Pork composite foam for preparing artificial skull implants, method for preparing the same and porous antibacterial pork artificial skull

Abstract

The application provides a PAEK composite foam material for preparing artificial skull implants and a preparation method and a porous antibacterial PAEK artificial skull, relates to the technical field of medical biomaterials, and the PAEK composite foam material takes polyaryletherketone as a matrix and has a porous structure, the porous structure is formed by supercritical carbon dioxide foaming, and the pore wall of the porous structure is dispersed with a metal antibacterial component and an optional metal bone promoting component. The surface porous structure of the PAEK composite foam material for preparing artificial skull implants provided by the application can have better cell adhesion capacity, wherein the metal antibacterial component can act as a nucleating agent to ensure product cell uniformity, and can be fixed in the cell after processing, contact the human body after implantation, and continuously release metal ions for antibiosis, so that the release process is more stable and the release time is longer.

Description

Technical Field

[0001] This invention relates to the field of medical biomaterials technology, and in particular to a PAEK composite foam material for preparing artificial skull implants, its preparation method, and a porous antibacterial PAEK artificial skull. Background Technology

[0002] Skull defects are a common neurosurgical condition, often caused by brain trauma, intracranial lesions, congenital malformations, or other factors that damage the patient's own skull. This results in the loss of protection for brain tissue, leading to problems such as cerebrospinal fluid circulation disorders, abnormal cerebral blood flow, and nervous system dysfunction, significantly impacting the patient's neurological function and quality of life. With advancements in medical technology, skull repair currently primarily employs two methods: autologous bone grafting and artificial skull grafting. Autologous bone grafting presents challenges in terms of preservation during the initial surgical period and from transplantation, including high costs, susceptibility to infection or necrosis, and difficulties in fixation during transplantation and potential postoperative bone resorption. With advancements in medical materials and manufacturing processes, artificial skull grafting is gradually becoming the mainstream approach for defect repair.

[0003] Artificial cranial implants have gradually shifted from traditional titanium alloys to medical polymer materials such as PAEK, ultra-high molecular weight polyethylene, and PMMA. Titanium alloy artificial skulls are often used for covering repairs, allowing for intraoperative shaping as needed, and offer advantages such as low manufacturing costs and fast processing speeds. However, they also have some limitations after implantation: due to the thinness of titanium alloys, their mechanical properties often cannot perfectly match those of the natural skull; improperly treated edges can be sharp, increasing the risk of scalp abrasions; metals are relatively sensitive to temperature, potentially causing postoperative intracranial discomfort. Furthermore, the metal-bone interface can easily create stress shielding, leading to bone loss in the surrounding tissue. Metal implants can also corrode surrounding tissues and trigger cytotoxic reactions by releasing metal ions.

[0004] Among polymer-based artificial skull products, PMMA (bone cement) artificial skulls, after curing, have mechanical strength similar to that of the skull, possessing good compressive and impact resistance, as well as superior bioactivity, which is beneficial for osseointegration. Its good plasticity allows it to be shaped according to the different defects. However, this material also has drawbacks in use: bone cement needs to be mixed and prepared on-site, has high initial fluidity, requires molds for shaping, and the process is relatively complex; moreover, it releases significant heat during curing. Because it must be implanted into the human body before it is fully cured, the material temperature is high at this time, which may cause cerebral edema after implantation.

[0005] PAEK (polyaryletherketone) is currently a highly regarded material in the field of artificial skulls, and as a mainstream choice, it has several advantages: its mechanical properties are close to those of the human skull, and its elastic modulus is well-matched, which helps reduce the stress shielding effect after implantation and lowers the risk of surrounding bone resorption; it has excellent biocompatibility, and long-term implantation is unlikely to cause inflammation or foreign body reactions; it has strong corrosion resistance and good stability in the human body environment; and it has good imaging compatibility, not affecting CT, MRI, and other examinations, facilitating postoperative follow-up and evaluation. However, it also has limitations: the material itself is biologically inert, making it difficult to achieve bony integration with the host bone after implantation, and its integration with the dura mater is also poor, easily forming a cavity between the two and causing fluid accumulation.

[0006] Ultra-high molecular weight polyethylene (UHMWPE), as an artificial skull implant material, shares some advantages with PAEK: excellent biocompatibility, strong chemical stability, low likelihood of causing inflammation, allergies, or rejection reactions after implantation, and high long-term safety; good toughness, superior impact resistance compared to PAEK, and lower brittleness, effectively buffering external impacts, making it more suitable for sports enthusiasts or people working at heights; and lower production costs than PAEK, facilitating its adoption at the grassroots level. However, its shortcomings are also prominent: its mechanical strength is lower than that of metals and PAEK materials, and it may experience creep or deformation under long-term loads, making it difficult to meet the rigid support requirements for large-area defects; in addition, it is prone to oxidative degradation during sterilization, which may affect the stability of material properties, thus requiring a high level of sterilization expertise.

[0007] Furthermore, skull defects are often exposed to the external environment, making them susceptible to bacterial invasion, leading to scalp infections, cranial osteomyelitis, and even intracranial infections, thus affecting the repair outcome. Currently, debridement of the implantation site and systemic antibiotic treatment are common strategies for the clinical management of infected bone defects. However, antibiotics are ineffective against complex infections caused by drug-resistant bacteria and may also cause an imbalance in the body's microbial ecosystem, reducing the implant's ability to promote bone tissue regeneration and increasing the risk of loosening and failure.

