A method for preparing a gradient dual-function 3D printed PEEK implant in situ

Abstract

The application discloses a preparation method of an in-situ gradient bifunctional 3D printing PEEK implant, which introduces a bioactive component with a bone integration promoting effect and a functional component with an antibacterial function into a PEEK base printing material through a multi-material co-extrusion molding mode, and realizes the functionalization regulation of different regions of the implant by combining a gradient structure design; the method avoids the adverse effects on the PEEK molecular structure and mechanical properties in the traditional blending modification process, and solves the problems of insufficient coating bonding strength, uneven coverage of complex structures and low utilization rate of functional components; the gradient structure matching the mechanical property region and the biological function region is formed through in-situ printing, so that the implant has the functions of bone integration promotion and antibiosis, and the comprehensive service performance of the PEEK implant is improved; and the preparation process is suitable for personalized manufacturing of medical PEEK implants with complex structures.

Description

Technical Field

[0001] This invention belongs to the field of medical polymer additive manufacturing and orthopedic implant technology, specifically relating to a method for preparing an in-situ gradient dual-function 3D printed PEEK implant. Background Technology

[0002] Polyetheretherketone (PEEK), with its excellent mechanical properties, biocompatibility, fatigue resistance, and elastic modulus similar to human cortical bone, has become the mainstream permanent implant polymer material in orthopedics, craniofacial surgery, and dentistry. Utilizing fused deposition modeling (FDM) 3D printing technology, personalized PEEK implants matching the patient's anatomy can be rapidly fabricated, effectively addressing the industry pain points of poor fit and long customization cycles of traditional machined prostheses, leading to a continuous expansion of its clinical application.

[0003] Implantable PEEK prostheses face two major challenges in clinical use: implantation site infection and insufficient osseointegration. On the one hand, orthopedic surgery is an invasive procedure, prone to bacterial colonization, incision infection, and even deep prosthesis-related infection post-surgery. These complications can range from prolonged recovery to requiring a second surgery to remove the prosthesis, significantly increasing medical risks and patient suffering. On the other hand, pure PEEK material has an inert surface, resulting in weak cell adhesion and bone ingrowth. A fibrous capsule can easily form between the prosthesis and the patient's own bone, leading to long-term failure issues such as prosthesis loosening and displacement. Therefore, the industry generally focuses on functional modification of PEEK materials, primarily in two areas: osseointegration-promoting modifications and antibacterial modifications.

[0004] Current modification and 3D printing technologies have many shortcomings, failing to simultaneously achieve optimal mechanical properties, dual-function synergy, molding process stability, and long-term safety. Specific problems include:

[0005] 1. Primarily focused on single-function modification, it is difficult to achieve a synergistic effect of bone integration and antibacterial activity.

[0006] Most existing technologies only perform single-function modifications: one type involves integrally blending bioactive ceramics such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) into a PEEK matrix to enhance bone induction capacity; however, this type of modified material lacks antibacterial effects and cannot inhibit postoperative infection. Another type involves doping PEEK with antibacterial components such as silver ions, quaternary ammonium salts, and antimicrobial peptides, or spraying an antibacterial coating onto the surface of the finished prosthesis. While this achieves antibacterial effects, it cannot promote bone tissue integration. Neither of these single-modification approaches can simultaneously address the two major clinical challenges of infection and prosthesis loosening.

[0007] 2. Integral blended bifunctional filler, severely sacrificing the mechanical properties of the matrix.

[0008] Some studies have attempted to simultaneously incorporate bioactive ceramics and antibacterial components into a PEEK matrix for overall modification, followed by uniform filament drawing and 3D printing. However, a large amount of inorganic powder and antibacterial filler disrupts the continuity of the PEEK polymer chains, significantly reducing the material's tensile strength, flexural strength, and toughness. Simultaneously, high filler content leads to poor melt flowability, poor extrusion, and decreased interlayer bonding in 3D printing materials, resulting in delamination, warping, and porosity defects in the printed product. This not only fails to meet implant mechanical safety standards but also reduces the yield rate. Furthermore, the uniform distribution of antibacterial components throughout the prosthesis prevents internal antibacterial components from contacting bacteria, resulting in wasted functional materials and long-term continuous leaching, posing potential risks of cytotoxicity and accumulation in vivo.

[0009] 3. The post-treatment coating of the functional layer has poor adhesion, is prone to peeling, and has a short service life.

[0010] The mainstream composite functional approach involves first printing a pure PEEK matrix prosthesis, and then preparing an osseointegration coating or antibacterial coating on the prosthesis surface through post-processing methods such as spraying, soaking, and grafting. This method has significant drawbacks: the coating and the PEEK matrix are only physically bonded, making them prone to peeling and flaking under the influence of bodily fluids and micro-friction from bone, with the detached coating particles potentially causing local inflammation. Furthermore, the complex porous structure, internal cavities, and micropores make it difficult to achieve uniform coating coverage, resulting in poor functional consistency and failing to meet the requirements for long-term implantation. Simultaneously, the secondary coating process increases the production steps, making automated mass production difficult and leading to high production costs.

[0011] 4. The functional layer structure design is unreasonable, and the mechanical zoning does not match the functional zoning.

[0012] Human implant prostheses have clearly defined mechanical and functional zones: the core area of ​​the prosthesis primarily bears the mechanical load, requiring dense, high-strength, and high-toughness materials; the surface layer, the inner walls of the pores, and the interface with autologous bone need to have bone ingrowth and antibacterial capabilities, and can employ porous structures with high-functional filler content. Current technologies do not incorporate gradient structural designs based on the stress characteristics of the prosthesis; either they are entirely dense and lack porosity, resulting in poor osseointegration, or they have high porosity, leading to insufficient overall mechanical strength, failing to meet the differentiated usage requirements of implants for both load-bearing and biological function.

[0013] 5. Conventional single-nozzle 3D printing cannot achieve in-situ gradient co-extrusion molding.

