Three-dimensional printing method for manufacturing metal embedded medical implants and devices

Abstract

A three-dimensional (3D) printing method for manufacturing metal embedded medical implants and devices is provided. The newly developed 3D printing technology and surface modification method will contribute to wider application of 3D printed patient-customized products in many medical fields, thereby exhibiting excellent clinical safety.

Description

Cross - Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 381,626, filed October 31, 2022, which is incorporated herein by reference in its entirety. Technical Field

[0002] The present invention generally relates to 3D printing technology and medical implant technology. More specifically, the present invention enables the embedding of metal plates and wires into 3D printed polymeric medical devices, implants, and orthodontic appliances, such as prosthetic implants, spinal fusion cages, bone scaffolds, dental braces, and retainers. Background Art

[0003] In recent years, driven by the convergence of advanced manufacturing technologies, significant progress has been made in the field of medical implant technology. Specifically, three - dimensional (3D) printing technology has emerged as a transformative force, making it possible to manufacture complex and patient - specific medical implants and devices.

[0004] For example, 3D printing technologies using photocurable resins (e.g., stereolithography (SLA), digital light processing (DLP), and lithography - based ceramic manufacturing) are being steadily adopted by the dental industry due to their accuracy, speed, cost - effectiveness, and even high productivity in dental clinics and laboratories. Small, complex structures, including indirect restorations, dental bridges, dentures, orthodontic appliances, implant abutments, and surgical guides, can be easily fabricated based on intra - oral and dental data of patients.

[0005] Clear aligners have become a popular solution due to their aesthetic features. However, traditional thermoformed aligners have some inherent limitations, including dimensional instability, poor abrasion resistance, and low strength. These aligners are made of thermoplastic materials with viscoelastic properties and exhibit behaviors such as creep and stress relaxation over time. This can lead to discomfort due to excessive force applied to the teeth or minimal tooth movement due to insufficient force applied. Additionally, due to the thermoplastic nature, thermoformed aligners tend to exhibit weak compressive strength and large - area irreversible deformation. The development of 3D printing technology has paved the way for the research and development of 3D printed clear dental aligners, providing a better alternative to dental aligners. For example, Jindal et al. 1 found that 3D printed clear aligners cured after printing have superior dimensional accuracy and compressive mechanical properties compared to thermoformed aligners. McCarty et al. 2 applied 3D surface analysis techniques to study the effects of printing angle and post - curing duration on the dimensional accuracy of 3D printed clear aligners.

[0006] Traditionally, titanium, titanium alloys, or polyetheretherketone (PEEK) have been selected for medical implants due to their good mechanical properties and biocompatibility. Both titanium and PEEK implants exhibit similar prosthesis implantation rates. Although these traditional implants and fixation devices provide sufficient load-bearing capacity, problems have arisen with titanium implants having metal components, especially in orthopedic fusion cases. This is because of their high elastic modulus and stress shielding effect, which may lead to problems such as subsidence or gradual penetration into the endplate surface. As a result, weaker interfacial bone bonding can lead to a high implant failure rate, causing bone instability, subsidence, implant displacement, and severe pain or discomfort, and may even require a secondary operation.

[0007] On the other hand, due to the elastic modulus of PEEK implants with polymer groups being almost the same as that of bone (in the range from cortical bone to cancellous bone), the PEEK implants have higher compliance compared to titanium or titanium alloy implants. However, PEEK implants tend to be hydrophobic and bio-inert, resulting in limited fusion with surrounding tissues after implantation.

[0008] In addition, due to the high melting and glass transition temperatures of PEEK (which vary based on the polymer crystallinity level), there are significant challenges in applying PEEK implants during pre- and post-3D printing processes. This variation results in significant fluctuations in the mechanical and physical properties of 3D printed PEEK implants, thus limiting the adaptability of PEEK 3D printing in medical device applications that require strict quality control and assurance.

[0009] There is still a need in the art for improved designs and technologies over the prior art for manufacturing medical implants for various medical devices and instruments, including prosthesis implants, spinal fusion cages, bone scaffolds, orthodontic appliances and retainers, and other medical devices. Summary of the Invention

[0010] A simplified overview of the present invention is presented below to provide a basic understanding of some aspects of the present invention. This overview is not a comprehensive overview of the invention. It is neither intended to identify the key or important elements of the invention nor to delineate the scope of the invention. Indeed, the sole purpose of this overview is to present some concepts of the present invention in a simplified form as a prelude to the more detailed description presented below.

[0011] According to a first aspect of the present invention, there is provided a three-dimensional (3D) printing method for manufacturing a metal-embedded medical implant. The method includes: performing a first computed tomography (CT) scan on one or more teeth and oral regions of a test subject to design a customized medical implant; designing the customized medical implant based on the results of the first CT scan; designing a metal structure to be embedded in the customized medical implant; performing data segmentation and 3D printing on the metal structure; converting the data into a stereolithography (STL) data format; performing 3D printing on the customized medical implant embedded with the metal structure; performing a second CT scan on the customized medical implant to analyze the internal structure of the customized medical implant; and performing surface modification on the customized medical implant based on the results of the second CT scan.

[0012] In one embodiment, the first CT scan may be a CT scan of the mandible of the test subject.

