3D Printable Biocomposites

Abstract

Disclosed herein is a biocomposite that can be formed from a composition that includes at least one monomer suitable for photopolymerization, a photoinitiator, and a filler composition that includes at least one inorganic compound. The biocomposite can be formed by a process that includes 3D printing. Also disclosed herein are applicability of the composition and biocomposite, including any treatment of bone defects or repair of a portion of bone in a subject.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to Australian Provisional Patent Application No. 2021903920, filed December 3, 2021, the contents of which are incorporated herein by reference in their entirety.

[0002] The present disclosure relates to a biocomposite that can be formed from a composition that includes at least one monomer suitable for photopolymerization, a photoinitiator, and a filler composition that includes at least one inorganic compound. The biocomposite can be formed by a process that includes 3D printing. The biocomposite can also be used to treat bone defects or repair a portion of a bone in a subject. [Background technology]

[0003] The global spinal implants and devices market was worth US$9.5 billion in 2020 and is expected to reach US$13.8 billion by 2025 (Markets and Markets Research Private, 2020). Both polyetheretherketone (PEEK) and titanium interbody fusion cages are by far the most used stand-alone devices in spinal fusion procedures. With the use of advanced 3D surgical imaging systems, the introduction of 3D printed implants has become an emerging trend in the global spinal implant market, and the spine field continues to expand its applications for three-dimensional (3D) printing.

[0004] Among global spinal device companies, Orthofix has developed the Construx Mini Ti Spacer System, a 3D printed titanium cervical interbody designed with a functional gradient porous structure, which received FDA clearance in April 2021. Medtronic markets its titanium 3D printing platform, TiONIC Technology, which allows for more complex designs and integrated surface technology for spinal surgery implants. The company has also introduced Pure Titanium Coating (PCT™) on PEEK implant surfaces, combining the benefits of both PEEK and titanium in a single interbody application. Johnson & Johnson medical devices, Zimmer Biomet, Nexxt Spine, and Stryker are also developing 3D printed titanium implants. HAPPE Spine has patented a dense and porous dual design of hydroxyapatite (HAP) and PEEK composites by anatomically mimicking cortical and cancellous bone.

[0005] The integration of functionalized materials with optimized architectural structures is of great importance in the development of orthopedic implants, such as interbody fusion cages (or spacers).

[0006] Due to their good mechanical properties and biocompatibility, titanium (or titanium alloys) and PEEK are commonly chosen for medical implants. Although conventional implants and spinal fusion cages offer adequate load-bearing capacity, their surfaces are generally inert or have limited ability to support osteointegration with the surrounding bone.

[0007] As a result, the weakening of the interfacial bone bonding can lead to advanced implant destruction causing bone instability, subsidence, implant migration, and severe pain or discomfort, which may result in a second surgery. Although many surface coating techniques have been developed using osteoconductive / osteoinductive agents such as calcium phosphate in the implant structure to improve the bone / implant response, there is a potential risk of coating failure due to cracking and delamination resulting from poor bonding between two different materials, which may lead to implant loosening and result in catastrophic implant failure.

[0008] Titanium implant surfaces can stimulate bone growth. However, they are sometimes insufficient because they cause large radiodensities and magnetic field distortions at the tissue-metal interface in X-ray imaging, computed tomography, and magnetic resonance imaging. Secondary electrons induced from the metal surface by X-rays can contribute to DNA damage or DNA mutations near the metal implant.

[0009] Both titanium and PEEK cages met at similar fixation rates, but titanium cages (metal group) caused an increased rate of subsidence or the implant gradually penetrated the endplate surface due to its high elastic modulus and stress shielding effect. On the other hand, PEEK cages (polymer group) are much more flexible compared to titanium because their elastic modulus is almost equal to that of bone in the range of those in cortical and cancellous bone. However, PEEK is hydrophobic and biologically inert, which leads to poor integration with surrounding tissues after implantation. In addition, due to the semi-crystalline nature and high melting temperature of PEEK, PEEK is highly sensitive to pre- / post-3D printing processing conditions, which leads to high variability in the mechanical performance of PEEK structures. This has limited the adoption of 3D printing of PEEK in medical applications where high quality assurance and reproducibility are required.

[0010] New materials and / or methods are needed to overcome these limitations that arise from many conventional implants.

[0011] Any discussion of documents, acts, materials, devices, articles, or the like contained in this specification should not be construed as an admission that any or all of those items form part of the prior art base or were common general knowledge in the art relevant to this disclosure as they existed prior to the priority date of each claim of this application. Summary of the Invention

[0012] at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition comprising at least one inorganic compound; Disclosed herein is a biocomposite formed from a composition comprising:

[0013] Disclosed herein is a method for synthesizing a biocomposite, the method comprising: - at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition comprising at least one inorganic compound; providing a composition comprising: - 3D printing said biocomposite; Also disclosed herein is the above method, comprising:

[0014] An exemplary schematic diagram of the proposed method for developing a multifunctional spinal fusion cage is shown in Figure 1. In Figure 1, several steps are illustrated: A-multifunctional resin system; B-3D printing; C-3D printing implant; D-3D printing spinal cage (layered and porous); E-surface texturing; and F-smart fusion cage / implant.

[0015] Disclosed herein are biocomposites formed from the methods disclosed herein.

[0016] Also disclosed herein is a method of treating or repairing bone, e.g., damaged or defective bone, in a subject, said method comprising administering to a subject in need thereof a biocomposite disclosed herein.

[0017] Also disclosed herein is a biocomposite as defined herein for use in the treatment or repair of bone, eg, damaged or defective bone, in a subject.

[0018] In forming the biocomposite disclosed herein: at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition, Also disclosed herein is the use of a composition comprising:

[0019] Also disclosed herein is the use of the biocomposites disclosed herein in the formation of articles for treating or repairing bone in a subject.

[0020] The biocomposites disclosed herein extend the application of orthopedic implants / cages to "metal-free" medical implants that require one or more of the following biological properties: good radiopacity, high mechanical strength, and osteoconductivity, osteoinductivity, and / or biocompatibility. Exemplary collapse strengths and compressive moduli of the biocomposites defined herein and PEEK are shown in FIG. 4.

[0021] The presence of materials such as nano-hydroxyapatite (n-HAP), silica nanoparticles, and / or short micro-sized glass fibers in the composite can improve the mechanical and / or biological performance of the material in vivo, among other potential benefits.

[0022] When biocomposites are formed as 3D micro / nano hierarchical porous structures of implants (which can be fabricated by stereolithography (SLA) 3D printing and low-temperature plasma surface treatment), bone growth and adhesion can be promoted. 3D printed microporous structures within the implant can potentially provide a larger contact area at the interface between the implant and new bone, and long-term stability with bone ingrowth and mechanical interlocking. Nanotextured surfaces of implants, such as by treatment with cold argon-oxygen plasma treatment, can also create multifunctional hierarchical topographies with surface-exposed n-HAP that improve surface "hydrophilicity," osteointegration, and / or new bone growth.

[0023] It will be understood that embodiments of each aspect of the disclosure are equally applicable to each other aspect.

