Biocompatible printable poly-mma-egdma resins for orthopedic implants

Abstract

Systems and methods for additive-manufactured biocompatible implants. Many embodiments are directed to 30-printed biocompatible resins for fabricating custom implants. In several embodiments, the biocompatible resin is based on a ratio of biocompatible polymers. The biocompatible resin, in accordance with various embodiments, incorporates an antibacterial and / or antimicrobial agent, In some embodiments, the biocompatible resin incorporates a bioceramic to mimic native tissue.

Description

KPPB Ref: S94-12318.PCTBIOCOMPATIBLE PRINTABLE POLY-MMA-EGDMA RESINS FOR ORTHOPEDIC IMPLANTSSTATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0001] This invention was made with Government support under Contract No. W91 1 NF2310329 titled Materials Design: Long-range interactions in Non-equilibrium Self-assembly, awarded 9 / 1 / 2023 by Department of Defense (US ARMY), and Contract No. 2035663 titled Density-graded Auxetic Foams, granted by National Science Foundation (NSF). The Government has certain rights in this invention.CROSS-REFERENCES TO RELATED APPLICATIONS

[0002] The current application claims priority to Provisional Application No. 63 / 695,019, filed September 16, 2024, the disclosure of which is incorporated herein by reference.FIELD OF THE INVENTION

[0003] This disclosure generally refers to systems and methods for additive- manufactured implants used to treat musculoskeletal conditions. Several embodiments are directed to systems and methods for biocompatible 3D-printable resins.BACKGROUND

[0004] Additive manufacturing (AM) prints components from a resin or feedstock. AM processes include vat photopolymerization (VPP) printing from a liquid resin and fused filament fabrication (FFF) from a solid filament. In VPP printing, the part is divided into two-dimensional (2D) segments and projected through a thin layer of liquid resin, building the component layer-by-layer. Once the VPP process is done, the part is post-processed to remove uncured resin residue and terminate any open radicals. In FFF printing, a polymer filament is softened through a heated nozzle saddled on a gantry or robotic motion system. The molten filament is deposited on the print plate one road at a time to fabricate the part in a layer-by-layer manner. FFF printed parts require longer processingKPPB Ref: S94-12318.PCT time and exhibit rougher surface finish than VPP printed parts. Direct ink printing extrudes liquid resin on a heated plate to fabricate 2D geometries, such as wires and films.SUMMARY OF THE INVENTION

[0005] Systems and methods in accordance with some embodiments of the invention are directed to additive-manufactured implants used to treat musculoskeletal conditions. Several embodiments are directed to systems and methods for biocompatible 3D- printable resins.

[0006] In some embodiments, the techniques described herein relate to a biocompatible resin including: a base resin polymer including a methyl methacrylate (MMA) monomer, a crosslinking agent, and a poly(methyl methacrylate) (PMMA) powder.

[0007] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the crosslinking agent is an ethylene glycol dimethacrylate (EGDMA).

[0008] In some embodiments, the techniques described herein relate to a biocompatible resin, further including an antibacterial agent.

[0009] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the antibacterial agent is selected from at least one of: silver oxide, copper oxide, or cupronickel.

[0010] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the antibacterial agent has a weight percent less than 0.5 wt.%.

[0011] In some embodiments, the techniques described herein relate to a biocompatible resin, further including a bioceramic.

[0012] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the bioceramic is a hydroxyapatite.

[0013] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the bioceramic has a weight percent less than 0.5 wt.%.KPPB Ref: S94-12318.PCT

[0014] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein a ratio of the MMA monomers, the crosslinking agent, and the PMMA powder is 45.5:45.5:9 wt.%.

[0015] In some embodiments, the techniques described herein relate to a biocompatible resin, further including a photoinitiator.

[0016] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the photoinitiator is compatible with an exposure wavelength of an additive manufacturing process.

[0017] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the photoinitiator is a phenylbis (2,4,6-trimethylbenzoyl)- phosphine oxide (BAPO).

[0018] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the photoinitiator has a weight percent less than 0.5 wt.%.

[0019] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the biocompatible resin is configured for an additive manufacturing process.

[0020] In some embodiments, the techniques described herein relate to a biocompatible resin, wherein the additive manufacturing process is selected from at least one of: fused filament fabrication, vat photo polymerization, and direct ink writing.

[0021] In some embodiments, the techniques described herein relate to a method of synthesizing a biocompatible resin, including: forming a base resin including: mixing a methyl methacrylate (MMA) monomer and a crosslinking agent; and dissolving a poly(methyl methacrylate) (PMMA) powder in the MMA monomer and the crosslinking agent.

[0022] In some embodiments, the techniques described herein relate to a method, wherein the crosslinking agent is an ethylene glycol dimethacrylate (EGDMA).

[0023] In some embodiments, the techniques described herein relate to a method, wherein a ratio of the MMA monomers, the crosslinking agent, and the PMMA powder is 45.5:45.5:9 wt.%.KPPB Ref: S94-12318.PCT

[0024] In some embodiments, the techniques described herein relate to a method 16 to 18, further including: mixing an antibacterial agent in the base resin.

[0025] In some embodiments, the techniques described herein relate to a method, wherein the antibacterial agent is selected from at least one of: silver oxide, copper oxide, or cupronickel.

[0026] In some embodiments, the techniques described herein relate to a method, wherein the antibacterial agent has a weight percent of less than 0.5 wt.%.

