WO2024093647A1

WO2024093647A1 - Three-dimensional printing methods for making metal-embedded medical implants and devices

Info

Publication number: WO2024093647A1
Application number: PCT/CN2023/124453
Authority: WO
Inventors: Kiho Cho; James Kit Hon TSOI; Richard Yuxiong SU
Original assignee: The University Of Hong Kong
Priority date: 2022-10-31
Filing date: 2023-10-13
Publication date: 2024-05-10

Abstract

Three-dimensional (3D) printing methods for making metal-embedded medical implants and devices are provided. The newly developed 3D printing technology and surface modification method will contribute to the wider application of 3D-printed patient-specific products in many medical fields showing excellent clinical safety.

Description

THREE-DIMENSIONAL PRINTING METHODS FOR MAKING METAL-EMBEDDED MEDICAL IMPLANTS AND DEVICES

Inventors: Kiho CHO; James Kit Hon TSOI; Richard Yuxiong SU

Cross-refence to Related Applications:

The present application claims the priorities from the U.S. provisional patent application serial number 63/381,626 filed October 31, 2022, and the disclosure of which is incorporated herein by reference in its entirety.

Field of the Invention:

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 appliances, such as prosthetic implants, spinal fusion cages, bone scaffolds, dental aligners and retainers.

Background of the Invention:

In recent years, the field of medical implant technology has witnessed significant advancements driven by the integration of cutting-edge manufacturing techniques. Three-dimensional (3D) printing technology, in particular, has emerged as a transformative force, enabling the creation of intricate and patient-specific medical implants and devices.

For instance, 3D printing technologies using light-curable resins (e.g., stereolithography (SLA) , digital light processing (DLP) , and lithography-based ceramic manufacturing) are being steadily adopted by dental industries due to their accuracy and speed, cost-effectiveness, and high productivity even in the dental office and laboratory. Small and complex structures, including indirect restorations, bridges, dentures, aligners, implant abutments, and surgical guides can be easily fabricated based on the patient intra-oral and tooth data.

Clear aligners have gained widespread popularity as an aesthetically pleasing solution. However, traditional thermoformed aligners are burdened by several inherent limitations, including dimensional instability, poor wear resistance, and low strength. These aligners are constructed from thermoplastic materials that exhibit viscoelastic properties, resulting in behaviors such as creep and stress relaxation over time. This can lead to either excessive force application on the teeth, causing discomfort, or insufficient force, resulting in minimal tooth movement. Furthermore, thermoformed aligners tend to display weaker compression strength and extensive irreversible deformation due to their thermoplastic-based nature. The evolution of 3D printing technology has paved the way for the development of 3D-printed clear dental aligners that offer a superior alternative. For example, Jindal et al. ¹ find the dimensional accuracy and the compressive mechanical properties of 3D-printed clear aligners cured after printing to be superior in comparison with thermoformed aligners. McCarty et al. ² apply 3D surface analysis techniques to investigate the effect of print angle and duration of post-curing on the dimensional accuracy of 3D-printed clear aligners.

Conventionally, titanium (Ti) , Ti alloy, or polyether ether ketone (PEEK) are selected for medical implants due to their good mechanical properties and biocompatibility. Both Ti and PEEK implants exhibit similar prosthesis implant rates. While these conventional implants and fixtures provide adequate load-bearing capacity, concerns have arisen regarding the Ti implants with metal components, specifically in orthopedic fusion cases. This is due to their high elastic modulus and stress shielding effects, which can lead to issues like subsidence or gradual penetration into endplate surfaces. Consequently, weak interfacial bone-bonding can lead to high implant failure causing bone instability, subsidence, implant migration, and severe pain or discomfort, which may require second surgery.

On the other hand, the PEEK implants having polymer groups are much more compliant compared to the Ti or Ti alloy implants, because their elastic modulus is nearly identical to bone (ranging from cortical to cancellous bone) . However, the PEEK implants tend to be hydrophobic and biologically inert, resulting in limited integration with surrounding tissues post-implantation.

Moreover, the application of PEEK implants in pre-and post-3D printing processes poses considerable challenges due to PEEK's high melting and glass transition temperatures, which vary based on polymer crystallinity levels. This variance leads to significant fluctuations in the mechanical and physical performance of 3D-printed PEEK implants, thus restricting the adaptability of PEEK 3D printing in medical device applications that demand stringent quality control and assurance.

There continues to be a need in the art for improved designs and techniques for methods for making medical implants for various medical devices and appliances, including prosthetic implants, spinal fusion cages, bone scaffolds, dental aligners and retainers, as well as other medical devices.

Summary of the Invention:

The following presents a simplified summary of the invention to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the invention. It is intended to neither identify key or critical elements of the invention nor delineate the scope of the invention. Rather, the sole purpose of this summary is to present some concepts of the invention in a simplified form as a prelude to the more detailed description that is presented hereinafter.

