A biocompatible material for a biomimetic porous intervertebral cage and method of making

Abstract

The application discloses a kind of biocompatible materials and preparation method for bionic porous intervertebral fusion cage, belong to intervertebral fusion cage material technical field.A kind of biocompatible materials for bionic porous intervertebral fusion cage, by weight parts includes the following components: polyether ether ketone 65-80 parts, modified functional filler 15-25 parts, hydroxyapatite 8-12 parts, flow modifier 0.5-1 part;The modified functional filler is graphene oxide coated modified barium titanate functional filler.By introducing surface conductive modified nano piezoelectric ceramic particles, realize the effective conversion and transmission of mechanical stimulation to bioelectric signal, this microstructure design makes the insulating polyether ether ketone matrix possess the electric activity of simulating natural bone stress-electric signal response mechanism, so as to be favorable to activate osteoblast activity and promote bone integration of implant interface.

Description

Technical Field

[0001] This invention belongs to the field of intervertebral fusion device material technology, specifically, it relates to a biocompatible material for a biomimetic porous intervertebral fusion device and its preparation method. Background Technology

[0002] Spinal fusion is the gold standard for treating degenerative disc disease, spondylolisthesis, and other conditions. Polyetheretherketone (PEEK) has replaced titanium alloys as the mainstream material for interbody fusion devices because its elastic modulus (3-4 GPa) is close to that of human cortical bone, and it has excellent chemical stability and radiation permeability.

[0003] However, as a bioinert material, PEEK lacks the bioactivity to induce bone regeneration; natural bone tissue is not a static structure, but a dynamic electrical environment with piezoelectric effect and physiological microcurrent; this force-electric coupling mechanism is the biophysical basis of Wolf's law and is crucial for regulating the proliferation and differentiation of osteoblasts.

[0004] To endow PEEK implants with this biomimetic bone microenvironment, existing technologies have made numerous attempts in material modification: extensive explorations have been conducted to endow PEEK materials with bioactivity and electrostimulation functions. For example, Chinese patent application CN120617629A discloses a 3D-printed functionally enhanced polyetheretherketone composite material and its preparation method. Specifically, this application discloses the melt blending of polyetheretherketone with fillers such as modified carbon nanotubes and modified hydroxyapatite, followed by the preparation of composite granules using a twin-screw extruder at a high temperature of 350°C, and finally, the acquisition of the implant through 3D printing.

[0005] This technical solution primarily utilizes carbon nanotubes to construct a conductive network to enhance mechanical properties and hydroxyapatite to improve osteoinductivity. However, this melt-blending strategy faces an irreconcilable physical contradiction when constructing biomimetic electroactive bone repairs: according to Wolf's law, natural bone possesses piezoelectric properties, and to achieve complete biomimicry, piezoelectric ceramics need to be introduced into the matrix; however, if conductive phases such as carbon nanotubes are introduced according to the aforementioned existing technology, the percolation conductive network formed inside the matrix will directly cause short circuits in the piezoelectric phase, making the matrix unable to withstand high-voltage polarized electric fields, thus preventing the piezoelectric function from being activated.

[0006] Furthermore, Chinese patent application CN105233335A discloses a bioactive porous polyaryletherketone (PEEK) material and its preparation method. Specifically, regarding improving surface bioactivity, this patent discloses sulfonation treatment of the PEEK porous material using concentrated sulfuric acid to introduce hydrophilic sulfonic acid groups onto the surface, followed by immersion in simulated body fluids to induce the deposition of a bone-like apatite layer. This technology effectively improves the material's hydrophilicity and mineralization ability.

[0007] However, a simple sulfonated layer is essentially an insulator and cannot transmit endogenous bioelectrical signals generated by bone movement, nor can it act as an electrode to actively regulate cells. Existing conductive coating technologies, such as physically coated conductive polymers, often rely on van der Waals forces for adhesion, resulting in weak bonding. Furthermore, the small molecule dopants in these coatings are easily lost in the body fluid environment, leading to a rapid decline in conductivity over time, which is insufficient to meet the needs of long-term implantation.

[0008] In addition, for example, Chinese patent application CN115607309A discloses a 3D-printed PEEK material guided bone regeneration membrane and its preparation method. The above-mentioned prior art prepares PEEK implants with interconnected microporous structures by 3D printing and subsequent dissolution of pore-forming agents, constructing a porous structure to simulate bone trabeculae, aiming to promote the penetration of nutrients by utilizing the porous structure.

[0009] However, the aforementioned existing technologies neglect the air resistance effect in microfluidics. Due to the inherent strong hydrophobicity of PEEK materials, when the pore size is small, body fluids can easily form air emboli at the pore inlet under the action of surface tension, preventing the liquid from penetrating into deeper pores. This results in well-designed microporous structures often becoming dead spaces without cell ingrowth in vivo because they cannot be wetted by nutrient solutions.

