Implantable medical device with micro-nano structure
By combining micron- and nano-structured medical polymers with medical metal substrates on the surface of implantable medical devices to form micro- and nano-structures, the problem of poor surface compatibility of implantable medical devices is solved, and cell adhesion and biocompatibility are improved.
Patent Information
- Application Number
- CN202421761905.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-07-24
- Publication Date
- 2025-10-31
- Estimated Expiration
- 2034-07-24
AI Technical Summary
Existing implantable medical devices have low surface compatibility, and the ability of cells to attach, proliferate, and differentiate on their surfaces needs to be improved.
A medical polymer coating is applied to the surface of a medical metal substrate, and micron- and nano-structured medical polymers are bonded to the surface to form a micro-nano structure, increasing the contact area between the implantable medical device and cells. The device is then integrated through processes such as hot pressing.
It improves the adhesion between implantable medical devices and cells, promotes cell proliferation and differentiation on their surface, and enhances the biocompatibility and stability of implantable medical devices.
Smart Images
Figure CN223490139U_ABST
Abstract
Description
Technical Field
[0001] This application belongs to the field of medical device technology, and in particular relates to an implantable medical device with a micro-nano structure. Background Technology
[0002] Currently, implantable medical devices are typically composed of a medical metal substrate and a medical polymer coating on its surface. Implantable medical devices can combine the excellent mechanical properties and corrosion resistance of medical metal substrates with the good biocompatibility and biodegradability of medical polymer coatings, making them a research direction with great development potential in the medical industry.
[0003] In the practical application of implantable medical devices, it is necessary to improve the biocompatibility of medical polymer coatings to promote the attachment, proliferation, and differentiation of cells such as bone cells on their surface. On the other hand, it is also necessary to improve the interfacial bonding strength between the medical metal substrate and the medical polymer coating to minimize the mechanical impact and friction of implantable medical devices on biological tissues, improve their adhesion to bone cells, and maintain stability. Therefore, for metal-polymer implantable medical devices, improving the bonding strength of the composite interface between the medical metal substrate and the medical polymer coating, as well as the biocompatibility of the medical polymer coating, is of great significance for further expanding the application range of medical implantable devices. However, there is currently little research on the structural improvement of medical polymer coatings for implantable medical devices, resulting in low surface compatibility of implantable medical devices and the need to improve the performance of cells attaching, proliferating, and differentiating on their surface. Utility Model Content
[0004] In view of this, this application provides an implantable medical device with a micro-nano structure to solve the technical problem of poor surface compatibility of implantable medical devices in the prior art.
[0005] The first aspect of this application provides an implantable medical device with a micro / nano structure, the implantable medical device comprising a medical metal substrate, a medical polymer coating, and a micro / nano structured medical polymer;
[0006] The medical polymer coating covers the surface of the medical metal substrate;
[0007] The micro / nano-structured medical polymers include micron-structured medical polymers and nano-structured medical polymers;
[0008] The medical polymer coating surface is bonded with the micron-structured medical polymer, and the micron-structured medical polymer surface is bonded with the nano-structured medical polymer.
[0009] Preferably, the surface of the medical polymer coating is integrally combined with a micron-structured medical polymer;
[0010] The micron-structured medical polymer surface is integrally combined with a nanostructured medical polymer.
[0011] Preferably, in the microstructured medical polymer, the shape of the microstructure is a hemispherical microstructure;
[0012] In the medical polymer with the nanostructure, the shape of the nanostructure is a hemispherical nanostructure.
[0013] Preferably, in the micron-structured medical polymer, the radius of the hemispherical micron structure is 20–200 μm;
[0014] In the medical polymer with the nanostructure, the radius of the hemispherical nanostructure is 100-500 nm.
[0015] Preferably, the micron-structured medical polymer is distributed in an equally spaced array on the surface of the medical polymer coating;
[0016] The nanostructured medical polymers are distributed in an equally spaced array on the surface of the microstructured medical polymers.