According to a first aspect of the present invention, a three-dimensional (3D) printing method for making a metal-embedded medical implant is provided. The method includes performing a first computerized tomography (CT) scanning of one or more teeth and mouth areas of a test subject for designing a customized medical implant; conducting a design of the customized medical implant based on results of the first CT scanning; conducting a design of metal structures to be embedded in the customized medical implant; performing data segmentation and 3D printing of the metal structures; converting data into a stereolithography (STL) data format; performing 3D printing of the customized medical implant embedded with the metal structures; performing a second CT scanning of the customized medical implant for analyzing internal structures of the customized medical implant; and performing surface modifications on the customized medical implant based on results of the second CT scanning.

In one of the embodiments, the first CT scanning may be a CT scanning of mandible of the test subject.

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

In one of the embodiments, the metal structures include metal plates, metal wires, or metal lattice structures.

In one of the embodiments, the step of 3D printing of customized medical implant embedded with the metal structures is implemented by a polymeric stereolithography 3D printing method.

In one of the embodiments, the step of 3D printing of metal structures can be implemented by a metallic selective laser sintering (SLS) 3D printing method.

In one of the embodiments, the customized medical implant has a hierarchical porous structure.

In one of the embodiments, the customized medical implant includes a prosthetic implant, a spinal fusion cage, a bone scaffold, a dental aligner, and a retainer.

In one of the embodiments, the metal structures are made of one of titanium (Ti) , Ti alloy such as Ti-6Al-4V, cobalt-chromium (CoCr) , stainless steel, or a combination thereof. For example, the Ti-6Al-4V plate structures with 0.5 mm thicknesses can be fabricated using metallic SLS micro-printing.

In one of the embodiments, the surface modification is implemented by depositing an atomic layer on the surface of the customized medical implant. The atomic layer is selected from the group consisting of Al₂O₃, MgO, ZrO₂, and TiO₂. In another embodiment, the surface modification is achieved through silane coupling agent grafting processes.

In a second aspect, a three-dimensional printing method for making a metal-embedded medical device is provided. The method comprises synthesizing a biocomposite matrix; performing metallic selective laser sintering (SLS) 3D printing to embed metal structures in the biocomposite matrix to obtain the metal-embedded medical device; and; performing surface modifications on the metal-embedded medical device for increased bonding of the metal structures with the biocomposite matrix.

The method may further comprise performing cold plasma surface etching onto surfaces of the metal-embedded medical devices to increase bone growth and adhesion.

In one of the embodiments, the step of synthesizing a biocomposite matrix includes mixing a photocurable monomer, at least one nano-filler, and wherein the biocomposite matrix comprises 50-90 wt%of the photocurable monomer and 10-30 wt%of the at least one nano-filler.

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 normally form cross-linked polymers during free radical polymerization can be used.

In one of the embodiments, the biocomposite matrix further comprises one or more silica nano-particulates. They have diameters in a range of 50-700 nm.

In one of the embodiments, the at least one nano-filler comprises a nanohydroxyapatite, or a nanodiamond. Moreover, the nanohydroxyapatites have diameters in a range of 50-200 nm; the nanodiamonds have diameters in a range of 10-100 nm; and the silica nano-particulates have diameters in a range of 50-700 nm.

In one of the embodiments, the metal structures are made of one of titanium (Ti) , Ti alloy, cobalt-chromium (CoCr) , or stainless steel. The metal structures comprise metal plates having thicknesses in a range of 0.10-1.0 mm.

In one of the embodiments, the surface modification is implemented by depositing an atomic layer on the surface of the customized medical implant. The atomic layer is selected from the group consisting of Al₂O₃, MgO, ZrO₂, and TiO₂.

In another embodiments, the surface modification is achieved through silane coupling agent grafting processes.

In one of the embodiments, an interfacial bonding force between the metal structures and the biocomposite matrix is enhanced through the application of Al₂O₃ atomic layer deposition (ALD) .

In a third aspect, the present invention provides a customized medical implant, which has a biocomposite matrix embedded with metal structures. The biocomposite matrix includes a photocurable monomer, at least one nano-filler, and the biocomposite matrix includes 50-90 wt%of the photocurable monomer and 10-30 wt%of the at least one nano-filler. Preferably, the biocomposite matrix further includes one or more silica nano-particulates.

In one of the embodiments, the metal structures comprise metal plates, metal wires, or metal lattice structures.

In one of the embodiments, the metal structures are made of either titanium (Ti) , Ti alloy, cobalt-chromium (CoCr) , or stainless steel.

In one of the embodiments, the photocurable monomer is selected from the group consisting of methacrylate, urethane-dimethacrylate, and triethylene glycol dimethacrylate.