[0024] It will be understood that various embodiments of the present disclosure may be utilized, and certain examples will now be described with reference to the following drawings, in which: [Brief description of the drawings]

[0025] [Figure 1] FIG. 1 is a schematic diagram of the proposed development method of a multi-functional spinal fusion cage. [Diagram 2] An exemplary implant: 1 is the body of a 3D printed multi-scale recombinant orthopedic implant; 2 is a multi-layer structure; and 3 is a microporous structure. [Diagram 3] 1 is an image of nano-hydroxyapatite. [Figure 4] 13 shows the collapse strength and compressive modulus of the biocomposites described herein and PEEK. [Diagram 5] Nanotexturing of biocomposite surfaces using an atmospheric low-temperature plasma etching process showing hydrophilic / hydrophobic changes. [Figure 6]Nanotexturing of biocomposite surfaces using an atmospheric low-temperature plasma etching process. [Figure 7] Surface etching thickness and plasma etching time for n-HAP reinforced biocomposites. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] General Definitions and Terminology With respect to the definitions provided herein, unless otherwise stated or implied from the context, the defined terms and phrases include the meanings provided. In addition, unless otherwise stated or apparent from the context, the following terms and phrases do not exclude the meaning that the term or phrase would have by one of ordinary skill in the relevant art. The definitions are provided to facilitate the description of particular embodiments and are not intended to limit the claimed invention, since the scope of the invention is limited only by the claims.

[0027] The term "creeping replacement" will be understood to mean the process by which a biocomposite graft or implant is gradually replaced by living tissue or gradually incorporated into the subject's body. The subject's cells fill the porous surfaces of the biocomposite, and in particular the inorganic structures composed of hydroxyapatite, tricalcium phosphate, collagen, etc., into a new physical and physiological bone structure, essentially transforming the biocomposite, or a portion thereof, into new bone.

[0028] All publications discussed and / or referenced herein are incorporated herein in their entirety unless otherwise noted.

[0029] Unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. Throughout this disclosure, unless specifically stated otherwise or the context requires otherwise, references to a single step, single composition, group of steps, or group of compositions shall be construed to include one and more (i.e., one or more) of those steps, compositions, steps, or groups of compositions. Thus, as used herein, the singular forms "a," "an," and "the" include plural aspects unless the context indicates otherwise. For example, reference to "a" includes two or more in addition to the singular; reference to "an" includes two or more in addition to the singular; reference to "the" includes two or more in addition to the singular, etc.

[0030] Those skilled in the art will understand that the disclosure herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the disclosure herein includes all such variations and modifications. The disclosure also includes all of the examples, steps, features, methods, compositions, formulations, and processes referred to or shown herein, individually or collectively, and further includes any two or more of those steps or features, and all combinations of any two or more of those steps or features.

[0031] The term "and / or," e.g., "X and / or Y," is understood to mean either "X and Y" or "X or Y," and is deemed to provide clear support for both meanings or either meaning.

[0032] Unless otherwise indicated, the terms "first," "second," and the like are used herein merely as labels, and are not intended to impose any order, position, or hierarchical requirements on the items to which they refer. Moreover, a reference to a "second" item does not require or exclude the presence of a numerically lower item (e.g., the "first" item) and / or a numerically higher item (e.g., the "third" item).

[0033] As used herein, the phrase "at least one of" or "one or more" when used with a list of items means that one or more different combinations of the listed items can be used and only one of the items in the list may be required. The items can be specific objects, things, or categories. In other words, "at least one of" means that any combination of items or any number of items from the list can be used, but not all of the items in the list may be required. For example, "at least one of item A, item B, and item C" may mean item A; item A and item B; item B; item A, item B, and item C; or item B and item C. In some cases, "at least one of item A, item B, and item C" may mean, for example, but not limited to, two items A, one item B, and ten items C; four items B and seven items C; or some other suitable combination.

[0034] It should be understood that certain features that are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination.

[0035] Throughout this specification, various aspects and components of the disclosure may be presented in the form of a range. The range format is included for convenience and should not be construed as an inflexible limitation on the scope of the disclosure. Thus, the description of a range should be considered to have specifically disclosed all possible subranges and individual numerical values ​​within that range, unless otherwise expressly stated. For example, the description of a range such as 1-5 should be considered to have specifically disclosed subranges such as 1-3, 1-4, 1-5, 2-4, 2-5, 3-5, and individual and partial numbers within the described range, such as 1, 2, 3, 4, and 4.5, unless an integer is required or is implicit from the context. This applies regardless of the breadth of the disclosed range. If specific values ​​are required, they are indicated in the specification.

[0036] Throughout this specification the word "comprise" or variations such as "comprises" or "comprising" will be understood to be meant to include a stated element, integer or step, or group of elements, integers or steps, but not to exclude any other element, integer or step, or group of elements, integers or steps.

[0037] Throughout this specification, the term "consisting essentially of" is intended to exclude elements that materially affect the properties of the claimed composition, method, or process.

[0038] The terms "comprising," "comprise," and "comprises," as used herein, are intended to be optionally interchangeable, respectively, in each instance, with the terms "consisting essentially of," "consists essentially of," "consist of," and "consists of," respectively.

[0039] In this specification, unless otherwise specified, the term "about" encompasses a tolerance of 10% for any value or values ​​associated with that term.

[0040] As used herein, "weight %" may be abbreviated as "wt%" or "wt.%".

[0041] The recipient of the described biocomposite is referred to herein by the interchangeable terms "patient," "recipient," "individual," and "subject." These four terms are used interchangeably and refer to any human or animal (unless otherwise specified) as defined herein.

[0042] The recipient of the biocomposite described herein can be a human of any gender. Alternatively, the recipient of the biocomposite described herein, e.g., a patient or subject, can also be a non-human animal. "Non-human animals" or "non-human animals" refers to the animal kingdom excluding humans, including vertebrates and invertebrates, both male and female, and includes warm-blooded animals, including mammals (including but not limited to primates, dogs, cats, cows, pigs, sheep, goats, rats, guinea pigs, horses, or other bovine, ovine, equine, canine, feline, rodent, or murine species), birds, insects, reptiles, fish, and amphibians.

[0043] As used herein, the term "active agent" refers to any agent capable of imparting a therapeutic, prophylactic, or other biological effect in a subject or patient. The active agent can also be a diagnostic agent or for enhancing healing at an in vivo site.

[0044] Unless expressly defined or clear from context, the term "pharmacologically active agent" or "active agent" as used herein can mean any protein, peptide, sugar, saccharide, nucleoside, inorganic compound, lipid, nucleic acid, small synthetic chemical compound, or organic compound that appreciably alters or appreciably affects a biological system into which it is introduced.

[0045] Biocomposite at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition comprising at least one inorganic compound; Disclosed herein is a biocomposite formed from a composition comprising:

[0046] A method for the synthesis of a biocomposite as defined herein, said method comprising the steps of: · At least one monomer suitable for photopolymerization; A photoinitiator, A filler composition, providing a composition comprising: - 3D printing said biocomposite; Also disclosed herein is the above method, comprising:

[0047] Also disclosed herein are biocomposites formed from the methods described herein.

[0048] In forming the biocomposite disclosed herein: at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition, Also disclosed herein is the use of a composition comprising:

[0049] In one embodiment, the biocomposite is formed by 3D printing. In some embodiments, the composition used in forming the biocomposite is fluid in its uncured state, allowing for 3D printing. Examples of suitable 3D printing methods include, but are not limited to, stereolithography (SLA), digital light processing (DLP), and mask stereolithography (MSLA). For 3D printing applications, the rheological properties can be tailored to the specific application, the specific monomers being utilized, and / or the presence of any additional additives.

