Medical polyaryletherketone implant and surface modification method thereof

Abstract

The invention discloses a medical polyaryletherketone implant and a surface modification method thereof, and the method comprises the following steps: immersing a polyaryletherketone material matrix into a saturated sodium carbonate solution used as a foaming agent, taking out the polyaryletherketone material matrix, and carrying out concentrated sulfuric acid ultrasonic treatment at room temperature; alternately treating with a saturated sodium carbonate solution and concentrated sulfuric acid until a microporous network is formed on the surface of the polyaryletherketone material matrix; carrying out surface phosphorylation on the polyaryletherketone material matrix with the microporous network formed on the surface by using a diazo reaction to obtain a surface phosphorylated matrix; treating the surface phosphorylated matrix by adopting a hydrothermal method and a chemical coprecipitation method, and forming a biomineralization layer doped with antibacterial metal ions on the surface of the matrix; and freeze-drying a hydrogel coating doped with antibacterial fatty acid on the surface of the matrix to obtain the medical polyaryletherketone implant.

Description

Technical Field

[0001] This invention belongs to the field of medical implant materials, specifically relating to a medical polyaryletherketone implant and its surface modification method. Background Technology

[0002] Implant-related infections pose a significant challenge to clinicians. Studies show that the infection rate after hip and knee replacement surgery is approximately 1%-3%, while the infection rate after pelvic and tibial tumor prosthesis reconstruction is as high as 15%-43%. Implant-related infections can lead to local and systemic infectious lesions, as well as severe bone loss, bone defects, and even multiple organ failure and death. More than one million people are affected annually, with a long-term mortality rate reaching 20%, resulting in a severe burden on medical resources. Excellent reconstructive implants should not only focus on repair and reconstruction but also on preventing complex surgical complications to achieve optimal surgical outcomes. Therefore, the development of implants with both antibacterial and bone differentiation-promoting properties for clinical reconstructive surgery is urgently needed.

[0003] Polyaryletherketone (PEEK) medical implants, such as polyetheretherketone (PEEK) and polyetherketoneketone (PEKK), are widely used in clinical practice as representative orthopedic, oral and maxillofacial, and neurosurgical repair implants due to their biomechanical properties close to the elastic modulus of bone, excellent biocompatibility, and natural radiopermeability. Applications include spinal fusion, joint replacement, sports injury repair, and craniofacial injury repair. However, PEEK and PEKK often exhibit poor integration with host bone, especially under pathological conditions, affecting their long-term stability and prognostic efficacy. To address this issue, researchers have developed various strategies for surface modification, including magnetron sputtering, plasma treatment, and chemical solution treatment, to enhance the osseointegration capacity of PEEK implants. However, these surface modification techniques involve numerous and complex processes, requiring sophisticated equipment and processes, and the resulting implants often exhibit poor overall antibacterial and osteogenic effects. Therefore, there is an urgent need to develop a surface modification method for medical PEEK implant materials that combines antibacterial and osteogenic properties.

[0004] The rapid rise of multidrug-resistant superbugs has accelerated the development of antibiotic alternative strategies. Fatty acids, as natural broad-spectrum antibacterial agents, possess direct bactericidal, immunomodulatory, and drug-enhancing functions, and their applications range from drug formulation design (e.g., stabilization of ophthalmic preparations) to bioengineering applications (e.g., the production of antimicrobial lipopeptides by genetically engineered bacteria), representing a new direction for next-generation non-antibiotic therapies. Furthermore, metal ions (such as copper, silver, strontium, iron, zinc, and gallium) have attracted attention due to their broad-spectrum antibacterial properties and low resistance potential. Copper and silver ions are renowned for their excellent bactericidal and immunomodulatory effects, effectively disrupting cell structure and interfering with the expression of genetic material, thereby clearing existing biofilms. Moreover, silver ions have been approved by the US Food and Drug Administration (FDA) and are widely used in various antibacterial clinical products. This undoubtedly lays a solid foundation for the further clinical application of antibacterial metal ion-loaded coatings. However, unlike titanium alloy implants, where metal ions can be electroplated to form a sustained-release layer on the surface of titanium alloy materials, the chemical stability of polyaryletherketone materials makes it difficult to form a sustained-release metal ion layer on their surface. Previously, scientists obtained metal sustained-release layers by biomineralizing polyaryletherketone materials. However, due to their chemical stability, the implant surface lacks nucleation sites for hydroxyapatite, making it difficult to form a large amount of biomineralized layer on its surface through this method, thus failing to achieve a long-term sustained-release effect. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a medical polyaryletherketone implant and a method for surface modification thereof.

