Bacteriostatic and degradable magnesium metal stent

Abstract

The application belongs to the field of degradable magnesium metal medical devices, and particularly relates to a bacteriostatic and degradable magnesium metal stent. 2 The degradable magnesium metal stent comprises a stent body and a plurality of micro-nano structures with different degradation rates arranged on the surface of the stent body. 2 The micro-nano structures with different degradation rates comprise: a particle array structure with a degradation rate of 0.5-5 mg / (cm 2 ·d), a stripe array structure with a degradation rate of 3-16 mg / (cm 2 ·d), and a convex array structure with a degradation rate of 13-32 mg / (cm 2 ·d). The micro-nano structures with different degradation rates are arranged according to a set degradation direction to realize directional degradation of the magnesium metal stent. The magnesium metal stent has the functions of bacteriostasis and controllable directional degradation.

Description

Technical Field

[0001] This invention belongs to the field of biodegradable magnesium metal medical devices, and particularly relates to an antibacterial and biodegradable magnesium metal stent. Background Technology

[0002] In medicine, stents are commonly used medical devices in the repair of internal cavities. Traditional stents are mostly made of inert metals and their alloys. Although these materials have the advantages of high strength and good corrosion resistance, they have poor bioactivity and are non-degradable, requiring a second surgery for removal, which causes secondary pain to patients.

[0003] Absorbable stents made primarily of magnesium metal, a biodegradable material, overcome many shortcomings of traditional stent materials. They have been extensively studied by numerous scholars, and the WE43 magnesium alloy vascular stent invented by German company Bacler Medical has entered clinical application. However, there are still two main problems with magnesium metal stent implantation. Firstly, there is the risk of bacterial contamination during surgery; infection of the device surface leads to surgical failure. Secondly, there is the degradation problem of magnesium metal. Magnesium degradation mainly involves pitting or uniform corrosion. Although the stent has the same contact with human tissue, stress corrosion and pitting can cause different degradation rates in different areas, and the degradation process after implantation is difficult to control. Premature degradation of the stent in support areas can lead to stent failure. Patent CN102485184A discloses a plastic bile duct stent with uniformly deposited nano-silver particles on its inner and outer walls for antibacterial properties; however, the plastic material used in this patent has inferior mechanical properties compared to metal materials and is non-biodegradable. Patent CN102284086A discloses a biodegradable polymeric bile duct stent for treating bile duct stones. However, this stent, also made of polymeric material, has inferior mechanical properties compared to metal materials. Patent CN106668952A improves biocompatibility by setting a first temperature-controlled coating on the inner surface of the stent body and a second temperature-controlled coating on the outer surface, with the drug coating placed on the outer surface of the second temperature-controlled coating. However, its coating preparation process is relatively complex, and because it is a monolithic coating, it cannot change the regional degradation rate of the magnesium metal stent, thus failing to achieve controlled degradation.

[0004] Therefore, it is necessary to develop simple, fast, convenient, and precise antibacterial and directional degradation technologies to solve the current problems encountered by magnesium metal stents. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a magnesium scaffold with antibacterial properties and controllable directional degradation. Based on existing approved magnesium scaffolds and structures, this method uses an ultrafast pulsed laser to construct specific micro / nano structures at specific locations on the magnesium scaffold. These micro / nano structures provide temporary resistance to bacterial adhesion and long-term resistance to localized corrosion of the metal device. By adjusting the size of the laser-treated area and the morphology of the micro / nano structures, the scaffold achieves antibacterial function in the early stages of degradation within the implanted body, and then degrades directionally from both sides towards the central support area after implantation. This invention leverages the advantages of ultrafast pulsed lasers—low thermal impact on the substrate, high power density, high processing precision, and direct-write processing—to achieve precise and personalized processing of specific structures on degradable magnesium surfaces. Furthermore, the laser processing location, area size, and micro / nano structure morphology can be flexibly adjusted according to application needs to meet various requirements.

[0006] The technical solution for achieving the objective of this invention is as follows:

[0007] An antibacterial and biodegradable magnesium metal scaffold includes a magnesium metal scaffold body, and micro / nano structures with different degradation rates are formed on the surface of the magnesium metal scaffold body. The micro / nano structures with different degradation rates include those with a degradation rate of 0.5-5 mg / (cm³). 2 The particle array structure of d) has a degradation rate of 3-16 mg / (cm³). 2 The striped array structure and degradation rate of d) were 13-32 mg / (cm³). 2 The protruding array structure of ·d) and the micro-nano structures with different degradation rates are arranged in a set degradation direction to achieve directional degradation of the magnesium metal scaffold.