[0027] In some embodiments, the techniques described herein relate to a method, further including mixing a bioceramic in the base resin.

[0028] In some embodiments, the techniques described herein relate to a method, wherein the bioceramic is a hydroxyapatite powder.

[0029] In some embodiments, the techniques described herein relate to a method, wherein the bioceramic has a weight percent less than 0.5 wt.%.

[0030] In some embodiments, the techniques described herein relate to a method, further including preparing the biocompatible resin for an additive manufacturing process.

[0031] In some embodiments, the techniques described herein relate to a method, wherein the additive manufacturing process is a vat photopolymerization.

[0032] In some embodiments, the techniques described herein relate to a method, further including mixing a photoinitiator in the base resin.

[0033] In some embodiments, the techniques described herein relate to a method, wherein the photoinitiator is compatible with an exposure wavelength of the vat photopolymerization.

[0034] In some embodiments, the techniques described herein relate to a method, wherein the photoinitiator is a phenylbis (2,4,6-trimethylbenzoyl)-phosphine oxide (BAPO).

[0035] In some embodiments, the techniques described herein relate to a method, wherein the photoinitiator has a weight percent less than 0.5 wt.%.

[0036] In some embodiments, the techniques described herein relate to a method, wherein the additive manufacturing process is a fused filament fabrication.KPPB Ref: S94-12318.PCT

[0037] In some embodiments, the techniques described herein relate to a method, wherein the additive manufacturing process is a direct ink writing.

[0038] Additional embodiments and features are set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the disclosure. A further understanding of the nature and advantages of the present disclosure may be realized by reference to the remaining portions of the specification and the drawings, which form a part of this disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The description will be more fully understood with reference to the following figures, which are presented as embodiments of the invention and should not be construed as a complete recitation of the scope of the invention, wherein:

[0040] Figs. 1 A and 1 B schematically illustrate a 3D printed cranioplasty implant.

[0041] Fig. 2A schematically illustrates a femur bone and its internal structure.

[0042] Figs. 2B and 2C illustrate a computer model of the 3D printed implant mimicking the internal structure of bone.

[0043] Fig. 3 schematically illustrates the constituents of a biocompatible resin in accordance with an embodiment.

[0044] Fig. 4 schematically illustrates a process to synthesize a biocompatible resin.

[0045] Fig. 5 schematically illustrates the mixture of constituents within a biocompatible resin before and after printing.

[0046] Fig. 6 schematically illustrates the drag and buoyancy of HAp.

[0047] Figs. 7A to 7D illustrate the viscosity of biocompatible resins with nanoparticles of HAp and silver oxide.

[0048] Fig. 8 illustrates the chemical reaction of a biocompatible resin.

[0049] Fig. 9 illustrates the viscosity-shear rate of a biocompatible resin.

[0050] Figs. 10A and 10B illustrate the shear stress and shear strain of a biocompatible resin.

[0051] Figs. 11 A and 11 B illustrate the shear strain of a biocompatible resin.KPPB Ref: S94-12318.PCT

[0052] Fig. 12 illustrates the viscosity of biocompatible resins with different weight percentages of PMMA.

[0053] Figs. 13A to 13C illustrate the storage modulus, the loss modulus, and the loss tangent of biocompatible resins.

[0054] Fig. 14 illustrates the compressive mechanical properties of cortical bone and trabecular bone.

[0055] Fig. 15 illustrates the mechanical stability of printed biocompatible resins.

[0056] Figs. 16A and 16B illustrate the thermal history of printed biocompatible resins.

[0057] Figs. 17A to 17C illustrate examples of printed biocompatible resins.

[0058] Figs. 18A and 18B illustrate the chemical signatures of biocompatible resins.

[0059] Figs. 19A to 19D illustrate the thermal history of powdered biocompatible resins.

[0060] Figs. 20A to 20I illustrate the dynamic thermomechanical behavior of printed biocompatible resins.

[0061] Figs. 21 A and 21 B illustrate the nano-mechanics of biocompatible resins.

[0062] Figs. 22A to 22D schematically illustrate examples of TPMS structures for printed biocompatible resins.

[0063] Fig. 23 illustrates the deformation distribution of printed gyroid biocompatible resins.

[0064] Fig. 24 illustrates the compressive stiffness of biocompatible resins in different TPMS geometries.

[0065] Fig. 25 illustrates the compressive force-displacement of biocompatible resins in different TPMS geometriesDETAILED DESCRIPTION OF THE INVENTION

[0066] Turning now to the figures and data, many embodiments are directed to additive manufacturing (AM) biocompatible implants. Several embodiments are directed to a biocompatible resin for 3D printing biocompatible implants. In many embodiments, the biocompatible implant can be customized through modification of the weight percent ratio of the biocompatible polymers. Biocompatible implants can be printed in structuralKPPB Ref: S94-12318.PCT geometries to mimic native tissue microstructures. In some embodiments, the biocompatible resins incorporate bioceramics that mimic the microstructure of the native tissue. The biocompatible resins can further incorporate an antibacterial and / or an antimicrobial agent, in accordance with various embodiments, to prevent implant site rejection.