In one of the embodiments, the at least one nano-filler includes a nanohydroxyapatite, nanodiamond, silica glass particles, glass fibers, ceramic, metal particles, halloysite nanotubes, or pre-polymerized polymer particles. In one of the embodiments, the nanohydroxyapatites has a diameter of 50-200 nm. The nanodiamond has a diameter of 10-100 nm.

In one of the embodiments, the biocomposite matrix further comprises 0.1-3 wt%of photoinitiator.

In one of the embodiments, the photoinitiator includes 2, 4, 6-trimethylbenzoyldiphenyl phosphine oxide, phenylbis (2, 4, 6-trimethylbenzoyl) -phosphine oxide, 2-hidroxy-1- [4- (2-hidroxyethoxy) phenyl] -2-methyl-1-propanone, 1-hidroxycyclohexyl-1-phenyl ketone, or 2, 2-dimethoxy-2-phenylacetophenone.

The present invention has the following advantages:

(1) Compared to current biomedical metal materials (e.g., Ti, Ti alloy, CoCr and stainless steel) and biomedical polymer materials (e.g., PEEK, dental resins) , the three-dimensional printing of metal-embedded medical implants and devices exhibits superior mechanical and physical properties, including high-strength and lightweight characteristics.

(2) By controlling the structure of the metal layers, it is possible to manufacture a functionally graded implant with mechanical properties that gradually change in relation to the dimensions along the printing direction. This approach mimics the structural characteristics of both cortical and cancellous bone.

(3) The fabricated medical implants and devices are characterized by their non-corrosive nature and the absence of adverse effects resulting from the release of metal ions and wear particles. In addition, the fabricated medical implants and devices eliminate the risk of metal allergy reactions associated with conventional metal wire-bracket systems, as the metal wires are embedded within the resin.

(4) Multifunctionalized biocomposites can be applied in 3D printing to increase osteogenic capability, or provide the esthetic invisible aligner/retainer with high mechanical strength and longer active retraction forces, thereby improving the control over the orthodontic movement in teeth roots.

(5) The present invention offers a cost-effective orthodontic treatment option compared to conventional fixed appliances and thermoformed aligners.

Brief Description of the Drawings:

Embodiments of the invention are described in more details hereinafter with reference to the drawings, in which:

FIG. 1 shows a schematic representation of the workflow for application of the metal embedded mandibular implant to prosthetics, according to an embodiment of the present invention;

FIG. 2 shows a schematic representation of design and 3D printing processes for application of the metal embedded mandibular implant to prosthetics, according to an embodiment of the present invention;

FIG. 3 shows a schematic representations of fabrication process for application of the metal embedded mandibular implant to orthodontics, according to an embodiment of the present invention;

FIG. 4 shows a plot diagram and results demonstrating mechanical properties of application to orthodontics, according to an embodiment of the present invention;

FIG. 5 shows the synthesis process of biocomposite;

FIG. 6A shows a SEM image of Ti alloy surface after chemical etching and Al₂O₃ deposition. FIG. 6B shows a comparison of interfacial shear strength between Ti alloy and polymer composite with and without Al₂O₃ coating;

FIG. 7 depicts strain relaxation test results of two samples fabricated with pure clear resin without metal wire and one metal wire embedded resin;

FIG. 8 shows the layered structure of a mandibular implant with high interfacial shear strength;

FIG. 9 illustrates the application of the implant of the present invention in both in vitro and in vivo scenarios; and

FIG. 10 depicts the compressive strength and density of the implant of the present invention.

Detailed Description:

The embodiments of the present invention pertain to three-dimensional (3D) printing methods for making metal-embedded medical implants and devices (e.g, dental aligners/retainers) .

In a first aspect, the present invention provides a 3D printing method for making polymeric medical implants embedded with metal structures (e.g., metal plates or metal wires) . The method includes performing a first computerized tomography (CT) scanning of one or more teeth and mouth areas of a test subject for designing a customized medical implant; conducting a design of the customized medical implant based on results of the first CT scanning; conducting a design of metal structures to be embedded in the customized medical implant; performing data segmentation and 3D printing of the metal structures; converting data into a stereolithography (STL) data format; performing 3D printing of the customized medical implant embedded with the metal structures; performing a second CT scanning of the customized medical implant for analyzing internal structures of the customized medical implant; and performing surface modifications on the customized medical implant based on results of the second CT scanning.

The 3D-printed metal thin layers formed of a material such as titanium (Ti) , Ti alloy, cobalt-chromium, or stainless steel and fabricated by the SLS 3D printing are gradually embedded into the resin-based composite during the SLA 3D printing process. As a result, the mechanical and physical properties, such as strength, modulus, resilience, fracture toughness, creep, and volume shrinkage of the structure are enhanced compared to the polymer composites, ensuing lightweight implants compared to the conventional metal or metal alloy implants. Moreover, adverse effects due to metal ion release from metal prosthesis can be removed by inhibiting direct contact between the metal component and the bone tissues.