[0013] In one embodiment, the design of the customized medical implant is implemented by a three-dimensional (3D) computer-aided design (CAD) method.

[0014] In one embodiment, the metal structure includes a metal plate, a metal wire, or a metal lattice structure.

[0015] In one embodiment, the step of performing 3D printing on the customized medical implant embedded with the metal structure is implemented by a polymer stereolithography 3D printing method.

[0016] In one embodiment, the step of performing 3D printing on the metal structure may be implemented by a metal selective laser sintering (SLS) 3D printing method.

[0017] In one embodiment, the customized medical implant has a hierarchical porous structure.

[0018] In one embodiment, the customized medical implant includes a prosthetic implant, a spinal fusion device, a bone scaffold, an orthodontic appliance, and a retainer.

[0019] In one embodiment, the metal structure is made of one of titanium, a titanium alloy (such as Ti-6Al-4V), cobalt chromium (CoCr), stainless steel, or a combination thereof. For example, a Ti-6Al-4V plate structure with a thickness of 0.5 mm can be fabricated using metal SLS microprinting.

[0020] In one embodiment, the surface modification is implemented by depositing atomic layers on the surface of the customized medical implant. The atomic layers are selected from the group consisting of: Al2O3, MgO, ZrO2, and TiO2. In another embodiment, the surface modification is achieved through a silane coupling agent grafting process.

[0021] In a second aspect, a three-dimensional printing method for manufacturing a metal-embedded medical device is provided. The method includes: synthesizing a biocomposite matrix; performing metal selective laser sintering (SLS) 3D printing to embed a metal structure in the biocomposite matrix to obtain the metal-embedded medical device; and performing surface modification on the metal-embedded medical device to enhance the bonding between the metal structure and the biocomposite matrix.

[0022] The method may further include performing cold plasma surface etching on the surface of the metal-embedded medical device to increase bone growth and adhesion.

[0023] In one embodiment, the step of synthesizing the biocomposite matrix includes mixing a photocurable monomer and at least one nanofiller, and wherein the biocomposite matrix includes 50 wt% to 90 wt% of the photocurable monomer and 10 wt% to 30 wt% of the at least one nanofiller.

[0024] In another embodiment, the photocurable monomer is selected from the group consisting of: methacrylate, urethane-dimethacrylate, and triethylene glycol dimethacrylate. Other methacrylate or acrylate monomers and oligomers that typically form crosslinked polymers during free radical polymerization can be used.

[0025] In one embodiment, the biocomposite matrix further includes one or more silica nanoparticles. The one or more silica nanoparticles have a diameter range of 50 nanometers to 700 nanometers.

[0026] In one embodiment, the at least one nanofiller includes nano-hydroxyapatite or nano-diamond. Additionally, the nano-hydroxyapatite has a diameter in the range of 50 nanometers to 200 nanometers; the nano-diamond has a diameter in the range of 10 nanometers to 100 nanometers; and the silica nanoparticles have a diameter range of 50 nanometers to 700 nanometers.

[0027] In one embodiment, the metal structure is made of one of titanium, titanium alloy, cobalt-chromium (CoCr), or stainless steel. The metal structure includes a metal plate with a thickness in the range of 0.10 millimeters to 1.0 millimeter.

[0028] In one embodiment, the surface modification is implemented by depositing atomic layers on the surface of the customized medical implant. The atomic layers are selected from the group consisting of: Al2O3, MgO, ZrO2, and TiO2.

[0029] In another embodiment, the surface modification is achieved through a silane coupling agent grafting process.

[0030] In one embodiment, the interfacial bonding force between the metal structure and the biocomposite matrix is enhanced by applying Al2O3 atomic layer deposition (ALD).

[0031] In a third aspect, the present invention provides a customized medical implant having a biocomposite matrix embedded with a metal structure. The biocomposite matrix comprises a photocurable monomer, at least one nanofiller, and the biocomposite matrix comprises 50 wt% to 90 wt% of the photocurable monomer and 10 wt% to 30 wt% of the at least one nanofiller. Preferably, the biocomposite matrix further comprises one or more silica nanoparticles.

[0032] In one embodiment, the metal structure includes a metal plate, a metal wire, or a metal lattice structure.

[0033] In one embodiment, the metal structure is made of titanium, a titanium alloy, cobalt-chromium (CoCr), or stainless steel.

[0034] In one embodiment, the photocurable monomer is selected from the group consisting of: methacrylate, urethane-dimethacrylate, and triethylene glycol dimethacrylate.

[0035] In one embodiment, the at least one nanofiller comprises nano-hydroxyapatite, nanodiamond, silica glass particles, glass fibers, ceramics, metal particles, halloysite nanotubes, or pre-polymerized polymer particles. In one of the embodiments, the nano-hydroxyapatite has a diameter of 50 nanometers to 200 nanometers. The nanodiamond has a diameter of 10 nanometers to 100 nanometers.

[0036] In one embodiment, the biocomposite matrix further includes 0.1 wt% to 3 wt% of a photoinitiator.

[0037] In one embodiment, the photoinitiator comprises (2,4,6-trimethylbenzoyl) diphenylphosphine oxide, phenylbis(2,4,6-trimethylbenzoyl)-phosphine oxide, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, 1-hydroxycyclohexyl phenyl ketone, or 2,2-dimethoxy-2-phenylacetophenone.

