0.11-0.73 mm / year at 28 days.

7. The application of the biodegradable zinc alloy of claim 6 in clinical medical implant devices.

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