The surface modification is implemented by depositing an atomic layer on the surface of the customized medical implant. The atomic layer is selected from the group consisting of Al₂O₃, MgO, ZrO₂, and TiO₂. Alternately, the surface modification is achieved through silane coupling agent grafting processes. In particular, a silane coupling agent is subsequently applied to the Ti alloy, enabling the formation of a robust chemical bond with the resin composite. Experimental tests may be performed to measure the interfacial bonding force (strength) between the 3D-printed Ti alloy and resin composites, and the surface modified Ti alloy shows highly increased interfacial shear strength (IFSS) . Especially, IFSS values increase by up to 50%with Al₂O₃ ALD coating compared to without the coating.

In one of the embodiments, the metal structures comprise metal plates with a thickness in a range of 0.10-1.0 mm. For instance, the embedded Ti alloy plates should establish a strong mechanical and chemical bond with the resin composites to achieve a high mechanical fracture strength of the composites.

In one of the embodiments, the 3D-printed metal plate undergoes mechanical polishing using ceramic sandblasting and chemical etching with HCl and H₂SO₄ acidic solutions, as well as an NaOH alkaline solution. Subsequently, a 10 nm-thick TiO₂ atomic layer deposition (ALD) is applied to the etched Ti alloy surface. Alternatively, Al₂O₃, ZrO₂, and MgO can be deposited using the ALD process in place of TiO₂.

To optimize the mechanical properties such as strength and modulus of the resulting composites, in a third aspect, the present invention provides a customized medical implant, which has a biocomposite matrix embedded with metal structures. The biocomposite matrix includes a photocurable monomer, at least one nano-filler, and the biocomposite matrix includes 50-90 wt%of the photocurable monomer and 10-30 wt%of the at least one nano-filler. Preferably, the biocomposite matrix further includes one or more silica nano-particulates.

The photocurable and biocompatible bio-composites as a matrix material for the polymeric medical devices and appliances are formed by stereolithography (SLA) 3D printing methods, and thin metal structures (such as plates, wires, or complex lattice structures) fabricated by using metallic selective laser sintering (SLS) 3D printing methods are assembled by a layer-by-layer embedding technique during the 3D printing processes.

In one of embodiments, the biocomposite matrix can be dental resin-based biocomposites, which can extend the application of dental restoration materials to “metal-contact-free” medical implants.

Different types of functionalized fillers can be blended with resin systems to enhance the physical, mechanical, and biological capabilities of the resulting composites. UDMA-based resins have also been studied for occlusal splint and crown applications. The feasibility and applicability of using dental monomers such as Bis-EMA, UDMA, and TEGDMA as 3D printing resins has been explored.

In one of embodiments, two nano-fillers (e.g. 20 wt%glass particle (GP) and 2 wt%nano-hydroxyapatite (nHAP) ) are mixed with 78 wt%of resin. The resin can be a mixture of UDMA and TEGDMA with a mixing ratio of 7: 3. The resulting biocomposite matrix shows high mechanical properties and good applicability (good viscosity/flowability) to be applied in photo-curing 3D printing.

In one of embodiments, the metal structures include metal plates, metal wires, or metal lattice structures. For instance, the metal plates made from a titanium alloy (Ti-6Al-4V) were fabricated with a 3D metal printing machine. Printed thin metal plates with a thickness of 0.3 to 1.0 mm were embedded one by one in the resin composite during photocuring 3D printing process.

These implants require lightweight, high mechanical strength, as well as biocompatible materials with biological properties, such as osteoconductivity and osteoinductivity. For example, composites containing nano-hydroxyapatites (nHAPs) and silica nano-particulates can be used to increase biological performance, whereas implants with three-dimensional micro/nano-hierarchical porous structures fabricated by SLA 3D printing and cold plasma surface treatment can promote bone growth and adhesion. The composite is able to release calcium (Ca₂ ⁺) and phosphate (PO₄ ^3-) ions with improved osteogenic properties, while being non-toxic.

The polymeric medical devices and appliances include, but are not limited to, prosthetic implants, spinal fusion cages, bone scaffolds, dental aligners, or retainers, enabling new bone reconstruction or bone fixation along with lightweight high-strength mechanophysical characteristics.

Interfacial delamination and crack propagation occur at the interface when there is a weak bond strength between the metal and resin composite, leading to a degradation in the mechanical performance of metal-embedded composite structures, such as scaffolds and implants. Therefore, it is of utmost importance 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) .

To overcome the weak interfacial bonding between the metal layers and the resins which may significantly degrade the mechanical properties of the laminated structures, surface modifications can be applied onto the 3D-printed metal layers by a combination of Al₂O₃, MgO, ZrO₂, or TiO₂ atomic layer deposition and silane coupling agent grafting processes.