[0038] The present invention has the following advantages: (1) Compared with current biomedical metal materials (e.g., Ti, Ti alloys, CoCr, and stainless steel) and biomedical polymer materials (e.g., PEEK, dental resins), three-dimensional printing of metal-embedded medical implants and devices exhibits excellent mechanical and physical properties, including high strength and lightweight characteristics. (2) By controlling the structure of the metal layer, it is possible to fabricate functionally graded implants whose mechanical properties gradually change with respect to the dimensions along the printing direction. This approach mimics the structural characteristics of cortical and cancellous bone. (3) The fabricated medical implants and devices are characterized by being non-corrosive and not having adverse effects due to the release of metal ions and wear particles. Additionally, since the metal wires are embedded in the resin, the fabricated medical implants and devices eliminate the risk of metal allergy reactions associated with conventional metal bracket systems. (4) Multifunctional biocomposites can be applied to 3D printing to increase osteogenic ability or provide high mechanical strength and long active retraction force for aesthetically invisible orthodontic appliances / retainers, thereby improving the control of orthodontic movement of tooth roots. (5) The present invention provides a cost-effective orthodontic treatment option compared to conventional fixed appliances and thermoformed orthodontic appliances. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Embodiments of the present invention are described in more detail below with reference to the drawings, in which:

[0040] Figure 1 A schematic diagram showing the workflow for applying a metal-embedded mandibular implant to a prosthesis according to an embodiment of the present invention;

[0041] Figure 2 A schematic diagram showing the design and 3D printing process for applying a metal-embedded mandibular implant to a prosthesis according to an embodiment of the present invention;

[0042] Figure 3 A schematic diagram showing the fabrication process for applying a metal-embedded mandibular implant to orthodontics according to an embodiment of the present invention;

[0043] Figure 4 A drawing and results showing the mechanical properties applied to orthodontics according to an embodiment of the present invention;

[0044] Figure 5 A schematic diagram showing the synthesis process of the biocomposite;

[0045] Figure 6A A SEM image of the Ti alloy surface after chemical etching and Al2O3 deposition. Figure 6BShow the comparison of the interfacial shear strength between Ti alloy and polymer composites with and without Al2O3 coating;

[0046] Figure 7 Depict the strain relaxation test results of two samples made of pure transparent resin without wire and resin embedded with a wire;

[0047] Figure 8 Show the layered structure of a mandibular implant with high interfacial shear strength;

[0048] Figure 9 Illustrate the application of the implant of the present invention in both in vitro and in vivo scenarios; and

[0049] Figure 10 Depict the compressive strength and density of the implant of the present invention. Detailed Description

[0050] Embodiments of the present invention relate to a three-dimensional (3D) printing method for manufacturing metal-embedded medical implants and devices (e.g., orthodontic appliances / retainers).

[0051] In a first aspect, the present invention provides a 3D printing method for manufacturing a polymer medical implant embedded with a metal structure (e.g., a metal plate or wire). The method includes: performing a first computed tomography (CT) scan of one or more teeth and oral regions of a test subject to design a customized medical implant; designing the customized medical implant based on the results of the first CT scan; designing a metal structure to be embedded in the customized medical implant; performing data segmentation and 3D printing on the metal structure; converting the data into a stereolithography (STL) data format; performing 3D printing on the customized medical implant embedded with the metal structure; performing a second CT scan on the customized medical implant to analyze the internal structure of the customized medical implant; and performing surface modification on the customized medical implant based on the results of the second CT scan.

[0052] In a second aspect, a three-dimensional printing method for manufacturing a metal-embedded medical device is provided. The method includes: synthesizing a biocomposite matrix; performing metal selective laser sintering (SLS) 3D printing to embed a metal structure in the biocomposite matrix to obtain a metal-embedded medical device; and performing surface modification on the metal-embedded medical device to enhance the bonding between the metal structure and the biocomposite matrix.

[0053] A 3D printed metal thin layer formed of a material such as titanium, titanium alloy, cobalt chrome, or stainless steel and fabricated by SLS 3D printing is gradually embedded into a resin-based composite material during the SLA 3D printing process. Accordingly, the mechanical and physical properties (such as strength, modulus, elasticity, fracture toughness, creep, and volume shrinkage) of the structure are enhanced compared to polymer composites, and subsequently the implant weight is lighter compared to conventional metal or metal alloy implants. In addition, by suppressing direct contact between the metal component and bone tissue, the adverse effects resulting from the release of metal ions from the metal prosthesis can be removed.

[0054] Surface modification is implemented by depositing atomic layers on the surface of a customized medical implant. The atomic layers are selected from the group consisting of: Al2O3, MgO, ZrO2, and TiO2. Alternatively, surface modification is achieved by a silane coupling agent grafting process. Specifically, the silane coupling agent is subsequently applied to the titanium alloy, enabling it to form a strong chemical bond with the resin composite material. Experimental tests can be performed to measure the interfacial bonding force (strength) between the 3D printed titanium alloy and the resin composite material, and the surface-modified titanium alloy exhibits a significantly increased interfacial shear strength (IFSS). In particular, the IFSS value of the Al2O3 ALD-coated one increases by up to 50% compared to those without a coating.