[0006] According to a first aspect of the present invention, a method for surface modification of medical polyaryletherketone implants is provided, the method comprising: The polyaryletherketone (PAK) material matrix was immersed in a saturated sodium carbonate solution as a foaming agent, and then ultrasonically treated with concentrated sulfuric acid at room temperature. The process was repeated by alternating treatment with saturated sodium carbonate solution and concentrated sulfuric acid until a microporous network was formed on the surface of the PAK material matrix. A diazo reaction was applied to phosphorylate the surface of a polyarylether ketone material matrix with a microporous network on the surface to obtain a phosphorylated matrix. A phosphorylated substrate was treated with a hydrothermal method and a chemical co-precipitation method to form a biomineralized layer doped with antibacterial metal ions on the surface of the substrate. A layer of hydrogel coating containing antibacterial fatty acids is freeze-dried on the surface of the substrate to obtain a medical polyaryletherketone implant.

[0007] According to a second aspect of the present invention, a medical polyaryletherketone-based medical implant is provided, which is prepared by the surface modification method described above.

[0008] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention employs surface foaming technology, immersing a polyaryletherketone (PAK) material matrix in a saturated sodium carbonate solution as a foaming agent, and then ultrasonically treating it with concentrated sulfuric acid at room temperature. Through alternating treatment with saturated sodium carbonate solution and concentrated sulfuric acid, a layered microporous structure resembling natural bone is formed on the surface of the medical PAK implant, increasing its roughness and contact area, which is beneficial for bone ingrowth and integration. At the same time, it can significantly increase the specific surface area of ​​the implant, which is beneficial for increasing the load of subsequent coatings.

[0009] 2. To address the current problem that hydroxyapatite is difficult to deposit on the surface of medical polyaryletherketone materials lacking nucleation sites, this invention applies a diazo reaction to phosphorylate the surface to graft phosphate groups as efficient nucleation sites for hydroxyapatite, thereby improving its biocompatibility and providing nucleation sites for hydroxyapatite. This method can significantly increase the loading of hydroxyapatite on the implant surface and improve the biocompatibility of the implant.

[0010] 3. This invention involves freeze-drying a layer of hydrogel coating containing antibacterial fatty acids onto the surface of the substrate. This coating has wide applications, is FDA-approved for safety, exhibits good biocompatibility, strong antibacterial activity, and good osteogenic properties. Unlike other coatings that require surface modification of medical implants and involve complex manufacturing processes, this invention features a simple process. Unlike chemical grafting, physical blending, electrostatic interactions, or acid-base etching, this invention only requires simple brushing or spraying, followed by freeze-drying in a freeze dryer to form a hydrogel freeze-dried coating on the surface of the medical implant. Furthermore, the coating can be customized.

[0011] 4. Wide range of applications: The medical polyaryletherketone implants provided by this invention can effectively improve the current shortcomings of medical polyaryletherketone implants in orthopedics, oral and maxillofacial surgery and neurosurgery, and reduce the occurrence of early postoperative infection and related complications such as implant loosening after implantation. Attached Figure Description