[0010] Therefore, developing a biocompatible material for biomimetic porous interbody fusion devices that can simultaneously address the issues of deep microporous infiltration, electroactivity, and mechanical safety under long-term load-bearing is of great significance for improving the clinical outcomes of spinal fusion surgery. Summary of the Invention

[0011] To address the deficiencies in the aforementioned technical solutions, the present invention aims to provide a biocompatible material and its preparation method for a biomimetic porous intervertebral fusion device.

[0012] To achieve the above objectives, the present invention provides a biocompatible material for a biomimetic porous intervertebral fusion device. By weight, the biocompatible material for the biomimetic porous intervertebral fusion device comprises the following components: 65-80 parts of polyetheretherketone, 15-25 parts of modified functional filler, 8-12 parts of hydroxyapatite, and 0.5-1 parts of flow modifier.

[0013] The modified functional filler is a barium titanate functional filler coated with graphene oxide.

[0014] The barium titanate in the graphene oxide-coated modified barium titanate functional filler is in the tetragonal phase crystal form.

[0015] The polyetheretherketone is a fine polyetheretherketone powder with an average particle size of 10~50μm;

[0016] The hydroxyapatite is needle-shaped nano-hydroxyapatite with an average length of 50-100 nm and an aspect ratio of >10.

[0017] The flow modifier is polytetrafluoroethylene micro powder.

[0018] The preparation method of the graphene oxide-coated modified barium titanate functional filler includes the following steps:

[0019] Step 1: Take barium titanate nanoparticles and place them in a 10%~15% hydrogen peroxide aqueous solution. Disperse them ultrasonically at 60℃ for 30~60 minutes. Then, heat the suspension to 80℃ and mechanically stir and reflux for 2~4 hours. After treatment, separate them by centrifugation at 8000~10000 rpm and wash them repeatedly with deionized water until the pH of the supernatant is neutral. Finally, dry them in a vacuum oven at 100℃ for 12 hours to obtain activated barium titanate particles with hydroxyl-rich surfaces.

[0020] Step 2: In a three-necked flask, add 500 mL of a mixed solvent of anhydrous ethanol and deionized water at a volume ratio of 95:5. Adjust the pH of the mixed solvent to 4.5-5.5 with glacial acetic acid. Weigh 3.0 g of 3-aminopropyltriethoxysilane and add it dropwise to the above solvent. Stir at room temperature for 30 minutes to hydrolyze the mixture. Then, disperse 50 g of the activated barium titanate particles obtained in Step 1 in the above hydrolysate. Sonicate the mixture at 25℃-40℃ for 40-60 minutes, and then reflux it at 75℃-80℃ for 6-8 hours with mechanical stirring. After the reaction is complete, centrifuge the mixture and wash the precipitate 3-5 times with anhydrous ethanol to remove unreacted silane oligomers. Dry the product under vacuum at 80℃ for 24 hours to obtain modified barium titanate powder with a positively charged surface.

[0021] Step 3: Prepare a monolayer graphene oxide aqueous dispersion with a concentration of 0.5~1.0 mg / mL, and ultrasonically exfoliate it for 1~2 hours to stabilize its Zeta potential between -30mV and -50mV; under vigorous mechanical stirring (500~800 rpm), slowly and in batches add the modified barium titanate powder obtained in Step 2 to the GO dispersion; after the addition is complete, continue stirring at low speed (100~200 rpm) for 2~4 hours; the reaction solution is centrifuged and the supernatant is discarded; the precipitate is freeze-dried to obtain a fluffy, gray graphene oxide-coated modified barium titanate functional filler.

[0022] In step 1, the barium titanate has an average particle size of 50 nm to 150 nm and is a tetragonal phase crystal.

[0023] The modified barium titanate particles have a Zeta potential of not less than +30mV in an aqueous dispersion at pH=7.

[0024] The freeze-drying process in step 3 is as follows: drying at -50℃ and vacuum degree <10Pa for 24~48 hours;

[0025] In step 3, the mass ratio of modified barium titanate powder to graphene oxide is 100:(1.5~3.0).

[0026] A method for preparing a biocompatible material for a biomimetic porous intervertebral fusion device includes the following steps:

[0027] Step A: Premixing: Place the modified functional filler and polyether ether ketone fine powder in a high-speed mixer; then add the flow modifier and mix at a speed of 2000~2500 rpm for 5~10 minutes to make the filler uniformly adhere to the surface of the PEEK resin particles, thus obtaining the premix.