[0008] Among the existing technologies, Chinese invention patent application CN201810000736.7 discloses a porous biomimetic skull repair material and a personalized manufacturing method, and Chinese utility model patent application CN202320734567.6 discloses a skull mesh plate. However, the following defects still exist: (1) Complexity of the mixed molding process: This method requires alternating layers of different powders before hot pressing. Uneven powder distribution is very likely to occur during this process, leading to uneven cell distribution within the final product. Since cell formation depends on pore-forming agents, their size and distribution are difficult to control precisely, resulting in significant variations. This not only affects the uniformity and stability of the material but also causes inconsistent mechanical properties in different batches of products due to differences in cell structure.

[0009] (2) The bubble forming process is complex, and impurities are easily left behind, and the bubble shape is uneven.

[0010] (3) Key drawbacks shared by both processes: Both hybrid molding and 3D printing require the porogen to be dissolved in water after molding. However, due to the hydrophobicity of the polymer material itself and the tight coating of the porogen particles by the material after molding, the porogen is difficult to remove completely and effectively. Residual porogen will become a potential source of infection, significantly increasing the risk of infection after product implantation.

[0011] (4) The antibacterial process is complex and requires pretreatment of the substrate surface before coating with antibacterial substances. After implantation into the human body, the release is rapid but the duration is short. At the same time, the use of salting out to prepare porous materials can lead to uneven surface pores and uneven coating of antibacterial substances, resulting in local overdose or underdose of the drug after implantation into the human body.

[0012] (5) Poor interface integration: PAEK itself is biologically inert and has a smooth, hydrophobic surface. After being implanted into the human body, the cell adhesion effect is poor and it cannot stably adhere to the artificial skull.

[0013] In view of this, the present invention is proposed. Summary of the Invention

[0014] One of the objectives of this invention is to provide a PAEK composite foam material for preparing artificial skull implants, so as to at least solve one of the technical problems existing in the prior art.

[0015] The second objective of this invention is to provide a method for preparing PAEK composite foam material for artificial skull implants.

[0016] The third objective of this invention is to provide a porous, antibacterial PAEK artificial skull.

[0017] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: In a first aspect, the present invention provides a PAEK composite foam material for preparing artificial cranial implants, wherein the PAEK composite foam material is based on polyaryletherketone and has a porous structure, wherein the porous structure is formed by supercritical carbon dioxide foaming, and wherein the pore walls of the porous structure are dispersed with metal antibacterial components and optional metal bone-promoting components.

[0018] Furthermore, the metal antibacterial component includes one or more elements, oxides, or zeolite-loaded salts selected from zinc, silver, copper, and tin.

[0019] Furthermore, the metal bone-promoting component includes magnesium.

[0020] Furthermore, the raw materials for preparing the PAEK composite foam material include: metal antibacterial components, metal bone-promoting components, fillers, and polyaryletherketones.

[0021] Preferably, the filler comprises hydroxyapatite.

[0022] Furthermore, the raw materials for preparing the PAEK composite foam material include, by mass percentage: 5%-15% metal antibacterial component, 2%-10% metal bone-promoting component, 15%-25% filler and the balance polyarylether ketone; Preferably, the porosity of the PAEK composite foam material is 50%-60%.

[0023] Secondly, the present invention provides a method for preparing PAEK composite foam material for artificial skull implants, comprising the following steps: (a) A composite powder containing polyaryletherketone, a metal antibacterial component and an optional metal bone-promoting component is pressed to obtain a PAEK composite board. (b) The PAEK composite board is foamed by supercritical carbon dioxide foaming to obtain the PAEK composite foam material.

[0024] Furthermore, the pressing pressure is 10-30 MPa, the temperature is 300-420℃, the pre-molding time is 5-20 minutes, and the formal molding time is 20-50 minutes.

[0025] Furthermore, the foaming treatment temperature is 200-280℃, the carbon dioxide pressure is 8-12 MPa, and the treatment time is 30-180 minutes.

[0026] Thirdly, the present invention provides a porous antibacterial PAEK artificial skull, comprising the PAEK composite foam material used for preparing artificial skull implants or the PAEK composite foam material used for preparing artificial skull implants prepared by the aforementioned preparation method.

[0027] Furthermore, the porous antibacterial PAEK artificial skull is a solid implant that has been cut and shaped, and its outline matches the three-dimensional morphology of the patient's skull defect.