[0067] Personalized medicine has become the primary focus of healthcare providers to improve outcomes and care delivery. AM can accelerate personalized medicine by enabling the custom fabrication of implants with tailored functionalities on demand. To meet this need, materials suitable for agile customization to meet the patient’s needs while being biologically compatible are required. In AM of implants, materials are shaped into complex, organic geometries congruent with each patient’s anatomical and anthropometric features. These requirements are specifically essential in orthopedics and reconstructive surgery. Advancements in two-dimensional and three-dimensional scanning and imaging have given rise to tailorable and customizable advanced care delivery. Additionally, improved scanning and imaging allow for high-fidelity reconstruction of the patient’s anatomy for the proper fit and function of the implants.

[0068] AM provides customization of manufactured components, offering a pathway for personalized orthopedics. AM extends over several techniques, ranging from solid to resin polymers with limited fillers or modifiers, including (but not limited to) fused filament fabrication, vat photopolymerization, and direct ink printing. AM processes utilize polymers in all forms, including (but not limited to) powders, pellets, filaments, films, or resins, depending on the specific AM and fabrication application.

[0069] Figs. 1 A and 1 B provide an example of a printable biocompatible resin implant incorporated within a cranioplasty implant. In many embodiments, the biocompatible resin is printed via AM techniques to form an implant. The biocompatible resin, in accordance with several embodiments, mimics the internal structure of the native tissue surrounding the implant. Fig. 2A provides an example of native bone tissue and its internal structure. The biocompatible resin, in accordance with numerous embodiments, can be printed to mimic the internal structure of the bone tissue. AM enables prefabrication of custom designs via computer-aided design (CAD). In many embodiments, the implant to beKPPB Ref: S94-12318.PCT printed can be designed in CAD to mimic the internal structure of native tissue and / or the patient’s tissue. Fig. 2B provides an example of a CAD for an implant to mimic the internal structure of bone. Fig. 2C schematically provides the implant printed with the biocompatible resin according to the CAD of Fig. 2B.

[0070] Polymers are utilized in biomedical applications due to biocompatibility while exhibiting mechanical properties comparable to native tissue. However, standard biocompatible printable resins are a mixture of acrylates and photoinitiators, only suitable for vat photopolymerization (VPP) printing. Standard resins have limited agility and facility for use in personalized medicine. Acrylates are bioinert materials with limited interactions with surrounding tissues, but may lead to a foreign body reaction that impedes integration and leads to rejection or malunion.

[0071] Polymethyl methacrylate (PMMA) is a stable polymer widely implemented as a bone cement or a bone replacement in orthopedics. In several embodiments, PMMA is a suitable base polymer for biocompatible resin mixtures. Conventional PMMA is not suitable for 3D printing after functionalization with bioactive and antibacterial constituents since it needs photoreactive or thermo-reactive species to initiate the polymerization process. Various embodiments are directed to synthesizing a 3D printable PMMA-based resin comprising photoinitiators, bio-integrators, and antibacterials for tailorable functionalization of species. In many embodiments, the biocompatible resins can be used for VPP printing or solidified into filament for fused filament fabrication (FFF) printing, or thermally cured for direct ink writing. In some embodiments, the biocompatible resins can be integrated into various 3D printing processes, including (but not limited to) two-photon polymerization or other processes apparent to those skilled in the art.

[0072] Various embodiments are directed to a 3D printable resin for fabricating implants using vat photopolymerization (VPP). In many embodiments, the liquid polymer resin further comprises one or more photoinitiator chemicals to nucleate the polymerization process upon exposure to light. In some embodiments, the VPP process incorporates monochromatic light, such as (but not limited to) ultraviolet lasers or LED banks. In several embodiments, the photoinitiator chemicals activate according to the wavelength of the VPP process being applied. A free-radical photoinitiator, in accordanceKPPB Ref: S94-12318.PCT with various embodiments, triggers photopolymerization when the light emitted by the printer yields free radicals for the monomers to react. In some embodiments, the photoinitiator is phenylbis (2,4,6-thmethylbenzoyl)-phosphine oxide (BAPO). The photoinitiator, in accordance with many embodiments, can be replaced by other types of organic and chemical photoinitiators. In some embodiments, the type of photoinitiator is dependent on the overall requirements of the implant or the activating wavelength of the printer light.

[0073] Several embodiments are directed at biocompatible resins further comprising methyl methacrylate (MMA) monomers and a crosslinking agent, ethylene glycol dimethacrylate (EGDMA). In many embodiments, a PMMA powder is mixed with the MMA monomer and crosslinking agent EGDMA. The proper polymerization conditions and ratios of the polymers in the resin, in accordance with several embodiments, affect the resulting structural properties of the fabricated implant. In some embodiments, the ratios of PMMA, MMA, and EGDMA within the biocompatible resin are adjusted to control the viscosity of the base resin. In several embodiments, the ratio of PMMA:MMA:EGDMA is 9:45.5:45.5 wt.%, resulting in a resin with proper pot-life and printing viscosity. The chemicals, in accordance with certain embodiments, can be mechanically mixed in a sequence. In some embodiments, the MMA and EGDMA are homogenized before adding a dissolution of PMMA powder. In several embodiments, the mixing is conducted at a controlled temperature. In many embodiments, the temperature of mixing is between 40°C and 60°C. The chemicals, in accordance with numerous embodiments, are mixed for a controlled period of time. In several embodiments, the chemicals are mixed for 30 minutes to 60 minutes.