[0028] Step B: Reactive melt extrusion and in-situ reduction: The premix is ​​added to the main feed port of the twin-screw extruder;

[0029] Melt processing was performed using a co-rotating twin-screw extruder (length-to-diameter ratio L / D=40, screw diameter 20mm);

[0030] Key process parameters are set, including the temperature distribution of the extruder, from the feed port to the die head as follows:

[0031] Conveying section: 330℃~340℃;

[0032] Melting zone: 360℃~370℃;

[0033] Reaction section: 380℃~395℃;

[0034] Metering range: 370℃~380℃;

[0035] Machine head: 365℃~375℃;

[0036] Screw speed: 180-250 rpm;

[0037] The average residence time of the material in the reaction section is 120 to 240 seconds.

[0038] Step C: Granulation and molding: The composite material melt strip extruded from the die head is cooled by a circulating water bath, then granulated and dried in a forced-air dryer at 150°C for 4 hours to obtain biocompatible granules.

[0039] Step D: Post-processing: Place the molded material in a silicone oil bath and heat it to 120℃~140℃; apply a DC high voltage electric field for corona polarization treatment, with an electric field strength of 3~5kV / mm and a polarization time of 30~60 minutes; then cool it naturally to room temperature while maintaining the electric field, thus obtaining a biocompatible material for a biomimetic porous intervertebral fusion device.

[0040] Furthermore, the biocompatible granules prepared in step C can be used to prepare a porous intervertebral fusion device through injection molding or additive manufacturing, and then the post-processing in step D can be performed.

[0041] The beneficial effects of this invention are:

[0042] 1. This invention constructs a core-shell structure filler with partially reduced graphene oxide as the shell layer, and uses the appropriate amount of oxygen-containing polar groups remaining on the shell surface to perform essential hydrophilic modification on the polyether ether ketone matrix, thereby significantly improving the wetting dynamics of the material surface. This enables body fluids and blood to overcome the capillary resistance of the microporous structure and actively wet and fill the interior of the porous fusion device, effectively eliminating the air resistance effect commonly found in traditional hydrophobic materials in complex porous structures, and opening up physical channels for early adhesion and deep ingrowth of osteocytes.

[0043] 2. This invention introduces nano-piezoelectric ceramic particles modified with surface conductivity and constructs a semi-interpenetrating semiconductor conductive network in a polymer matrix, thereby achieving the effective conversion and transmission of mechanical stimulation into bioelectric signals. This microstructure design enables the insulating polyetheretherketone matrix to possess electroactivity that simulates the stress-electric signal response mechanism of natural bone. It can utilize the physiological load of the human body to generate and conduct microcurrent stimulation on the implant surface, which is beneficial to activating osteoblast activity and promoting bone integration at the bone-implant interface.

[0044] 3. This invention solves the problem of easy agglomeration and stress concentration of high-filling inorganic fillers in organic matrices by using silane coupling agent-induced electrostatic self-assembly prefabricated core-shell structure and interface anchoring effect during in-situ reduction. Thus, while endowing the material with excellent electroactivity and hydrophilicity, it effectively avoids the precipitous drop in mechanical properties commonly seen in traditional blending modification. The modified material can still maintain excellent tensile strength and elongation at break comparable to medical-grade polyether ether ketone, ensuring the mechanical safety of the intervertebral fusion device under long-term load in the body.

[0045] 4. This invention utilizes the unique high melt processing temperature of polyetheretherketone resin as a thermal trigger for chemical reactions, innovatively realizing the controllable in-situ conversion of graphene oxide into conductive graphene derivatives. This one-step processing method not only avoids the use of toxic chemical reducing agents and ensures the biosafety of the material, but also ensures that the conductive network is formed and fixed in the final stage of matrix melting and flow, thereby ensuring the uniformity of the material's microstructure and batch stability, making it suitable for large-scale industrial production. Attached Figure Description

[0046] Figure 1 This is a bar graph comparing the elongation at break and tensile strength of the embodiments and comparative examples;

[0047] Figure 2 This is a line graph comparing the surface resistivity and piezoelectric coefficient of the embodiments and comparative examples. Detailed Implementation

[0048] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The illustrative embodiments and descriptions of this invention are for explanation only and are not intended to limit the invention. Furthermore, regarding numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0049] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0050] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0051] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0052] Example 1

[0053] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 65 parts polyetheretherketone, 15 parts modified functional filler, 8 parts hydroxyapatite, and 0.5 parts flow modifier.

[0054] The modified functional filler is a barium titanate functional filler coated with graphene oxide.

[0055] The polyetheretherketone is a fine polyetheretherketone powder with an average particle size of 10~50μm;

[0056] The hydroxyapatite is needle-shaped nano-hydroxyapatite with an average length of 50-100 nm and an aspect ratio of >10.