[0017] Preferably, the spacing between adjacent micron-structured medical polymers is 10–100 μm;
[0018] The spacing between adjacent medical polymer nanostructures is 10–200 nm.
[0019] Preferably, the surface of the medical metal substrate is distributed with micron-sized pores;
[0020] The bottom surface of the medical polymer coating is embedded in micron-sized recesses distributed on the surface of the medical metal substrate.
[0021] Preferably, the inner surface of the micron-sized concave hole is distributed with nano-circular wells.
[0022] Preferably, the shape of the micron-shaped ...
[0023] Preferably, the radius of the hemispherical micron-sized concave hole is 20–200 μm;
[0024] The radius of the spherical cap-shaped micron-sized concave hole is 20–200 μm, and the height is 30–300 μm.
[0025] The height of the nanowell is 10–100 μm, and the bottom radius is 50–500 nm.
[0026] Preferably, the surface of the medical metal substrate has micron-sized recesses arranged in an array at equal intervals;
[0027] The inner surface of the micron-sized concave holes is equidistantly arrayed with nano-circular wells.
[0028] Preferably, the spacing between adjacent micron-sized recesses is 10–100 μm.
[0029] The spacing between adjacent nanowells is 10–500 nm.
[0030] In summary, this application provides an implantable medical device with a micro / nano structure. The implantable medical device includes a medical metal substrate, a medical polymer coating, and a micro / nano structured medical polymer. The surface of the medical metal substrate is covered with the medical polymer to form the implantable medical device, while the surface of the medical polymer coating is combined with micro / nano structured medical polymers of micron and nano structures to form a micro / nano structured medical polymer. The micron-structured medical polymer has a hemispherical shape with a radius of 20–200 μm, and the nano-structured medical polymer has a hemispherical shape with a radius of 100–500 nm. The micro / nano structured medical polymer significantly increases the contact area between the implantable medical device and cells, enabling the formation of more stable, large-area adhesion spots. This strengthens the adhesion between cells and the implantable medical device, thereby promoting cell proliferation and differentiation on its surface. The biocompatibility between the implantable medical device and the organism is improved, thus solving the technical problem of low surface compatibility in existing implantable medical devices. Attached Figure Description
[0031] To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0032] Figure 1 This is a schematic diagram of the overall structure of the implantable medical device provided in Embodiment 1 of this application;
[0033] Figure 2 This is a partial structural diagram of the micron-sized recesses on the surface of the metal substrate for implantable medical devices provided in Embodiment 1 of this application. Detailed Implementation
[0034] This application provides an implantable medical device with a composite micro / nano structure to solve the technical problem of poor surface compatibility of implantable medical devices in the prior art.
[0035] The technical solutions of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.
[0036] Currently, implantable medical devices are typically constructed by combining medical-grade metal substrates with medical-grade polymer coatings. While biocompatibility can be improved by adhering bioactive substances such as cell adhesion proteins to the surface of the polymer coating, besides modifying the physiological properties of the implantable medical device itself to enhance biocompatibility, improvements to its surface structure can also be made to promote cell attachment, proliferation, and differentiation. However, current research on improving the structure of implantable medical devices is limited, resulting in low surface compatibility and hindering cell attachment, proliferation, and differentiation, thus limiting the performance of the implantable medical devices. Therefore, this application provides a technical solution for improving the surface structure of a medical-grade polymer coating on an implantable medical device. In this technical solution, the implantable medical device... The device comprises a medical metal substrate and a medical polymer coating, with the surface of the medical polymer coating featuring protruding micro / nano-structured medical polymers. Traditional implantable medical devices typically have a flat surface structure with low roughness and a small surface area. The implantable medical device provided in this application incorporates micro / nano-structured medical polymers on its surface, including micron-structured medical polymers and those with protruding nano-structures. These micro / nano-structured medical polymers increase the roughness and surface area of the implantable medical device, thereby increasing the contact area between the implantable medical device and cells, resulting in more stable, large-area adhesion spots. This strengthens the adhesion between cells and the implantable medical device, promotes cell proliferation and differentiation on the surface of the implantable medical device, and improves the biocompatibility of the medical implant.