[0008] Furthermore, the degradation rate is 0.5-5 mg / (cm³). 2 The particle array structure of ·d) consists of particles with a diameter of 1-200 nm and a height of 1-100 nm.

[0009] Furthermore, the degradation rate is 3-16 mg / (cm³). 2 The stripe array structure of ·d) consists of stripes with a width of 300-800 nm and a height of 100-300 nm.

[0010] Furthermore, the degradation rate is 13-32 mg / (cm³). 2 The protrusion array structure of ·d) consists of array protrusions with a diameter of 100-3000nm and a height of 10-10000nm.

[0011] Furthermore, the degradation rate is 0.5-5 mg / (cm³). 2 The particle array structure of ·d) is located at the center, with degradation rates of 3-16 mg / (cm³) arranged on both sides of the particle array structure.2 The striped array structure (d) has a degradation rate of 13-32 mg / (cm²) on both sides. 2 The raised array structure of ·d) enables the magnesium metal scaffold to undergo directional degradation from both ends to the center.

[0012] Furthermore, the micro- and nanostructures with different degradation rates are fabricated using ultrafast pulsed laser processing.

[0013] Furthermore, the parameters for the ultrafast pulsed laser processing are as follows: laser frequency 2000K-30MHz, pulse energy 1000J-2MJ, spot diameter 20-80μm, line spacing 60-1000μm, and scanning speed 50-1000mm / s.

[0014] Furthermore, the magnesium metal support material is pure magnesium or WE43 magnesium alloy.

[0015] This magnesium metal stent can be used for cardiac stents, vascular stents, bile duct stents, and urethral stents.

[0016] The overall structure of this bracket is a common type on the market, made from extruded magnesium metal bars through machining. The diameter of the magnesium metal bracket body is 2-10mm, and the length is 30-120mm.

[0017] Through experiments, we found that surfaces with different micro / nanostructures possess antibacterial capabilities, primarily because the presence of these surface structures affects wettability, making it difficult for bacteria to adhere to their surfaces. Furthermore, surfaces with different micro / nanostructure characteristics influence the material's degradation rate; specifically, the degradation rates of particles, stripes, and protruding magnesium metal scaffolds are 0.5-5 mg / (cm³). 2 ·d), 3-16mg / (cm) 2 ·d), 13-32mg / (cm) 2 (d) This change in degradation rate is mainly related to surface structure. Due to differences in surface structure, the surface properties of the material, such as wettability and surface potential, also differ. The wettability and surface potential of different structures affect the contact area between the surface and the corrosive liquid, thus affecting the degradation rate of the material. However, the surface potential of different sizes with the same surface structure does not differ significantly. In summary, the changes in the antibacterial properties and degradation rate of the material are mainly caused by differences in surface structure.

[0018] The micro / nano structures were fabricated using pulsed laser processing. The specific steps of pulsed laser processing are as follows: First, the dimensions of the magnesium metal support and the processing location are measured. Then, the laser is turned on, and processing parameters such as power, frequency, scanning speed, and line spacing are adjusted to ensure the laser spot illuminates the starting position of the support. Maintaining a constant distance between the laser focus and the processing location, the surface of the specific area is scanned. The parameters for pulsed laser processing are: 1 kHz–100 MHz, pulse energy 20 μJ–2 mJ, spot diameter 30–60 μm, line spacing 200–600 μm, and scanning speed 10–1000 mm / s.