[0057] The flow modifier is polytetrafluoroethylene micro powder;

[0058] In specific implementation, the polyetheretherketone (PEEK) is designated as: PEEK450PF;

[0059] In specific implementation, the grade of the polytetrafluoroethylene micro powder is: MP1100;

[0060] In practice, the barium titanate was purchased from Sakai Chemical Industry's BT-01.

[0061] The preparation method of the graphene oxide-coated modified barium titanate functional filler includes the following steps:

[0062] Step 1: Take barium titanate nanoparticles and place them in a 15% (w / w) hydrogen peroxide aqueous solution. Disperse the nanoparticles ultrasonically at 60°C for 60 minutes. Then, heat the suspension to 80°C and reflux with mechanical stirring for 2-4 hours. After treatment, centrifuge at 8000-10000 rpm and wash repeatedly with deionized water until the supernatant pH is neutral. Finally, dry the supernatant in a vacuum oven at 100°C for 12 hours to obtain activated barium titanate particles with hydroxyl-rich surfaces.

[0063] Step 2: In a three-necked flask, add 500 mL of a mixed solvent of anhydrous ethanol and deionized water at a volume ratio of 95:5. Adjust the pH of the mixed solvent to 4.5-5.5 with glacial acetic acid. Weigh 3.0 g of 3-aminopropyltriethoxysilane and add it dropwise to the above solvent. Stir at room temperature for 30 minutes to hydrolyze the mixture. Then, disperse 50 g of the activated barium titanate particles obtained in Step 1 in the above hydrolysate. Sonicate the mixture at 25℃-40℃ for 60 minutes, and then reflux it at 75℃-80℃ for 8 hours. After the reaction is complete, centrifuge the mixture and wash the precipitate five times with anhydrous ethanol to remove unreacted silane oligomers. Dry the product under vacuum at 80℃ for 24 hours to obtain modified barium titanate powder with a positively charged surface.

[0064] Step 3: Prepare a 1.0 mg / mL monolayer graphene oxide aqueous dispersion and ultrasonically exfoliate it for 1-2 hours to stabilize its Zeta potential between -30 mV and -50 mV. Under vigorous mechanical stirring (500-800 rpm), slowly and in batches add the modified barium titanate powder obtained in Step 2 to the GO dispersion. After the addition is complete, continue stirring at low speed (100-200 rpm) for 2-4 hours. Utilize electrostatic attraction to spontaneously adsorb and coat the negatively charged graphene oxide sheets onto the surface of the positively charged modified barium titanate powder. After centrifugation, discard the supernatant. The precipitate is freeze-dried to obtain a fluffy gray modified functional filler powder.

[0065] The barium titanate in step 1 has an average particle size of 50 nm to 150 nm and is a tetragonal phase.

[0066] The zeta potential of the modified barium titanate particles in an aqueous dispersion at pH 7 should not be less than +30mV.

[0067] The freeze-drying process in step 3 is as follows: drying at -50℃ and vacuum degree <10Pa for 24~48 hours;

[0068] In step 3, the mass ratio of modified barium titanate powder to graphene oxide is 100:1.5.

[0069] A method for preparing a biocompatible material for a biomimetic porous intervertebral fusion device includes the following steps:

[0070] Step A: Premixing: Place 15 parts by weight of modified functional filler and 65 parts by weight of polyetheretherketone fine powder in a high-speed mixer; then add 0.5 parts by weight of flow modifier and mix at 2000~2500 rpm for 5~10 minutes to make the filler uniformly adhere to the surface of PEEK resin particles, thus obtaining the premix.

[0071] Step B: Reactive melt extrusion and in-situ reduction: The premix is ​​added to the main feed port of the twin-screw extruder;

[0072] A co-rotating twin-screw extruder with a length-to-diameter ratio of L / D=40 and a screw diameter of 20mm was used for melt processing.

[0073] Key process parameters are set, including the temperature distribution of the extruder, from the feed port to the die head as follows:

[0074] Conveying section: 330℃~340℃;

[0075] Melting zone: 360℃~370℃;

[0076] Reaction section: 380℃~395℃;

[0077] Metering range: 370℃~380℃;

[0078] Machine head: 365℃~375℃;

[0079] Screw speed: 180-250 rpm;

[0080] The average residence time of the material in the reaction section is 120 to 240 seconds.

[0081] Under the influence of high temperature and strong shear field, the graphene oxide coated on the surface of piezoelectric particles undergoes a thermochemical reduction reaction, removing unstable oxygen-containing functional groups and transforming in situ into partially reduced graphene oxide with conductivity, while retaining some stable carboxyl groups to maintain compatibility with the PEEK matrix.