[0014] Traditional single-nozzle fused deposition modeling equipment can only use a single formula of consumables and cannot simultaneously achieve in-situ molding of different components and functional materials in layers / areas during the printing process. If multiple printing processes are used for molding in stages, it will result in weak interlayer interface bonding, insufficient overall sealing, and easy seepage of body fluids into the interface, causing potential hazards. It also cannot achieve integrated continuous manufacturing.

[0015] In summary, there is currently a lack of a PEEK implant fabrication process that enables in-situ integrated molding, possesses excellent mechanical properties, has a surface layer with both long-lasting osseointegration and antibacterial functions, and ensures strong bonding between the functional layers. Developing a dual-functional gradient molding method based on two-material co-extrusion 3D printing to achieve integrated manufacturing of the prosthesis's "load-bearing matrix + functional surface layer" is an urgent need to address the aforementioned technical bottlenecks. Summary of the Invention

[0016] To address the shortcomings of existing 3D printing technologies for PEEK medical implants, this invention aims to solve the following problems: Existing technologies mostly employ single-function modification methods, failing to simultaneously achieve bone integration and antibacterial effects, making it difficult to address the two major clinical challenges of postoperative infection and long-term prosthesis loosening; If bioactive fillers and antibacterial fillers are co-mixed into the PEEK matrix, it will damage the polymer chain structure, causing a significant decrease in the material's mechanical properties and easily leading to problems such as filament breakage and product defects. Furthermore, the uniform distribution of antibacterial components within the matrix results in material waste and poses safety risks such as ion precipitation and accumulation, potentially causing cytotoxicity; The method of printing the matrix first and then coating the functional layer results in weak adhesion between the coating and the matrix, making it prone to detachment under the influence of body fluids and friction. Moreover, it is difficult to achieve uniform coating coverage for complex structures, leading to cumbersome production processes and poor product durability; Conventional single-nozzle printing cannot create in-situ gradient structures that match the mechanical and functional zones, and the multi-stage assembly molding process can produce interface defects, further affecting the safety and lifespan of the implant.

[0017] The technical solution adopted by the present invention to solve the above-mentioned technical problems is as follows:

[0018] To address the shortcomings of existing 3D printing technologies for PEEK medical implants, this invention aims to solve the following problems: Existing technologies mostly employ single-function modification methods, failing to simultaneously achieve bone integration and antibacterial effects, making it difficult to address the two major clinical challenges of postoperative infection and long-term prosthesis loosening; If bioactive fillers and antibacterial fillers are co-mixed into the PEEK matrix, it will damage the polymer chain structure, causing a significant decrease in the material's mechanical properties and easily leading to problems such as filament breakage and product defects. Furthermore, the uniform distribution of antibacterial components within the matrix results in material waste and poses safety risks such as ion precipitation and accumulation, potentially causing cytotoxicity; The method of printing the matrix first and then coating the functional layer results in weak adhesion between the coating and the matrix, making it prone to detachment under the influence of body fluids and friction. Moreover, it is difficult to achieve uniform coating coverage for complex structures, leading to cumbersome production processes and poor product durability; Conventional single-nozzle printing cannot create in-situ gradient structures that match the mechanical and functional zones, and the multi-stage assembly molding process can produce interface defects, further affecting the safety and lifespan of the implant.

[0019] To achieve the above-mentioned objectives, this invention adopts the following complete technical solution, which is divided into three main stages: functional filament preparation, two-material co-extrusion 3D printing molding, and finished product post-processing. The specific steps are as follows:

[0020] 1. First stage: Preparation of two types of differentiated functional PEEK filaments

[0021] This invention uses two special printing filaments: a pure medical-grade PEEK matrix filament and a bioactive-antibacterial composite modified PEEK filament. The two filaments have the same specifications and are compatible with dual-nozzle co-extrusion equipment to ensure extrusion synchronization.

[0022] (1) Step S1 Raw material pretreatment

[0023] Matrix raw materials: Select implant-grade pure PEEK resin particles that meet the YY / T0660 standard, place them in a hot air circulating drying oven, and dry them at 120~130℃ for 8~12h. Control the moisture content of the raw materials to ≤0.02% to prevent moisture from vaporizing and generating bubbles and breaking fibers during high-temperature melting.

[0024] Pretreatment of modified fillers:

[0025] Bioactive filler: Nano-hydroxyapatite (n-HA) or β-tricalcium phosphate (β-TCP) with a particle size of 200~500nm is selected and vacuum dried at 110℃ for 6h to remove adsorbed moisture;

[0026] Antibacterial filler: Select nano-silver particles, silver-loaded zirconium phosphate or medical antibacterial peptides with a particle size of 100~300nm. Surface modification treatment is carried out with silane coupling agent to improve the interfacial bonding force with the PEEK matrix and avoid filler agglomeration.

[0027] Flow aid: Medical-grade polyimide (PI) micro powder is selected as a processing flow modifier to improve the melt extrusion performance of the high-filler system.

[0028] (2) Step S2: Compounding and granulation of composite modified PEEK material

[0029] The dried implantable PEEK resin, bioactive filler, antibacterial filler, and flow aid were uniformly mixed according to the mass ratio, and the mixture was melt-blended, water-cooled into strands, and pelletized using a twin-screw extruder to prepare modified PEEK masterbatch.

[0030] Raw material quality ratio: 75~88 parts implantable PEEK resin, 8~15 parts nano hydroxyapatite / β-tricalcium phosphate, 1~3 parts antibacterial filler, and 1~4 parts medical-grade polyimide flow aid; all components are medical implantable raw materials with no toxic or harmful substances released.

[0031] Twin-screw blending process: The temperature of each section is set to 340~370℃, and the screw speed is 180~240r / min to ensure that the filler is uniformly dispersed in the PEEK matrix without agglomeration; the extruded strip is cooled to room temperature by circulating water and pelletized to obtain cylindrical modified masterbatch with a particle size of 2~3mm.