[0050] In one embodiment, the biocomposite is formed by 3D printing using a light source to initiate photopolymerization of the materials or compositions used in forming the biocomposite. The light source may be an ultraviolet (UV) light source. The light source may have a wavelength in the range of about 280 nm to about 400 nm. For example, a wavelength of about or at least about 280 nm, 285 nm, 290 nm, 295 nm, 300 nm, 305 nm, 310 nm, 315 nm, 320 nm, 325 nm, 330 nm, 335 nm, 340 nm, 345 nm, 350 nm, 355 nm, 360 nm, 365 nm, 370 nm, 375 nm, 380 nm, 385 nm, 390 nm, 395 nm, or 400 nm.

[0051] In some embodiments, the biocomposite is light cured during the curing process. In some embodiments, the light curing is done with UV light. In some embodiments, the light curing is done with UV light. In some embodiments, the light curing process also sterilizes the biocomposite.

[0052] In one embodiment, the biocomposite can be adapted to be tailored for a particular application and / or for a particular target.

[0053] In one embodiment, a layer comprising one or more components is applied to at least a portion of the surface of the biocomposite. In some embodiments, the layer comprising one or more components comprises hydroxyapatite and glass fibers and / or glass particles. For example, a layer comprising hydroxyapatite is applied to at least a portion of one or more surfaces of the biocomposite. In one embodiment, the layer increases the bioactivity and mechanical properties of the surface layer. The layer can be applied by techniques known in the art and disclosed herein. For example, one or more of the layers can be applied using 3D printing techniques.

[0054] Once formed from the composition, the biocomposite can be used directly. Alternatively, at least one surface of the biocomposite can be optionally modified with a process selected from chemical etching, chemical coating (optionally chemical grafting), electrochemical grafting, laser etching, mechanical surface modification, plasma-assisted coating, plasma-assisted etching, physical vapor deposition (optionally using plasma or ion beam), chemical vapor deposition, atomic layer deposition, or mixtures thereof. Figures 5-7 show nanotexturing of a biocomposite surface using an atmospheric low-temperature plasma etching process showing hydrophilic / hydrophobic changes due to water droplets; nanotexturing of a biocomposite surface using an atmospheric low-temperature plasma etching process; and surface etch thickness versus plasma etching time for n-HAP reinforced biocomposite.

[0055] In one embodiment, at least one surface is etched to remove at least a portion of said surface, the etching comprising at least one of chemical etching, laser etching, plasma assisted etching, or mechanical etching. Any etching or modification to the biocomposite is performed at a temperature below the glass transition temperature (T gIn one embodiment, the etching (or another process disclosed herein) is carried out at a temperature in the range of about 20° C. to about 50° C., optionally in the range of about 25° C. to about 42° C. For example, a temperature of about, or at least about, 20° C., 25° C., 30° C., 35° C., 40° C., 45° C., or 50° C.

[0056] Herein, at least one surface of the biocomposite can be treated with plasma. For example, at least one surface can be etched with plasma to remove at least a portion of the surface. Any suitable plasma known in the art can be used to modify the biocomposite, for example, the plasma can be an argon-oxygen plasma, an oxygen plasma, a helium plasma, a nitrogen plasma, an argon plasma, or a combination thereof. In one embodiment, the plasma treatment is at a temperature ranging from about 20°C to about 40°C. For example, a temperature of about or at least about 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, or 40°C.

[0057] Optional modification of the biocomposite can change the chemical composition of at least one surface of the biocomposite. For example, plasma treatment can increase the concentration of at least one of hydroxyl groups, hydroxyl radicals, and / or reactive oxygen species on at least a portion of the surface treated with the plasma. At least one surface of the biocomposite can become or exhibit antimicrobial properties after treatment, such as plasma treatment.

[0058] The biocomposite can be formulated to be visualized in vivo using low dose X-rays, hi one embodiment, the low dose X-rays are from about 52 kV x 1.9 mA to about 60 kV x 6.2 mA.

[0059] Monomers / Polymers The compositions used in forming the biocomposite preferably contain at least one monomer suitable for photopolymerization.

[0060] In one embodiment, the biocomposite is formed by photopolymerization, where the light source uses light (e.g., visible or UV light) to initiate and / or drive the polymerization reaction. In another embodiment, the photopolymerization is a radical polymerization.

[0061] In one embodiment, at least one monomer comprises a functional group available for radical polymerization. At least one monomer suitable for photopolymerization can comprise at least one photopolymerizable group selected from, but not limited to, alkenes, allyls, vinyl methacrylates, and / or acrylates. In one embodiment, at least one monomer comprises at least an alkene group. In one embodiment, at least one monomer comprises at least one acrylate group. In one embodiment, at least one monomer comprises at least one methacrylate group. In one embodiment, at least one monomer comprises at least one vinyl group. In one embodiment, at least one monomer comprises at least one allyl group.

[0062] The at least one monomer suitable for photopolymerization can be selected from, but is not limited to, bisphenol A glycidyl methacrylate (bisGMA), ethoxylated bisphenol A dimethacrylate (bisEMA), urethane dimethacrylate (UDMA), triethylene glycol dimethacrylate (TEGDMA), decanediol dimethacrylate (D3MA), 2-hydroxyethyl methacrylate (HEMA), and mixtures thereof. In some embodiments, the monomer suitable for photopolymerization can be selected from, but is not limited to, mono(meth)acrylate, di(meth)acrylate, tri(meth)acrylate, or dimethacrylate monomers (e.g., PEGMA, UDMA, HDDMA, and TEGDMA). In some embodiments, a mixture of UDMA and TEGDMA can be used. In some embodiments, the ratio of the mixture of UDMA and TEGDMA is 8:2.

[0063] The at least one monomer suitable for photopolymerization can optionally include at least one monomer containing multiple photopolymerizable groups selected from alkene, allyl, vinyl, methacrylate, and / or acrylate groups. The at least one monomer suitable for photopolymerization can include two or three methacrylate groups; two or three acrylate groups; two or three vinyl groups; or two or three allyl groups.

[0064] In some embodiments, at least one monomer, such as one or more of bisGMA, bisEMA, and / or UDMA, can be used as a “base.” In some embodiments, the at least one monomer can be a diluent or comonomer for one or more base monomers, such as TEGDMA, D3MA, and / or HEMA.

[0065] Photopolymerizable monomers can be set or cured by methods well known in the art, common methods including, for example, exposure to light (e.g., at 400-470 nm), oxidation by exposure to air, oxidation by exposure to a chemical oxidant present in the composition (usually mixed into the biocomposite just prior to use), or other forms of chemical reaction that initiate polymerization of the monomer.

[0066] In one embodiment, the biocomposite is crosslinked. Polymers formed from compositions that include at least one photopolymerizable monomer can be reacted to form interconnecting links between polymer chains (or as growth sites for copolymer chains), thereby crosslinking the final biocomposite. In alternative embodiments, the biocomposite may not be crosslinked, but may optionally be crosslinked.

[0067] One potential benefit of crosslinking is the resulting stability of the biocomposite. For example, crosslinking can reduce the solubility of the biocomposite compared to a similar composition that is not crosslinked. In addition, the crosslinked nature of the biocomposite can increase the chemical and / or biological resistance of the biocomposite. Crosslinking can also be used to provide a biocomposite with a surface that has increased heat resistance, reduced permeability, better abrasion resistance, and / or increased life span compared to a non-crosslinked biocomposite. Crosslinking can also increase desirable mechanical properties. Crosslinking can occur through hydrogen bonding. Hydrogen bonding can be either intramolecular bonds between moieties in a polymer segment or intermolecular bonds between one or more polymers. Physical crosslinking can be achieved through specific hydrogen bonding between polymer segments. Crosslinking can be introduced by using reagents or polymer segments that are branched and contain multiple branches or arms.