[0074] In some embodiments, the ratio of the photoinitiator within the resin is adjusted to prevent toxicity. The concentration of the photoinitiator and / or the time of exposure, in accordance with several embodiments, is adjusted to provide sufficient nucleation and prevent reaction within the patient. In many embodiments, the photoinitiator is less than 0.5 wt.%. In some embodiments, the photoinitiator is mixed rapidly and homogenously into the PMMA-MMA-PGDMA mixture.KPPB Ref: S94-12318.PCT

[0075] In various embodiments, a bioceramic is incorporated into the base resin. A bioceramic, in accordance with several embodiments, adjusts the internal structure of the implant. In many embodiments, the bioceramic is an inorganic ceramic that mimics the mineral composition of bone. By mimicking mineral bone composition, in accordance with various embodiments, the incorporated bioceramic aids in forming the bone junction with the implant and reduces rejection or malunion when implanted. In many embodiments, the biocompatible resin incorporating a bioceramic exhibits improved agility and compatibility upon implantation. Various bioceramics, in accordance with several embodiments, can be incorporated to facilitate proper fitment and function. In many embodiments, bioceramics can be incorporated based on the size and / or composition of the bioceramic.

[0076] In some embodiments, the biocompatible resin incorporates hydroxyapatite. The ceramic particles of hydroxyapatite, in accordance with several embodiments, are not soluble with the base biocompatible resin but are suspended in the mixture. In many embodiments, the viscosity of the base biocompatible resin controls the settling velocity of the bioceramic particles. The settling velocity of the bioceramic particles, in accordance with certain embodiments, is directly proportional to the size of the particles and the densities of the components. In some embodiments, the settling velocity is indirectly proportional to the viscosity of the biocompatible resin mixture. In several embodiments, the slower the settling velocity, the more bioceramic particles will be incorporated into the biocompatible resin mixture when the biocompatible resin is poured. This phenomenon, in accordance with many embodiments, occurs during printing, so it is important to control the velocity to ensure a homogeneous distribution of the bioceramic particles throughout the printed specimens. In some embodiments, the settling velocity can be modified by modulating the viscosity of the mixture and / or the size of the bioceramic particles. For example, the addition of PMMA powder is added to the base MMA-EGDMA mixture to dissolve the MMA monomer, in accordance with various embodiments, to retard the biocompatible particles settling.

[0077] Several embodiments incorporate an antibacterial and / or antimicrobial compound. In some embodiments, the biocompatible resin incorporates any antibacterialKPPB Ref: S94-12318.PCT compound, including (but not limited to) silver, silver oxides, copper, copper oxides, and / or cupronickel. Adding silver oxide antibacterial compounds, in accordance with many embodiments, is important to biocompatibility since implant site infection is common in biomedical integrations. In some embodiments, silver compounds react positively with bacterial species by penetrating the microorganism’s cell walls, resulting in the death of the bacterial cell.

[0078] In some embodiments, the antimicrobial and / or antibacterial reactivity of silver is conferred by the silver oxide to the biocompatible resin. Silver oxide is converted into silver ions by the activity of photoinitiators, reacting with other suspended silver ions, producing silver nanoparticles. In many embodiments, when in the body, the silver nanoparticles perform antibacterial activity by attaching to bacterial membranes or entering the bacterial cells to kill the bacterial cells. The addition of antibacterial agents, in accordance with several embodiments, increases the acceptance rate and reduces rejection of implants made from the biocompatible resin.

[0079] In certain embodiments, an antibacterial agent is added in a similar ratio as the bioceramic. A biocompatible resin, in accordance with many embodiments, can comprise the same ratio of bioceramic particles and antibacterial agents. In some embodiments, the antibacterial agent is silver oxide. As described herein, silver oxide nanoparticles exhibit remarkable antibacterial properties with lower infection rates in integrated orthopedics. However, higher concentrations of silver oxide nanoparticles, greater than 1.0 wt.%, can adversely toxify osteoblasts. Furthermore, concentrations of silver oxide are ineffective as an antibacterial at lower concentrations, less than 0.1 wt.%. In some embodiments, silver oxide nanoparticle concentrations are maintained between 0.1 wt.% and 1.0 wt.%. The printing process, in accordance with various embodiments, maintains an effective concentration of the antibacterial agent within the resulting implant. In some embodiments, the concentration of silver oxide in the implant is controlled through light- nanoparticle interactions (including but not limited to diffraction and scattering) during the printing process. In many embodiments, the printing process comprises resting the combined biocompatible resin for a period of time to facilitate light-nanoparticleKPPB Ref: S94-12318.PCT interactions. For example, a biocompatible resin with silver oxide- EGDMA / MMA / PMMA(2.5 wt.%) is left to rest for 24 hours prior to printing.

[0080] Fig. 3 schematically provides the structure of components of the biocompatible resin in accordance with an embodiment. The MMA and EGDMA base chemicals are mixed with a PMMA to form the base resin. A bioceramic is incorporated into the base resin to facilitate the structural requirements of the target tissue. Fig. 3 provides an example of an osteoinductive agent, such as nanoparticle hydroxyapatite (nHAp). The biocompatible resin, in accordance with an embodiment, further incorporates an antibacterial agent. Fig. 3 provides an example of an antibacterial agent, silver oxide, incorporated in the biocompatible resin. The biocompatible resin, in accordance with an embodiment, can incorporate a photoinitiator. Fig. 3 provides an example of the structure of a photoinitiator, BAPO, to be incorporated in the biocompatible resin.