[0032] (3) Step S3: Co-extrusion molding of two types of filaments

[0033] Two types of 3D printing filaments with the same diameter were prepared using a single-screw extruder. The nominal diameter of the filaments was 1.75 mm or 2.85 mm, and the diameter tolerance was controlled within ±0.03 mm to ensure the accuracy of synchronous extrusion of the two nozzles.

[0034] Pure PEEK matrix filament: Dry pure PEEK granules are fed into an extruder at an extrusion temperature of 350~365℃ and a traction speed of 20~30m / min. After water cooling and shaping, online outer diameter detection, and winding, pure PEEK filament is obtained and used to prepare the inner layer load-bearing structure of implants.

[0035] Composite modified PEEK filament: The above modified PEEK masterbatch is fed into an extruder of the same type, the extrusion temperature is 345~360℃, the traction speed is 18~28m / min, the roundness and diameter of the filament are detected online, and the bioactive-antibacterial dual-functional composite filament is obtained by winding, which is used to prepare the outer functional structure of implants.

[0036] Post-treatment of filaments: Both types of filaments are dried in a vacuum environment at 110℃ for 4 hours, then sealed and stored away from light to avoid moisture absorption and oxidation.

[0037] Phase Two: Dual-Nose Co-extrusion FFF 3D Printing Integrated Molding

[0038] Using a dual-channel independent feeding and dual-nozzle synchronous co-extrusion fused deposition modeling 3D printing equipment, two types of filaments are extruded layer by layer and zone by zone according to the mechanical and functional zoning of the implant. The implant is formed in situ as a gradient composite structure implant with "inner dense load-bearing zone + outer porous functional zone". The entire process is high temperature sealed and nitrogen protected to prevent PEEK thermal oxidation degradation.

[0039] (4) Step S4 Model processing and printing parameter preset

[0040] 3D model layered design: Based on the patient's CT / MRI images, a 3D model of the implant is reconstructed. Layered path planning is carried out using slicing software. According to the structural regions, it is divided into an inner matrix layer and an outer functional layer: the implant core and the main stress-bearing area are set as a pure PEEK dense layer with a layer thickness of 0.10~0.20mm; the outer surface of the implant, the bone contact interface, the edge area, and the pre-set porous area are set as a composite modified PEEK functional layer with a functional layer thickness controlled at 0.3~1.0mm.

[0041] Printing environment pretreatment: High-purity nitrogen is introduced into the printing cavity, the oxygen content is controlled at ≤80ppm, and the cavity preheating temperature is set to 320~350℃ to reduce the thermal stress and warping deformation of PEEK material during printing.

[0042] (5) Step S5 Two-material co-extrusion in-situ gradient printing

[0043] The dual nozzles correspond to two different filament materials: the first nozzle is loaded with pure PEEK filament, and the second nozzle is loaded with composite modified PEEK filament. The two nozzles are independently temperature-controlled and move synchronously, co-extruding according to the slicing path in two zones, with two main modes: dense inner layer printing and porous outer layer printing.

[0044] Dense inner layer molding: The temperature of the first nozzle is set to 360~375℃, the extrusion speed is 2.5~4.0mm / s, the scanning speed is 800~1500mm / s, and the filling density is 100%. A fully dense pure PEEK inner layer structure is prepared to ensure the overall mechanical load-bearing capacity. This area has no pores or fillers, and its mechanical properties are consistent with those of pure medical PEEK.

[0045] Porous outer layer forming: The temperature of the second nozzle is set to 355~370℃, the extrusion speed is 2.0~3.5mm / s, the scanning speed is 900~1600mm / s, and the filling density is 40%~70%, constructing an interconnected porous network structure; the pore size is controlled at 200~800μm, forming interconnected channels, which facilitates the ingrowth of human tissue and the flow of body fluids, while ensuring that the antibacterial components are in full contact with the outside world.

[0046] Interface fusion control: The inner and outer layer interface area adopts a cross-over printing path, and the two materials are interlocked at the interface with an interface overlap width of 0.15~0.30mm. This allows the pure PEEK matrix and the composite functional layer to form a metallurgical bond, completely eliminating interface gaps, improving interlayer bonding strength, and preventing delamination and peeling.

[0047] Overall molding rules: For implants with relatively small overall stress (such as dental abutments and small maxillofacial repairs), an "outer layer fully encapsulates the inner layer" structure can be adopted; for large load-bearing implants (spinal fusion devices and orthopedic bone plates), a "local functional layer zoning" arrangement is adopted, with a composite functional layer only set on the bone contact surface, and the remaining areas being a pure PEEK dense structure.

[0048] (6) Step S6: The printed part is discharged after natural cooling.

[0049] After printing, keep the cavity under nitrogen protection and cool it down to below 80°C in stages at a rate of 3~5°C / min. Remove the blank and avoid residual stress, deformation and microcracks caused by rapid cooling.

[0050] Phase 3: Finished Product Post-Processing and Performance Stabilization

[0051] For co-extruded implant blanks, stress relief, surface finishing, and activation treatments are performed to further improve interfacial bonding strength, osseointegration capacity, and long-lasting antibacterial properties. The entire process is completed in a Class 10,000 cleanroom to meet the hygiene requirements for medical implants.

[0052] (7) Step S7 Stepped vacuum stress-relief annealing

[0053] The printed blank is placed in a vacuum annealing furnace for a stepped stress relief treatment to eliminate residual interlayer stress generated by 3D printing. The process parameters are: vacuum degree ≤100Pa, first stage heating to 220℃ and holding for 2h, second stage heating to 260℃ and holding for 3h, and then slowly cooling to room temperature at 2℃ / min. This process can increase the bonding strength between the inner and outer layers by 15%~25% and prevent interface cracking after long-term stress.