[0068] The acidic nature of the degradation products of common biodegradable materials, such as polylactic acid (PLA) and polyglycolic acid (PGA), can lead to unpredictable clinical outcomes, including scarring and narrowing at the interface with underlying tissue. In one embodiment, the biocomposite can be formulated to allow for creeping displacement, as opposed to being formulated to degrade in vivo and / or in vitro.

[0069] One or more of the monomers used in the formulation can be functionalized with a functional moiety selected from, but not limited to, hydroxyl groups, amine groups, thiol groups, carboxylic acid groups, carbonyl groups, halo groups, nitro groups, and mixtures thereof.

[0070] The one or more monomers can be present in a range of about 70 to about 95 wt% of the biocomposite, for example, the one or more monomers are present in an amount in a range of at least about 70 wt%, 72.5 wt%, 75 wt%, 77.5 wt%, 80 wt%, 82.5 wt%, 85 wt%, 87.5 wt%, 90 wt%, 92.5 wt%, or 95 wt% of the biocomposite.

[0071] Photoinitiators The compositions used in forming the biocomposites disclosed herein can include at least one photoinitiator.

[0072] Examples of photoinitiators include, but are not limited to, camphorquinone (CQ), bisacylphosphine oxide (BAPO), benzophenone (BP), N,N-dimethyl-p-toluidine (DMPT), ethyl-4-(dimethylamino)benzoate (EDMAB), and 2-4-6-trimethylbenzoyl-diphenyl-phosphine oxide (TPO), and mixtures thereof.

[0073] The concentration of the one or more photoinitiators will depend on several factors, including but not limited to, the type of photoinitiator, the monomer used, the concentration of the monomer, and / or the conditions (e.g., wavelength of light) utilized to generate the biocomposite.

[0074] Filler Composition The composition used in forming the biocomposite preferably includes a filler composition.

[0075] The filler composition can include one or more inorganic compounds. The filler composition can include at least one compound selected from hydroxyapatite, silica, such as silica fine particles, glass powder, glass fiber (optionally selected from E-type and S-type glass fiber), and mixtures thereof.

[0076] In one embodiment, the filler composition comprises hydroxyapatite, optionally in particulate form. An image of nano-hydroxyapatite is shown in FIG. 3. The particulate form can be selected from nanospheres, nanowhiskers, and / or nanorods. The hydroxyapatite, optionally in particulate form, can have a diameter of about 50 nm to about 200 nm. For example, the diameter can be about or at least about 50 nm, 55 nm, 60 nm, 65 nm, 70 nm, 75 nm, 80 nm, 85 nm, 90 nm, 95 nm, 100 nm, 105 nm, 110 nm, 115 nm, 120 nm, 125 nm, 130 nm, 135 nm, 140 nm, 145 nm, 150 nm, 155 nm, 160 nm, 165 nm, 170 nm, 175 nm, 180 nm, 185 nm, 190 nm, 195 nm, or 200 nm.

[0077] The filler composition can optionally include silica nanoparticles having a particle size of about 50 nm to about 700 nm. For example, the diameter can be about or at least about 50 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm, 500 nm, 550 nm, 600 nm, 650 nm, or 700 nm.

[0078] In some embodiments, the filler composition described herein can be any fiber or fibrous material, such as polymeric fibers or glass fibers. The filler composition can include glass fibers (optionally selected from E-type and S-type). In some embodiments, the filler composition can include bioactive glass fibers. In some embodiments, the filler composition can include high strength fibers, which are fibers having a tensile strength (measured by ASTM C1557-14) of greater than about 1 GPa and / or a flexural strength (using ISO 4049 3-point bending test) of greater than about 150 MPa.

[0079] In one embodiment, the glass fiber can be selected from aluminosilicate glass, barium glass, fluorine glass, quartz, opaque quartz glass, borosilicate glass, aluminofluorosilicate glass, high calcium glass, high magnesium glass, and mixtures thereof. In one embodiment, the glass is S-glass (structural glass). S-glass is an aluminosilicate glass that typically has negligible CaO content and high MgO content. S-glass is named "hard glass" due to its high tensile strength or modulus of elasticity. Examples of other types of glass, glass fiber, or fiberglass that can be used include E-glass (aluminoborosilicate glass with less than 1% w / w alkali oxide), A-glass (alkali-lime glass with little or no boron oxide), E-CR-glass (electrically / chemically resistant aluminoborosilicate glass with less than about 1% w / w alkali oxide), C-glass (alkali-lime glass with high boron oxide content), D-glass (borosilicate glass named for its low dielectric constant), and R-glass (aluminosilicate glass with negligible MgO and CaO content used as reinforcement and for high mechanical requirements). In one embodiment, the filler comprises glass powder. In another embodiment, the filler comprises a mortar composition of glass powder and concrete. In another embodiment, the mortar composition comprises about 10% to about 40% glass powder. In yet another embodiment, the filler comprises one or more of GP10, GP20, GP30, and / or GP40.

[0080] Glass fibers are commercially available with many different diameters. In one embodiment, obtaining a glass fiber with a desired aspect ratio typically involves selecting a glass fiber with the desired diameter and cutting the length appropriately.

[0081] The glass fibers can have a length of about 250 to about 350 μm, e.g., about or at least about 250 μm, 260 μm, 270 μm, 280 μm, 290 μm, 300 μm, 310 μm, 320 μm, 330 μm, 340 μm, or 350 μm. The glass fibers can have a diameter of about 5 to 10 μm, e.g., about or at least about 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, or 10 μm.

[0082] The filler composition can be present in a range of about 5 to about 30 wt% of the biocomposite, for example, in an amount of about, or at least about, 5 wt%, 7.5 wt%, 10 wt%, 12.5 wt%, 15 wt%, 17.5 wt%, 20 wt%, 22.5 wt%, 25 wt%, 27.5 wt%, or 30 wt%.

[0083] Other Additives At least one additive can be added before, during, or after the formation of the biocomposite. Examples of additional additives can be selected from plasticizers, dyes, pigments, modifiers, stabilizers, acid scavengers, compatibilizers, other polymers, or mixtures thereof. At least one additive can be a pharma- ceutical active compound.

[0084] Examples of suitable active agents include, but are not limited to, synthetic inorganic and organic compounds, drugs, proteins, peptides, polysaccharides and other sugars, lipids, and oligonucleotides, as well as DNA and RNA nucleic acid sequences. In one embodiment, the patient's cells can be used as the active agent. Additionally, peptides such as endothelial cell adhesive ligands, and proteins such as growth factors can also be incorporated into structures that are partially or entirely composed of the copolymers and / or compositions defined herein.