[0028] Compared with the prior art, the present invention has the following beneficial effects: The PAEK composite foam material provided by this invention for preparing artificial skull implants utilizes supercritical carbon dioxide foaming to construct a porous structure. Metallic antibacterial components and optional metallic osteogenic components are stably loaded within the pore walls. Simultaneously, the metallic antibacterial components act as nucleating agents during the foaming process, promoting uniform distribution and size control of the pores, improving the controllability of pore density. The uniform foam structure facilitates the uniform release of antibacterial substances from the antibacterial product. Furthermore, the surface-formed pore structure effectively improves the surface roughness of the PAEK material, promoting tissue ingrowth and enhancing interfacial integration. Therefore, the PAEK composite foam material provided by this invention, while ensuring sufficient mechanical support strength, achieves both antibacterial effects and improves material surface roughness, promoting cell adhesion, proliferation, and dura mater / bone tissue ingrowth, thereby synergistically solving the long-standing problems of infection and poor osseointegration performance in artificial skulls. Attached Figure Description

[0029] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in 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 the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0030] Figure 1 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 1 over time in simulated body fluid. Figure 2 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 2 as a function of time. Figure 3 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 3 as a function of time. Figure 4 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 4 as a function of time. Figure 5 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 5 as a function of time. Figure 6 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 6 as a function of time. Figure 7 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 7 over time. Figure 8 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 8 as a function of time. Figure 9 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 9 over time. Figure 10 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 10 over time in simulated body fluid. Figure 11 This is a graph showing the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 11 over time in simulated body fluid. Figure 12 This is a graph showing the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 12 over time in simulated body fluid. Figure 13 The graph shows the cumulative ion release conversion rate of the metal antibacterial component in the composite foam material of Example 13 over time in simulated body fluid. Figure 14 This is a bar chart showing the relative expression levels of alkaline phosphatase mRNA. Figure 15 SEM images of PAEK pure material, Example 6, and Example 1 after foaming; Figure 16 SEM images of Examples 9, 6, and 1 after foaming; Figure 17 A cross-sectional schematic diagram of the composite foam material provided by the present invention; Figure 18 A schematic diagram of an artificial skull after machining of foam material. Detailed Implementation

[0031] Unless otherwise defined herein, the scientific and technical terms used in conjunction with this invention shall have the meanings commonly understood by one of ordinary skill in the art. The meaning and scope of terms shall be clear; however, in any case of potential ambiguity, the definitions provided herein shall prevail over any dictionary or foreign definitions. In this application, unless otherwise stated, the use of "or" means "and / or". Furthermore, the use of the term "comprising" and other forms is non-limiting.

[0032] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] like Figure 17 As shown, the first aspect of the present invention provides a PAEK composite foam material for preparing artificial cranial implants. The PAEK composite foam material uses polyaryletherketone as a matrix and has a porous structure. The porous structure is formed by supercritical carbon dioxide foaming, and the pore walls of the porous structure are dispersed with metal antibacterial components and optional metal bone-promoting components.

[0034] The PAEK composite foam material for preparing artificial skull implants provided by this invention has a porous surface structure that provides better cell adhesion. The metal antibacterial component can act as a nucleating agent to ensure the uniformity of the foam cells and can also be fixed in the foam cells after processing. After implantation, it will continuously release metal ions for antibacterial purposes upon contact with the human body. The release process is more stable and the release time is longer.

[0035] To further explain, the conventional nucleating agent in supercritical carbon dioxide foaming technology is carbon dioxide gas molecules, which belongs to homogeneous nucleation. However, in this homogeneous nucleation process of gas self-dispersion nucleation, when supercritical CO2 is rapidly released from the polymer melt, gas molecules need to spontaneously aggregate in the homogeneous melt to form stable bubble nuclei. This requires extremely high supersaturation (i.e., extremely high pressure or extremely fast depressurization rate) because the formation of bubble nuclei must overcome the huge free energy barrier brought about by the nascent gas-liquid interface. This process is difficult to control and easily leads to low pore density, uneven size, or even macropores or collapse. The metal antibacterial component added in this invention belongs to heterogeneous nucleating agents. Metal nanoparticles, as heterogeneous nucleating agents, provide a large number of readily available, lower-energy nucleation sites on their surface. Gas molecules are more likely to aggregate at these solid interfaces and form stable bubble nuclei, thereby significantly reducing the energy barrier required for nucleation. This allows for the initiation of a large number of uniform nucleation at lower supersaturation levels, improving the dispersion effect and thus improving pore uniformity. In some preferred embodiments, the metal antibacterial component includes one or more elements, oxides, or zeolite-loaded salts selected from zinc, silver, copper, and tin.

[0036] In this invention, metallic antibacterial components (such as nano-zinc, nano-silver, nano-copper, nano-tin, zinc oxide, silver oxide, copper oxide, zeolite-loaded silver / zinc / copper / tin, etc.) are selected as high-temperature resistant metallic antibacterial components. PAEK powder (particle size 10-200 nm) is uniformly incorporated through physical blending. This method is simple and efficient, and the metallic antibacterial agents remain stable during high-temperature processing; nano-metallic elements can be converted into metal oxides at high temperatures while retaining their antibacterial ability. These antibacterial components achieve broad-spectrum antibacterial activity by disrupting bacterial structure, exhibiting good biocompatibility and low susceptibility to inducing drug resistance. Simultaneously, the metallic antibacterial components act as nucleating agents during foaming, ensuring uniform cell size and number; the uniform cell structure results in uniform drug loading concentration.

[0037] In addition, the added metal antibacterial components, such as nano zinc, nano silver and nano copper, not only have excellent antibacterial capabilities, but can also promote cell proliferation and differentiation through local ion release, thereby enhancing the bone regeneration effect and bone integration capacity of the implanted material.