[0019] The key challenges in the application of biodegradable magnesium scaffolds currently lie in pre-implantation antibacterial treatment and the non-uniform degradation and uncontrollable degradation sequence after implantation in complex physiological environments. This invention addresses these challenges by using ultrafast pulsed laser treatment on the surface of the magnesium scaffold to construct adjustable protruding structural morphology, size, and surface micro / nanostructures. This alters the surface energy and surface potential of the material, influencing bacterial adhesion. Furthermore, the presence of these micro / nanostructures induces corrosion behavior in the affected area, achieving controlled degradation and allowing the magnesium scaffold to undergo directional degradation from both ends to the central support region in a specific sequence. The laser used in this invention features minimal thermal impact on the substrate, high power density, high processing precision, and direct-write processing, enabling precise and personalized processing of specific structures on the magnesium surface. Simultaneously, the design allows for flexible adjustment of the laser processing position, area size, and micro / nanostructure morphology on the scaffold surface to meet different degradation requirements. The presence of micro / nanostructures on the scaffold surface increases surface energy and alters the surface potential, creating galvanic cells in different areas, thus allowing preferential corrosion from structures with lower potentials. Different structures also provide antibacterial adhesion effects. This magnesium metal scaffold surface treatment technology has great application potential in the field of biodegradable biomedical devices.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] 1) It can achieve an antibacterial effect on magnesium metal scaffolds before implantation. The magnesium metal scaffold of the present invention has a special micro-nano structure morphology on its surface, which changes the surface energy and surface potential of the metal, thereby achieving an antibacterial adhesion effect and maximizing the success of the surgery.

[0022] 2) It enables directional and sequential degradation of magnesium metal stents, such as directional degradation from both ends to the central support region. This invention designs micro / nano structures with special surface morphologies on the surface of the magnesium metal stent. This structure increases the metal surface area, thereby increasing the contact area with the external environment. Furthermore, the difference in surface potential between different structures can induce a galvanic cell effect in different regions, inducing corrosion to occur first at the structures with lower potential, and then proceeding with directional degradation from both ends to the central support region. This avoids uneven degradation of the biodegradable stent implanted in the body, maximizing the mechanical integrity and degradation adaptability of the stent during implantation.

[0023] 3) Only physical processing is used, without introducing other chemical elements. Ultrafast pulsed laser processing is a physical processing technology. By constructing micro-nano structures using ultrafast pulsed lasers, the magnesium metal scaffold is degraded in a directional manner without introducing other chemical elements, thus ensuring the biosafety of the material.

[0024] 4) High processing precision. Ultrafast pulsed lasers have the characteristics of minimal thermal impact on the substrate, high power density, high processing precision, and direct-write processing, enabling precise positioning of specific structures and processing of complex and fine micro-nano structures on the surface of magnesium metal supports.

[0025] 5) Personalized processing is possible. The design of this invention allows for flexible changes in the laser processing position, area size, and micro / nano structure morphology according to application needs, meeting different degradation time and degradation sequence requirements.

[0026] 6) Broad application prospects. The antibacterial and controllable directional degradation magnesium metal scaffold involved in this invention has the characteristics of antibacterial and directional degradation, maintaining mechanical integrity for a long time, adjustable corrosion initiation position and corrosion rate, and personalized processing, which can better meet the needs of the medical field. At the same time, the preparation of this surface micro-nano structure only involves the surface treatment of magnesium metal scaffolds, does not conflict with existing scaffold production processes, and can also reduce the difficulty of registration and approval of related scaffold products. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the femtosecond laser-treated area on the surface of the magnesium metal support in Example 1;

[0028] Figure 2 The microstructure of the surface of the femtosecond laser processing area in Example 1 is shown in (a) as the particle structure of the third degradation region, (b) as the stripe structure of the second degradation region, and (c) as the protrusion structure of the first degradation region.

[0029] Figure 3 This is a surface composition analysis diagram of the femtosecond laser-processed area in Example 1;

[0030] Figure 4The results show the bacterial survival rates of samples with different surface structures in Example 1;

[0031] Figure 5 The surface potentials of different structures and the untreated surface in Example 1;

[0032] Figure 6 The graph shows a comparison of the degradation length versus time between Example 1, Example 2, and the femtosecond-processed directional degradable stent and the untreated stent;

[0033] Figure 7 The surface potential of the samples with different particle sizes in Comparative Example 1 is shown.

[0034] Figure 8 The surface potential of the strip structure samples of different sizes in Comparative Example 2 is shown.

[0035] Figure 9 The surface potential of the samples with protrusions of different sizes in Comparative Example 3 is shown. Detailed Implementation

[0036] The present invention will be further described in detail below through specific embodiments. The following embodiments are merely descriptive and not limiting, and should not be used to limit the scope of protection of the present invention.

[0037] Example 1

[0038] In this embodiment, an ultrafast pulsed laser processing method is used to prepare micro-nano structures on the surface of a magnesium metal support.

[0039] The specific femtosecond laser processing steps and processes are as follows:

[0040] (1) Pure magnesium support structure is obtained by machining.