In one embodiment, the surface modification on Ti alloy plates, such as mechanical blasting, acidic and alkaline chemical etching, silane coupling agent grafting, and Al₂O₃ ALD (thickness: approximately 10 nm) , is performed to improve the bonding strength with polymer composites.

Referring to FIG. 1, the workflow for application of the metal embedded mandibular implant in prosthetics is illustrated. First, a mandibular computerized tomography (CT) scan is conducted on the teeth and mouth areas of the test subject, and customized implants are designed using 3D CAD methods based on the CT mandible scan results. Next, metal plates and assemblies are designed based on the results of the customized implants. Data segmentation is then performed on the metal plates and assembly such that 3D metal printing can be carried out. Surface modifications such as atomic layer deposition of TiO₂ or Al₂O₃, mechano-/electro-chemical etching, and silane coupling agent grafting can be applied to the printed metal plates. Subsequently, data conversion to STL data format is performed. Next, 3D printing of the metal embedded mandibular implant is performed. Then, a second CT scanning is performed for an analysis of the internal structures of the metal embedded mandibular implant. Following this, surface modifications are performed, leading to the final customized metal-embedded mandibular implant designed for the specific teeth and mouth areas of the test subject.

Turning to FIG. 2, design and 3D printing processes for application of the metal embedded mandibular implant to prosthetics are illustrated. First, 3D CAD design of mandibular implant is performed. Then, design of the metal plates is carried out. Next, 3D metal printing is performed. Then, surface modifications such as etching and applying coupling agent are carried out and the metal plate embedded implant is obtained by assembling the individual 3D printed metal pieces. Next, 3D polymer printing is performed.

Referring to FIG. 3, the fabrication processes for application of the metal embedded mandibular implant to orthodontics are illustrated. In particular, a tensile test specimen formed by white milky resin (Phrozen) having a specimen thickness of about 1 mm and a tensile test specimen formed by clear resin (NextDent) having a specimen thickness of about 2 mm were tested. In addition, the tensile test specimen has orthodontic metal wire embedded within which is made of stainless steel having a size of 0.47 mm x 0.64 mm is shown.

FIG. 4 shows a plot diagram of results demonstrating mechanical properties of application of the metal embedded mandibular implant to orthodontics. The results reveal that the orthodontic metal wire embedded structures produce significantly increased mechanical properties (up to 80-120%increase in a single wire embedded structure) in tensile strength, elastic modulus, and resilience with the enhanced dimensional precision and low shrinkage. Accordingly, the embodiments of the subject invention are advantageous over the conventional archwire-bracket and thermoformed clear aligners, showing great potentials for orthodontic treatments, opening a new area of orthodontics, and offering superior teeth retraction capability for the digitally planned orthodontic treatments.

The resin-based and metal-embedded medical implants fabricated by the 3D print manufacturing technology can be customized to be patient-specific. Moreover, the digital control design and 3D print manufacturing allow fabricating the functionally graded implants to enhance the range of applications in prosthetics, thanks to the minimized stress concentration on the implants and bones, thereby imposing significant impacts on spinal fusion, maxillomandibular reconstruction, orthodontic appliances, and other areas of the prosthetic industry.

The enhanced mechanical properties of the 3D-printed implants may be determined by theoretical prediction, computational simulations, and experimental measurements. Further, the biocompatibility and osteogenic effects of the implants can be measured via in vivo and in vitro studies.

Thus, the methods of the embodiments of the subject invention can provide esthetic invisible aligner/retainer with high mechanical strength and longer active retraction forces; increase the control over the orthodontic movement in teeth roots; avoid metal allergy reactions associated with the conventional metal wire-bracket systems since the metal wires are embedded inside the resin; and supply low-cost orthodontic treatment which is advantageous over the conventional fixed dental appliances and thermoformed aligners.

All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

EXAMPLE

EXAMPLE 1

Compositions of the resin-based biocomposite

Referring to FIG. 5, the dental resin-based biocomposite system contained a photocurable monomer, such as a mixture of methacrylate monomers (e.g., urethane dimethacrylate, 2-hydroxyethyl methacrylate, and triethylene glycol dimethacrylate) , one or more traditional photo-polymerization initiators (e.g., camphorquinone, ethyl 4-dimethylaminobenzoate, and trimethylbenzoyl-diphenyl-phosphine oxide) , a filler containing nHAPs, and nano-silica particles.

The dental resin-based biocomposite system included 70-95 wt%of the blended or single monomer and 5-30 wt%of the filler with various mixing ratios of the three fillers. The nHAPs were in the form of nano-spheres or nano-rods having a diameter of 50-200 nm, whereas the silica nano-particulates had a particle size from 50-700 nm.