[0038] In some preferred embodiments, the metal osteogenic component includes magnesium, which has osteogenic function. In addition, Mg also has nucleation function and forms a heterogeneous nucleating agent, similar to the metal antibacterial component.

[0039] Magnesium, in particular, exhibits good biocompatibility and metabolic activity. Magnesium ions (Mg...) 2+ It can be normally metabolized and excreted through the kidneys, with no risk of accumulation in the body. More importantly, Mg... 2+ It is an essential cofactor for more than 300 enzymes in the body, activating key enzymes such as ATPase and creatine kinase, and directly participating in cellular energy metabolism and bone mineral deposition. Insufficient magnesium levels in the body can significantly inhibit the activity and function of osteoblasts. Mg 2+ It plays a multi-pathway regulatory role in bone repair: 1. It controls gene expression, releases signaling factors to alleviate inflammatory response, promotes stem cell differentiation into endothelial cells, improves local microvascular endothelial function and promotes osteogenic differentiation of cells; 2. During the degradation process, magnesium alloys can form a bone-like apatite layer on the surface, which directly stimulates osteoblast proliferation and bone matrix mineralization.

[0040] In some preferred embodiments, the raw materials for preparing the PAEK composite foam material include, by weight percentage: 5%-15% of a metallic antibacterial component, for example, 5%, 10%, 15%; 2%-10% of a metallic bone-promoting component, for example, 2%, 6%, 10%; 15%-25% of a filler, for example, 15%, 20%, 25%; and the balance being polyaryletherketone.

[0041] Preferably, the filler comprises hydroxyapatite.

[0042] Preferably, the porosity of the PAEK composite foam material is 50%-60%, for example, 50%, 55%, 60%, etc. The pore size may vary slightly between different batches, but the pore size and number are uniform within the same batch. Furthermore, in this invention, the foam morphology is synergistically controlled by the content of antibacterial and bone-promoting components in the metal and the supercritical CO2 foaming process parameters. When the porosity is stably maintained within the 50%-60% range, the pore density is higher and the uniformity is better.

[0043] The formula for determining porosity is as follows: Foaming ratio = Volume of board after foaming / Volume of board before foaming; Porosity = 1 - (1 / foaming ratio).

[0044] The PAEK composite foam material provided by this invention has the following effects: if the foaming ratio is too high (corresponding to excessive porosity, such as >60%), the mechanical properties of the product will decrease significantly, resulting in brittleness and softness, and the product will be unable to provide support; while if the foaming ratio is too low (corresponding to excessive porosity, such as <50%), the number of cells will be too small, the nucleation rate of the antibacterial agent will be low, and the formation of a continuous foam structure cannot be guaranteed. After machining, the surface will have fewer cells and will not be able to maintain a certain level of antibacterial performance.

[0045] A second aspect of the present invention provides a method for preparing PAEK composite foam material for artificial skull implants, comprising the following steps: (a) A composite powder containing polyaryletherketone, a metal antibacterial component and an optional metal bone-promoting component is pressed to obtain a PAEK composite board. (b) The PAEK composite board is foamed by supercritical carbon dioxide foaming to obtain the PAEK composite foam material.

[0046] The preparation method provided by this invention features a simpler mechanism for adding antibacterial components. It only requires uniformly adding the antibacterial component to PAEK powder in its powder state. During processing, the nano-metal undergoes a chemical change at high temperatures to generate metal oxides, which possess antibacterial capabilities. Furthermore, it achieves better cell adhesion without surface treatment: after machining, the pores are exposed, containing the antibacterial product, while simultaneously increasing the surface roughness of the product, which is beneficial for cell adhesion and ensures the uniform and stable release of antibacterial metal ions.

[0047] Optionally, the metal antibacterial component can be added directly in the early powder stage, and if necessary, antibacterial substances can be further coated on the surface later. Due to its porous structure, it is beneficial to coat the antibacterial product.

[0048] In some preferred embodiments, the pressing pressure is 10-30 MPa, for example, 10 MPa, 20 MPa, 30 MPa, etc., the temperature is 300-420℃, for example, 300℃, 350℃, 400℃, 420℃, etc., the pre-molding time is 5-20 minutes, for example, 5 minutes, 15 minutes, 20 minutes, etc., and the formal molding time is 20-50 minutes, for example, 20 minutes, 30 minutes, 40 minutes, 50 minutes, etc.

[0049] In some preferred embodiments, the foaming treatment temperature is 200-280℃, for example, 200℃, 220℃, 240℃, 260℃, 280℃, etc., the carbon dioxide pressure is 8-12 MPa, for example, 8 MPa, 9 MPa, 10 MPa, 11 MPa, 12 MPa, etc., and the treatment time is 30-180 minutes, for example, 30 minutes, 50 minutes, 100 minutes, 150 minutes, 180 minutes, etc.