[0085] The biocomposite can include one or more growth factors. Broadly speaking, the one or more growth factors can be one or more substances that promote and / or control cell division and cell survival. For example, the one or more growth factors can be one or more of bone morphogenetic proteins (BMPs) or active fragments thereof, including, but not limited to, BMP2, BMP4, BMP6, BMP7, BMP9, BMP14, etc.; platelet-derived growth factors (PDGFs), e.g., PDGF AA, PDGF β ... BB; insulin-like growth factors (IGFs), e.g., IGF-I, IGF-II; fibroblast growth factors (FGFs), e.g., acidic FGF, basic FGF, β-endothelial growth factor, FGF4, FGF5, FGF6, FGF7, FGF8, and FGF9; transforming growth factors (TGFs), e.g., TGF-β1, TGF-β1.2, TGF-β3, TGF-β5; vascular endothelial growth factors (VEGFs), e.g., VEGF, epidermal growth factors (EGFs), e.g., EGF, amphibian growth factors (AMFs), Regulin, betacernin, heparin-binding EGF; interleukins, e.g., IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-11, IL-12, IL-13, IL-14; colony-stimulating factors (CSFs), e.g., CSF-G, CSF-GM, CSF-M, BMP cytokine proteins; nerve growth factor (NGF), stem cell factor, hepatocyte growth factor, and ciliary neurotrophic factor.

[0086] Polyols such as glycerol or sorbitol can be used, for example, as plasticizers to facilitate 3D printing.

[0087] Exemplary plasticizers include, but are not limited to, materials such as mineral oils, low molecular weight esters, glycol ethers, glycol ether esters of fatty acids, glycol ether esters of aliphatic diacids, glycol ether esters of cinnamic acid, polyethylene glycols, polypropylene glycols, ortho- and terephthalates, citrates, adipates, combinations, mixtures, etc. In certain embodiments, the plasticizer may be a glycol ether or an ester of a glycol ether with a fatty acid or aliphatic diacid or an ester of a glycol ether with cinnamic acid, diethylene glycol dibutyl ether, bis[2-(2-butoxyethoxy)ethyl]adipate, bis(2-butoxyethyl)sebacate, bis[2-(2-butoxypropoxy)propyl]adipate, bis[2-(2-butoxypropoxy)propyl]sebacate, bis(2-ethoxyethyl)adipate, bis(2-ethoxyethyl)sebacate, dipropylene glycol methyl ether, bis[2-(2-butoxyethoxy)ethyl]adipate, bis(2-but ...[2-(2-butoxypropoxy)propyl]adipate, bis[2-(2-butoxypropoxy)propyl]sebacate, bis(2-ethoxyethyl)adipate, bis(2-ethoxyethyl)sebacate, dipropylene glycol methyl ether, bis[2-(2-butoxyethoxy)ethyl]adipate, bis[2-(2-but In certain embodiments, the plasticizer may be used to improve the T of the resulting blend, such as dipropylene glycol methyl ether cinnamate, diethylene glycol butyl ether cinnamate, dipropylene glycol butyl ether acetate, tripropylene glycol methyl ether acetate, tripropylene glycol methyl ether butyrate, tripropylene glycol butyl ether acetate, diethylene glycol methyl ether acetate, diethylene glycol butyl ether acetate, triethylene glycol butyl ether acetate, triethylene glycol methyl ether acetate, combinations thereof, and the like. g can be reduced, placing the blend in the elastomeric region and flexible at room temperature (i.e., about 25° C.) The plasticizer can be present in an amount of about 1% to about 60%, for example, about 2% to about 45%, based on the total weight of the composition.

[0088] Exemplary modifiers include, but are not limited to, any reasonable modifier, such as an additional nucleating agent, such as boron nitride, or a crosslinking agent, such as a silane or a diisocyanate.

[0089] Exemplary stabilizers include, but are not limited to, any reasonable stabilizer, such as hindered amines, phenolic UV stabilizers, metal based heat stabilizers, butylated hydroxytoluene, and combinations thereof.

[0090] Exemplary acid scavengers include, but are not limited to, any reasonable acid scavenger, such as calcium or zinc stearate.

[0091] Exemplary compatibilizers include, but are not limited to, any reasonable compatibilizer, such as low to medium molecular weight polymers that act similarly to surfactants.

[0092] In certain embodiments, additives such as other polymers may be used to improve the T of the resulting composition and / or the final biocomposite. g can be lowered.

[0093] The biocomposite can be substantially free or free of transition metals. The metals can optionally be selected from titanium, iron, aluminum, magnesium, and copper, and alloys thereof.

[0094] The biocomposite can be substantially free or free of polyaryletherketones, which can be selected from polyetheretherketones (PEEK), polyetherketones (PEK), polyetheretherketones (PEEKK), polyetherketones (PEKK), or mixtures thereof.

[0095] Purpose Disclosed herein are biocomposites for the treatment or repair of bone in a subject.

[0096] Also disclosed herein is a method of treating or repairing bone defects in a subject, e.g., in the metaphysis, subchondral region, or diaphysis, or in any region of a flat bone or vertebra, e.g., as a result of low or high energy trauma, tumor, infection, said method comprising administering to a subject in need thereof a biocomposite as disclosed herein.

[0097] Also disclosed herein is the use of the biocomposites disclosed herein in the formation of articles for treating or repairing injured or defective bone in a subject.

[0098] Treatments or repairs can be selected from biocomposites in the shape of appropriate forms, e.g., screws, plates, rods, or molded to fill the defect, either in prefabricated modular forms or by printing after measuring the defect, e.g., with CT scan dicom data, allowing for personalized solutions to subject-specific bone-related pathologies.

[0099] The treatment or repair may involve one or more bones in the subject, for example, the bones may be fractures of the radial or ulnar shaft requiring a threaded plate, fractures of the tibial shaft requiring an intramedullary nail with interlocking screws, proximal or distal tibial plateau or tibial plafond fractures that may require bone graft augmentation with plates and screws, low impact fractures of vertebral bodies requiring polymethylmethacrylate injection, and distal radial fractures requiring plates, screws with or without bone graft augmentation. In non-fracture conditions, the current biocomposites or compositions disclosed herein may be applied in situations such as spinal fusion for degenerative disc disease and scoliosis correction. Herein, the biocomposites may be designed as one of many interbody devices, including those for anterior, lateral, posterior, transforaminal, and oblique interbody fusion in either the lumbar, thoracic, or cervical regions. Similarly, in non-fracture conditions, rods, screws, and plates may be designed using the biocomposites described herein.

[0100] As used herein, biocomposites can be formulated or manufactured into articles, which can be medical devices. Examples of medical devices include bone replacement endoprosthetic devices, bone fixation devices such as screws and plates and intramedullary rods, and bone augmentation devices such as cancellous bone fillers for bone voids and defects.

[0101] As used herein, the biocomposite and / or article can be in the form of an implant, which can include a partial component of a joint replacement prosthesis, such as the base of the femoral component of a hip arthroplasty device, or a portion of the tibial or femoral components of a knee arthroplasty device, as well as the biocomposites can be utilized in making parts of other joint replacements, such as shoulder, elbow, wrist, intervertebral disc, ankle, etc. An exemplary implant is shown in FIG.

[0102] As used herein, the biocomposite and / or article can be in the form of an orthopedic implant.

[0103] As used herein, the biocomposite and / or article may be in the form of an orthopedic screw, rod, or plate.

[0104] Imaging Disclosed herein are biocomposites that can be imaged with low doses of x-rays in a subject. In one embodiment, the low dose of x-rays is from about 52 kV x 1.9 mA to about 60 kV x 6.2 mA.

[0105] Low dose x-rays are not highly ionizing and may reduce the potential for DNA damage in a subject.

[0106] Exemplary embodiments The present disclosure can be described by one or more of the following exemplary embodiments.

[0107] 1. at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition comprising at least one inorganic compound; A biocomposite formed from a composition comprising:

[0108] 2. The biocomposite of exemplary embodiment 1, wherein said biocomposite is formed by 3D printing, optionally by stereolithography 3D printing, mask stereolithography 3D printing, or digital light processing.