[0012] To more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0013] Figure 1 This is a schematic flowchart of the surface modification method for polyarylether ketone materials of the present invention; Figure 2 The J774A.1 macrophages in Example 1 were subjected to different Cu... 2+ CCK-8 assay for cell viability at LA concentration; Figure 3 Characterization diagrams of surface-foamed PEEK (FPEEK) in Example 1: (A) Representative photographs, scanning electron microscope images and cross-sectional images of PEEK implants with different surface foaming times, scale bars, 250 μm, 25 μm, 500 μm and 50 μm; (B) Representative high-resolution confocal laser scanning microscope (CLSM) images of PEEK implants with different surface foaming times, and corresponding (C) surface roughness, (D) specific surface area, (E) Fourier transform infrared (FTIR) spectra, (F) pore size distribution and (G) porosity; Figure 4 Characterization of phosphorylated FPEEK (PFPEEK) in Example 1: (A) Representative photographs of PPFPEEK; (B) Water contact angles of SPEEK, FPEEK, and PPFPEEK; (C) Representative high-resolution N 1s (First line) and P 2p (Second row) X-ray photoelectron spectroscopy (XPS) results of the spectra show the properties of FPEEK and PFPEEK surfaces. The raw experimental data are shown in black lines. Figure 5 Characterization of PPEEK (nCuHA@PFPEEK) after surface biomineralization treatment: (A) X-ray diffraction (XRD) patterns and Fourier transform infrared (FTIR) spectra of different PEEK matrices; (B) representative elemental energy spectra of nCuHA@PFPEEK and its corresponding materials; and (C) atomic ratios, scale bar, 25 μm; (D) representative scanning electron microscope images of the pore-to-pore structure and nano-hydroxyapatite on the nCuHA@PFPEEK surface, scale bar, 50 μm and 10 μm; (E) different initial Cu... 2+ nCuHA@PFPEEK prepared with concentrated mineralization solution in DMEM medium Cu 2+ Release behavior; Figure 6 These are scanning electron microscope images of FPEEK and PPFEEK after surface biomineralization treatment; Figure 7 Characterization of PEEK matrices at four different treatment stages: (A) representative photographs, scanning electron microscope images, and (B) high-resolution confocal laser scanning microscope (CLSM) images, showing the surface characteristics of PEEK matrices with different surface modifications, and their corresponding (C) surface roughness, (D) specific surface area, and (E) water contact angle, scale bars, 10 μm and 1 μm; (F) hydrogel release behavior with different LA doping concentrations; (G) Cu 2+ and (H)Ca 2+ Release behavior of various surface-modified PEEK implants in phosphate buffer solutions of different pH values; Figure 8 This is a photograph of a PEEK rod after surface modification according to the present invention; Figure 9 These are actual images of medical PEEK sports medicine interface screws and spinal interbody fusion devices after surface modification according to the present invention. Figure 10 This is a fluorescent photograph of rat bone marrow mesenchymal stem cells stained with live and dead cells 48 hours after inoculation on the surface of PEEK disks and modified LAnCuHAPFPEEK disks in Example 1 of the present invention. Figure 11 This is a schematic diagram showing the expression of osteogenic-related genes Runx2 and Sp7 72 hours after rat bone marrow mesenchymal stem cells were inoculated onto the surface of PEEK discs and modified LAnCuHAPFPEEK discs in Example 1 of the present invention. Figure 12 This is a schematic diagram illustrating the application of medical polyaryletherketone implants provided in the embodiments of the present invention. Detailed Implementation

[0014] like Figure 1 As shown, this invention provides a surface modification method for polyaryl ether ketone materials that possesses both antibacterial and osteogenic properties. The following examples further describe this invention, but the scope of protection of this invention is not limited thereto. The descriptions of the following examples are merely for the purpose of helping to understand this invention. It should be noted that those skilled in the art can make various improvements and modifications to this invention without departing from the principles of this invention, and these improvements and modifications also fall within the scope of protection of the claims of this invention.

[0015] It should be noted that, unless otherwise specified, the features in the following embodiments and implementation methods can be combined with each other.

[0016] like Figure 1 As shown, this invention provides a flowchart of a surface modification method for medical polyaryletherketone implants. The method employs surface foaming to form a layered microporous structure that mimics natural bone on the surface of the polyaryletherketone implant, increasing its roughness and contact area. Based on this, this invention uses a diazo reaction to chemically graft phosphate groups onto its surface as efficient nucleation sites for hydroxyapatite. Subsequently, a hydrothermal method and a chemical co-precipitation method are applied to form a large-area biomineralized layer doped with antibacterial metal ions on its surface. Finally, a hydrogel doped with antibacterial fatty acids is uniformly freeze-dried on the porous rough surface, and its antibacterial and osteogenic biological properties are characterized.