[0055] In one embodiment, the metal structure includes a metal plate having a thickness in the range of 0.10 mm to 1.0 mm. For example, the embedded titanium alloy plate should establish a strong mechanical and chemical bond with the resin composite material to achieve a high mechanical fracture strength of the composite material.

[0056] In one embodiment, the 3D printed metal plate is mechanically polished using ceramic sandblasting and chemically etched using HCl and H2SO4 acidic solutions and NaOH alkaline solution. Subsequently, a 10-nm-thick TiO2 atomic layer deposition (ALD) is applied to the etched titanium alloy surface. Alternatively, the ALD process can be used to deposit Al2O3, ZrO2, and MgO instead of TiO2.

[0057] To optimize the mechanical properties such as strength and modulus of the resulting composite material, in a third aspect, the present invention provides a customized medical implant having a biocomposite matrix embedded with a metal structure. The biocomposite matrix contains a photocurable monomer, at least one nanofiller, and the biocomposite matrix contains 50 wt% to 90 wt% of the photocurable monomer and 10 wt% to 30 wt% of at least one nanofiller. Preferably, the biocomposite matrix further contains one or more silica nanoparticles.

[0058] A photocurable and biocompatible biocomposite is formed by a stereolithography (SLA) 3D printing method as a matrix material for polymeric medical devices and orthodontic appliances, and thin metal structures (e.g., plates, wires, or complex lattice structures) fabricated using a selective laser sintering (SLS) 3D printing method for metals are assembled during the 3D printing process by a layer-by-layer embedding technique.

[0059] In one embodiment, the biocomposite matrix can be a dental resin-based biocomposite, which can extend the application of tooth repair materials to "metal-free contact" medical implants.

[0060] Different types of functionalized fillers can be blended with the resin system to enhance the physical, mechanical, and biological capabilities of the resulting composite. UDMA-based resins have also been studied for use in bite splints and crown applications. The feasibility and practicality of using dental monomers such as Bis-EMA, UDMA, and TEGDMA as 3D printing resins have been explored.

[0061] In one embodiment, two types of nanofillers (e.g., 20 wt% glass particles (GP) and 2 wt% nano-hydroxyapatite (nHAP)) are mixed with 78 wt% of the resin. The resin can be a mixture of UDMA and TEGDMA in a mixing ratio of 7:3. The resulting biocomposite matrix exhibits high mechanical properties and good practicality (good viscosity / fluidity) for application in photocurable 3D printing.

[0062] In one embodiment, the metal structure comprises a metal plate, a metal wire, or a metal lattice structure. For example, a metal plate made of a titanium alloy (Ti-6Al-4V) is fabricated using a 3D metal printer. The printed thin metal plates with a thickness of 0.3 mm to 1.0 mm are embedded one by one into the resin composite during the photocurable 3D printing process.

[0063] These implants require lightweight, high mechanical strength, and biocompatible materials with biological properties (such as osteoconductivity and osteoinductivity). For example, composites containing nano-hydroxyapatite (nHAP) and silica nanoparticles can be used to improve biological performance, while implants with a three-dimensional micro / nano hierarchical porous structure fabricated by SLA 3D printing and cold plasma surface treatment can promote bone growth and adhesion. The composite material is capable of releasing calcium (Ca2 + ) and phosphate (PO4 3- ) ions, has improved osteogenic properties, and is non-toxic.

[0064] Polymeric medical devices and orthodontic appliances include, but are not limited to, prosthetic implants, spinal fusion devices, bone scaffolds, tooth braces, or retainers, thereby enabling new bone reconstruction or bone fixation while having lightweight high-strength mechanical and physical properties.

[0065] When the bonding strength between the metal and the resin composite is weak, interfacial delamination and crack propagation occur at the interface, leading to the deterioration of the mechanical properties of metal-embedded composite structures (such as brackets and implants). Therefore, it is crucial to mechanically modify the surface morphology of the metal plate to establish a strong interfacial bond between the metal (inorganic material) and the resin (organic material).

[0066] To overcome the weak interfacial bond between the metal layer and the resin, which may significantly deteriorate the mechanical properties of the laminated structure, surface modification can be applied to the 3D-printed metal layer by combining atomic layer deposition of Al2O3, MgO, ZrO2, or TiO2 with a silane coupling agent grafting process.

[0067] In one embodiment, surface modification is performed on a titanium alloy plate, such as mechanical sandblasting, acidic and alkaline chemical etching, silane coupling agent grafting, and Al2O3 ALD (thickness: approximately 10 nanometers), to improve the bonding strength with the polymer composite.

[0068] Reference Figure 1 illustrates the workflow for applying a metal-embedded mandibular implant to a prosthesis. First, a mandibular computed tomography (CT) scan is performed on the teeth and oral region of the test subject, and based on the CT mandible scan results, a custom implant is designed using 3D CAD methods. Next, the metal plate and assembly are designed based on the results of the custom implant. Then, data segmentation is performed on the metal plate and assembly so that 3D metal printing can be carried out. Surface modification, such as atomic layer deposition of TiO2 or Al2O3, mechanical / electrochemical etching, and silane coupling agent grafting, can be applied to the printed metal plate. Subsequently, the data is converted to the STL data format. Next, 3D printing of the metal-embedded mandibular implant is performed. Then, a second CT scan is performed to analyze the internal structure of the metal-embedded mandibular implant. Finally, surface modification is performed to design the final custom metal-embedded mandibular implant for the specific teeth and oral region of the test subject.