[0081] The biocompatible resin, in accordance with many embodiments, incorporates bioinert formulations with osteoinductive-antimicrobial features. In several embodiments, the mechanical and chemical properties are adjusted by modifying the weight ratio of PMMA in the base resin. Fig. 4 provides an example of synthesizing and printing a biocompatible resin for a bone replacement implant in accordance with an embodiment. In Fig. 4, the base resin comprises homogenized MMA monomer and EGDMA in a 50:50 weight ratio, mixed with BAPO for 180 seconds. PMMA powder is added to the base resin. In accordance with several embodiments, the amount of PMMA powder added can range to fine tune the rheological and chemical properties of the finished biocompatible resin. In some embodiments, the amount of PMMA ranges between 0 wt.% to 10 wt.%. The PMMA powder is mixed with the MMA / EGDMA base resin while continuously stirring in a heated bath at 50°C for 210 minutes. In many embodiments, the PMMA powder is mixed with the MMA / EGDMA base resin at a temperature and / or duration to provide homogenous mixing without premature gelation. The solubility of PMMA in the MMA monomer, in accordance with various embodiments, is dependent on the weight ratio and the synthesis temperature to control the Trommsdorf effect to prevent rapid polymerization. In some embodiments, the mixing prevents the formation of PMMA powder beads suspended within the flash-cured gel. Suspended PMMA powder beadsKPPB Ref: S94-12318.PCT result in ultrahigh viscosity and prevent movability and mixing for a 3D printer. In certain embodiments, for VPP printing, a photoinitiator is added to induce the P M MA / M MAZE G DMA to induce radical polymerization upon ultraviolet exposure during 3D printing. Fig. 5 schematically illustrates the mixture of constituents within the biocompatible resin before and after printing.

[0082] In many embodiments, the biocompatible resin further incorporates a bioceramic to mimic the desired tissue structure. The bioceramic, in accordance with numerous embodiments, is nanoparticle HAp (nHAp) to mimic bone structure. In some embodiments, the mixing process to incorporate the bioceramic comprises adding the bioceramic to the base resin. The bioceramic, in accordance with certain embodiments, is added to the base resin at specific weight ratios based on the desired application. For example, nHAp mineralized nanoparticles are added at weight ratios of 0.1 %, 0.5% and 1 % with respect to the total weight of the EGDMA / MMA / PMMA(2.5% wt.%) base resin. In several embodiments, the upper bound of nHAp hybridization balances between sufficient potential osteointegration, matching the mechanical properties of the native tissue, and / or subduing light diffraction from particles during printing. During the mixing process, in accordance with numerous embodiments, the nHAp is added to the base resin in a planetary mixer for 240 seconds. Other mixing methods can be used, including (but not limited to) ultrasonic mixers, shear mixers, homogenizers, and / or roller mixers at different durations without affecting the outcomes. In many embodiments, the bioceramic mixed base resin rests for a period of time. The resting period, in accordance with certain embodiments, allows for proper dispersion and / or stabilization of the nHAp within the biocompatible resin. In some embodiments, the bioceramic is rested for approximately 24 hours.

[0083] During the mixing process, in accordance with various embodiments, the planetary mixer is dictated by Maragoni flow initially. The planetary mixer initially provides an apparent homogenized solution with the bioceramic fully suspended throughout. In many embodiments, the nHAp agglomerates and rapidly settles at the bottom of the mixing vessel. The settling of nHAp is due to Stokes' law, where g is gravitational acceleration, d is particle diameter, the particle and liquid densities, and the viscosity ofKPPB Ref: S94-12318.PCT the resin. In several embodiments, the settling velocity is directly proportional to the squared diameter of the nHAp. In various embodiments, the settling velocity is inversely proportional to the dynamic viscosity. These proportionalities, in accordance with certain embodiments, result in a settling time that coincides with the visual estimation of the settling during the synthesis process. In many embodiments, after 24 hours, the nHAp percolates throughout the solution, resulting in a two-phase system. In the first phase of the two-phase system, in accordance with several embodiments, the smaller diameter particles are suspended in an equilibrium between weight-penalized drag and buoyancy forces. The drag coefficient, the velocity, the density, the area, the mass, and gravity determine the weight-penalized drag. In the second phase of the two-phase system, in accordance with various embodiments, the larger nHAp particles remained settled. Fig. 6 schematically provides an example of the two-phase system.

[0084] As described herein, the biocompatible resin incorporating a bioceramic and / or antibacterial, in accordance with many embodiments, is suitable for various 3D printing processes, including (but not limited to) VPP, FFF, and direct ink writing. In several embodiments, the biocompatible resin can be solidified and extruded into filaments to be used in commercial 3D printers, irrespective of the motion system. Liquid biocompatible resins, in accordance with numerous embodiments, can be packaged in cartridges for strategic dispensing using a direct ink printer. In some embodiments, the biocompatible resin is adjusted for VPP printing processes. For example, the photoinitiator incorporated is compatible with the activation wavelength of the VPP printer. Most VPP printers operate with low viscosity resins, such as 0.1 Pa s to 0.2 Pa s, with a limit of approximately 5.0 Pa s. The viscosity threshold of VPP printers is based on the detachment force that the printing platform can exert without compromising the printed part’s integrity. As described herein, the viscosity of the biocompatible resin controls the distribution of particles, in many embodiments, the viscosity of the biocompatible resin is compatible with the constraints of the VPP printer. In some embodiments, the viscosity of the biocompatible resin can be adjusted to provide particle distribution while ensuring 3D printing functionality. Figs. 7A to 7D provide the nHAp powder results in a higher viscosity than the silver oxide particles due to the difference in the atomic weight.KPPB Ref: S94-12318.PCT

[0085] Fig. 8 provides an example of the chemical reaction of MMA, EGDMA, PMMA, silver oxide, HAp, and BAPO when a UV light is applied. The photoinitiated (BAPO) poly(MMA-EGDMA) incorporates an orthopedic agent (HAp) and an antibacterial agent (silver oxide).