[0082] Step C: Granulation and molding: The composite material melt strip extruded from the die head is cooled by a circulating water bath, then granulated and dried in a forced-air dryer at 150°C for 4 hours to obtain biocompatible granules.

[0083] The biocompatible granules prepared in step C can be used to prepare porous intervertebral fusion devices through injection molding or additive manufacturing, and then the post-processing in step D is performed.

[0084] Step D: Post-processing:

[0085] The shaped material is placed in a silicone oil bath and heated to 120℃~140℃. A DC high-voltage electric field is applied for corona polarization treatment with an electric field strength of 3~5kV / mm and a polarization time of 30~60 minutes. Then, it is naturally cooled to room temperature while maintaining the electric field, thus obtaining a biocompatible material for a biomimetic porous intervertebral fusion device.

[0086] Example 2

[0087] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts modified functional filler, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0088] The modified functional filler is a barium titanate functional filler coated with graphene oxide.

[0089] The polyetheretherketone is a fine polyetheretherketone powder with an average particle size of 10~50μm;

[0090] The flow modifier is polytetrafluoroethylene micro powder;

[0091] The hydroxyapatite is needle-shaped nano-hydroxyapatite with an average length of 50-100 nm and an aspect ratio of >10.

[0092] The flow modifier is polytetrafluoroethylene micro powder;

[0093] In step 3 of the preparation process of the modified functional filler, the mass ratio of modified barium titanate powder to graphene oxide is 100:2.

[0094] The preparation methods of the modified functional filler in Example 2 and the preparation methods of the biocompatible materials used in the biomimetic porous intervertebral fusion device are the same as those in Example 1.

[0095] Example 3

[0096] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 75 parts polyetheretherketone, 22 parts modified functional filler, 11 parts hydroxyapatite, and 0.8 parts flow modifier.

[0097] The modified functional filler is a barium titanate functional filler coated with graphene oxide.

[0098] The polyetheretherketone is a fine polyetheretherketone powder with an average particle size of 10~50μm;

[0099] The flow modifier is polytetrafluoroethylene micro powder;

[0100] The hydroxyapatite is needle-shaped nano-hydroxyapatite with an average length of 50-100 nm and an aspect ratio of >10.

[0101] The flow modifier is polytetrafluoroethylene micro powder;

[0102] In step 3 of the modified functional filler preparation process, the mass ratio of modified barium titanate powder to graphene oxide is 100:2.5.

[0103] The preparation methods of the modified functional filler in Example 3 and the preparation methods of the biocompatible materials used in the biomimetic porous intervertebral fusion device are the same as those in Example 1.

[0104] Example 4

[0105] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 80 parts polyetheretherketone, 25 parts modified functional filler, 12 parts hydroxyapatite, and 1 part flow modifier.

[0106] The modified functional filler is a barium titanate functional filler coated with graphene oxide.

[0107] The polyetheretherketone is a fine polyetheretherketone powder with an average particle size of 10~50μm;

[0108] The flow modifier is polytetrafluoroethylene micro powder;

[0109] The hydroxyapatite is needle-shaped nano-hydroxyapatite with an average length of 50-100 nm and an aspect ratio of >10.

[0110] The flow modifier is polytetrafluoroethylene micro powder;

[0111] In step 3 of the preparation process of the modified functional filler, the mass ratio of modified barium titanate powder to graphene oxide is 100:3.

[0112] The preparation methods of the modified functional filler in Example 4 and the preparation methods of the biocompatible materials used in the biomimetic porous intervertebral fusion device are the same as those in Example 1.

[0113] Comparative Example 1

[0114] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 90 parts polyetheretherketone, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0115] The difference between Comparative Example 1 and Example 2 is that Comparative Example 1 did not add modified functional fillers, but increased the amount of polyether ether ketone to make up the parts.

[0116] Apart from the above, the other components, their amounts, and preparation methods in Comparative Example 1 are the same as in Example 2.

[0117] Comparative Example 2

[0118] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts pure graphene oxide powder, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0119] The difference between this comparative example and Example 2 is that this comparative example uses an equal amount of pure graphene oxide powder, replacing the modified functional filler in Example 2.

[0120] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0121] Comparative Example 3

[0122] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts modified barium titanate powder, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0123] The modified barium titanate powder in Comparative Example 3, namely the modified barium titanate powder prepared in step 2 during the preparation of the modified functional filler, replaced the modified functional filler in Example 2.

[0124] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0125] Comparative Example 4

[0126] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts of a mixture of modified barium titanate powder and graphene oxide, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0127] The mixture of modified barium titanate powder and graphene oxide in Comparative Example 4 is a physical mixture. The modified barium titanate powder is the modified barium titanate powder prepared in step 2 of the modified functional filler preparation process, which contains 16 parts of modified barium titanate powder and 2 parts of graphene oxide. This physical mixture is directly used as a functional filler and is melt-extruded together with polyether ether ketone, hydroxyapatite and flow modifier.