[0041] (2) Measure the dimensions of the pure magnesium metal bracket and the dimensions of the processing position. The bracket used in this example has a total length of 40mm and a diameter of 4mm.

[0042] (3) Fix the pure magnesium support onto the four-axis translation stage. Turn on the laser and adjust the laser parameters. Adjust the spot position so that the laser spot illuminates the starting position of the support. Use a partitioned processing method, with the ratio of particles, stripes, and protrusions being 3:2:1, starting processing from the tip of the support. The processing techniques are as follows: a) Laser frequency 3kHz, pulse energy 7000uJ, spot diameter 45μm, line spacing 550μm, scanning speed 1000mm / s; b) Laser frequency 500kHz, pulse energy 9000uJ, spot diameter 65μm, line spacing 550μm, scanning speed 150mm / s; c) Laser frequency 5kHz, pulse energy 12000uJ, spot diameter 35μm, line spacing 550μm, scanning speed 50mm / s. During processing, the rotating axis rotates once, the Y-axis translates by 0.1 mm, and the X-axis moves at the same time to ensure that the distance from the laser focus to the sample surface remains unchanged. This process is repeated to synchronously induce the formation of micro- and nano-structures on the surface of specific locations. Figure 3 This is the area for laser processing. Figure 2 The image shows the surface morphology of the area after processing, where a, b, and c represent the micro / nano structure.

[0043] (4) Remove the processed magnesium metal support, clean and sterilize it and then seal it.

[0044] Figure 1 This is a schematic diagram of the laser-processed area on the surface of the support. Figure 2 The surface morphology of this part after processing is shown in (a) for the granular structure of the third degradation zone, (b) for the striped structure of the second degradation zone, and (c) for the protruding structure of the first degradation zone.

[0045] Figure 3 The image shows the surface composition analysis of the femtosecond laser-processed area in Example 1. It can be seen from the image that the sample composition did not change and no harmful substances were generated, but oxides were generated on the laser-processed surface.

[0046] Figure 4 The results show the adhesion of bacteria to different structures and untreated surfaces in Example 1.

[0047] Figure 5 The surface potentials of different structures and untreated surfaces in Example 1 are shown.

[0048] Figure 6 The figure shows the relationship between the degradation length and time of the femtosecond-processed directional degradable scaffold in Example 1. As can be seen from the figure, the degradation rate of the scaffold with the structure changed significantly, indicating that the surface structure modulates the degradation rate of the scaffold.

[0049] Comparative Example 1

[0050] In this comparative example, an ultrafast pulsed laser processing method was used to prepare particle micro / nano structures of different sizes on the surface of a magnesium metal support.

[0051] The difference from Example 1 lies in the processing technology in step 3. Specifically, the processing technology is as follows: laser frequency 5kHz, pulse energy 4000uJ, spot diameter 45μm, line spacing 525μm, and scanning speeds of 500, 650, and 800 mm / s are used to process specific areas of the sample surface. During processing, the rotation axis rotates one revolution, the Y-axis translates 0.1mm, and the X-axis moves simultaneously to ensure the distance from the laser focus to the sample surface remains constant. This process is repeated. After processing, three different particle structures with diameters of 10nm and heights of 3nm, 50nm and 10nm respectively, and 150nm and 30nm respectively are synchronously induced on the surface of the specific area.

[0052] Figure 7 The results represent the surface potential of particles with different sizes. The surface potentials of particles with different sizes are not significantly different, making it difficult to form a large potential difference between different regions, thus failing to produce a sequential degradation effect.

[0053] Comparative Example 2

[0054] In this comparative example, an ultrafast pulsed laser processing method was used to prepare strip structures of different sizes on the surface of magnesium metal samples.

[0055] The difference from Example 1 lies in the processing method in step 3. Specifically, the processing technology is as follows: laser frequency 400kHz, pulse energy 7500uJ, spot diameter 60μm, line spacing 450μm, and scanning speeds of 100, 120, and 150mm / s are used to process the sample surface. During processing, the T-axis rotates one revolution, the Y-axis translates 0.2mm, and the X-axis moves simultaneously to ensure the distance from the laser focus to the sample surface remains constant. This process is repeated to cover the entire sample surface. After processing, three different array strip structures with dimensions of 300nm width and 100nm height, 350nm width and 150nm height, and 450nm width and 100nm height are synchronously induced on specific areas of the surface.