[0054] (8) Step S8 Surface finishing and pore clearing

[0055] Medical-grade ultrasonic cleaning equipment is used, along with anhydrous ethanol and deionized water, to clean the implant in sequence, removing trace amounts of dust and precipitated additives left over from the printing process, while also clearing the micropores that are blocked inside the porous layer. After cleaning, the implant is dried in a vacuum environment at 80°C for 3 hours to ensure that it is clean and dry.

[0056] (9) Step S9 Surface activation and enhancement (optional)

[0057] For craniofacial and spinal implants with higher requirements for osseointegration, low-temperature plasma surface activation treatment is performed on the outer porous functional area: argon plasma is used with a treatment power of 150~250W and a treatment time of 3~8min to improve the surface hydrophilicity and cell adhesion of the functional layer and further enhance the bone induction effect.

[0058] Supplementary solution: Variable proportion co-extrusion and mixed zone molding

[0059] This invention can also achieve localized co-extrusion according to the functional requirements of different parts of the implant: in the transition area, the two nozzles simultaneously extrude two kinds of filaments at a volume ratio of 1:2 to 2:1 to form a transition layer with gradually changing composition, realizing a smooth transition from pure PEEK to composite modified materials, further reducing interfacial stress, and is suitable for personalized implants with complex structures and large stress gradient changes.

[0060] The beneficial effects of this invention: Compared with existing technologies such as single modification, overall blending, post-coating, and single-nozzle printing, this invention has many outstanding technical advantages and clinical and industrial value, as detailed below:

[0061] 1. The zoned functional design simultaneously achieves bone integration and long-lasting antibacterial effect, completely resolving two major clinical pain points.

[0062] This invention employs a gradient structure of "inner load-bearing layer + outer dual-function layer." The outer composite layer simultaneously loads bioactive ceramics and medical antibacterial components, combined with a porous interconnected structure. On one hand, it relies on hydroxyapatite / β-tricalcium phosphate to induce osteoblast adhesion and proliferation, accelerating bone tissue ingrowth, preventing fibrous capsule formation, and solving the problem of long-term prosthesis loosening. On the other hand, it relies on antibacterial fillers to achieve broad-spectrum antibacterial activity, with an inhibition rate of ≥98% against common postoperative pathogens such as Staphylococcus aureus and Staphylococcus epidermidis, effectively inhibiting bacterial colonization and deep infection. Both functions are concentrated in the surface area where the implant contacts human tissue, maximizing functional utilization.

[0063] 2. Mechanical and functional zones are separated to balance high strength and dual functionality, avoiding the performance defects of overall blending.

[0064] The main load-bearing inner layer uses 100% dense, pure medical-grade PEEK, fully preserving the excellent mechanical properties, toughness, and fatigue resistance of the PEEK substrate. Its tensile and flexural strengths fully meet the standards for Class III implantable medical devices. Functional fillers are concentrated only in the non-primary load-bearing outer layer, without compromising the overall mechanical structure of the matrix, completely resolving issues such as reduced strength, insufficient toughness, and filament breakage caused by traditional integral blended fillers. Simultaneously, the antibacterial components are distributed only on the surface, with no redundant antibacterial material inside, significantly reducing the safety risks of antibacterial ion accumulation and cytotoxicity.

[0065] 3. The dual-material co-extrusion integrated in-situ molding process results in high bonding strength between the functional layer and the substrate, eliminating the risk of coating peeling.

[0066] This invention utilizes dual-nozzle co-extrusion melt deposition, where the inner and outer layers fuse together at high temperatures during printing to form an integrated structure. The interface is a fusion bond rather than a physical adhesion, resulting in a much stronger interlayer bond than post-treatment coatings such as spraying or immersion. Tests show that the interfacial bond strength is ≥85% of the PEEK substrate strength. Under conditions of immersion in bodily fluids and repeated micro-friction, the functional layer will not peel or fall off, and its service life is consistent with that of the implant itself. At the same time, it eliminates the need for a secondary coating process, simplifying the production process.

[0067] 4. The porous structure allows for precise and controllable bone ingrowth, resulting in excellent bone ingrowth.

[0068] The outer functional layer adopts a controllable filling density molded interconnected porous structure. The pore size and porosity can be flexibly adjusted according to clinical needs. The through-channel provides space for bone tissue and capillary ingrowth, and the bone integration rate is increased by more than 40% compared with pure PEEK implants. At the same time, the porous structure increases the contact area between the antibacterial layer and body fluids and bacteria, further improving the antibacterial effect.

[0069] 5. The process is highly versatile and adaptable to various implants and mass production needs.

[0070] This invention adopts a mature FFF dual-nozzle co-extrusion process, which has low equipment modification costs and can be adapted to mainstream PEEK implant products such as spinal fusion devices, cranial repair prostheses, orthopedic bone plates, dental implant abutments, and maxillofacial bone prostheses. The entire process can realize automated slicing, printing, and post-processing, with stable process parameters and good batch consistency, making it suitable for large-scale and standardized production by medical device companies.

[0071] 6. Low residual stress, resulting in excellent product dimensional accuracy and long-term stability.

[0072] The printing process employs a combination of cavity preheating, nitrogen anti-oxidation, and stepped cooling + vacuum annealing, which effectively eliminates interlayer residual stress and deformation generated by 3D printing. The implant size accuracy deviation is ≤±0.06mm, and there is no warping, deformation, or cracking after long-term implantation, significantly improving product safety and reliability.

[0073] 7. High raw material utilization rate and good safety.

[0074] All raw materials meet medical implant-grade standards, and no toxic solvents or adhesives are used throughout the entire process, making the production process green and environmentally friendly. The functional fillers are centrally arranged, which reduces the amount of high-value bioactive fillers and antibacterial fillers by more than 60% compared to the overall blending solution, effectively reducing raw material costs and demonstrating good economic benefits and promotional value.

[0075] The present invention will be explained in detail below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0076] Figure 1 This is a flowchart illustrating the overall preparation process of the present invention.