The viscosity of biocomposite systems was controlled by adjusting the weight fractions of the monomers and fillers. This allowed for precise and structured designs when using 3D printing. A higher fraction of glass particulates generally improved the physical and mechanical properties of the composite structures, but extremely high viscosity hindered the 3D printing. Thus, the present invention also found the optimal mixing ratios of monomers and fillers in the resin composite system. The addition of nHAPs modified the surface characteristics of the implants by increasing biomechanical activity, such as water wettability and osseointegration at the bone-implant interface. Moreover, the outer surface of the implants was etched by cold plasma treatment to expose embedded nHAPs, which could directly stimulate bone tissue regeneration.

EXAMPLE 2

Fabrication of hierarchically structured prosthesis implant

In this example, the hierarchically structured prosthesis implants were fabricated by combining metallic SLS and polymeric SLA 3D printings with surface treatment techniques such as ALD coating, SCA grafting, and atmospheric cold plasma treatment.

First, simple implant structures were designed using 3D CAD and segmented for SLS and SLA 3D printing. Then, 3D-printed Ti alloy plate structures with various thicknesses ranging from 300-800 μm were fabricated using metallic SLS micro-printing.

Surface modification on Ti alloy plates was important, especially the interfacial bonding kinetics, as the existing nanopores had weak bonding to the currently available resins, leading to degraded mechanical properties of the composite. The TiO₂ and Al₂O₃ ALD coatings and SCA grafting techniques improved the surface morphology by reducing nanopores and enhancing chemical (covalent) bonds at the interface. The effects of the surface modifications on the mechanical properties were verified through micro pull-out, three-point bend, and compression-shear tests.

Second, the surface-modified Ti alloy plates were embedded layer by layer during SLA 3D printing. They were designed to have seamless microporous structures, including gyroid or diamond lattice structures at the center of the implant, which increased implant stability and allowed for bone growth into porous structures.

Next, nHAPs-rich layers were printed on the top and bottom of the implants that could directly contact bones and stimulate the progress of bone tissue growth via an osteoblast adhesion mechanism. Finally, the fabricated implants were post-processed under atmospheric cold plasma, which etched the surface without causing thermal deformation or degradation of the resin-based implants, forming hierarchically structured multifunctional implants. The plasma-textured surface exposed the nano-fillers such as nHAPs, providing a much higher bioactive surface that led to increased osteoconductive and osteoinductive activity.

EXAMPLE 3

Fabrication of mandibular implant

Synthetic mandibular implants were fabricated using multifunctional bio-composites and the combined-3D printing method. These implants showed light weight high-strength. Specific strength (strength/density) of the Ti alloy-embedded implant structure increased by up to 200%compared to the jaw bone and PEEK. The Al₂O₃ ALD on Ti alloy contributed to improve the mechanical properties of the synthesized implants (FIGs. 6A-6B) .

EXAMPLE 4

Fabrication of 3D-printed and metal-wire embedded dental clear aligner/retainer

The dental resin-based biocomposites were synthesized by mixing 2-5 wt%of nano-hydroxyapatites (n-HAPs, diameter: 50-200 nm) , 2-5 wt% nanodiamonds (diameter: 10-100 nm) , 5-20 wt. %of silica nano-particulates (diameter: 50-700 nm) with a photocurable dental monomer.

One or more thin metal layers (Ti, Ti-alloy, CoCr, stainless steel) with a thickness of 0.10-0.50 mm were fabricated using metallic selective laser sintering 3D printing, and they were treated under TiO₂ atomic layer deposition and silane coupling agent grafting to increase the bonding with the biocomposite matrix. Finally, a hierarchical porous structure was fabricated through polymeric stereolithography 3D printing. Additionally, cold plasma surface etching, which promotes bone growth and adhesion, can be applied onto the surface of the dental clear aligner/retainer.

EXAMPLE 5

Material properties testing

To develop composite materials with optimal characteristics, material properties such as interfacial debonding, strength, modulus, and toughness needed to be determined accurately and reliably. The present invention developed state-of-the-art micro-mechanical measurement techniques, computational FEM analysis, and molecular dynamics simulations to determine the materials properties to derive the relationships with the desired bioactivity, mechanical properties, and performance of the developed novel materials.

Referring to FIG. 7, the strain relaxation test results of two samples were depicted: one was fabricated with pure clear resin without a metal wire, and the other had a metal wire embedded in the resin. When a metal wire was embedded, it exhibited high stiffness and a low velocity of decay during 21 repeated cyclic loadings.