[0069] Turning Figure 2 illustrates the design and 3D printing process for applying a metal-embedded mandibular implant to a prosthesis. First, a 3D CAD design of the mandibular implant is performed. Next, the metal plate is designed. Then, 3D metal printing is carried out. Next, surface modification, such as etching and application of a coupling agent, is performed, and the implant with the metal plate embedded is obtained by assembling individual 3D-printed metal parts. Finally, 3D polymer printing is performed.

[0070] Reference Figure 3, showing the manufacturing process for applying a metal-embedded mandibular implant to orthodontics. Specifically, tensile test samples formed of a milky white resin (Phrozen) with a thickness of approximately 1 mm and tensile test samples formed of a transparent resin (NextDent) with a thickness of approximately 2 mm were tested. Additionally, orthodontic wires embedded within the tensile test samples are shown, the wires being made of stainless steel and sized at 0.47 mm × 0.64 mm.

[0071] Figure 4 A chart showing the results demonstrating the mechanical properties of applying a metal-embedded mandibular implant to orthodontics is presented. The results show that the mechanical properties of the orthodontic wire-embedded structure are significantly improved in terms of tensile strength, elastic modulus, and elasticity (increasing by up to 80% to 120% in a single wire-embedded structure), dimensional accuracy is improved, and shrinkage rate is reduced. Thus, embodiments of the present invention are more advantageous than conventional arch wire brackets and thermoformed clear aligners, showing great potential in orthodontic treatment, opening up new fields in orthodontics, and providing superior tooth traction force for digitally planned orthodontic treatment.

[0072] Resin-based and metal-embedded medical implants fabricated through 3D printing manufacturing technology can be customized according to the specific needs of patients. Additionally, digital control design and 3D printing manufacturing technology allow for the fabrication of functionally graded implants, thereby enhancing the scope of application in prostheses by minimizing stress concentration on the implant and bone, thus having a significant impact on spinal fusion, maxillofacial reconstruction, orthodontic appliances, and other fields of the prosthetics industry.

[0073] The enhanced mechanical properties of 3D-printed implants can be determined through theoretical prediction, computational simulation, and experimental measurement. Additionally, the biocompatibility and osteogenic effects of the implants can be measured via in vivo and in vitro studies.

[0074] Therefore, the method of embodiments of the present invention can provide aesthetically pleasing invisible aligners / retainers having high mechanical strength and long active retraction force; increased control over orthodontic movement of tooth roots; avoidance of metal allergy reactions associated with conventional wire bracket systems since the wires are embedded within the resin; and provision of low-cost orthodontic treatment, which is more advantageous than conventional fixed tooth appliances and thermoformed aligners.

[0075] All patents, patent applications, provisional applications, and publications mentioned or cited herein are incorporated herein by reference in their entirety to the extent that they are not inconsistent with the explicit teachings in this specification, including all drawings and tables.

[0076] Examples

[0077] Example 1

[0078] Composition of resin-based biocomposites

[0079] Reference Figure 5 , the dental resin-based biocomposite system contains: photocurable monomers, such as a mixture of methacrylate monomers (e.g., urethane dimethacrylate, 2-hydroxyethyl methacrylate, and triethylene glycol dimethacrylate); one or more conventional photoinitiators (e.g., camphorquinone, ethyl 4-dimethylaminobenzoate, and trimethylbenzoyl-diphenyl-oxide phosphine); a filler containing nHAP; and nano-silica particles.

[0080] The dental resin-based biocomposite system comprises 70 wt% to 95 wt% of blended or single monomers and 5 wt% to 30 wt% of fillers, and the mixing ratios of the three fillers are different. The nHAP is in the form of nano-spheres or nano-rods with a diameter of 50 nanometers to 200 nanometers, while the silica nanoparticles have a particle size of 50 nanometers to 700 nanometers.

[0081] By adjusting the weight fractions of the monomers and fillers, the viscosity of the biocomposite system can be controlled, thereby achieving precise and structured designs during the 3D printing process. A higher fraction of glass particles generally improves the physical and mechanical properties of the composite structure, but an extremely high viscosity hinders 3D printing. Therefore, the present invention also discovers the optimal mixing ratio of monomers and fillers in the resin composite system. Adding nHAP changes the surface characteristics of the implant by enhancing the biomechanical activity (e.g., water wettability and bone fusion at the bone-implant interface). In addition, the outer surface of the implant is etched by cold plasma treatment to expose the embedded nHAP, which can directly promote bone tissue regeneration.

[0082] Example 2

[0083] Fabricating a hierarchically structured prosthetic implant

[0084] In this example, a hierarchically structured prosthetic implant is fabricated by combining metal SLS and polymer SLA 3D printing with surface treatment techniques such as ALD coating, SCA grafting, and atmospheric cold plasma treatment.