[0050] In a preferred embodiment of the present invention, the method for preparing the PAEK composite foam material for artificial skull implants includes the following steps: PAEK fine or ultrafine powder with suitable viscosity is selected, and one or more metallic antibacterial agents are chosen. These are then blended with the antibacterial agents through physical (stirring, ball milling) or chemical (extrusion granulation) methods to ensure uniform dispersion, thus obtaining a PAEK composite powder containing the antibacterial agent. Subsequently, PAEK composite material sheets are prepared using a high-temperature molding press. The density of the above composite powder is approximately 1-2 g / cm³. 3 Preferably 1.3 g / cm 3 During the molding process, the pressure is controlled at 10-30 MPa and the temperature at 300-420℃. Pre-molding is performed for 5-20 minutes, with three consecutive venting cycles; followed by formal molding for 20-50 minutes. After reaching the set time, the material is cooled to 100℃ for 2-5 hours to obtain the final PAEK composite material sheet.

[0051] The board is then placed in a supercritical carbon dioxide foaming device and treated at 200-280℃ and 8-12 MPa carbon dioxide pressure for 30-180 minutes. After treatment, the pressure is quickly released to obtain PAEK composite foam material, which is a prefabricated antibacterial PAEK foam artificial skull board. The foaming ratio can be controlled by adjusting the reaction temperature and time.

[0052] A third aspect of the present invention provides a porous antibacterial PAEK artificial skull, comprising the PAEK composite foam material for preparing artificial skull implants or the PAEK composite foam material for preparing artificial skull implants prepared by the aforementioned preparation method.

[0053] In some preferred embodiments, the porous antibacterial PAEK artificial skull is a solid implant that has been cut and shaped, and its outline matches the three-dimensional morphology of the patient's skull defect.

[0054] To address the issue of long lead times for customized porous artificial skulls, this invention pre-prepares prefabricated artificial skulls of uniform specifications. PAEK powder is blended with a metal antibacterial agent in a specific ratio, and after high-temperature molding, supercritical carbon dioxide foaming technology is used to produce a polyaryletherketone foam material with antibacterial properties, i.e., the prefabricated artificial skull product.

[0055] In subsequent clinical applications, to meet personalized repair needs, the patient's skull defect area is first scanned using medical imaging techniques such as CT, X-ray, or MR to obtain relevant data, which is then imported into modeling software (such as Mimics, Freeform, etc.). After morphological processing, a three-dimensional visualization model is generated. Geomagic software is then used to optimize the mesh of the model, obtaining solid model data, which is then machined to form an implant that fits the shape of the patient's defect.

[0056] This invention can mass-produce PAEK foam boards with antibacterial effects. After scanning the defective part of the patient's head, a personalized PAEK artificial skull can be directly obtained according to the machining method. The time to generate porous boards from the base board is short, only 2-5 hours, which greatly shortens the preparation time.

[0057] Optionally, after the artificial skull is customized, its porous surface can be used as a drug carrier to further coat it with anti-inflammatory and antibacterial products.

[0058] The present invention will be further illustrated by the following examples. Unless otherwise specified, the materials in the examples are prepared according to existing methods or purchased directly from the market.

[0059] Example 1 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, and its preparation process is as follows: S1, Material blending: PAEK ultrafine powder with low viscosity (particle size 150nm) was selected as the base material, and nano-zinc and nano-copper were used as metal antibacterial components (both with a particle size of 300nm-400nm and a mass ratio of 1:1), Mg was used as the metal bone-promoting component, and hydroxyapatite was used as the filler. The antibacterial agent was uniformly dispersed by physical stirring, ultimately obtaining a PAEK composite powder containing antibacterial components. The raw materials for preparing the PAEK composite foam material include, by mass percentage: 10% metal antibacterial component, 6% metal bone-promoting component, 20% filler, and the balance is made up to 100% using polyaryletherketone.

[0060] S2, Compression molding: The above composite powder was pressed into sheets using a high-temperature molding machine. Specific parameters are as follows: sheet density is approximately 1.7 g / cm³.3 The sheet thickness was set at 10 mm, the dimensions at 150 mm × 150 mm, and the theoretical feed amount was 383 g. The molding process conditions were: pressure 15 MPa, temperature 320℃. Pre-pressing was performed for 15 minutes, with three consecutive venting cycles; followed by formal molding for 40 minutes. After molding, the sheet was cooled to 100℃ in stages over 2 hours to obtain a dense PAEK composite material sheet.

[0061] S3. Foaming treatment: The pressed PAEK board was placed in a supercritical carbon dioxide foaming equipment and treated at 260°C and 10 MPa pressure for 60 minutes. Then the pressure was quickly released to obtain PAEK composite foam material, namely prefabricated antibacterial PAEK foam artificial skull board with a porosity of 55.6%.

[0062] Example 2 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that: the raw materials for preparing the PAEK composite foam material include, by mass percentage: 5% metal antibacterial component, 10% metal bone-promoting component, 15% filler, and the balance is made up to 100% using polyaryletherketone. The density of the board material in S2 is approximately 1.7 g / cm³. 3 The final porosity obtained was 57.8%.

[0063] Example 3 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that: the raw materials for preparing the PAEK composite foam material include, by mass percentage: 15% metal antibacterial component, 2% metal bone-promoting component, 25% filler, and the balance is made up to 100% using polyaryletherketone. The density of the board in S2 is approximately 1.7 g / cm³. 3 The final porosity obtained was 51.7%.

[0064] Example 4 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that: In S2, the molding process conditions are: pressure 10 MPa, temperature 420℃. Pre-press for 5 minutes, during which venting is performed 3 times; then formal molding lasts for 20 minutes.