[0017] The preparation method is as follows: (1) Surface foaming: The polyaryletherketone matrix was immersed in a sodium carbonate solution as a foaming agent, and then ultrasonically treated with concentrated sulfuric acid at room temperature. Then, the sample was treated by alternating between sodium carbonate solution and concentrated sulfuric acid solution until a microporous network was formed on the sample surface. After the above surface foaming, the matrix was immersed in sodium carbonate solution for ultrasonic cleaning to remove residual concentrated sulfuric acid, and then removed after 12 hours.

[0018] Furthermore, the medical polyaryletherketone materials include polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyetherketone (PEK), etc.

[0019] (2) Surface phosphorylation: The above matrix was immersed in 0.4-0.8M hydrochloric acid containing 0.8-1.6% sodium nitrite (w / w) and 1.4-1.8% p-phenylenediamine (w / w) at 0°C for 5 minutes. Then, 3-5% hypophosphoric acid (w / w) was added, followed by magnetic stirring for another 5 hours. The matrix was then removed and immersed in ultrapure water for ultrasonic treatment for 1 hour to remove any physically adsorbed diazonium cations. Subsequently, the matrix was immersed in 0.4-0.8M hydrochloric acid containing 0.8-1.6% sodium nitrite (w / w) and 0.1-0.4% 2-aminoethylphosphonic acid (w / w) at 0°C for 5 minutes. Then, 3-5% hypophosphoric acid (w / w) was added, followed by magnetic stirring for another 5 hours. The matrix was then removed and ultrasonicated in ultrapure water for 1 hour to obtain a surface phosphorylated matrix.

[0020] (3) Hydrothermal method and chemical coprecipitation method: The above matrix is ​​immersed in a simulated body fluid mineralization solution containing metal ions, ammonia water is added to adjust the pH of the solution to 10, and the solution is placed in a high-temperature reactor and heated at 200°C for 24 hours. After that, it is gradually cooled and left to stand for 48 hours to form a biomineralization layer doped with antibacterial metal ions on the surface of the matrix.

[0021] Furthermore, the antibacterial metal ions include copper, silver, strontium, iron, zinc, gallium, etc.

[0022] (4) The surface of the above-mentioned substrate is uniformly sprayed with hydrogel containing antibacterial fatty acids, and then freeze-dried in a freeze dryer to form a hydrogel freeze-dried coating, thereby obtaining a medical polyarylether ketone type medical implant.

[0023] Furthermore, the antibacterial fatty acids include lauric acid, capric acid, myristic acid, oleic acid, linoleic acid, etc.

[0024] Furthermore, the hydrogel comprises methacrylamide gelatin, methacrylamide sodium alginate, methacrylamide chitosan, methacrylamide methyl chitosan, methacrylamide dextran, and methacrylamide chondroitin sulfate.

[0025] Furthermore, the medical implants include sports medicine rivets, interface screws, spinal interbody fusion devices, artificial joint prostheses, 3D-printed prostheses, etc. Figure 12 As shown.

[0026] Example 1: Surface modification of medical PEEK disks loaded with copper ions and lauric acid. 1. Cytotoxicity assays of different concentrations of copper ions and lauric acid This embodiment uses copper ions (Cu) 2+ Cu and lauric acid (LA) are used as antibacterial agents, but are not limited to Cu. 2+ And LA, other antibacterial metal ions and fatty acids are also suitable for this invention. Furthermore, this example uses mouse mononuclear macrophages (J774A.1) as experimental cells, but is not limited to J774A.1; various cell types from other species are suitable for this study. Figure 2 As shown, Cu was detected using the CCK-8 method. 2+ And the cytotoxicity of LA, when Cu 2+ No cytotoxicity was observed at concentrations below 0.8 mM and LA concentrations below 90 μg / mL.