[0056] Figure 8 The results show the surface potential of strip structures of different sizes. The surface potentials of strip structures of different sizes are not significantly different, and it is difficult to form a large potential difference between different regions, thus failing to produce a sequential degradation effect.

[0057] Comparative Example 3

[0058] In this comparative example, an ultrafast pulsed laser processing method was used to prepare protruding micro / nano structures of different sizes on the surface of a magnesium metal sample.

[0059] The difference from Example 1 lies in the processing technology in step 3. Specifically, the processing technology is as follows: laser frequency 5 kHz, pulse energy 18000 uJ, spot diameter 35 μm, line spacing 500 μm, and scanning speeds of 10, 30, and 40 mm / s. During processing, the T-axis rotates one revolution, the Y-axis translates 0.2 mm, and the X-axis moves simultaneously to ensure the distance from the laser focus to the sample surface remains constant. This process is repeated to cover the entire sample surface. After processing, specific areas of the surface are synchronously induced to form three different protrusion structures with diameters of 100 nm and heights of 200 nm, 300 nm and heights of 100 nm, and 550 nm and heights of 300 nm.

[0060] Figure 9 The results show the surface potential of protrusions of different sizes. The surface potentials of protrusions of different sizes are not significantly different, and it is difficult to form a large potential difference between different regions, thus failing to produce a sequential degradation effect.

[0061] Example 2

[0062] The difference from Example 1 is that a WE43 magnesium alloy scaffold was used; the other preparation methods were the same as in Example 1. The results are as follows: Figure 6 As shown in the figure, the WE43 magnesium alloy sample with partitioned treatment has a slower degradation rate in the early stage compared to the partitioned degradation of pure magnesium sample. This is because the alloy material contains elements other than magnesium, which can make its surface oxide layer slightly thicker than that of pure magnesium material during laser ablation, resulting in a degradation rate slightly lower than that of pure magnesium material. After a period of degradation, its surface oxide layer disappears, exposing a larger specific surface area. Therefore, its corrosion rate accelerates and exceeds that of pure magnesium material.

[0063] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several modifications and improvements can be made without departing from the inventive concept, and these all fall within the protection scope of the present invention.

Claims

1. A magnesium metal scaffold that is antibacterial and biodegradable, comprising a magnesium metal scaffold body, characterized in that, Micro- and nanostructures with different degradation rates were fabricated on the surface of a magnesium metal scaffold. These micro- and nanostructures included those with degradation rates of 0.5-5 mg / (cm²). 2 The particle array structure of d) has a degradation rate of 3-16 mg / (cm³). 2 The striped array structure and degradation rate of d) were 13-32 mg / (cm³). 2 The protruding array structure of ·d) and the micro-nano structures with different degradation rates are arranged according to a set degradation direction to achieve directional degradation of the magnesium metal scaffold; The degradation rate is 0.5-5 mg / (cm³). 2 The particle array structure of d) consists of particles with a diameter of 1-200 nm and a height of 1-100 nm; The degradation rate is 3-16 mg / (cm³). 2 The stripe array structure of d) consists of stripes with a width of 300-800 nm and a height of 100-300 nm; The degradation rate is 13-32 mg / (cm³). 2 The protrusion array structure of ·d) consists of array protrusions with a diameter of 100-3000 nm and a height of 10-10000 nm.

2. The magnesium metal support according to claim 1, characterized in that, The degradation rate is 0.5-5 mg / (cm³). 2 •d) The particle array structure is located at the center, with degradation rates of 3-16 mg / (cm³) arranged on both sides of the particle array structure. 2 The striped array structure (d) has a degradation rate of 13-32 mg / (cm³) on both sides. 2 The raised array structure of ·d) enables the magnesium metal scaffold to undergo directional degradation from both ends to the center.

3. The magnesium metal support according to claim 1, characterized in that, The micro- and nanostructures with different degradation rates were fabricated using ultrafast pulsed lasers.

4. The magnesium metal support according to claim 3, characterized in that, The parameters for ultrafast pulsed laser processing are as follows: laser frequency 2000 K-30 MHz, pulse energy 1000 J-2 MJ, spot diameter 20-80 μm, line spacing 60-1000 μm, and scanning speed 50-1000 mm / s.

5. The magnesium metal support according to claim 1, characterized in that, The magnesium metal support material is pure magnesium or WE43 magnesium alloy.

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