[0085] First, a simple implant structure is designed using 3D CAD, and the implant structure is segmented for SLS and SLA 3D printing. Then, metal SLS microprinting is used to fabricate a 3D printed titanium alloy plate structure with various thicknesses in the range of 300 microns to 800 microns.

[0086] Surface modification of titanium alloy plates is important, especially in terms of interfacial bonding kinetics, because the existing nanopores have weak bonding with currently available resins, resulting in deterioration of the mechanical properties of the composite material. TiO2 and Al2O3 ALD coatings and SCA grafting techniques improve the surface morphology by reducing nanopores and enhancing the chemical (covalent) bonding at the interface. The effect of surface modification on mechanical properties is verified by micro pull-out, three-point bending, and compression shear tests.

[0087] Secondly, the surface-modified titanium alloy plates are embedded layer by layer during SLA 3D printing. It is designed to have a seamless microporous structure, including a helical icosahedron or diamond lattice structure at the center of the implant, which improves implant stability and allows bone growth into the porous structure.

[0088] Next, an nHAP-rich layer is printed on the top and bottom of the implant. This layer can directly contact the bone and stimulate the process of bone tissue growth via the osteoblast adhesion mechanism. Finally, the fabricated implant is post-treated under atmospheric cold plasma, which etches the surface without causing thermal deformation or deterioration of the resin-based implant, thus forming a hierarchically structured multifunctional implant. The plasma-textured surface exposes nano-fillers such as nHAP, providing a higher bioactive surface that induces increased osteoconductivity and osteoinductive activity.

[0089] Example 3

[0090] Fabricating a mandibular implant

[0091] Multifunctional biocomposites and a combined 3D printing method are used to fabricate synthetic mandibular implants. These implants are lightweight and strong. Compared with the jawbone and PEEK, the specific strength (strength / density) of the titanium alloy-embedded implant structure increases by up to 200%. Al2O3 ALD on the titanium alloy helps improve the mechanical properties of the synthetic implant ( Figures 6A to 6B ).

[0092] Example 4

[0093] Fabricating a 3D printed and wire-embedded transparent dental aligner / retainer

[0094] A dental resin-based biocomposite is synthesized by mixing 2 wt% to 5 wt% of nano-hydroxyapatite (n-HAP, diameter: 50 nm to 200 nm), 2 wt% to 5 wt% of nano-diamond (diameter: 10 nm to 100 nm), and 5 wt.% to 20 wt.% of silica nanoparticles (diameter: 50 nm to 700 nm) with a photocurable dental monomer.

[0095] One or more thin metal layers (titanium, titanium alloy, CoCr, stainless steel) with a thickness of 0.10 mm to 0.50 mm are fabricated using selective laser sintering of metals for 3D printing, and are subjected to TiO2 atomic layer deposition and silane coupling agent grafting treatment to increase the bonding with the biocomposite matrix. Finally, a hierarchical porous structure is fabricated by polymer stereolithography 3D printing. Additionally, cold plasma surface etching that promotes bone growth and adhesion can be applied to the surface of dental clear aligners / retainers.

[0096] Example 5

[0097] Material property testing

[0098] In order to develop composite materials with optimal properties, it is necessary to accurately and reliably determine material properties such as interfacial debonding, strength, modulus, and toughness. The present invention has developed state-of-the-art micro-mechanical measurement techniques, computational FEM analysis, and molecular dynamics simulations to determine material properties, thereby deriving relationships with the required bioactivity, mechanical properties, and performance of the newly developed materials.

[0099] Reference Figure 7 , depicts the strain relaxation test results of two samples: one sample is made of pure transparent resin without a wire, and the other sample has a wire embedded in the resin. When a wire is embedded, it exhibits high hardness and a low attenuation rate during 21 repeated cyclic loads.

[0100] In another embodiment, a newly developed metal-polymer 3D printing technique and an nHAP-reinforced composite material are used to fabricate a mandibular implant embedded with titanium and characterized by a microporous internal structure. It is precisely designed using a 3D CAD program (SolidWorks), and then a thin metal plate and a partial mandibular implant assembly are produced using metal and polymer 3D printers. Reference Figure 8 , cone beam computed tomography (CBCT) is used to observe the internal structure and bone-like porous structure of the embedded titanium alloy plate, confirming that it has been successfully constructed as designed. To enhance the interfacial properties between the titanium alloy and the resin composite, the 3D printed metal layer undergoes mechanical and chemical polishing processes. Subsequently, the metal layer is treated with Al2O3 using atomic layer deposition (ALD). Finally, a silane coupling agent is grafted onto the external surface, thereby enhancing the interfacial bonding strength and mechanical properties of the metal-embedded implant / stent. For example, with the deposition of the Al2O3 layer, the increased interfacial shear strength (IFSS) value increases by up to 50%.

[0101] This technology has the potential to transform high-strength lightweight medical implants / stents from concept to clinical application in the long term (5 to 10 years).

[0102] Example 6

[0103] Animal testing

[0104] In addition, the present invention also uses a rat bone defect model. After 4-week and 12-week observation periods, in vitro evaluations of osteoblast adhesion, cytocompatibility, proliferation, viability, and morphology of the 3D printed implant, as well as in vivo osteogenesis analysis, are performed to provide a biological and mechanical framework for cell growth and differentiation.