[0128] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0129] Comparative Example 5

[0130] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts graphene oxide-coated unmodified barium titanate filler, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0131] The difference between this comparative example and Example 2 is that, in the preparation of the modified functional filler, the step of modifying barium titanate in step 2 is omitted; instead, unmodified barium titanate is directly mixed with an aqueous dispersion of graphene oxide to attempt coating.

[0132] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0133] Comparative Example 6

[0134] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts reduced graphene oxide-coated modified barium titanate filler, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0135] The difference between this comparative example and Example 2 is that, in the preparation of the modified functional filler, commercially available, fully chemically reduced graphene oxide was used to replace the graphene oxide used in Example 2 for coating the modified barium titanate filler.

[0136] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0137] Comparative Example 7

[0138] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts barium titanate functional filler coated with excess graphene oxide, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0139] The difference between this comparative example and Example 2 is that in step 3 of preparing the modified functional filler, the mass ratio of modified barium titanate powder to graphene oxide is controlled at 100:10.

[0140] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0141] Comparative Example 8

[0142] A biocompatible material for a biomimetic porous intervertebral fusion device, comprising, by weight, the following components: 72 parts polyetheretherketone, 18 parts graphene oxide-coated modified barium titanate functional filler, 10 parts hydroxyapatite, and 0.6 parts flow modifier.

[0143] The difference between this comparative example and Example 2 lies in the following differences in the preparation process:

[0144] In this comparative example, during the reactive melt extrusion step, the temperature distribution of the twin-screw extruder from the feed port to the die head was set sequentially as follows: conveying section 335℃, melting section 355℃, reaction section 365℃, metering section 360℃, and die head 355℃.

[0145] Apart from the above, the other components, their amounts, and preparation methods in this comparative example are the same as in Example 2.

[0146] Test case

[0147] Static water contact angle test: Referring to GB / T30693-2014 "Determination of wetting tension of plastic films and sheets", a contact angle measuring instrument was used to complete the water contact angle tests of Examples 1-4 and Comparative Examples 1-8;

[0148] Tensile property testing: Referring to GB / T1040.2-2006 "Determination of tensile properties of plastics", an electronic universal testing machine was used to complete the tensile strength and elongation at break of Examples 1-4 and Comparative Examples 1-8.

[0149] Surface resistivity test: Using a high-resistivity meter with concentric ring electrodes, in accordance with ASTM D257-14, the surface resistivity of Examples 1-4 and Comparative Examples 1-8 was tested.

[0150] Quasi-static d 33 Piezoelectric coefficient testing: Silver electrodes with a thickness of approximately 100 nm were deposited on the upper and lower surfaces of the sample after step D using a magnetron sputtering system; subsequently, quasi-static d... 33 The measuring instrument clamps the prepared sample between the measuring probes; the test frequency is set to 110Hz, and a dynamic force of approximately 0.25N is applied; the instrument directly reads and displays the test value. 33 Value (unit: pC / N)

[0151] The biocompatible materials for biomimetic porous intervertebral fusion devices prepared in Examples 1-4 and Comparative Examples 1-8 were processed in steps A, B, and C. Then, the biocompatible granules were prepared into strips for tensile property testing, contact angle testing, surface resistivity testing, and piezoelectric property testing. Finally, step D was performed for post-processing, followed by various experimental treatments.

[0152] The test results are shown in Table 1:

[0153] Table 1

[0154]

[0155] Performance test data analysis, including Figure 1 This is a bar graph comparing the elongation at break and tensile strength of the embodiments and comparative examples;

[0156] Figure 2 This is a line graph comparing the surface resistivity and piezoelectric coefficient of the embodiments and comparative examples.

[0157] Combining the data in Table 1 and Figure 1 , Figure 2 As can be seen, the biocompatible materials prepared in Examples 1-4 of this invention exhibit excellent balance across all test dimensions. The static water contact angles shown in Examples 1-4 are between 50-58°, significantly lower than the 85° static water contact angle shown in Comparative Example 1 (polyetheretherketone + hydroxyapatite), reaching a suitable biocompatibility range for cell adhesion and effectively solving the air resistance problem under porous structures.

[0158] Furthermore, the quasi-static d of embodiments 1-4 of this application 33 The piezoelectric coefficient reaches 3.1~3.8 pC / N, and the surface resistivity is all above 10. 6 -10 8 The technical solution of this application successfully simulates the weak piezoelectric effect of natural bone and has the ability to conduct charge. Moreover, its mechanical properties are also excellent, indicating that the introduction of functional fillers does not damage the mechanical integrity of the matrix.