[0077] Figure 2 This is a schematic diagram of the two-material co-extrusion 3D printing process;

[0078] Figure 3 This is a schematic diagram of the cross-sectional structure of the implant;

[0079] Figure 4 This is an enlarged schematic diagram of the outer porous structure;

[0080] Figure 5 This is a schematic diagram comparing the traditional solution with the present invention; Detailed Implementation

[0081] The technical solution of the present invention is fully described below with reference to multiple detailed embodiments and comparative examples. All raw materials, consumables and additives are medical implant-grade and comply with the YY / T0660 standard for "Polyetheretherketone (PEEK) Resin for Surgical Implants" and the GB / T16886 series of standards for biological evaluation of medical devices. The printing equipment adopts a medical FFF / FDM 3D printer with dual nozzles, independent temperature control, synchronous motion and nitrogen protection. The nominal diameter of the matching filament is uniformly 1.75mm, which is the industry standard.

[0082] General raw material and equipment parameter specifications:

[0083] Implantable pure PEEK granules: melt flow rate 14g / 10min (380℃, 2.16kg), virgin granule moisture content ≤0.02%, for medical implantation purposes;

[0084] Bioactive filler 1: Nano hydroxyapatite (n-HA), particle size 200~500nm, medical grade, free of heavy metal residue;

[0085] Bioactive filler 2: β-tricalcium phosphate (β-TCP), particle size 300~600nm, for bone induction;

[0086] Antibacterial filler: Silane-modified silver-loaded zirconium phosphate powder, particle size 100~300nm, broad-spectrum antibacterial, temperature resistance ≥380℃;

[0087] Processing aid: Medical-grade polyimide (PI) micro powder, which improves the melt flowability of high-filler systems and prevents precipitation;

[0088] Auxiliary consumables

[0089] Anhydrous ethanol (medical analytical grade), deionized water (resistivity ≥18.2 MΩ・cm), high-purity nitrogen (purity ≥99.999%), and high-purity argon (for plasma activation).

[0090] General equipment

[0091] Hot air circulating drying oven, vacuum drying oven, twin-screw granulator, single-screw wire drawing machine, dual-nozzle FFF 3D printer, vacuum annealing furnace, medical ultrasonic cleaner, low-temperature plasma treatment instrument, mechanical testing machine, antibacterial testing equipment, cell culture testing platform.

[0092] Example 1: Spinal Implant: PEEK Interbody Fusion Device (Main Load-Bearing Product)

[0093] In this embodiment, a conventional lumbar PEEK interbody fusion device was prepared. The structure is "dense pure PEEK core + full-area outer porous dual-functional layer". It is a high-load implant and strictly distinguishes between the mechanical load-bearing area and the biological functional area.

[0094] 1.1 Raw material pretreatment (class 10,000 clean environment throughout)

[0095] Pretreatment of pure PEEK granules: Take 10 kg of implant-grade pure PEEK granules, spread them evenly in a hot air circulating drying oven with a layer thickness of ≤3 cm, dry at a constant temperature of 125℃ for 10 h, and after drying, quickly transfer them to a sealed container, cool to room temperature, and test the moisture content to ≤0.02% for later use.

[0096] Functional filler pretreatment:

[0097] 2.4 kg of nano-hydroxyapatite (n-HA) and 0.4 kg of silver-loaded zirconium phosphate were placed in a vacuum drying oven and dried at 110℃ for 6 hours to completely remove surface adsorbed moisture and prevent agglomeration during high-temperature processing.

[0098] Take 0.8 kg of medical-grade polyimide flow aid and dry it under the same conditions for 2 hours.

[0099] Material premixing: According to the mass ratio: 82 parts pure PEEK, 12 parts n-HA, 2 parts silver-loaded zirconium phosphate, and 4 parts PI additive; put all the dried materials into a high-speed mixer and stir at room temperature for 15 minutes at a speed of 600 r / min to achieve preliminary uniform mixing of powder and resin.

[0100] 1.2 Melt Blending Granulation

[0101] The premixed material is conveyed to a co-rotating twin-screw extruder, and the temperature of each section of the equipment is precisely controlled in stages.

[0102] Zone 1: 342℃, Zone 2: 350℃, Zone 3: 358℃, Zone 4: 362℃, Die head: 355℃; Screw speed: 210r / min.

[0103] After continuous melting, shearing, and mixing, the material is extruded into round strips from the die head. The strips enter a circulating ambient temperature water bath for water cooling and shaping, with the water temperature controlled at 20~25℃. The shaped strips are then fed into a pelletizer and cut into cylindrical modified PEEK masterbatches with a particle size of 2~3mm. The masterbatches are collected and stored in a sealed, light-proof container.

[0104] 1.3 Preparation of Dual-Specification 3D Printing Filaments

[0105] Pure PEEK matrix filaments and composite modified functional filaments were prepared simultaneously using two identical single-screw drawing machines:

[0106] Pure PEEK matrix filament

[0107] Feed: Dried pure PEEK granules; Extrusion temperature: 358℃; Die head pressure: 8~10MPa; Traction speed: 25m / min;

[0108] Process: Melt extrusion → circulating water cooling and shaping → online laser outer diameter detection → tension winding;

[0109] Finished product specifications: Diameter 1.75mm, diameter tolerance ≤ ±0.03mm, roundness deviation ≤ 0.02mm.

[0110] Composite modified functional filaments

[0111] Feed: Modified PEEK masterbatch; Extrusion temperature: 352℃; Die head pressure: 9~11MPa; Traction speed: 22m / min;

[0112] The finished product specifications and dimensional tolerances are completely consistent with the base filament material, ensuring the synchronization of dual-nozzle extrusion.

[0113] Secondary drying of the filaments: The two types of filaments are placed in a vacuum drying oven and dried at 110℃ for 4 hours to remove the moisture adsorbed during storage and transportation. After that, they are vacuum sealed with aluminum foil and stored at room temperature away from light.