[0109] 3. The biocomposite of exemplary embodiment 1 or exemplary embodiment 2, wherein the biocomposite is formed by 3D printing using an ultraviolet light source.

[0110] 4. The biocomposite of any one of exemplary embodiments 1 to 3, wherein the biocomposite is formed by 3D printing using a light source having a wavelength in the range of about 280 nm to about 400 nm.

[0111] 5. the biocomposite further comprises at least one of hydroxyapatite, n-hydroxyapatite, glass fibers, and / or glass particles, or - a layer comprising hydroxyapatite, n-hydroxyapatite, glass fibers and / or glass particles is applied to at least a portion of one or more surfaces of said biocomposite; The biocomposite of any one of the preceding exemplary embodiments.

[0112] 6. The biocomposite of exemplary embodiment 5, wherein the layer comprising hydroxyapatite is applied using 3D printing techniques.

[0113] 7. The biocomposite of any one of the preceding exemplary embodiments, wherein at least one surface of said biocomposite is modified by a process selected from chemical etching, chemical coating (optionally chemical grafting), electrochemical grafting, laser etching, mechanical surface modification, plasma-assisted coating, plasma-assisted etching, physical vapor deposition (optionally using a plasma or an ion beam), chemical vapor deposition, atomic layer deposition, or a mixture thereof.

[0114] 8. The biocomposite of any one of the preceding exemplary embodiments, wherein at least one surface of said biocomposite is etched to remove at least a portion of said surface, said etching optionally comprising at least one technique selected from chemical etching, laser etching, plasma assisted etching, mechanical etching, or a mixture thereof.

[0115] 9. The biocomposite of exemplary embodiment 8, wherein the etching is performed at a temperature in the range of about 20°C to about 50°C, optionally in the range of about 25°C to about 42°C.

[0116] 10. The biocomposite of any one of the preceding exemplary embodiments, wherein at least one surface of said biocomposite is treated with plasma.

[0117] 11. The biocomposite of exemplary embodiment 10, wherein the plasma treatment increases the concentration of at least one of hydroxyl groups, hydroxyl radicals, and / or reactive oxygen species on at least a portion of the surface treated with the plasma.

[0118] 12. The biocomposite of any one of the preceding exemplary embodiments, wherein at least one surface is etched with a plasma to remove at least a portion of said surface.

[0119] 13. The biocomposite of any one of exemplary embodiments 10-12, wherein the plasma is selected from the group including low-temperature argon-oxygen plasma, oxygen plasma, helium plasma, nitrogen plasma, argon plasma, or a combination thereof.

[0120] 14. The biocomposite of any one of the preceding exemplary embodiments, wherein the filler comprises at least one inorganic compound selected from hydroxyapatite, silica (optionally, silica particulates), glass fibers (optionally selected from E-type and S-type glass fibers), bioactive glass fibers, and mixtures thereof.

[0121] 15. The biocomposite of any one of the preceding exemplary embodiments, wherein the filler comprises hydroxyapatite in a particulate form selected from nanospheres, nanowhiskers, and nanorods.

[0122] 16. The biocomposite of any one of the preceding exemplary embodiments, wherein the filler comprises hydroxyapatite in particulate form having a diameter of about 50 nm to about 200 nm.

[0123] 17. The biocomposite of any one of the preceding exemplary embodiments, wherein the filler comprises silica nanoparticles having a particle size of about 50 nm to about 700 nm.

[0124] 18. The above filler is a length of about 250 to about 350 μm, and / or Approximately 5 to 10 μm in diameter 2. The biocomposite of any one of the preceding claims, comprising glass fibres (optionally selected from E-type and S-type) having:

[0125] 19. The biocomposite of any one of the preceding exemplary embodiments, wherein the at least one monomer suitable for photopolymerization comprises at least one monomer comprising at least one photopolymerizable alkene, allyl, vinyl methacrylate, and / or acrylate group, and mixtures thereof.

[0126] 20. The biocomposite of any one of the preceding exemplary embodiments, wherein the at least one monomer suitable for photopolymerization optionally comprises at least one monomer comprising a plurality of photopolymerizable groups selected from alkene, allyl, vinyl, methacrylate, and / or acrylate groups.

[0127] 21. The biocomposite of any one of the preceding exemplary embodiments, wherein the at least one monomer suitable for photopolymerization comprises two or three methacrylate groups; two or three acrylate groups; two or three vinyl groups; or two or three allyl groups.

[0128] 22. The biocomposite of any one of the preceding exemplary embodiments, wherein the at least one monomer suitable for photopolymerization comprises at least one monomer selected from urethane dimethacrylate, 2-hydroxyethyl methacrylate, triethylene glycol dimethacrylate, bisphenol A glycidyl methacrylate, ethoxylated bisphenol A dimethacrylate, decanediol dimethacrylate, and mixtures thereof.

[0129] 23. The biocomposite of any one of the preceding exemplary embodiments, wherein the photoinitiator is selected from camphorquinone, ethyl 4-dimethylaminobenzoate, trimethylbenzoyl-diphenyl-phosphine oxide, and mixtures thereof.

[0130] 24. The biocomposite of any one of the preceding exemplary embodiments, wherein the one or more monomers are present in the range of about 70 to about 95 wt % of the biocomposite.

[0131] 25. The biocomposite of any one of the preceding exemplary embodiments, wherein the filler composition is present in a range of about 5 to about 30 wt% of the biocomposite.

[0132] 26. The biocomposite of any one of the preceding exemplary embodiments, further comprising at least one additive selected from plasticizers, dyes, pigments, modifiers, stabilizers, acid scavengers, compatibilizers, other polymers, pharma- ceutical active compounds, or mixtures thereof.

[0133] 27. The biocomposite of any one of the preceding exemplary embodiments, further comprising at least one additive which is a pharma- ceutical active compound.

[0134] 28. The biocomposite of any one of the preceding exemplary embodiments, optionally wherein the biocomposite is substantially free of, or free of, metals selected from titanium, iron, aluminum, magnesium, and copper, and alloys or mixtures thereof.

[0135] 29. The biocomposite of any one of the preceding exemplary embodiments, optionally substantially free of, or free of, polyaryletherketones selected from polyetheretherketone (PEEK), polyetherketone (PEK), polyetheretherketoneketone (PEEKK), polyetherketoneketone (PEKK), or mixtures thereof.

[0136] 30. The biocomposite of any one of the preceding exemplary embodiments, wherein said biocomposite is used to treat or repair damaged or defective bone in a subject.

[0137] 31. The biocomposite of exemplary embodiment 30, wherein said treatment or repair is the result of trauma, optionally low or high energy trauma; a tumor; and / or an infection.

[0138] 32. The biocomposite of exemplary embodiment 30 or exemplary embodiment 31, wherein the treatment or repair is in the metaphysis, subchondral region, or diaphysis, or any region in a flat bone or vertebra.

[0139] 33. The biocomposite of any one of the preceding exemplary embodiments, wherein said biocomposite is in the form of a medical device.

[0140] 34. The biocomposite of any one of the preceding exemplary embodiments, wherein the biocomposite is in the form of an implant.

[0141] 35. The biocomposite of any one of the preceding exemplary embodiments, wherein the biocomposite is in the form of an orthopedic implant.

[0142] 36. A method for synthesizing a biocomposite according to any one of exemplary embodiments 1 to 35, comprising: - at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition comprising at least one inorganic compound; providing a composition comprising: - 3D printing said biocomposite; The above method.