[0159] This invention does not use readily available conductive fillers, but instead utilizes the unique high melt processing temperature of polyetheretherketone resin as a thermal trigger for the chemical reaction, innovatively achieving the controllable in-situ conversion of graphene oxide into conductive graphene derivatives; the necessity of this inventive design is confirmed by the following comparison:

[0160] Comparative Example 6 used commercially available fully reduced graphene oxide. The test results showed that its water contact angle was as high as 91.5°, exhibiting strong hydrophobicity. This is because complete reduction eliminates the polar oxygen-containing groups on the surface.

[0161] This explains that pursuing complete reduction for conductivity would sacrifice the hydrophilicity of the material, making it impossible to overcome the gas barrier effect. However, the technical solution of this application, through the control of the preparation process, achieves moderate reduction, restoring conductivity while retaining hydrophilicity, thus achieving a balance and coexistence of the two properties.

[0162] In contrast, Comparative Example 8 used a conventional low-temperature processing method for the reactive melt extrusion step. Although Comparative Example 8 achieved excellent hydrophilicity, its surface resistivity was greater than 10. 13 The graphene oxide shell is in an insulating state, resulting in a piezoelectric coefficient of only 0.5. This indicates that if the temperature is insufficient during the reactive melt extrusion step, the shell of graphene oxide cannot be converted into a conductive path, and the charge generated by the piezoelectric core is trapped inside the insulating shell. This demonstrates that the relevant temperature setting of the reactive melt extrusion step in this embodiment is crucial for activating electroactivity.

[0163] The difference between Comparative Example 2 and Example 2 is that this comparative example uses an equal amount of pure graphene oxide powder, replacing the modified functional filler in Example 2.

[0164] Because Comparative Example 2 only contains graphene oxide powder, although it is hydrophilic and has a conductive surface, its piezoelectric coefficient is 0.4, which may be due to test noise. This indicates that without piezoelectric particles, the material cannot respond to mechanical stimuli and generate electrical signals.

[0165] Regarding Comparative Example 3, the modified barium titanate powder in Comparative Example 3, i.e., the modified barium titanate powder prepared in step 2 of the modified functional filler preparation process, replaced the modified functional filler in Example 2. Comparative Example 3 only contains piezoelectric particles, but due to the polyetheretherketone matrix, which is inherently insulating, the piezoelectric coefficient is 1.2. In contrast, the piezoelectric coefficient of the embodiments of this application represents an increase of over 200% compared to Comparative Example 3. This demonstrates that only the technical solution constructed in Example 2 of this application can realize and form biomimetic electrical stimulation.

[0166] Comparative Example 4 used physical blending, while Comparative Example 5 used a material that omitted the step 2 of modifying barium titanate. The elongation at break of both dropped to 12.4% and 11.6%, respectively, exhibiting significant brittleness in their mechanical properties. This indicates that without a stable core-shell structure or sufficient chemical bonding, the nanofiller agglomerates in the matrix, becoming a stress concentration defect. The technical solution of this application can achieve the technical effect of nano-reinforcement and toughening.

[0167] Regarding Comparative Example 7, in step 3 of preparing the modified functional filler, the mass ratio of modified barium titanate powder to graphene oxide was controlled at 100:10.

[0168] This indicates that increasing the amount of graphene oxide used does not lead to a linear improvement in performance; instead, it results in a worse technical effect, with the surface resistivity of Comparative Example 7 decreasing to 3.6 × 10⁻⁶. 3 This may lead to excessive leakage current during polarization, making it impossible to establish an effective polarization electric field. Ultimately, the piezoelectric coefficient is only 0.8, indicating that the surface resistivity is not necessarily better the higher it is, but needs to be controlled within a reasonable range. Furthermore, the tensile strength also drops sharply to 68.3 MPa, and the elongation at break is only 4.8%. The possible reason is that the excessive graphene shell forms a lubricating layer between the particles and the matrix, which causes severe interlayer slippage when subjected to force.