[0037] Preferably, in implantable medical devices, this application further improves the connection method between micron-structured and nano-structured medical polymers in micro / nano-structured medical polymers. Compared to sequentially bonding micron-structured and nano-structured medical polymers to the surface of a medical polymer coating using adhesives, hot pressing and other processes allow for an integral connection between the micron-structured and polymer coatings. This integral connection makes the micron-structured medical polymer coating and the medical polymer a single unit, resulting in higher bonding strength and better stability of the micron-structured medical polymer, thus improving the durability of the implantable medical device. Simultaneously, the nano-structured medical polymer is also integrally connected with the micron-structured medical polymer, thereby enhancing the stability and durability of the implantable medical device.
[0038] As a preferred embodiment, in implantable medical devices, this application further adjusts the shape and size of the micron-structured medical polymers and the nano-structured medical polymers. In this application, the micron-structured medical polymers are hemispherical micro-nano structures with a radius of 20–200 μm; while the nano-structured medical polymers are also hemispherical micro-nano structures with a radius of 100–500 nm. The radius of the nano-structured medical polymers is smaller than that of the micron-structured medical polymers.
[0039] As a preferred embodiment, in implantable medical devices, this application further optimizes the positional distribution of micron-structured and nano-structured medical polymers within the micro / nano-structured medical polymers. This results in the distribution of micron-structured medical polymers in an equally spaced array on the surface of the medical polymer coating. An equally spaced array means that any adjacent micro / nano-structured medical polymers are spaced equidistantly, with a spacing of 10–100 μm. Similarly, nano-structured medical polymers are also equally spaced on the upper surface of the micron-structured medical polymers, with an even smaller spacing of 10–200 nm. This equally spaced array distribution helps reduce excessive local stress after the implantable medical device is implanted into the human body and subjected to mechanical impact, resulting in more uniform stress distribution and improved stability and durability of the implantable medical device.
[0040] As a preferred embodiment, this application further improves the surface structure of the medical metal substrate in implantable medical devices. The upper surface of the medical metal substrate is distributed with micron-sized recesses. These micron-sized recesses are hemispherical in shape with a radius of 20–200 μm. Nano-wells are prepared on the inner surface of the micron-sized recesses. The nano-wells increase the contact area between the medical polymer and the medical metal substrate, thereby stabilizing the connection between the medical metal substrate and the medical polymer in the implantable medical device and improving the stability and durability of the implantable medical device. The height of the nano-wells is 10–100 μm, and the bottom radius is 50–500 nm.
[0041] As a preferred embodiment, this application further improves the shape of the micron-sized recess on the surface of the medical metal substrate in implantable medical devices. In addition to the hemispherical micron-sized recess, another technical solution for the micron-sized recess is provided. The shape of the micron-sized recess is a spherical cap, which is a geometric body, referring to the part of a sphere after it has been cut off by a plane. The cross section serves as the bottom surface of the spherical cap, and the length of the line segment remaining after the diameter perpendicular to the cross section is cut off serves as the height of the spherical cap. The bottom surface of the spherical cap faces the medical polymer coating. The radius is 20-200 μm, and the height is 30-300 μm. The height of the spherical cap is greater than the radius. Because the micron-sized recess in the shape of the spherical cap is narrow at the top and wide at the bottom, it forms a mechanically interlocked structural connection with the nano-circular well prepared on the inner surface, which greatly improves the connection stability between the medical metal substrate and the medical polymer coating in implantable medical devices.
[0042] As a preferred embodiment, in implantable medical devices, this application further optimizes the positional distribution of micron-sized recesses and nano-sized circular wells in the medical metal substrate, such that the micron-sized recesses are distributed in an equally spaced array on the surface of the medical metal substrate with a spacing of 10–100 μm, and the nano-sized circular wells are distributed in an equally spaced array on the surface of the micron-sized recesses with a spacing of 10–500 nm. This further ensures that the implantable medical device is subjected to uniform force, reducing the occurrence of excessive local force after being subjected to impact.