In another embodiment, a mandibular implant embedded with Ti and featuring a microporous inner structure was fabricated using newly developed metal-polymer 3D printing technology with nHAP-reinforced composites. Thin metal plates and a partial mandible implant assembly were precisely designed using a 3D CAD program (SolidWorks) and then produced using metal and polymer 3D printers. Referring to FIG. 8, cone beam computed tomography (CBCT) was used to observe the internal structure of the embedded Ti alloy plates and the bone-like porous structure, confirming their successful construction as designed. To enhance the interfacial properties between the Ti alloy and resin composites, the 3D-printed metal layers underwent mechanical and chemical polishing processes. Subsequently, they were treated with atomic layer deposition (ALD) using Al₂O₃. Finally, a silane coupling agent was grafted onto the outer surface, enhancing the interfacial bonding strength and mechanical performance of metal-embedded implants/scaffolds. For instance, the increased interfacial shear strength (IFSS) value was increased by up to 50%with Al₂O₃ layer deposition.

This technique has the potential to transition high-strength lightweight medical implants/scaffolds from concept to clinical applications over the long term (5-10 years) .

EXAMPLE 6

Animal testing

Furthermore, the present invention also conducted in vitro evaluations of osteogenic cell adhesion, cytocompatibility, proliferation, viability, and morphology, as well as in vivo osteogenic analysis of the 3D-printed implants using a rat bone defect model after 4-and 12-week observation periods to provide a biological and mechanical framework for cell growth and differentiation.

With the increasing filler fraction, the mean values of the compressive strength and modulus of the 3D-printed composites increased by 16.5%and 56.4%, respectively. The cold plasma treatment of the biocomposites resulted in a nanotextured surface, changing the hydrophobic surface to a hydrophilic one and transforming the surface characteristics from hydrophobic to hydrophilic due to the exposure of nHAPs on the outer surface. They exhibited improved cell adhesion and proliferation capacities for MC3T3-E1 mice pre-osteoblasts after 1, 3, and 5 days of seeding. In vivo animal studies using rats also demonstrated good bone regeneration performance (FIG. 9) .

In summary, the present invention discloses the successful fabrication of 3D-printed mandible implants and spinal fusion cages using multifunctional biocomposites and newly developed 3D printing technology. These implants exhibit lightweight, high-strength, and metal-contact-free characteristics (FIG. 10) . The application of Al₂O₃ ALD on 3D-printed Ti alloy plates significantly enhances interfacial (up to 50%) and mechanical properties, effectively preventing catastrophic failure under high compressive loads.

Industrial Applicability

The present invention has the potential to create significant market share in the prosthetic industry including spinal fusion, maxillomandibular reconstruction, and orthodontic appliances.

DEFINITION

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the 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, the singular forms “a, ” “an, ” and “the” are intended to include the plural forms as well as the singular forms, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising, ” when used in this specification, specify the presence of 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.

Reference throughout this specification to “one embodiment” , “an embodiment” , “an example” , “an implementation, ” “adisclosed aspect” , or “an aspect” means 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 appearances of the phrase “in one embodiment” , “in one example” , “in one aspect” , “in an implementation” , or “in an embodiment” , in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in various disclosed embodiments.

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 Centigrade, and pressure is at or near atmospheric pressure. Other than in the operating examples, or where otherwise indicated, all numbers, values and/or expressions referring to quantities of ingredients, reaction conditions, etc., used in the specification and claims are to be understood as modified in all instances by the term "about" .

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

With respect to any figure or numerical range for a given characteristic, a figure or a parameter from one range may be combined with another figure or a parameter from a different range for the same characteristic to generate a numerical range.

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

While the invention is explained in relation to certain embodiments, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification. Therefore, it is to be understood that the invention disclosed herein is intended to cover such modifications as fall within the scope of the appended claims.

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

The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, thereby enabling others skilled in the art to understand the invention for various embodiments and with various modifications that are suited to the particular use contemplated.

References: The disclosures of the following references are incorporated 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

A three-dimensional (3D) printing method for making a metal-embedded medical implant, comprising:

performing a first computerized tomography (CT) scanning of one or more teeth and mouth areas of a test subject for designing a customized medical implant;

conducting a design of the customized medical implant based on results of the first CT scanning;

conducting a design of metal structures to be embedded in the customized medical implant;

performing data segmentation and 3D printing of the metal structures;

converting data into a stereolithography (STL) data format;

performing 3D printing of the customized medical implant embedded with the metal structures;

performing a second CT scanning of the customized medical implant for analyzing internal structures of the customized medical implant; and