[0114] 1.4 Presets for 3D Model Processing and Printing System

[0115] Model Construction and Slicing: Based on lumbar CT data from clinical patients, a 3D model of the interbody fusion cage was reconstructed; medical slicing software was used for layer planning.

[0116] Core, internal reinforcing ribs, and main pressure-bearing areas: are designed with a 100% dense pure PEEK inner layer;

[0117] Upper and lower bone contact surfaces, outer peripheral sidewalls, and hollow areas: are configured as a composite modified porous functional outer layer;

[0118] The overall thickness of the functional layer is uniformly 0.6mm; the thickness of a single printed layer is 0.15mm.

[0119] Printing cavity pretreatment: Close the chamber door and continuously introduce high-purity nitrogen gas, monitor the oxygen content in the cavity in real time, and stably control the oxygen content to ≤80ppm; preheat the entire cavity to 335℃ and keep it at that temperature for 30 minutes to ensure a uniform internal temperature field and suppress PEEK thermal oxidation and warping.

[0120] 1.5 Dual-nozzle co-extrusion integrated fused deposition modeling

[0121] Dual nozzle designations: Nozzle A (pure PEEK filament), Nozzle B (composite modified filament); dual nozzles operate synchronously and with independent temperature control.

[0122] Dense inner layer printing (printer A): printer temperature 368℃, extrusion speed 3.2mm / s, scanning speed 1100mm / s, filling density 100%, printing a fully dense load-bearing structure without pores.

[0123] Porous outer layer printing (printer B): printer temperature 362℃, extrusion speed 2.8mm / s, scanning speed 1200mm / s, filling density 55%; forming a three-dimensional interconnected porous structure with a pore size range of 300~600μm and interconnected channels.

[0124] Interface fusion process: The interface between the inner and outer layers adopts a cross-over printing path with an overlap width of 0.22mm. The two high-temperature molten materials are interlocked to form a metallurgical bonding interface, eliminating physical gaps.

[0125] Cooling and unloading: After the overall printing is completed, maintain a nitrogen protective atmosphere and cool down in stages at a rate of 4℃ / min until the cavity temperature drops below 75℃, then remove the printed blank.

[0126] 1.6 Stepped Vacuum Stress-Relieving Annealing

[0127] The printed blanks are neatly placed in a vacuum annealing furnace with a vacuum level ≤80Pa, and a two-stage heating and holding process is executed:

[0128] First stage: Heat to 220℃ and keep at a constant temperature for 2 hours to eliminate residual stress in the surface and shallow layers;

[0129] Second stage: Continue heating to 260℃, maintain constant temperature for 3 hours, deeply release interlayer stress and strengthen interface bonding;

[0130] Cooling: Cool slowly to room temperature at a rate of 2℃ / min. Do not cool rapidly.

[0131] 1.7 Cleaning, Drying and Plasma Surface Activation

[0132] Ultrasonic cleaning: Medical ultrasonic cleaner, first use anhydrous ethanol to clean for 10 minutes to remove surface dust and low molecular weight precipitates; then replace with ultrapure water to clean for 15 minutes to thoroughly wash away organic solvent residues.

[0133] Vacuum drying: After cleaning, the workpiece is transferred to a vacuum drying oven and dried at 80°C for 3 hours to completely dry the residual moisture inside the micropores.

[0134] Plasma activation (enhancing osseointegration): Argon low-temperature plasma equipment is used with a processing power of 200W and a processing time of 5min; it acts directionally on the outer porous surface to enhance surface hydrophilicity and cell adhesion.

[0135] The final product is a dual-function PEEK interbody fusion device.

[0136] Example 2: Craniofacial Prostheses: Personalized Skull Defect Repair Prostheses (Complex Curves, Low Load)

[0137] This embodiment prepares a customized cranial prosthesis. The product has a complex curved surface and low overall stress. It adopts a design that fully covers the entire outer surface with functional layers. The process parameters are adapted to the printing of complex curved surfaces. The process framework is the same as in Embodiment 1, with the following differences in parameters:

[0138] 2.1 Raw material ratio (parts by weight)

[0139] The mixture consisted of 85 parts pure PEEK, 10 parts nano-hydroxyapatite, 1.5 parts silver-loaded zirconium phosphate, and 3.5 parts PI flow aid; the pretreatment, mixing, and granulation processes were completely consistent with those in Example 1.

[0140] 2.2 Wire preparation

[0141] The wire diameter is 1.75mm, and the drawing temperature, traction speed, and drying conditions follow the general standards.

[0142] 2.3 Model and Printing Environment Setup

[0143] Model slice: The entire outer surface of the restoration is covered with a composite functional layer with a thickness of 0.4mm and a single printed layer thickness of 0.12mm (to improve the accuracy of curved surface forming).

[0144] The cavity is preheated to 328℃, and the oxygen content is ≤80ppm under nitrogen protection.

[0145] 2.4 Dual-head printing parameters

[0146] Nozzle A (pure PEEK inner layer): temperature 365℃, extrusion speed 2.8mm / s, scanning speed 950mm / s, filling density 100%;

[0147] Nozzle B (composite functional outer layer): temperature 358℃, extrusion speed 2.4mm / s, scanning speed 1050mm / s, filling density 45%; forming a porous structure with a pore size of 200~500μm;

[0148] Interface overlap width: 0.18mm; cooling rate: 3.5℃ / min.

[0149] 2.5 Post-processing steps

[0150] The vacuum annealing, ultrasonic cleaning, and drying processes remain unchanged.

[0151] Plasma activation: 180W power, 4min processing time, suitable for contact requirements of maxillofacial soft tissue;

[0152] Personalized craniofacial PEEK prostheses were fabricated.