[0027] 2. Surface modification technology (1) Surface foaming: The polyaryletherketone matrix was immersed in a sodium carbonate solution as a foaming agent, and then ultrasonically treated with concentrated sulfuric acid at room temperature. Next, the two solutions were used alternately until a microporous network formed on the sample surface. After surface foaming, the matrix was immersed in a sodium carbonate solution for ultrasonic cleaning to remove residual concentrated sulfuric acid, and then removed after 12 hours.

[0028] (2) Surface phosphorylation: As shown in Table 1, the above matrix was immersed in 0.4-0.8M hydrochloric acid containing 0.8-1.6% sodium nitrite (w / w) and 1.4-1.8% p-phenylenediamine (w / w) and magnetically stirred at 0°C for 5 minutes. Then, 3-5% hypophosphoric acid (w / w) was added, and the matrix was magnetically stirred again for 5 hours. The matrix was then removed and ultrasonically treated in ultrapure water for 1 hour to remove any physically adsorbed diazonium cations. Subsequently, the matrix was immersed in 0.4-0.8M hydrochloric acid containing 0.8-1.6% sodium nitrite (w / w) and 0.1-0.4% 2-aminoethylphosphonic acid (w / w) and magnetically stirred at 0°C for 5 minutes. Then, 3-5% hypophosphoric acid (w / w) was added, and the matrix was magnetically stirred again for 5 hours. The matrix was then ultrasonically treated in ultrapure water for 1 hour to obtain a surface phosphorylated matrix.

[0029] (3) Hydrothermal method and chemical coprecipitation method: The above matrix is ​​immersed in 1.2 times the simulated body fluid mineralization solution containing 0.01M metal ions, 40% ammonia water is added to adjust the pH of the solution to 10, and the matrix is ​​placed in a high-temperature reactor and heated at 200°C for 24 hours. After gradually cooling and standing for 48 hours, a biomineralization layer with antibacterial metal ions is formed on the surface of the matrix.

[0030] (4) The surface of the substrate is uniformly sprayed with hydrogel containing 5% antibacterial fatty acid, and then freeze-dried in a freeze dryer to form a hydrogel freeze-dried coating.

[0031] Table 1: Coverage of hydroxyapatite after surface mineralization treatment with different concentrations of various reagents used for surface phosphorylation. 3. Characterization of the successful formation of microporous structures on the surface of PEEK disks using foaming technology This embodiment uses a PEEK disk (10 mm in diameter and 3 mm in thickness, provided by Zhejiang Kehui Medical Co., Ltd.) as the substrate, but is not limited to PEEK material and disk shape; other polyaryletherketone materials are also applicable to this invention. Figure 3 As shown, surface foaming treatment of PEEK material resulted in an increasing number of three-dimensional interconnected biomimetic natural bone network structures on the PEEK surface with prolonged alternating treatment times, as revealed by scanning electron microscopy (SEM). The maximum pore size reached 200 μm. Cross-sectional SEM results showed that the biomimetic natural bone network structure layer gradually thickened with prolonged surface foaming treatment time, reaching a thickness of 200 μm. Furthermore, high-resolution confocal laser scanning microscopy (CLSM) revealed an increase in surface undulation, i.e., a gradual increase in surface roughness, with prolonged foaming treatment time. Pump pressure tests showed a significant increase in surface porosity and specific surface area with prolonged treatment time, with porosity reaching 40%-50%, indicating that this surface modification process can perfectly reshape the natural trabecular bone structure. Fourier transform infrared spectroscopy (FTIR) results showed the appearance of a characteristic peak (1159.51 cm⁻¹) of sulfonic acid groups after foaming treatment. -1 ), and the surface sulfonic acid groups were successfully mounted on the PEEK surface. We define the surface-foamed PEEK as FPEEK.

[0032] 4. Phosphorylation treatment of FPEEK surface using diazo reaction Figure 4 The image shows FPEEK after surface phosphorylation treatment. The surface is brown and is defined as PFPEEK. Compared to the unphosphorylated matrix material, its water contact angle is significantly increased, which is due to the introduction of hydrophobic benzene ring groups during the diazo reaction. Furthermore, compared to undiazo-treated FPEEK, X-ray photoelectron spectroscopy results show N=O and NH3 groups on the PFPEEK surface. - P=O (P2p3 ) and P=O (P 2p1 The characteristic peaks of ) indicate that the surface diazo reaction successfully modified the FPEEK surface with phosphate groups.