[0043] Example 1
[0044] Embodiment 1 of this application provides an implantable medical device with a micro / nano structure, the structure of which is as follows: Figure 1 As shown; the preparation method includes: the step of preparing a medical metal substrate, the step of preparing a micro / nano structure mold, and the step of preparing a micro / nano structure medical polymer on the surface of the medical metal substrate.
[0045] The steps for preparing medical-grade metal substrates include:
[0046] Step I: Use a femtosecond laser to prepare hemispherical micron-sized concave holes on the surface of titanium alloy medical metal.
[0047] The titanium alloy was first sanded, cleaned, and dried. Then, the entire titanium alloy sheet was sealed with polyethylene terephthalate (PET) adhesive. The sealed titanium alloy was then placed horizontally on a laser processing stage for femtosecond laser processing. The laser center wavelength for femtosecond laser processing was set to 1035nm and the power to 40W. The titanium alloy material was then subjected to laser ablation to obtain a micron-sized array of concave holes on the sealed titanium alloy surface. The micron-sized concave holes were hemispherical in shape with a radius of 20μm, and were evenly distributed in an array with a spacing of 5μm.
[0048] Step II: Use hydrochloric acid etching to expand the micron-sized concave holes and prepare spherical-shaped micron-sized concave holes.
[0049] The titanium alloy surface obtained in step I was ultrasonically cleaned to remove residual debris, and then dried with cold air, retaining the polyethylene terephthalate (PET) adhesive on the titanium alloy surface. It was then immersed in a 2 mol / L dilute hydrochloric acid solution for etching. Because the PET adhesive protected the titanium alloy surface from acid corrosion, the hemispherical micron-sized pores expanded inwards through etching, resulting in spherical micron-sized pores with a radius of 40 μm and a height of 60 μm, evenly spaced in an array with a spacing of 10 μm.
[0050] Step III: Nanoscale wells are prepared on the inner surface of the micron-sized concave holes by anodizing.
[0051] The PET adhesive on the titanium alloy surface obtained in step II was removed, and the surface was ultrasonically cleaned for 15 minutes each in acetone, anhydrous ethanol, and deionized water to remove the oil stains adhering to the surface. The surface was then polished in an electrochemical polishing solution with a volume ratio of hydrofluoric acid: nitric acid: deionized water = 1:1:8, followed by ultrasonic cleaning with deionized water and drying with cold air. This solution was used as the anode, with a graphite sheet as the cathode. An ammonium fluoride / ethylene glycol electrolyte system was selected, with an ammonium fluoride concentration of 0.2 mol / L, an oxidation voltage of 30 V, an oxidation temperature of 25 °C, and an oxidation time of 20 min. Nano-wells were prepared on the inner surface of the micron-sized concave holes. The height of the nano-wells was 50 μm, the bottom radius was 100 nm, and the nano-wells were evenly distributed in an array with a spacing of 200 nm.
[0052] Step IV: Annealing the titanium alloy medical metal substrate.
[0053] The titanium alloy obtained in step III was placed in ethanol, cleaned with low-power ultrasonication, and dried. Then it was placed in a miniature box furnace for annealing at a temperature of 450℃, a holding time of 60 min, and a heating rate of 5℃ / min. After annealing, the structure of the titanium alloy medical metal substrate was stable.
[0054] The steps for fabricating micro / nano structure molds include:
[0055] Step I: Micron-sized recesses are fabricated on the surface of an aluminum sheet using femtosecond laser technology.
[0056] The pretreated aluminum sheet is placed horizontally on the laser processing stage. Micron-sized holes are obtained on the surface of the aluminum sheet by laser femtosecond etching. The laser center wavelength of the femtosecond laser processing is set to 1035nm and the power is 40W. The process is repeated multiple times to obtain an aluminum sheet with an array of micron-sized holes distributed on the surface. The micron-sized holes are hemispherical in shape with a semicircular cross-section and a radius of 40μm. They are evenly distributed in an array with a spacing of 10μm.