performing surface modifications on the customized medical implant based on results of the second CT scanning.
The method of claim 1, wherein the first CT scanning is a CT scanning of a mandible of the test subject.
The method of claim 1, wherein the design of the customized medical implant is implemented by a three-dimensional (3D) computer-aided design (CAD) method.
The method of claim 1, wherein the metal structures comprise metal plates, metal wires, or metal lattice structures.
The method of claim 1, wherein step of 3D printing of the customized medical implant embedded with the metal structures is implemented by a polymeric stereolithography 3D printing method.
The method of claim 1, wherein step of 3D printing of the metal structures is implemented by a metallic selective laser sintering (SLS) 3D printing method.
The method of claim 1, wherein the customized medical implant has a hierarchical porous structure.
The method of claim 1, wherein the customized medical implant comprises a prosthetic implant, a spinal fusion cage, a bone scaffold, a dental aligner, and a retainer.
The method of claim 1, wherein the metal structures are made of either titanium (Ti) , Ti alloy, cobalt-chromium (CoCr) , stainless steel, or a combination thereof.
The method of claim 1, wherein the surface modification is implemented by depositing an atomic layer on the surface of the customized medical implant.
The method of claim 10, wherein the atomic layer is selected from the group consisting of Al₂O₃, MgO, ZrO₂, and TiO₂.
The method of claim 1, wherein the surface modification is achieved through silane coupling agent grafting processes.
A three-dimensional printing method for making a metal-embedded medical device, comprising:

synthesizing a biocomposite matrix;

performing metallic selective laser sintering (SLS) 3D printing to embed metal structures in the biocomposite matrix to obtain the metal-embedded medical device; and

performing surface modifications on the metal-embedded medical device for increased bonding of the metal structures with the biocomposite matrix.
The method of claim 13, further comprising performing cold plasma surface etching onto surfaces of the metal-embedded medical devices.
The method of claim 13, wherein step of synthesizing a biocomposite matrix comprises mixing a photocurable monomer, at least one nano-filler, and wherein the biocomposite matrix comprises 50-90 wt%of the photocurable monomer and 10-30 wt%of the at least one nano-filler.
The method of claim 15, wherein the photocurable monomer is selected from the group consisting of methacrylate, urethane-dimethacrylate, and triethylene glycol dimethacrylate.
The method of claim 15, wherein the biocomposite matrix further comprises one or more silica nano-particulates.
The method of claim 17, wherein the one or more silica nano-particulates have diameters in a range of 50-700 nm.
The method of claim 15, wherein the at least one nano-filler comprises a nanohydroxyapatite, or a nanodiamond.
The method of claim 19, wherein the nanohydroxyapatites has a diameter of 50-200 nm.
The method of claim 19, wherein the nanodiamond has a diameter of 10-100 nm.
The method of claim 13, wherein the metal structures are made of either titanium (Ti) , Ti alloy, cobalt-chromium (CoCr) , or stainless steel.
The method of claim 13, wherein the surface modification is implemented by depositing an atomic layer on the surface of the customized medical implant.
The method of claim 23, wherein the atomic layer is selected from the group consisting of Al₂O₃, MgO, ZrO₂, and TiO₂.
The method of claim 13, wherein the surface modification is achieved through silane coupling agent grafting processes.
The method of claim 13, wherein the metal structures comprise metal plates with a thickness in a range of 0.10-1.0 mm.
The method of claim 13, wherein an interfacial bonding force between the metal structures and the biocomposite matrix is enhanced through the application of Al₂O₃ atomic layer deposition (ALD) .
A customized medical implant, comprising a biocomposite matrix embedded with metal structures, wherein the biocomposite matrix comprises a photocurable monomer, at least one nano-filler, and wherein the biocomposite matrix comprises 50-90 wt%of the photocurable monomer and 10-30 wt%of the at least one nano-filler.
The customized medical implant of claim 28, wherein the biocomposite matrix further comprises one or more silica nano-particulates.
The customized medical implant of claim 28, wherein the metal structures comprise metal plates, metal wires, or metal lattice structures.
The customized medical implant of claim 30, wherein the metal structures are made of either titanium (Ti) , Ti alloy, cobalt-chromium (CoCr) , or stainless steel.
The customized medical implant of claim 28, wherein the photocurable monomer is selected from the group consisting of methacrylate, urethane-dimethacrylate, and triethylene glycol dimethacrylate.
The customized medical implant of claim 28, wherein the at least one nano-filler comprises a nanohydroxyapatite, nanodiamond, silica glass particles, glass fibers, ceramic, metal particles, halloysite nanotubes, or pre-polymerized polymer particles.
The customized medical implant of claim 33, wherein the nanohydroxyapatites has a diameter of 50-200 nm.
The customized medical implant of claim 33, wherein the nanodiamond has a diameter of 10-100 nm.
The customized medical implant of claim 28, wherein the biocomposite matrix further comprises 0.1-3 wt%of photoinitiator.
The customized medical implant of claim 36, wherein the photoinitiator comprises 2, 4, 6-trimethylbenzoyldiphenyl phosphine oxide, phenylbis (2, 4, 6-trimethylbenzoyl) -phosphine oxide, 2-hidroxy-1- [4- (2-hidroxyethoxy) phenyl] -2-methyl-1-propanone, 1-hidroxycyclohexyl-1-phenyl ketone, or 2, 2-dimethoxy-2-phenylacetophenone.