[0169] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A biocompatible material for a biomimetic porous intervertebral cage, characterized in that, The biocompatible material used in the biomimetic porous intervertebral fusion device, by weight: It includes the following components: 65-80 parts of polyetheretherketone, 15-25 parts of modified functional filler, 8-12 parts of hydroxyapatite, and 0.5-1 parts of flow modifier; The modified functional filler is a barium titanate functional filler coated with graphene oxide. The preparation method of the graphene oxide-coated modified barium titanate functional filler includes the following steps: Step 1: Take barium titanate nanoparticles and place them in an aqueous hydrogen peroxide solution. Disperse them ultrasonically at 60°C for 30-60 minutes. Then, heat the suspension to 80°C and reflux with mechanical stirring for 2-4 hours. After treatment, separate them by centrifugation and wash them repeatedly with deionized water until the pH of the supernatant is neutral. Finally, dry them in a vacuum oven at 100°C for 12 hours to obtain activated barium titanate particles with hydroxyl-rich surfaces. Step 2: In a three-necked flask, add a mixed solvent of anhydrous ethanol and deionized water, and adjust the pH of the mixed solvent to 4.5-5.5 with glacial acetic acid; add 3-aminopropyltriethoxysilane dropwise, and stir at room temperature for 30 minutes to hydrolyze; then, disperse the activated barium titanate particles obtained in Step 1 in the hydrolysate, and ultrasonically disperse at 25℃-40℃ for 40-60 minutes, and then mechanically stir and reflux at 75℃-80℃ for 6-8 hours; after the reaction is completed, centrifuge and wash the precipitate with anhydrous ethanol 3-5 times; finally, vacuum dry the obtained product at 80℃ for 24 hours to obtain modified barium titanate powder; Step 3: Prepare a single-layer graphene oxide aqueous dispersion and ultrasonically exfoliate it for 1-2 hours to stabilize its Zeta potential between -30mV and -50mV. Under vigorous mechanical stirring, slowly and in batches add the modified barium titanate powder obtained in Step 2 to the graphene oxide aqueous dispersion. After the addition is complete, continue stirring at low speed for 2-4 hours. Finally, the reaction solution is separated by centrifugation, and the supernatant is discarded. The precipitate is freeze-dried to obtain a fluffy, gray graphene oxide-coated modified barium titanate functional filler. The method for preparing a biocompatible material for a biomimetic porous intervertebral fusion device includes the following steps: Step A: Premixing: Place the modified functional filler and polyetheretherketone fine powder in a high-speed mixer; then add the flow modifier and mix at 2000~2500 rpm for 5~10 minutes to make the filler uniformly adhere to the surface of the PEEK resin particles, thus obtaining the premix. Step B: Reactive melt extrusion and in-situ reduction: Add the premix to the main feed port of the twin-screw extruder; A co-rotating twin-screw extruder with a length-to-diameter ratio of L / D=40 and a screw diameter of 20mm is used for melt processing. Key process parameters are set, including the temperature distribution of the extruder, from the feed port to the die head as follows: Conveying section: 330℃~340℃; Melting zone: 360℃~370℃; Reaction section: 380℃~395℃; Metering range: 370℃~380℃; Machine head: 365℃~375℃; Screw speed: 180-250 rpm; The average residence time of the material in the reaction section is 120 to 240 seconds; Step C: Granulation and molding: The composite material melt strip extruded from the die head is cooled by a circulating water bath, then granulated and dried in a forced-air dryer at 150°C for 4 hours to obtain biocompatible granules. Step D: Post-processing: Place the molded material in a silicone oil bath and heat it to 120℃~140℃; apply a DC electric field for corona polarization treatment, with an electric field strength of 3~5kV / mm and a polarization time of 30~60 minutes; then cool it naturally to room temperature while maintaining the electric field, thus obtaining a biocompatible material for a biomimetic porous intervertebral fusion device.

2. A biocompatible material for use in a bionic porous interbody fusion cage according to claim 1, wherein, The biocompatible material used in the biomimetic porous intervertebral fusion device, by weight: It includes the following components: 72 parts of polyetheretherketone, 18 parts of modified functional filler, 10 parts of hydroxyapatite, and 0.6 parts of flow modifier; The modified functional filler is a barium titanate functional filler coated with graphene oxide.

3. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, The polyetheretherketone is a fine polyetheretherketone powder with an average particle size of 10~50μm.

4. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, The hydroxyapatite is needle-shaped nano-hydroxyapatite with an average length of 50-100 nm and an aspect ratio >10.

5. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, The flow modifier is polytetrafluoroethylene micro powder.

6. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, In step 1, the average particle size of barium titanate is 50 nm to 150 nm, and the crystal form is tetragonal.

7. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, In step 3, the mass ratio of modified barium titanate powder to graphene oxide is 100:(1.5~3.0).

8. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, The modified barium titanate particles have a zeta potential of not less than +30mV in an aqueous dispersion at pH=7.

9. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, The freeze-drying process in step 3 is as follows: drying at -50℃ and a vacuum degree <10Pa for 24~48 hours.

10. The biocompatible material for use in a bionic porous intervertebral fusion cage according to claim 1, wherein, The biocompatible granules prepared in step C of the method for preparing a biocompatible material for a biomimetic porous intervertebral fusion device can be used to prepare a porous intervertebral fusion device by injection molding or additive manufacturing, and then the post-processing in step D is performed.

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