[0153] Example 3: Dental Implant: PEEK Implant Abutment (Small Precision Component, Microporous)

[0154] This embodiment prepares a dental implant abutment, which is a small and precision implant. The functional layer is only set in the local area in contact with the gums and bone tissue. The overall size is small and the precision requirements are high, which simplifies some post-processing procedures.

[0155] 3.1 Raw material ratio (parts by weight)

[0156] 88 parts pure PEEK, 8 parts β-tricalcium phosphate, 1 part silver-loaded zirconium phosphate, and 3 parts PI flow aid; the filler was replaced with β-TCP to suit dental bone tissue repair scenarios.

[0157] 3.2 Model and Printing Parameters

[0158] Functional layer arrangement: Functional layers are only set in the abutment osseointegration segment and gingival contact segment, with a thickness of 0.3 mm and a single printed layer thickness of 0.10 mm;

[0159] The cavity is preheated to 325℃ and protected by nitrogen.

[0160] Nozzle A: Temperature 362℃, Extrusion speed 2.5mm / s, Scanning speed 850mm / s;

[0161] Nozzle B: Temperature 355℃, Extrusion speed 2.2mm / s, Scanning speed 900mm / s, Filling density 50%.

[0162] 3.3 Post-processing

[0163] Vacuum annealing, ultrasonic cleaning, and vacuum drying are performed, eliminating the plasma activation process and avoiding damage to microstructures, ultimately resulting in a dental PEEK implant abutment.

[0164] Example 4: Orthopedic bone plate: PEEK long bone plate with gradient transition layer (stress gradient member)

[0165] This embodiment is for a bone plate for long bones of the limbs, where the stress gradient of the component changes greatly. A compositional gradient transition layer is added between the dense inner layer of pure PEEK and the porous functional outer layer to further reduce the interfacial stress, which is an optimized structural solution.

[0166] 4.1 Basic Processes

[0167] The raw material pretreatment, mixing and granulation, filament preparation, and cavity preheating are all consistent with those in Example 1.

[0168] 4.2 Layered design of printing path (three-layer structure from the inside out)

[0169] First layer: Pure PEEK dense load-bearing layer (100% filling density);

[0170] The second layer is a gradient transition layer with a total thickness of 0.25mm. It is co-extruded synchronously with dual nozzles at a volume ratio of 1:1, with alternating discharge to achieve a smooth transition of components and a filling density of 70%.

[0171] Third layer: Composite modified porous functional layer (filling density 55%).

[0172] 4.3 Printing and Post-processing

[0173] The printing parameters, cooling regime, vacuum annealing, cleaning, and plasma activation of the dense layer and functional layer were all performed in accordance with Example 1, with only the transition layer printing process added, and the rest remained unchanged.

[0174] Comparative Example 1: Traditional Process: Overall Blending Modification + Single Printer Printing

[0175] All raw materials from Example 1 were blended, granulated, and drawn into fibers in one go to obtain a single-component modified filament. A fully homogeneous intervertebral fusion device was printed using a single-nozzle FFF printer. The filament formulation, printing temperature, layer thickness, and post-processing procedures were completely consistent with those of Example 1, with no layered structure, no gradient design, and no pure PEEK dense core.

[0176] Comparative Example 2: Mainstream Process: Pure PEEK Printing + Post-Surface Spraying of Functional Coating

[0177] A pure PEEK dense interbody fusion device was printed using a single printhead. The substrate structure, dimensions, and printing parameters were the same as the inner layer of Example 1.

[0178] A composite coating solution containing nano-hydroxyapatite and silver-loaded antibacterial agent was prepared and applied to the outer surface of the workpiece by atmospheric pressure spraying. The coating thickness was 0.6 mm and the coating was cured naturally at room temperature.

[0179] Vacuum annealing and plasma activation are not performed; the remaining cleaning processes are the same.

[0180] Unified performance testing scheme and results description

[0181] Testing items and implementation standards

[0182] Mechanical properties: tensile strength, flexural strength (GB / T1040, GB / T9341).

[0183] Interfacial bonding strength: interlayer shear strength test, simulating the micro-friction conditions of the human body;

[0184] Antibacterial properties: effective against Staphylococcus aureus and Staphylococcus epidermidis (GB / T21866).

[0185] Cell compatibility and bone adhesion: MTT cytotoxicity test, osteoblast adhesion and proliferation assay (GB / T16886.5).

[0186] Functional layer shedding test: reciprocating friction + body fluid immersion accelerated aging test.

[0187] Overall test results

[0188] 1. Mechanical properties

[0189] The tensile strength and flexural strength of the finished products in Examples 1-4 of this invention deviate from those of pure implantable PEEK by ≤4%, which fully meets the mechanical requirements of Class III implants; the overall blend sample of Comparative Example 1 has a tensile strength that decreases by more than 18% due to the destruction of molecular chains by a large number of fillers, and its mechanical properties do not meet the standards.

[0190] 2. Interface integration reliability

[0191] Examples 1-4 show that the interlayer shear strength of the co-extruded integrated structure is ≥85% of the matrix strength, and there is no delamination or cracking after accelerated aging; Comparative Example 2 shows that the bonding strength of the sprayed coating is only 42% of the matrix, and the coating peels off over a large area after friction testing.

[0192] 3. Antibacterial effect

[0193] All embodiments have an outer porous structure with an antibacterial rate of ≥98% against two typical pathogenic bacteria, and long-lasting antibacterial stability; although the overall blended comparison ratio also has antibacterial properties, the antibacterial filler is distributed throughout the entire area, resulting in low material utilization.

[0194] 4. Osseointegration capacity

[0195] In the example, the porous functional layer showed an increase of more than 40% in osteoblast adhesion rate and proliferation activity compared to pure PEEK, and the interconnected pores could support the ingrowth of bone tissue and capillaries; in the comparative example, the bone integration ability rapidly declined after the coating detached.

[0196] 5. Biosafety

[0197] The functional filler of this invention is concentrated only in the surface layer, and the amount of antibacterial ion release is much lower than that of the overall blending scheme. The cytotoxicity is grade 0 to 1, which meets the implantation standards.