[0057] Step II: Nanopores are prepared on the inner surface of micron-sized pores by anodizing.
[0058] The aluminum sheet obtained in step I was cleaned and then ultrasonically cleaned for 15 minutes each in acetone, anhydrous ethanol, and deionized water to remove surface oil. It was then polished in an electrochemical polishing solution with a volume ratio of Vperchloric acid:Vethanol = 1:9, followed by ultrasonic cleaning with deionized water and drying with cold air. This was then used as the anode, with a graphite sheet as the cathode. An oxalic acid / ethanol electrolyte system with an oxalic acid concentration of 0.2 mol / L was used for a first anodizing treatment. The oxidation voltage for the first anodizing treatment was 60 V, the oxidation temperature was -5 °C, and the oxidation time was 20 min, thus preparing nanopores and obtaining a micro / nano structure mold. The nanopores were hemispherical in shape with a semi-circular cross-section and a radius of 200 nm, evenly distributed in an array with a spacing of 100 nm. Simultaneously, spherical micropores were prepared by enlarging the micropores using hydrochloric acid etching. To further increase the pore size of the nanopores, they could also be immersed in a 5 wt% phosphoric acid solution for pore enlargement. A second anodizing treatment could be performed as needed to obtain a porous structure.
[0059] The steps for preparing micro / nano-structured medical polymers on the surface of medical metal substrates include:
[0060] After placing the anodized micro / nano structure mold, polylactic acid (PLA), and annealed titanium alloy medical metal substrate in that order, the aluminum sheet is demolded. The shape and size of the micro- and nano-structured medical polymers are the same as the micro- and nano-pores in the micro / nano structure mold.
[0061] The above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.
Claims
1. An implantable medical device with a micro / nano structure, characterized in that, This includes medical-grade metal substrates, medical-grade polymer coatings, and micro / nano-structured medical polymers; The medical polymer coating covers the surface of the medical metal substrate; The micro / nano-structured medical polymers include micron-structured medical polymers and nano-structured medical polymers; The medical polymer coating surface is bonded with the micron-structured medical polymer, and the micron-structured medical polymer surface is bonded with the nano-structured medical polymer; In the medical polymer with the micron structure, the shape of the micron structure is a hemispherical micron structure; In the medical polymer with the nanostructure, the shape of the nanostructure is a hemispherical nanostructure.
2. An implantable medical device with a micro / nano structure according to claim 1, characterized in that, The surface of the medical polymer coating is integrally combined with a micron-structured medical polymer.
3. An implantable medical device with a micro / nano structure according to claim 1, characterized in that, The surface of the micron-structured medical polymer is integrally combined with the nanostructured medical polymer.
4. An implantable medical device with a micro / nano structure according to claim 1, characterized in that, In the medical polymer with micron-shaped structures, the radius of the hemispherical micron-shaped structures is 20–200 μm.
5. An implantable medical device with a micro / nano structure according to claim 1, characterized in that, In the medical polymer with the nanostructure, the radius of the hemispherical nanostructure is 100-500 nm.
6. An implantable medical device with a micro / nano structure according to claim 1, characterized in that, The micron-structured medical polymer is distributed in an equally spaced array on the surface of the medical polymer coating; The nanostructured medical polymers are distributed in an equally spaced array on the surface of the microstructured medical polymers.
7. An implantable medical device with a micro / nano structure according to claim 1, characterized in that, The surface of the medical metal substrate is distributed with micron-sized pores.
8. An implantable medical device with a micro / nano structure according to claim 7, characterized in that, The shape of the micron-shaped micron-shaped aperture is hemispherical and / or spherical-capped.
9. An implantable medical device with a micro / nano structure according to claim 7, characterized in that, The inner surface of the micron-sized concave hole is distributed with nano-circular wells.