[0086] Various embodiments are directed to a modified printing process. In many embodiments, a VPP printer is modified to print a component from a higher viscosity resin. The viscosity of the resin is a primary factor in the successful printing of components with VPP printers because viscosity impacts various parameters, including (but not limited to) approach and retraction speeds, layer height, and bottom layer exposure. In some embodiments, modifications to conventional VPP equipment can be made to address viscosity challenges, including (but not limited to) printing under an inert nitrogen atmosphere, printing parameters optimized to accommodate a wider viscosity range, and controlling the incubation period between resin formulation and print initiation. Several embodiments are directed to modifying VPP equipment to print a biocompatible resin as described herein. The modified VPP printing, in accordance with certain embodiments, is conducted under an inert nitrogen atmosphere to mitigate the reactivity of PMMA with ambient conditions. In many embodiments, the printing process is performed in a nitrogen-filled environment to prevent organic volatiles from destabilizing the resin and impairing the resulting print quality. In numerous embodiments, the modified VPP process transfers the biocompatible resin to a chamber and purges the printing chamber with nitrogen. In some embodiments, the chamber is purged with nitrogen at 0.75 MPa and 1.5 l / minute for 10 minutes. The nitrogen flow conditions, in accordance with various embodiments, are maintained during the printing process. In certain embodiments, maintaining the nitrogen flow conditions preserves the chemical stability of the remaining biocompatible resin and the resulting printed implant. In several embodiments, the optimized printing parameters include (but are not limited to) bottom exposure time, exposure time, and platform speed. The bottom exposure time, in accordance with some embodiments, is set to 30 seconds. In many embodiments, the exposure time is set to 10 seconds. The platform speed, in accordance with numerous embodiments, can vary between approximately 4 mm / second to 6 mm / second. In some embodiments, theKPPB Ref: S94-12318.PCT platform lift speed during printing is approximately 4 mm / second. In certain embodiments, the platform retraction speed during printing is approximately 6 mm / second. The lift speed and / or retraction speed can be correlated to the shear strains and / or the resin viscosity. In many embodiments, the resin viscosity is based on the shear strain rate. Fig. 9 provides the rheological properties of osteoinductive-antimicrobial biocompatible resins, in accordance with an embodiment, which are affected by dynamic printing parameters. As provided in Fig. 9, the viscosity-shear rate interrelationship is sensitive to the PMMA wt.% within the biocompatible resin. In some embodiments, biocompatible resins > 5.0 wt.% PMMA exhibits quasi-Newtonian fluid behavior. In many embodiments, biocompatible resins < 2.5 wt.% PMMA demonstrates a pronounced shear thinning phenomenon. The difference in rheological properties, in accordance with various embodiments, is based on the solute-solvent interactions stemming from the distinct molecular weight and chain mobility of the constituents. In several embodiments, increasing the wt.% of the higher molecular weight PMMA hinders the free movement of MMA and EGDMA molecules. The absence of large PMMA content, in accordance with numerous embodiments, in an osteoinductive-antimicrobial resin with approximately < 2.5 wt.% PMMA is conducive to solvent breakdown of MMA and EGDMA that transpires as shear thinning. In certain embodiments, the dichotomy between the biocompatible resin viscosity as a function of PMMA, shear thinning to quasi-Newtonian transition, is manifested during the transfer from the mixing container to the printing vat. In several embodiments, this evidences rapid FEP sheet wetting from resins with low wt.% PMMA as compared to forced wetting through (for example) forcibly spreading the resin onto the FEP sheet. Additionally, low wt.% PMMA biocompatible resins, in accordance with various embodiments, provide faster FEP sheet wetting as compared to higher wt.% PMMA biocompatible resins. As shown in Fig. 9, the printing shear rates correspond to dynamic viscosity in the range of approximately 0.05 Pa s and 10 Pa s defy the limits of off-the-shelf VP P resins. In many embodiments, modifying the VPP printing process, as described herein, provides robust printed components of both low viscosity resins and high viscosity resins without the need for significant alterations in the printing parameters.KPPB Ref: S94-12318.PCT

[0087] Figs. 10A and 10B provide how shear stress is related to the shear strain, the printing speed, and the viscosity of the resin. In many embodiments, the shear stress is important in determining the spreading of the biocompatible resin during the printing process because the printing platform regulates the layer height throughout the printing process. For example, retracting away from the FEP sheet to allow the fresh resin to seep into the printing region and approaching the LCD screen to commence exposure. Dynamic printing parameters can be determined by the rheology properties, in accordance with many embodiments, where the shear strain indicates the spreading of the resin within the printing area, as shown in Figs. 11A and 11 B. For example, where shear strain = 0.05 - 36 Pa within 1 and 1.5 s-1indicates spreading of the resin within a 12.9mm2printing area.