[0105] As the filler fraction increases, the average compressive strength and modulus of the 3D printed composite material increase by 16.5% and 56.4% respectively. Cold plasma treatment of the biocomposite produces a nano-textured surface, changing the hydrophobic surface to a hydrophilic surface, and the surface characteristics change from hydrophobic to hydrophilic due to the exposure of nHAP on the external surface. It exhibits improved cell adhesion and proliferation capabilities for MC3T3-E1 murine pre-osteoblasts after 1, 3, and 5 days of seeding. In vivo animal studies using rats also showed good bone regeneration performance ( Figure 9 ).

[0106] Generally speaking, the present invention discloses the use of multifunctional biocomposites and newly developed 3D printing technology to successfully fabricate 3D printed mandibular implants and spinal fusion cages. These implants exhibit the characteristics of being lightweight, high-strength, and metal-free contact ( Figure 10 ). The application of Al2O3 ALD on the 3D printed titanium alloy plate significantly enhances the interface (up to 50%) and mechanical properties, effectively preventing severe failure under high compressive loads.

[0107] Industrial Applicability

[0108] The present invention is expected to create a large market share in the prosthetics industry, including spinal fusion, maxillofacial reconstruction, and orthodontic appliances.

[0109] Definitions

[0110] The terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the present invention. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. As used herein, unless the context clearly indicates otherwise, the singular forms "a", "an", and "the" are intended to include the plural forms as well as the singular forms. It should be further understood that the terms "comprises" and / or "comprising", when used in this specification, specify the presence of the stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0111] References throughout this specification to "one embodiment", "an embodiment", "an example", "an implementation", "a disclosed aspect", or "an aspect" mean that a particular feature, structure, or characteristic described in connection with the embodiment, implementation, or aspect is included in at least one embodiment, implementation, or aspect of the present disclosure. Thus, the phrases "in one embodiment", "in an example", "in an aspect", "in an implementation", or "in an embodiment" that appear throughout this specification do not necessarily all refer to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in various disclosed embodiments.

[0112] Unless otherwise indicated in the examples and elsewhere in the specification and claims, all parts and percentages are by weight, all temperatures are in degrees Celsius, and the pressure is at or near atmospheric pressure. Except in the operating examples, or where otherwise indicated, all numbers, values, and / or expressions for amounts of ingredients, reaction conditions used in the specification and claims are to be understood as being modified in all instances by the term "about".

[0113] When the term "about" is used in connection with a numerical value herein, it is understood that the value can range from 90% to 110% of the stated value, i.e., the value can be + / - 10% of the stated value. For example, "about 1 kg" means 0.90 kg to 1.1 kg.

[0114] For any given illustration or numerical range of a property, numbers or parameters from one range can be combined with numbers or parameters from a different range to generate a numerical range for that property.

[0115] Unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It should be further understood that terms, such as those defined in a commonly used dictionary, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and this disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0116] Although the present invention is explained on the basis of certain embodiments, it should be understood that many modifications will be apparent to those skilled in the art after reading the specification. Therefore, it should be understood that the present invention disclosed herein is intended to cover such modifications that fall within the scope of the appended claims.

[0117] The foregoing description of the invention has been provided for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations will be apparent to those skilled in the art.

[0118] The embodiments are chosen and described in order to best explain the principles of the invention and its practical applications, thereby enabling other technicians in the relevant field to understand the various embodiments of the invention and the various modifications suitable for the specific purposes expected.

[0119] References: The disclosures of the following references are incorporated herein by reference [1] Jindal P, Juneja M, Siena F L, et al. Mechanical and geometric properties of thermoformed and 3D printed clear dental aligners. American Journal of Orthodontics and Dentofacial Orthopedics, 2019, 156(5): 694 - 701. [2] McCarty M C, Chen S J, English J D, et al. Effect of print orientation and duration of ultraviolet curing on the dimensional accuracy of a 3-dimensionally printed orthodontic clear aligner design. American Journal of Orthodontics and Dentofacial Orthopedics, 2020, 158(6): 889 - 897.

Claims

1. A three-dimensional printing method for manufacturing a metal-embedded medical implant, characterized in that, Comprising: Performing a first computed tomography (CT) scan on one or more teeth and oral regions of a test subject to design a customized medical implant; Designing the customized medical implant based on the results of the first CT scan; Designing a metal structure to be embedded in the customized medical implant; Performing data segmentation and three-dimensional printing on the metal structure; Converting the data into a stereolithography (STL) data format; Performing three-dimensional printing on the customized medical implant embedded with the metal structure; Performing a second CT scan on the customized medical implant to analyze the internal structure of the customized medical implant; And Performing surface modification on the customized medical implant based on the results of the second CT scan.

2. The method according to claim 1, wherein the first CT scan is a CT scan of the mandible of the test subject.

3. The method according to claim 1, wherein the design of the customized medical implant is implemented by a three-dimensional computer-aided design (CAD) method.

4. The method according to claim 1, wherein the metal structure comprises a metal plate, a metal wire or a metal lattice structure.

5. The method according to claim 1, wherein the step of performing 3D printing on the customized medical implant embedded with the metal structure is implemented by a polymer stereolithography 3D printing method.