[0065] In S3, foaming treatment is carried out at 250℃ and 12 MPa pressure for 180 minutes.

[0066] The density of the board in S2 is approximately 1.7 g / cm³. 3; and the final porosity obtained was 56.2%.

[0067] Example 5 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that: In S2, the molding process conditions are: pressure 30 MPa, temperature 300℃. Pre-press for 20 minutes, during which venting is performed three times; then formal molding is performed for 50 minutes.

[0068] In S3, foaming treatment is carried out at 280℃ and 11 MPa pressure for 30 minutes.

[0069] The density of the board in S2 is approximately 1.7 g / cm³. 3 The final porosity obtained was 52.9%.

[0070] Example 6 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that: The raw materials for preparing the PAEK composite foam material include, by weight percentage: 4% metal antibacterial component, 15% metal bone-promoting component, 20% filler, and the balance is made up to 100% using polyaryletherketone. The density of the board in S2 is approximately 1.7 g / cm³. 3 The final porosity obtained was 45.1%.

[0071] Example 7 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that: The raw materials for preparing the PAEK composite foam material include, by weight percentage: 20% metal antibacterial component, 1% metal bone-promoting component, 20% filler, and the balance is made up to 100% using polyaryletherketone. The density of the board in S2 is approximately 1.7 g / cm³. 3 The final porosity obtained was 44.8%.

[0072] Example 8 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that the metal antibacterial component is only nano-zinc; The density of the board in S2 is approximately 1.7 g / cm³. 3 ; and the final porosity obtained was 56.9%.

[0073] Example 9 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that the metal antibacterial component is only nano-copper.

[0074] The density of the board in S2 is approximately 1.7 g / cm³. 3 Furthermore, the final prepared porosity was 58.8%. Example 10 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that the metal antibacterial component is only nano-tin.

[0075] The density of the board in S2 is approximately 1.7 g / cm³. 3 Furthermore, the final porosity obtained was 55.3%. Example 11 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that the metal antibacterial component is only zeolite-loaded zinc.

[0076] The density of the board in S2 is approximately 1.7 g / cm³. 3 Furthermore, the final prepared porosity was 60.2%. Example 12 This embodiment provides a PAEK composite foam material for preparing artificial skull implants, which differs from Embodiment 1 in that the metal antibacterial component is only zinc oxide.

[0077] The density of the board in S2 is approximately 1.7 g / cm³. 3 Furthermore, the final prepared porosity was 52.6%. Example 13 This comparative example provides a PAEK composite foam material for preparing artificial skull implants, which differs from Example 1 in that it does not contain any metal bone-promoting components.

[0078] The density of the board in S2 is approximately 1.7 g / cm³. 3 The final porosity obtained was 58.6%.

[0079] Comparative Example 1 This comparative example provides a pure PAEK powder, which differs from Example 1 in that the material is only pure PAEK powder.

[0080] The density of the board in S2 is approximately 1.3 g / cm³. 3 ; and the final porosity obtained was 53.8%.

[0081] The composite materials prepared using the above embodiments and comparative examples are used for precise scanning and personalized processing of damaged area images: CT or MR imaging techniques were used to scan the skull defect area of ​​the patient, acquiring DICOM format scan data. Subsequently, the data was processed using Mimics 19.0 software to create a visualized 3D model. This digital model was then imported into CNC machining equipment for customized cutting and shaping of the PAEK foam board. It is important to note that a dense skin layer forms on the surface of the foamed board, which needs to be removed through machining to expose the internal cell structure, facilitating subsequent biological integration (e.g., ...). Figure 18 As shown, after the foam material is foamed, the surface has a smooth and dense structure, and the foam cells will be exposed after machining.

[0082] Test Example 1: Antibacterial and Bacteriostatic Effect Test (1) Release effect of metal antibacterial components Simulated body fluid: 0.9% physiological saline.

[0083] In simulated body fluids, the metal antibacterial components undergo dissolution and ion exchange reactions, releasing bioactive metal ions that enter the simulated body fluids. In the initial stage, the ion conversion rate of the metal antibacterial components in each embodiment exhibits a significant peak, reaching up to 70%-90%. This is because the selected metal antibacterial components (including nanomaterials, metal oxides, and zeolite-supported salts) have high specific surface areas and abundant surface active sites, allowing them to rapidly dissolve or undergo ion exchange reactions in simulated body fluids, releasing bioactive metal ions and thus quickly establishing an effective antibacterial concentration in the early stages. The fact that each embodiment maintains a cumulative conversion rate of 20%-32% after 500 hours indicates that the system possesses good sustained-release stability and can provide continuous and mild antibacterial effects.

[0084] Specifically, Figures 1-13 The figures show the cumulative ion release conversion rate of the metal antibacterial components in simulated body fluids in the composite foam materials of Examples 1-13 over time. Overall, Examples 1 and Examples 8-13 all exhibited good release performance. Example 1, as a representative of the compound system, combined high initial conversion rate with excellent long-term release stability. Examples 8-12, using single nano-metals or their oxides, and zeolite-supported salts respectively, achieved balanced release within a reasonable addition range, verifying the applicability and reliability of various high-temperature resistant antibacterial components in a PAEK matrix. Among them, such as... Figure 13 As shown, in Example 13, without the addition of the metal bone-promoting component (magnesium), the highest R value in the initial stage was approximately 68%, and the conversion rate after 500 hours was approximately 32%, indicating that the antibacterial component could still maintain a high release level even in the absence of magnesium, suggesting that magnesium is not a direct source of ion release.