[0088] Various embodiments are directed to biocompatible resins incorporating a photoinitiator. In many embodiments, the photoinitiator is configured to nucleate the polymers when exposed to a specific wavelength of light. The activation wavelength of the photoinitiator, in accordance with numerous embodiments, can be selected according to the exposure light of the printing equipment. In several embodiments, the affinity of photopolymerizable biocompatible resins to ultraviolet radiation during the printing process can affect the lifetime of the resin. In some embodiments, the lifetime of the resin changes the production yield from each batch of mixed biocompatible resin. The interaction between the exposure of the ultraviolet rays and the diffraction of light around the sample edges, in accordance with some embodiments, results in a change in the dynamic viscosity as a function of time. In many embodiments, the biocompatible resin becomes unprintable after a few printing cycles. The usable lifetime of a biocompatible resin can be determined by comparing the viscosity of each batch before and after printing. In many embodiments, the retention of idiosyncratic Newtonian or quasiNewtonian properties indicates the usable lifetime of the biocompatible resin. The wt.% of PMMA, in accordance with various embodiments, contributes to the usable lifetime of biocompatible resins. In many embodiments, biocompatible resins with > 5 wt.% PMMA become unusable after repeated uses. In several embodiments, biocompatible resins with 2.5 wt.% PMMA provides usable and effective printed implants.KPPB Ref: S94-12318.PCT

[0089] In many embodiments, the viscosity of the biocompatible resin is between 0.04 Pa s to 1 .60 Pa s. The viscosity of the biocompatible resin, in accordance with several embodiments, is dependent on the weight of the polymers. Fig. 12 shows the integration of modifying the nanoscale antibacterial and bioceramic particles of an implant printed with a modified VPP printer, rheological stability of the biocompatible resin implant, and the dynamic properties of the biocompatible resin implant at body temperature (37°C). Fig. 12 provides the change in viscosity as the PMMA weight percentage changes.

[0090] In several embodiments, the mechanical properties of the printed biocompatible resin are dependent on the weight percentage of the polymers within the biocompatible resin. By adjusting the ratio of the polymers, in accordance with many embodiments, the resulting mechanical properties of the printed implant are changed based on the change in the overall weight percent of the specific polymers. Different weight percents of PMMA in the biocompatible resin provide different storage moduli (Fig. 13A), loss modulus (Fig. 13B), and loss tangent (Fig. 13C). The plates printed, in accordance with an embodiment, exhibit an average storage modulus of 3.12 ± 0.13 GPa, further manifesting the manufacturing adaptability with stable mechanical properties independent of the PMMA concentration. Fig. 14 provides the required compressive mechanical properties for a suitable bone replacement implant. As shown, the printed biocompatible resin provides sufficient mechanical properties. Though only bone tissue is provided, many embodiments are directed to various tissue replacements, including (but not limited to) bone, cartilage, and tendon.

[0091] In various embodiments, the addition of bioceramics, such as osteoinductive agents, does not significantly affect the mechanical properties of the biocompatible resin. In many embodiments, the mechanical properties of the biocompatible resin are not impacted by the addition of bioceramics at different molecular weight ratios. Fig. 15 provides the lifetime change in the viscosity of biocompatible resins with different PMMA molecular weight ratios. At 0 wt.% PMMA, the viscosity before printing was 0.04 Pa s and 0.07 Pa s after printing. At 10 wt.% PMMA, the viscosity before printing was 13.42 Pa s and 34.72 Pa s after printing. Fig. 15 provides the mechanical stability of biocompatible resins with different concentrations of silver oxide antibacterial agents and HApKPPB Ref: S94-12318.PCT osteoinductive agents. As shown in Fig. 15, the mechanical stability of the biocompatible resins is maintained after hybridization, reporting a similar storage modulus of 3.15 GPa, on average, at body temperature (37°C). In several embodiments, the mechanical performance of the biocompatible resin is dampened at higher temperatures when bioceramics and antibacterial agents are added.

[0092] Figs. 16A and 16B provide the thermal history of the printed biocompatible resin via material extrusion, wherein the reported Tc = 116.4 ± 16.4°C (Fig. 16A) and Tm = 264.2 ± 9.7°C (Fig. 16B). As shown, using material extrusion as a manufacturing technique after pelletization or spoolization of the biocompatible resin does not impede the performance of the biocompatible resin.

[0093] Figs. 17A to 17C provide examples of printed biocompatible resins in accordance with several embodiments. The implants can be printed with an antibacterial agent (Fig. 17A), without antibacterial agent (Fig. 17B), or with different molecular weight ratios of the polymers, bioceramics, and antibacterial (Fig. 17C). As shown in Figs. 17A and 17B, implants can be printed according to the CAD schematics provided in Figs. 2B and 2C.