[0033] 5. Formation of biomineralized layer on PPFEEK surface using hydrothermal and chemical coprecipitation methods. This embodiment uses copper ions as antibacterial metal ions, but is not limited to copper ions; other antibacterial metal ions are also applicable to this invention. Figure 5 The image shows PPFEEK after surface biomineralization treatment, defined as nCuHA@PFPEEK. Its X-ray diffraction (XRD) pattern shows characteristic peaks of hydroxyapatite (HA), and its Fourier transform infrared spectrum is shown at a wavelength of 1100 cm⁻¹. - and 950cm - The appearance of a characteristic peak indicates that PO4 has been successfully introduced onto its surface. 2- Surface energy dispersive spectroscopy (EDS) results for nCuHA@PFPEEK showed that Ca, N, Cu, and P elements were uniformly distributed on the surface, and the (Cu+Ca) / P ratio of 1.6745 was close to the calcium-to-phosphorus ratio of hydroxyapatite (1.67). Furthermore, scanning electron microscopy (SEM) results showed that hydroxyapatite crystals were uniformly distributed within the microporous network structure of nCuHA@PFPEEK, indicating that hydroxyapatite can be stably deposited within the microporous network structure. The biomineralized Cu layer on the substrate surface... 2+ The release behavior shows that it can release explosively within 7 days, after which Cu 2+ The sustained release can last up to 35 days. For example... Figure 6 As shown, compared with the biomineralized layer on the FPEEK surface, the FPEEK surface, which provides phosphate nucleation sites, exhibits more deposited hydroxyapatite after surface phosphorylation treatment, thus solving the current problem that hydroxyapatite is difficult to deposit on the surface of medical polyaryletherketone materials lacking nucleation sites.

[0034] 6. Application of freeze-drying method to realize the freeze-drying of nCuHA@PFPEEK surface antibacterial hydrogel This embodiment uses lauric acid (LA) as an antibacterial metal ion, but is not limited to LA; other antibacterial fatty acids are also applicable to this invention. This embodiment uses methacrylamide gelatin, but is not limited to methacrylamide gelatin; other types of hydrogels are also applicable to this invention. For example... Figure 7As shown, lyophilized LA-doped methacrylamide gelatin was successfully loaded onto the substrate surface using a lyophilization method. The surface exhibited a white, frosty appearance and was defined as LAnCuHA@PFPEEK. Through a series of surface modification measures, the surface roughness, specific surface area, and water affinity of the PEEK substrate were significantly improved. To explore the optimized LA release curve of LA-doped GelMA, biodegradation experiments were conducted on LA-doped GelMA layers with different initial LA concentrations. Based on the biodegradation behavior curves (… Figure 7 (F) All samples rapidly released LA within 7 days in DMEM medium, with sustained release over the following 21 days. Furthermore, the biodegradation behavior of the copper-doped hydroxyapatite mineralization layer is a prerequisite for potential in vivo Ca²⁺ and Cu²⁺ release, and the acidic medium of the infection microenvironment provides a favorable platform for the ion-responsive release from nCuHA. (See kinetic curves). Figure 7 As shown in G, H), under acidic aqueous solution conditions, the mineralized layer released approximately 88.9% of Cu within 28 days. 2+ and Ca 2+ The other groups showed only trace background release. Furthermore, the biodegradation behavior of the mineralized layer was unaffected by the presence of the LA-doped hydrogel layer, indicating its ideal acid-responsive properties in the infected microenvironment.