[0085] In contrast, the 500-hour conversion rates of Examples 2 and 6 were reduced, with Example 6 approaching zero. This was due to insufficient release of the antibacterial component.

[0086] (2) Analysis of antibacterial effect Test Method: *Escherichia coli* and *Staphylococcus aureus* were used. Beef extract peptone basal medium was selected, with a formula of 3g beef extract, 10g peptone, 5g sodium chloride, 15-20g agar, and 1000ml water. The pH was adjusted to 7.4-7.6 using 1mol / L NaOH or HCl. The experimental procedure included: sterilizing 50ml of medium in an Erlenmeyer flask with moist heat at 121.3℃ for 20min, followed by UV irradiation for another 20min; melting the solid medium on a sterile work surface, pouring approximately 15ml onto a sterile agar plate, and incubating at 37℃ for 24h to confirm sterility; using an inoculation loop, picking ten *E. coli* and ten *Staphylococcus aureus* slant agar plates, incubating at 37℃ for 24h, and then storing in a refrigerator; and finally, scraping the bacterial cells with sterile water to prepare a bacterial suspension. After the samples were sterilized by UV irradiation for 30 minutes, they were placed in Erlenmeyer flasks containing culture medium. 0.1 ml of bacterial suspension was added to each flask, and the flasks were shaken at 37°C and 150 r / min.

[0087] Incubate for 24 hours; take 1.0 ml of culture medium and serially dilute 10-fold to 10⁻⁶. -10 Spread 0.2 ml of the diluted solution onto a plate, incubate upside down at 37°C for 24 h, and record the number of colonies. Calculate the inhibition rate by comparing the data of the control group and the experimental group.

[0088] Antibacterial rate = [(Control group colonies - Experimental group colonies) / Control group colonies] * 100%.

[0089] The antibacterial effects are shown in Table 1.

[0090] Table 1

[0091] As shown in Table 1, all examples containing metal antibacterial components (Examples 1-13) exhibited significant antibacterial effects against Staphylococcus aureus and Escherichia coli. Example 1, with its compound system, demonstrated the best antibacterial performance, indicating that zinc / copper synergy may enhance broad-spectrum antibacterial activity. Example 7 showed relatively low antibacterial effects. In Example 6, the addition of too little metal antibacterial component resulted in insufficient nucleation density, reduced pore number, sparse distribution, and a decrease in effective antibacterial surface area. In Example 7, the excessively high content of antibacterial component caused localized aggregation, interfering with the uniform diffusion and precipitation of supercritical carbon dioxide in the matrix, leading to pore collapse or increased closed pores, and hindering the release channels of metal ions.

[0092] Test Example 2: Osteogenesis Effect Test Osteogenic effect analysis: In vitro cell culture This experiment evaluated osteogenic capacity by measuring the activity of alkaline phosphatase in the culture medium.

[0093] Main reagents: DMEM medium, fetal bovine serum, 0.25% trypsin, penicillin-streptomycin, immunostaining blocking solution, CCK-8 kit, reverse transcription kit, SYBR Green quantitative PCR kit, Transwell plate, ICP-AES analyzer, quantitative PCR instrument, multi-functional microplate reader.

[0094] Cell isolation and culture: Two rats were euthanized by cervical dislocation. The tibia and femur were aseptically isolated, soft tissue was removed, and the epiphysis was excised. The bone marrow cavity was repeatedly flushed with DMEM complete medium containing 10% fetal bovine serum and 1% penicillin-streptomycin. The flushing fluid was collected, centrifuged, the supernatant was discarded, and the cells were resuspended and seeded into culture dishes. The cells were incubated at 37°C in a 5% CO2 incubator. The medium was changed after 3 days. When the cells reached 90% confluence, they were passaged, and the first and second generation cells were used for experiments. Flow cytometry confirmed that the cells were stem cells.

[0095] Preparation of extract: According to ISO / EN10993-5 standard, sterile magnesium alloy powder was added to complete culture medium at 200 g / L and incubated in a shaker at 37℃ for 72 h; the supernatant was collected by centrifugation, filtered through a 0.22 μm filter membrane, and diluted with complete culture medium to 1%, 6%, and 15% concentration groups, with complete culture medium as the control.

[0096] Cell proliferation assay: Rat bone marrow stem cells were used at a concentration of 1×10⁻⁶. 4 The culture medium was seeded in 96-well plates and cultured for 1 day. Different concentrations of extraction medium or control medium (100 μL per well) were added, and the medium was changed every 3 days. On days 1, 3, and 7, the culture medium was aspirated, and 100 μL of CCK-8 working solution was added to each well. The plates were incubated at 37°C in the dark for 30 min, and the absorbance was measured at 450 nm using a microplate reader. The experiment was performed in triplicate.