[0143] 37. The method of exemplary embodiment X, wherein the 3D printing is stereolithography 3D printing, mask stereolithography 3D printing, or digital light processing.

[0144] 38. The method of exemplary embodiment 36 or exemplary embodiment 37, wherein the 3D printing uses an ultraviolet light source.

[0145] 39. The method according to any one of exemplary embodiments 36 to 38, wherein the 3D printing uses a light source having a wavelength in the range of about 280 nm to about 400 nm.

[0146] 40. the composition further comprises at least one of hydroxyapatite, n-hydroxyapatite, glass fibers, and / or glass particles, or - the method comprises the step of applying a layer comprising hydroxyapatite to at least a portion of one or more surfaces of the biocomposite, The method according to any one of exemplary embodiments 36 to 39.

[0147] 41. The method of exemplary embodiment 40, wherein the layer comprising hydroxyapatite is applied using 3D printing technology.

[0148] 42. The method according to any one of exemplary embodiments 36 to 41, wherein at least one surface of the biocomposite is modified by a step comprising a process selected from chemical etching, chemical coating (optionally chemical grafting), electrochemical grafting, laser etching, mechanical surface modification, plasma-assisted coating, plasma-assisted etching, physical vapor deposition (optionally using a plasma or an ion beam), chemical vapor deposition, atomic layer deposition, or a mixture thereof.

[0149] 43. The method of any one of exemplary embodiments 36-42, wherein at least one surface of the biocomposite is etched to remove at least a portion of the surface, and the etching optionally comprises at least one technique selected from chemical etching, laser etching, plasma-assisted etching, mechanical etching, or a mixture thereof.

[0150] 44. The method of exemplary embodiment 43, wherein the etching is performed at a temperature in the range of about 20°C to about 50°C, optionally in the range of about 25°C to about 42°C.

[0151] 45. The method of any one of exemplary embodiments 36-44, wherein at least one surface of the biocomposite is treated with plasma.

[0152] 46. ​​The method of exemplary embodiment 45, wherein the plasma treatment increases the concentration of at least one of hydroxyl groups, hydroxyl radicals, and / or reactive oxygen species on at least a portion of the surface treated with the plasma.

[0153] 47. The method of any one of Exemplary embodiments 36-46, wherein at least one surface is etched with a plasma to remove at least a portion of said surface.

[0154] 48. The method according to any one of exemplary embodiments 36-47, wherein the plasma is selected from the group including low-temperature argon-oxygen plasma, oxygen plasma, helium plasma, nitrogen plasma, argon plasma, or a combination thereof.

[0155] 49. A biocomposite formed from the method described in any one of exemplary embodiments 36-48.

[0156] 50. A method for treating or repairing damaged or missing bone in a subject, said method comprising administering to a subject in need thereof a biocomposite described in any one of exemplary embodiments 1-35.

[0157] 51. The method of exemplary embodiment 50, wherein said treatment or repair is the result of trauma, optionally low or high energy trauma; a tumor; and / or an infection.

[0158] 52. The method of exemplary embodiment 50 or exemplary embodiment 51, wherein the treatment or repair is in the metaphysis, subchondral region, or diaphysis, or any region in a flat bone or vertebra.

[0159] 53. In the formation of the biocomposite according to any one of exemplary embodiments 1 to 35, at least one monomer suitable for photopolymerization, A photoinitiator, a filler composition, Use of a composition comprising:

[0160] 54. Use of a biocomposite according to any one of exemplary embodiments 1 to 35 in the formation of an article for the treatment or repair of bone in a subject.

[0161] 55. The use according to exemplary embodiment 54, wherein said treatment or repair is the result of trauma, optionally low or high energy trauma; a tumor; and / or an infection.

[0162] 56. The use of exemplary embodiment 54 or exemplary embodiment 55, wherein the treatment or repair is in the metaphysis, subchondral region, or diaphysis, or in any region of a flat bone or vertebra.

[0163] 57. The use of any one of exemplary embodiments 54 to 56, wherein the article is a medical device.

[0164] 58. The use according to any one of exemplary embodiments 54 to 57, wherein the article is an implant.

[0165] 59. The use according to any one of exemplary embodiments 54 to 57, wherein the article is an orthopedic implant.

[0166] Working Example The present disclosure will now be described with reference to the following non-limiting examples and with reference to the accompanying drawings.

[0167] Example 1 The development process of a multifunctional spinal fusion cage was designed and implemented using stereolithography 3D printing and atmospheric low-temperature plasma etching techniques, as shown in Figure 1. Pure dental resin (PDR) and composite materials were used in the preparation of the fusion cage (Figure 2). Nano-hydroxyapatite (n-HAP, spherical, D<200nm) and strontium-doped glass particles (D<700nm) were mixed as filler materials to impart mechanical, physical, and biological functions to the biocomposite. The n-HAP powder and its high-magnification scanning electron microscope (SEM) image are shown in Figure 3.

[0168] The PDR consisted of: A mixture of 1,6-bis(methacryloxy-2-ethoxycarbonylamino)-2,4,4-trimethylhexane (UDMA, 80 wt.%) and triethylene glycol dimethacrylate (TEGDMA, 20 wt.%); · Camphorquinone (CQ, 0.2 wt.%) - photoinitiator; Ethyl-4-dimethylaminobenzoate (EDMAB, 0.5 wt.%) - photoinitiator; and ·Butylated hydroxytoluene (BHT, 0.05 wt.%) - inhibitor.

[0169] The composite group consisted of: · GP10-PDR (90 wt.%) and strontium glass particles (10 wt.%); · GP10+nHAp02-PDR (88 wt.%), strontium glass particles (10 wt.%), and n-HAP (2 wt.%); · GP20-PDR (80 wt.%) and strontium glass particles (20 wt.%); · GP20+nHAp02-PDR (78 wt.%), strontium glass particles (20 wt.%), and n-HAP (2 wt.%).

[0170] A spinal fusion cage (Figure 2-Image 1) was designed in which the top and bottom of the cage are multi-layered (Figure 2-Image 2) to improve osteoinduction. A repeating microporous structure (Figure 2-Image 3) was also incorporated in the center of the cage to improve osteoconduction capability. The main body of the cage was 3D printed using PDR, and the functionalized top / bottom layers were printed using GP20+n-HAP composite. The 3D printed cage was rinsed in isopropyl alcohol in an ultrasonic bath and post-cured under UV and blue light at 60°C for 1 hour.

[0171] To evaluate the influence of fillers on mechanical properties, the compressive collapse strength and modulus of the printed specimens in each group were measured by compression testing. Cylindrical specimens (length: 10 mm, diameter: 7 mm) were prepared using 3D printing, and all 3D printed specimens were post-cured before testing. PDR was used as the control, and composite specimens were used as the experimental group. Polyetheretherketone (PEEK) was also tested for comparison. Figure 4 shows the compressive collapse strength and modulus, and statistically significant improvements are observed in both properties as the filler content increases in the composites compared to PDR. Compared to the measurements of PEEK, the composites have lower collapse strengths, but the modulus is higher than PEEK. All composites in this example show higher compressive properties than the control, and the two groups GP20 and GP20+nHAp02 show higher collapse strengths than PEEK, indicating the good suitability of the biocomposites of the present disclosure for use in high compressive stress areas.