[0035] II. Surface Modification of Medical PEEK Rods Loaded with Copper Ions and Lauric Acid, Example 2 This embodiment uses a PEEK rod (see dimensions). Figure 8 A (provided by Zhejiang Kehui Medical Co., Ltd.) was used as the matrix, and surface modification treatment was performed according to the above method. However, this method is not limited to PEEK materials and rod-shaped forms; other polyarylether ketone materials are also applicable to this invention. Figure 8 As shown, through the treatment of the present invention, the surface of PEEK rod-shaped material exhibits excellent surface modification effect. After surface modification, the smooth surface of PEEK, LAnCuHA@PFPEEK surface, presents a three-dimensional interconnected biomimetic porous network structure like a honeycomb, which significantly improves the loading of antibacterial hydrogel and copper-doped hydroxyapatite, while providing a scaffold structure for the ingrowth of new bone.

[0036] III. Example 3: Surface Modification of Copper Ion- and Lauric Acid-Loaded Medical Sports Medicine Interface Screws and Spinal Interbody Fusion Devices To better meet the needs of clinical translation, this embodiment uses medical PEEK interface screws (Model PA9A2, PEEK, φ4.5◊19 mm, provided by Beijing Keyi Medical Co., Ltd.) and spinal interbody fusion devices (Model RH-II, PEEK, 25◊14 mm, provided by Beijing Keyi Medical Co., Ltd.) as the substrate, but is not limited to medical PEEK interface screws and spinal interbody fusion devices; other polyaryletherketone clinical medical materials are also applicable to this invention. Figure 9 As shown, without altering the original structure of the medical PEEK interface screw and the spinal interbody fusion device, the present invention performs surface modification treatment according to the above method, exhibiting excellent surface modification effects on its surface.

[0037] IV. Biocompatibility and Osteogenesis Capacity of Surface-Modified PEEK Material in Example 4 This example uses rat bone marrow mesenchymal stem cells (rBMSCs) as experimental cells, but is not limited to rBMSCs; various cell types from other species are also suitable for this study.

[0038] In this example, blank PEEK disks and modified LAnCuHA@PFPEEK disks, 10 mm in diameter and 1 mm in height, were selected. Both sets of materials were sterilized with ethylene oxide at low temperature and placed in 24-well plates, with 3 replicates per set. rBMSCs cell suspension (10... 5 500 μl of the solution (per ml) was seeded into each well on both groups of PEEK discs and incubated at 37°C for 24 h, followed by washing three times with sterile PBS. The cells were then stained using a cell viability / death assay kit (Meilun, Dalian) and observed using a laser confocal microscope (CLSM, Germany). Calcein fluoresced to green fluorescence in live cells, while propidium iodide fluoresced to red fluorescence in dead cells. Figure 10 Fluorescent images of two groups of surface cells after 48 hours of culture, showing live and dead cell staining. Green represents live cells, and red represents dead cells. Figure 10 Both the blank PEEK disk and the modified LAnCuHA@PFPEEK disk can maintain the activity of rBMSCs, demonstrating the good biocompatibility of PEEK and the modified PEEK.

[0039] The rBMSCs cell suspension (10) was prepared using the same method as described above. 5 Cellular RNA was seeded at 500 μl per well on both groups of PEEK discs and incubated at 37°C for 72 hours. Cells were then washed three times with sterile PBS. RNA was subsequently extracted using the Trizol method, and the expression of osteogenic-related genes Runx2 and Sp7 was detected by qPCR. Figure 11 The expression of osteogenic-related genes Runx2 and Sp7 was observed in two groups of surface cells after culture. Figure 11The modified PEEK significantly enhanced Runx2 and Sp7 expression compared to the unmodified PEEK, demonstrating its superior osteogenic properties. The above embodiments are only used to illustrate the design concept and features of the present invention, and their purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. The protection scope of the present invention is not limited to the above embodiments. Therefore, all equivalent changes or modifications made based on the principles and design ideas disclosed in the present invention are within the protection scope of the present invention.