6. The method according to claim 1, wherein the step of performing 3D printing on the metal structure is implemented by a metal selective laser sintering (SLS) three-dimensional printing method.

7. The method according to claim 1, wherein the customized medical implant has a hierarchical porous structure.

8. The method according to claim 1, wherein the customized medical implant comprises a prosthetic implant, a spinal fusion cage, a bone scaffold, an orthodontic appliance and a retainer.

9. The method according to claim 1, wherein the metal structure is made of titanium, a titanium alloy, cobalt-chromium (CoCr), stainless steel or a combination thereof.

10. The method according to claim 1, wherein the surface modification is implemented by depositing atomic layers on the surface of the customized medical implant.

11. The method according to claim 10, wherein the atomic layers are selected from the group consisting of: Al2O3, MgO, ZrO2 and TiO2.

12. The method according to claim 1, wherein the surface modification is achieved by a silane coupling agent grafting process.

13. A three-dimensional printing method for manufacturing a metal-embedded medical device, characterized in that, Comprising: Synthesizing a biocomposite matrix; Performing metal selective laser sintering (SLS) three-dimensional printing to embed a metal structure in the biocomposite matrix to obtain the metal-embedded medical device; And Performing surface modification on the metal-embedded medical device to enhance the bonding between the metal structure and the biocomposite matrix.

14. The method according to claim 13, wherein the method further comprises performing cold plasma surface etching on the surface of the metal-embedded medical device.

15. The method according to claim 13, wherein the step of synthesizing the biocomposite matrix comprises mixing a photocurable monomer and at least one nanofiller, and wherein the biocomposite matrix comprises 50 wt% to 90 wt% of the photocurable monomer and 10 wt% to 30 wt% of the at least one nanofiller.

16. The method according to claim 15, wherein the photocurable monomer is selected from the group consisting of methacrylates, urethane-dimethacrylates, and triethylene glycol dimethacrylate.

17. The method according to claim 15, wherein the biocomposite matrix further comprises one or more silica nanoparticles.

18. The method according to claim 17, wherein the one or more silica nanoparticles have a diameter range of 50 nanometers to 700 nanometers.

19. The method according to claim 15, wherein the at least one nanofiller comprises nano-hydroxyapatite or nanodiamond.

20. The method according to claim 19, wherein the nano-hydroxyapatite has a diameter of 50 nanometers to 200 nanometers.

21. The method according to claim 19, wherein the nanodiamond has a diameter of 10 nanometers to 100 nanometers.

22. The method according to claim 13, wherein the metal structure is made of titanium, a titanium alloy, cobalt-chromium (CoCr), or stainless steel.

23. The method according to claim 13, wherein the surface modification is carried out by depositing atomic layers on the surface of the customized medical implant.

24. The method according to claim 23, wherein the atomic layers are selected from the group consisting of Al2O3, MgO, ZrO2, and TiO2.

25. The method according to claim 13, wherein the surface modification is achieved by a silane coupling agent grafting process.

26. The method according to claim 13, wherein the metal structure comprises a metal plate having a thickness in the range of 0.10 millimeters to 1.0 millimeter.

27. The method according to claim 13, wherein the interfacial bonding force between the metal structure and the biocomposite matrix is enhanced by applying Al2O3 atomic layer deposition (ALD).

28. A customized medical implant, characterized in that, wherein the customized medical implant comprises a biocomposite matrix embedded with a metal structure, wherein the biocomposite matrix comprises a photocurable monomer and at least one nanofiller, and wherein the biocomposite matrix comprises 50 wt% to 90 wt% of the photocurable monomer and 10 wt% to 30 wt% of the at least one nanofiller.

29. The customized medical implant according to claim 28, wherein the biocomposite matrix further comprises one or more silica nanoparticles.

30. The customized medical implant according to claim 28, wherein the metal structure comprises a metal plate, a metal wire, or a metal lattice structure.

31. The customized medical implant according to claim 30, wherein the metal structure is made of titanium, a titanium alloy, cobalt-chromium (CoCr), or stainless steel.

32. The customized medical implant according to claim 28, wherein the photocurable monomer is selected from the group consisting of: methacrylate, urethane-dimethacrylate, and triethylene glycol dimethacrylate.

33. The customized medical implant according to claim 28, wherein the at least one nano filler comprises nano hydroxyapatite, nano diamond, silica glass particles, glass fibers, ceramics, metal particles, halloysite nanotubes, or pre-polymerized polymer particles.

34. The customized medical implant according to claim 33, wherein the nano hydroxyapatite has a diameter of 50 nanometers to 200 nanometers.

35. The customized medical implant according to claim 33, wherein the nano diamond has a diameter of 10 nanometers to 100 nanometers.

36. The customized medical implant according to claim 28, wherein the biocomposite matrix further comprises 0.1 wt% to 3 wt% of a photoinitiator.

37. The customized medical implant according to claim 36, wherein the photoinitiator comprises (2,4,6-trimethylbenzoyl) diphenylphosphine oxide, phenylbis(2,4,6-trimethylbenzoyl)-phosphine oxide, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, 1-hydroxycyclohexyl phenyl ketone, or 2,2-dimethoxy-2-phenylacetophenone.

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