[0172] To improve the surface performance of the biocomposite for bone regeneration and adhesion, atmospheric cold plasma was applied to the 3D printed implant structures. The plasma was generated in a dielectric barrier discharge plasma reactor and at atmospheric pressure. The temperature of the reactor was maintained at 23-25 ​​°C during the process. A mixture of argon and oxygen gas (9:1) was used as the treatment gas and was directly introduced into the discharge area through a side gas tube. The RF power was set to 50 W and the specimens were treated with a plasma-on time of up to 4 min. Surface observation of the plasma-etched composites was performed by SEM, and the hydrophilicity of the treated surfaces was investigated by water contact angle measurements, shown in Figure 5.

[0173] The phenomenon of surface plasma etching or texturing is related to the difference in etching rates between different materials in a composite, and high etching selectivity can be achieved in combinations of materials of different phases, such as polymer composites reinforced with inorganic filler materials. As the plasma treatment time increases, the polymer matrix is ​​highly etched, and the inorganic fillers, such as glass particles and n-HAP, remain and are exposed on the outer surface of the composite, as shown in Figure 6. The surface roughness increases at the nanoscale. Oxygen atoms also create hydroxyl groups (-OH groups) on the surface of the exposed filler materials, which changes the surface properties of the composite from hydrophobic to hydrophilic with an increase in surface energy. As a result, the water contact angle, an indicator of wettability, decreased from 115° to 50° after 2 minutes of plasma treatment (Figure 5). The etching rate of the composite (GP20+nHAp02) under argon-oxygen plasma was calculated as shown in Figure 7.

[0174] Based on the experimental results, it is estimated that the disclosed composite material with the presented surface modification process will improve cell attachment and proliferation in 3D printed fixation cages and implants.

[0175] It will be understood by those skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments without departing from the broad general scope of the present disclosure, and the present embodiments are therefore to be considered in all respects as illustrative and not restrictive.

Claims

1. at least one monomer suitable for photopolymerization, a photoinitiator; a filler composition comprising at least one inorganic compound; A biocomposite formed from a composition comprising:

2. (a) at least one surface of the biocomposite is modified by a process selected from chemical etching, chemical coating, chemical grafting, electrochemical grafting, laser etching, mechanical surface modification, plasma-assisted coating, plasma-assisted etching, physical vapor deposition, physical vapor deposition using a plasma or an ion beam, chemical vapor deposition, atomic layer deposition, and mixtures thereof; (b) etching at least one surface of the biocomposite to remove at least a portion of the surface; and / or 10. The biocomposite of claim 1, wherein (c) at least one surface of said biocomposite is treated with plasma. (a) at least one surface of the biocomposite is treated with plasma, and said treatment with plasma increases the concentration of at least one of hydroxyl groups, hydroxyl radicals, and reactive oxygen species on at least a portion of the plasma-treated surface; and / or 3. The biocomposite of claim 2, wherein (b) the plasma is selected from low-temperature argon-oxygen plasma, oxygen plasma, helium plasma, nitrogen plasma, argon plasma, and combinations thereof. (a) the biocomposite is formed by 3D printing using an ultraviolet light source; and / or (b) the biocomposite of claim 1, wherein the biocomposite is formed by 3D printing using a light source having a wavelength in the range of 280 nm to 400 nm.

5. - the biocomposite further comprises at least one of hydroxyapatite, n-hydroxyapatite, glass fibers, and / or glass particles, or a layer comprising hydroxyapatite, n-hydroxyapatite, glass fibers, and / or glass particles is applied to at least a portion of one or more surfaces of said biocomposite; The biocomposite of claim 1 .

6. The filler is (a) at least one inorganic compound selected from hydroxyapatite, silica, glass fiber, E-type glass fiber, S-type glass fiber, bioactive glass fiber, and mixtures thereof; (b) hydroxyapatite in particulate form selected from nanospheres, nanowhiskers, and nanorods; (c) hydroxyapatite in particulate form with a diameter of 50 nm to 200 nm; and / or (d) silica nanoparticles having a particle size of 50 nm to 700 nm; 10. The biocomposite of claim 1, comprising:

7. The at least one monomer suitable for photopolymerization is (a) at least one monomer containing at least one photopolymerizable alkene, allyl, vinyl methacrylate, and / or acrylate group, and mixtures thereof; (b) at least one monomer containing a plurality of photopolymerizable groups selected from alkene, allyl, vinyl, methacrylate, and / or acrylate groups; (c) two or three methacrylate groups, two or three acrylate groups, two or three vinyl groups, or two or three allyl groups; and / or (d) at least one monomer selected from urethane dimethacrylate, 2-hydroxyethyl methacrylate, triethylene glycol dimethacrylate, bisphenol A glycidyl methacrylate, ethoxylated bisphenol A dimethacrylate, decanediol dimethacrylate, and mixtures thereof; 10. The biocomposite of claim 1, comprising:

8. 10. The biocomposite of claim 1, further comprising at least one additive that is a pharmaceutically active compound.

9. The biocomposite comprises: (a) a medical device; and / or (b) an implant, preferably an orthopedic implant; 2. The biocomposite of claim 1, in the form of:

10. A method for synthesizing the biocomposite of any one of claims 1 to 9, comprising: － at least one monomer suitable for photopolymerization, a photoinitiator; a filler composition comprising at least one inorganic compound; providing a composition comprising: - 3D printing said biocomposite; The method comprising:

11. The 3D printing (a) stereolithography 3D printing, mask stereolithography 3D printing, or digital light processing; (b) using an ultraviolet light source; and / or The method of claim 10, wherein (c) a light source having a wavelength in the range of 280 nm to 400 nm is used.

12. the composition further comprises at least one of hydroxyapatite, n-hydroxyapatite, glass fibers, and / or glass particles, or 11. The method of claim 10, wherein the method further comprises applying a layer comprising hydroxyapatite to at least a portion of one or more surfaces of the biocomposite, and optionally, the layer comprising hydroxyapatite is applied using a 3D printing technique.

13. (a) At least one surface of the biocomposite is modified by a process selected from chemical etching, chemical coating, chemical grafting, electrochemical grafting, laser etching, mechanical surface modification, plasma-assisted coating, plasma-assisted etching, physical vapor deposition, physical vapor deposition using a plasma or an ion beam, chemical vapor deposition, atomic layer deposition, and mixtures thereof; (b) etching at least one surface of the biocomposite to remove at least a portion of the surface; and / or 11. The method of claim 10, wherein (c) etching at least one surface of said biocomposite to remove at least a portion of said surface, wherein said etching optionally comprises at least one technique selected from chemical etching, laser etching, plasma-assisted etching, mechanical etching, and mixtures thereof.

14. (a) at least one surface of the biocomposite is treated with plasma, and optionally, said treatment with plasma increases the concentration of at least one of hydroxyl groups, hydroxyl radicals, and / or reactive oxygen species in at least a portion of the plasma-treated surface; and / or 11. The method of claim 10, wherein (b) the plasma is selected from the group consisting of a low-temperature argon-oxygen plasma, an oxygen plasma, a helium plasma, a nitrogen plasma, an argon plasma, and combinations thereof.

15. A biocomposite according to any one of claims 1 to 9 for treating or repairing damaged or defective bone in a subject, preferably comprising: (a) the damaged or defective bone is the result of trauma, such as low- or high-energy trauma, tumor, and / or infection; and / or (b) the treatment or repair is in the metaphysis, subchondral region, or diaphysis, or any region in a flat bone or vertebra; The biocomposite.

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