Claims

1. A method for surface modification of medical polyaryletherketone implants, characterized in that, The method includes: The polyaryletherketone (PAK) material matrix was immersed in a sodium carbonate solution used as a foaming agent, and then ultrasonically treated with concentrated sulfuric acid at room temperature. The process was repeated by alternating treatment with sodium carbonate solution and concentrated sulfuric acid until a microporous network was formed on the surface of the PAK material matrix. A diazo reaction was applied to phosphorylate the surface of a polyarylether ketone material matrix with a microporous network on the surface to obtain a phosphorylated matrix. A phosphorylated substrate was treated with a hydrothermal method and a chemical co-precipitation method to form a biomineralized layer doped with antibacterial metal ions on the surface of the substrate. A layer of hydrogel coating containing antibacterial fatty acids is freeze-dried on the surface of the substrate to obtain a medical polyaryletherketone implant.

2. The surface modification method for medical polyaryletherketone implants according to claim 1, characterized in that, The process of applying a diazo reaction to phosphorylate the surface of a polyarylether ketone matrix with a microporous network on its surface to obtain a phosphorylated matrix includes: The polyaryletherketone matrix with a microporous network on its surface is immersed in 0.4-0.8M hydrochloric acid containing 0.8-1.6% sodium nitrite and 1.4-1.8% p-phenylenediamine by volume, and stirred thoroughly; then 3-5% hypophosphoric acid is added, and stirred thoroughly. The substrate is removed and immersed in ultrapure water for ultrasonic treatment to remove any physically adsorbed diazonium cations; The matrix was then immersed in 0.4-0.8M hydrochloric acid containing 0.8-1.6% sodium nitrite and 0.1-0.4% 2-aminoethylphosphonic acid by volume, stirred thoroughly, and then 3-5% hypophosphoric acid was added. After stirring thoroughly, the matrix was removed and ultrasonically treated in ultrapure water to obtain a surface phosphorylated matrix.

3. The surface modification method for medical polyaryletherketone implants according to claim 1, characterized in that, The process of forming a biomineralized layer doped with antibacterial metal ions on the surface of a phosphorylated matrix by treating it with hydrothermal and chemical coprecipitation methods includes: The substrate is immersed in a simulated body fluid mineralization solution containing antibacterial metal ions, the pH of the solution is adjusted to 10, and the substrate is placed in a high-temperature reactor for full reaction. After gradient cooling, a biomineralization layer containing antibacterial metal ions is formed on the surface of the substrate.

4. The surface modification method for medical polyarylether ketone implants according to claim 3, characterized in that, The process of treating a phosphorylated substrate using hydrothermal and chemical co-precipitation methods to form a biomineralized layer doped with antibacterial metal ions on the surface of the substrate further includes: The substrate was immersed in a simulated body fluid mineralization solution containing 0.01M antibacterial metal ions at 1.2 times the volume. Ammonia water with a volume fraction of 40% was added to adjust the pH of the solution to 10. The solution was then placed in a high-temperature reactor for full reaction. After gradient cooling, a biomineralization layer containing antibacterial metal ions was formed on the surface of the substrate.

5. The surface modification method for medical polyaryletherketone implants according to claim 1, characterized in that, The process of freeze-drying a hydrogel coating containing antibacterial fatty acids on the surface of the substrate includes: The substrate surface is uniformly sprayed with a hydrogel containing 5% antibacterial fatty acid, and then freeze-dried in a freeze dryer to form a hydrogel freeze-dried coating.

6. The surface modification method for a medical polyaryletherketone implant according to claim 1, characterized in that, Polyaryletherketone materials include polyetheretherketone, polyetherketoneketone, and polyetherketone.

7. A method for surface modification of medical polyaryletherketone implants according to claim 1 or 3, characterized in that, The antibacterial metal ions include copper, silver, strontium, iron, zinc, gallium, etc.

8. The surface modification method for medical polyaryletherketone implants according to claim 1, characterized in that, The antibacterial fatty acids include lauric acid, capric acid, myristic acid, oleic acid, linoleic acid, etc.

9. The surface modification method for medical polyaryletherketone implants according to claim 1, characterized in that, The hydrogel comprises methacrylamide gelatin, methacrylamide sodium alginate, methacrylamide chitosan, methacrylamide methyl chitosan, methacrylamide dextran, and methacrylamide chondroitin sulfate.

10. A medical implant made of polyaryletherketone, characterized in that, It is prepared by the surface modification method according to any one of claims 1-9.

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