[0097] Alkaline phosphatase staining: Cells were seeded in 24-well plates (uniform density). After 60% confluence, different concentrations of extraction buffer and complete culture medium were added, and the cells were cultured for 7 days. The culture medium was removed, and the cells were fixed with 4% paraformaldehyde at room temperature for 30 min. After rinsing with PBS, ALP staining working solution was added, and the cells were incubated at 37°C for 30 min. The cells were then observed and photographed under an inverted microscope to detect ALP-induced mRNA expression.

[0098] The expression of osteogenic-related genes in rat bone marrow stem cells was detected, such as... Figure 14As shown in the experimental results, after 7 days of cell culture induced by magnesium alloy extract, the expression of osteogenic genes increased. The relative expression levels of alkaline phosphatase mRNA in each magnesium alloy concentration group were higher than those in the control group, showing a concentration-dependent effect. The expression level was directly proportional to the concentration, proving that magnesium alloy extract effectively improved osteogenic gene expression and promoted osteogenic effects. In addition, this experiment used extracts with three concentration gradients of 1%, 6%, and 15% for systematic evaluation. The results showed that within this test range, the expression level of ALP mRNA increased with the increase of extract concentration, confirming that magnesium release has a concentration-dependent osteogenic effect. However, considering that the amount of magnesium added in the composite material is limited by the stability of the foam structure (such as excessive addition leading to decreased porosity and cell collapse), and that the sustained-release properties of ions and tissue compatibility for long-term implantation need to be considered, Example 1 (containing 6 wt% magnesium) corresponding to the 6% extract was determined as the preferred solution that balances osteogenic efficacy and process feasibility.

[0099] Test Example 3: Foam Pore Formation Effect Test Figure 15 Figures a, b, and c show a comparison of the foaming effects of pure PAEK material, the composite material of Example 6, and the composite material of Example 1, respectively. It can be clearly seen that the pure material has matrix material backwalls of different sizes between the cells, resulting in uneven cell number. Heterogeneous nucleation, to a certain extent, can stably improve cell density and cell uniformity. Furthermore, from... Figure 15 It can be seen that the foam density of Example 1 is higher and the size is more uniform, and the foaming effect is significantly better than that of Example 6.

[0100] Figure 16 Figures a, b, and c in the figure are SEM images of the composite materials of Example 9, Example 6, and Example 1 after foaming under suitable temperature and pressure, respectively. As can be seen from the figures, at the same mass fraction (Figures a and c), both single metal particles and compound metal particles significantly improve the cell density and uniformity compared to pure PAEK foam material. Furthermore, within a suitable mass fraction range (Figures b and c), increasing the amount of metal particles added helps to further improve the uniformity of the cells.

[0101] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention 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; and these 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 the present invention.

Claims

1. A PAEK composite foam material for preparing artificial skull implants, characterized in that, The PAEK composite foam material uses polyaryletherketone as a matrix and has a porous structure. The porous structure is formed by supercritical carbon dioxide foaming, and the pore walls of the porous structure contain metal antibacterial components and optional metal bone-promoting components.

2. The PAEK composite foam material for preparing artificial skull implants according to claim 1, characterized in that, The metal antibacterial component includes one or more elements, oxides, or zeolite-loaded salts of zinc, silver, copper, and tin.

3. The PAEK composite foam material for preparing artificial skull implants according to claim 1, characterized in that, The metal bone-promoting component includes magnesium.

4. The PAEK composite foam material for preparing artificial skull implants according to claim 1, characterized in that, The raw materials for preparing the PAEK composite foam material include: metal antibacterial components, metal bone-promoting components, fillers, and polyaryletherketone. Preferably, the filler comprises hydroxyapatite.

5. The PAEK composite foam material for preparing artificial skull implants according to claim 4, characterized in that, The raw materials for preparing the PAEK composite foam material include, by weight percentage: 5%-15% metal antibacterial component, 2%-10% metal bone-promoting component, 15%-25% filler and the balance polyarylether ketone. Preferably, the porosity of the PAEK composite foam material is 50%-60%.

6. The method for preparing PAEK composite foam material for artificial skull implants as described in any one of claims 1-5, characterized in that, Includes the following steps: (a) A composite powder containing polyaryletherketone, a metal antibacterial component and an optional metal bone-promoting component is pressed to obtain a PAEK composite board. (b) The PAEK composite board is foamed by supercritical carbon dioxide foaming to obtain the PAEK composite foam material.

7. The preparation method according to claim 6, characterized in that, The pressing pressure is 10-30 MPa, the temperature is 300-420℃, the pre-molding time is 5-20 minutes, and the formal molding time is 20-50 minutes.

8. The preparation method according to claim 6, characterized in that, The foaming treatment is carried out at a temperature of 200-280℃, a carbon dioxide pressure of 8-12 MPa, and a treatment time of 30-180 minutes.

9. A porous antibacterial PAEK artificial skull, characterized in that, The material includes the PAEK composite foam material for preparing artificial skull implants as described in any one of claims 1-5, or the PAEK composite foam material for preparing artificial skull implants prepared by the preparation method described in any one of claims 6-8.

10. The porous antibacterial PAEK artificial skull according to claim 9, characterized in that, The porous antibacterial PAEK artificial skull is a solid implant that has been cut and shaped, and its outline matches the three-dimensional shape of the patient's skull defect.

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