[0198] This invention utilizes a dual-material co-extrusion in-situ gradient molding process to achieve integrated manufacturing of a "dense load-bearing inner layer + porous bone integration - antibacterial dual-functional outer layer," which not only retains the excellent mechanical properties of PEEK but also simultaneously addresses two major clinical pain points: postoperative infection and prosthesis loosening. The functional layer is fused and bonded to the substrate, ensuring a strong and reliable bond. The integrated production process and streamlined procedures allow for mass production of 3D-printed PEEK medical implants for all categories, including those for the spine, craniofacial region, orthopedics, and dentistry.

[0199] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and the scope of protection of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, but all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A method for preparing an in-situ gradient bifunctional 3D printed PEEK implant, characterized in that, The process includes three main stages: functional filament preparation, two-material co-extrusion 3D printing, and finished product post-processing. The specific steps are as follows: (1) Preparation of functional filaments: The implant-grade PEEK resin, bioactive filler, antibacterial filler and flow aid were dried and pretreated respectively. The raw materials were melt-blended and granulated according to the ratio to obtain modified PEEK masterbatch. Pure PEEK matrix filaments and bioactive-antibacterial composite modified PEEK filaments were prepared by single screw extruder respectively. The specifications of the two filaments were kept consistent. (2) Dual-material co-extrusion 3D printing: Based on the patient's medical images, the three-dimensional model of the implant is reconstructed and the slicing path is planned to divide the dense inner layer and the porous functional outer layer; a dual-nozzle fused deposition modeling 3D printing equipment is used to load pure PEEK matrix filament and composite modified PEEK filament respectively, and the partitioned and layered co-extrusion is carried out simultaneously under nitrogen protection and cavity preheating environment. The interface between the inner and outer layers is achieved by cross-overlapping path to achieve fusion and embedding; after printing, the blank is removed by step cooling. (3) Finished product post-processing: The printed blank is subjected to step-by-step vacuum stress relief annealing, followed by ultrasonic cleaning and vacuum drying. The porous functional layer is then subjected to low-temperature plasma surface activation as needed to obtain PEEK medical implants with both osseointegration and antibacterial functions.

2. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, In step (1), the raw materials are proportioned by mass as follows: 75-88 parts of implantable PEEK resin, 8-15 parts of bioactive filler, 1-3 parts of antibacterial filler, and 1-4 parts of medical-grade polyimide flow aid; the bioactive filler is nano-hydroxyapatite or β-tricalcium phosphate with a particle size of 200-600 nm; the antibacterial filler is silane-modified nano-silver particles, silver-loaded zirconium phosphate, or medical antibacterial polypeptide with a particle size of 100-300 nm.

3. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, Step (1) The raw material pretreatment process is as follows: the implant-grade PEEK resin is dried at 120~130℃ for 8~12h, and the moisture content is controlled to be ≤0.02%; the bioactive filler and antibacterial filler are vacuum dried at 110℃ for 6h; the twin-screw melt blending temperature range is 340~370℃, the screw speed is 180~240r / min, and the extruded strip is cut into modified PEEK masterbatch with a particle size of 2~3mm after water cooling.

4. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, The parameters for filament preparation in step (1) are as follows: extrusion temperature of pure PEEK matrix filament is 350~365℃, and traction speed is 20~30m / min; extrusion temperature of composite modified PEEK filament is 345~360℃, and traction speed is 18~28m / min; the nominal diameter of the two filaments is 1.75mm or 2.85mm, and the diameter tolerance is ≤±0.03mm; after the filaments are formed, they are dried in a vacuum environment at 110℃ for 4h and then sealed and stored.

5. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, In step (2), the model is layered: the implant core and the main stress area are pure PEEK dense inner layers with a thickness of 0.10~0.20mm and a filling density of 100%; the outer surface of the implant, the bone contact interface, and the edge area are composite modified porous functional outer layers with a thickness of 0.3~1.0mm, a filling density of 40%~70%, and pore size controlled at 200~800μm.

6. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, Step (2) Printing environment and process parameters: High-purity nitrogen gas is introduced into the printing cavity, with an oxygen content ≤80ppm, and the cavity preheating temperature is 320~350℃; the nozzle temperature loaded with pure PEEK filament is 360~375℃, the extrusion speed is 2.5~4.0mm / s, and the scanning speed is 800~1500mm / s; the nozzle temperature loaded with composite modified filament is 355~370℃, the extrusion speed is 2.0~3.5mm / s, and the scanning speed is 900~1600mm / s; the overlap width between the inner and outer layers is 0.15~0.30mm.

7. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, The cooling process of the printed part in step (2) is as follows: maintain a nitrogen protective atmosphere, cool down stepwise at a rate of 3~5℃ / min to below 80℃, and then take out the blank part.

8. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, Step (3) Stepped vacuum stress-relief annealing process: Vacuum degree ≤100Pa, first heat up to 220℃ and hold for 2h, then heat up to 260℃ and hold for 3h, and then slowly cool down to room temperature at a rate of 2℃ / min.

9. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, Step (3) Ultrasonic cleaning is performed by sequentially cleaning with medical anhydrous ethanol and deionized water. After cleaning, vacuum drying is carried out at 80°C for 3 hours. The low-temperature plasma activation is performed using argon plasma with a processing power of 150~250W and a processing time of 3~8 minutes.

10. The method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, A gradient transition layer is added between the dense inner layer and the porous functional outer layer. The transition layer is formed by simultaneous co-extrusion of two nozzles at a volume ratio of 1:2 to 2:1, and the filling density of the transition layer is 70%.

11. A method for preparing an in-situ gradient dual-function 3D printed PEEK implant according to claim 1, characterized in that, The implants are spinal fusion devices, craniofacial prostheses, orthopedic bone plates, or dental implant abutments.

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