[0094] In many embodiments, the physicochemical and thermochemical properties change for biocompatible resins with constituents (e.g., bioceramics and antibacterial agents) and without constituents. Figs. 18A and 18B provide the chemical signatures of biocompatible resin configurations to show the chemical stability of various embodiments. Fig. 18A provides the spectral peaks characteristic of PMMA and EGDMA. Fig. 18A provides an emphasis on the C-H stretching vibrations from the carbonyl group, primary polymer chain, and pendant methyl groups (A = 2945 cm-1), the C=O group (A = 1719 erm1), the C=CH2 stretching (A=1636 erm1), the C-CH2 and C-CH3 bending (A=1445 erm1), the C-O-C asymmetric stretching (A=1145 cm'1), the O-CH3 rocking (A=960, 980 cm'1), and the C-C skeletal mode (A=748 cm'1). In many embodiments, the biocompatible resins with constituents inherited the spectra of the 2.5 wt.% PMMA base resin, replicating the spectral peaks as shown by Fig. 18A. The concentration of nHAp, in accordance with an embodiment, exhibited a noticeable peak centered at 574 cm'1, specifically at 1 wt.% nHAp. In several embodiments, this can be attributed to the bending of the group. TheKPPB Ref: S94-12318.PCT spectroscopic results, in accordance with various embodiments, confirm the anticipated chemical structure of the printed implants with the inclusion of constituents.

[0095] Figs. 19A to 19D provide the thermal history of powdered biocompatible resins, in accordance with certain embodiments, including the effect of nHAp and silver oxide nanoparticles on the crystallization (Fig. 19C) and melting temperatures (Fig. 19D). In many embodiments, a DSC study shows the molecular interactions between poly(MMA- co-EGDMA) and PMMA. The DSC thermograms, in accordance with numerous embodiments, are based on a first heating cycle at a rate of 3°C / minute. Figs. 19A and 19B provide the suppression of Tg as the chain tacticity and heating rate influence it. As shown in Fig. 19C, the crystallization temperature varies between 93.2°C and 143.6°C. The lowest value was 10 wt.% PMMA because of its more amorphous structure and the increased content of the higher molecular with PMMA chains. At the end of the thermal history, in accordance with many embodiments, two peaks are observed: (1 ) corresponding to the melting temperature (Tm) and (2) attributing to the thermal decomposition. Fig. 19D provides the melting temperature exhibited minimal variation across various biocompatible resin compositions, in accordance with several embodiments, averaging at approximately 260°C. The biocompatible resins, in accordance with many embodiments, yield a higher value melting temperature than pure PMMA due to the apparition of crosslinking sites. In various embodiments, the diminution in Tm accentuates changes in PMMA molecular weight during the 3D printing process. In several embodiments, the change in PMMA molecular weight restricts molecular mobility and free volume due to the polymerization of poly(MMA-co-EGDMA), leading to a decrease in enthalpy during the non-isothermal process. The second endothermic peaks, in accordance with some embodiments, are centered approximately at 320°C, and are attributed to the thermal decomposition due to carbonization. In many embodiments, the carbonization is evidenced by notable color changes on the polymer powder beads remaining in the pan after testing. The endothermic decomposition peaks apodictically ascertain the thermal stability of the 3D-printed polymers, in accordance with certain embodiments, and corroborate the accompanying DMA analysis. In some embodiments, the biocompatible resin comprises constituents, such as nHAp and silver oxide. TheKPPB Ref: S94-12318.PCT melting temperature of biocompatible resins with silver oxide is higher than the base resin, but is only discernibly different at high concentrations of silver oxide.

[0096] Figs. 20A to 201 provide the dynamic thermomechanical behavior of printed biocompatible resin plates, in accordance with several embodiments, as a function of temperature. As described herein, many embodiments are directed towards bone tissue replacement implants. Several embodiments of biocompatible resin are printed as bone tissue replacement implants as described herein. The printed biocompatible resin bone implants, in accordance with various embodiments, have mechanical properties to mimic native bone tissue, including (but not limited to): congruent mechanics to avoid stress shielding, nanoscale adjustments and tailorable constituents to improve acceptability and lifetime, and / or comparable time-dependent attributes to manage dynamic loading scenarios (e.g., mundane, leisure, or occupational movements). The mechanical response of various embodiments is evaluated by dynamic mechanical analysis (DMA) and nanoindentation. In DMA testing, the samples, in accordance with an embodiment, are loaded in a double cantilever configuration. In many embodiments, the double cantilever has a 10 pm amplitude at 1 Hz and a temperature ramp between 26°C and 190°C.

[0097] Figs. 20A to 20C provide the storage modulus (Fig. 20A), loss modulus (Fig. 20B), and loss tangent (Fig. 20C) of printed biocompatible resin implants, in accordance with various embodiments. Regardless of the specific formulation, in accordance with certain embodiments, the storage and loss moduli exhibit a decaying behavior as a function of temperature, leading away from the glassy region, accentuating the previous discussion based on the physicochemical signatures. In several embodiments, the decaying trend in the moduli reveals the complex structure of the resulting macromolecule, inheriting the attributes of linear and crosslinked polymers that stem from photopolymerization during printing. The structure of printed and cured biocompatible resin, in accordance with certain embodiments, is a byproduct of the chemically crosslinked poly(EGDMA-co-MMA) and physically crosslinked high-molecular PMMA chains. In several embodiments, biocompatible resins without constituents at < 5 wt.% PMMA demonstrated higher amounts of crosslinking sites, resulting in a 50% drop inKPPB Ref: S94-12318.PCT during the glass-to-rubber transition (i.e. , = 3.22 GPa in the glassy regime = 1 .63 MPa in the rubbery plateau), while 7.5 wt.% and 10 wt.% PMMA reduced it by 82% and 76%, respectively (0.44 MPa and 0.72 MPa). The dependence on the PMMA content ratio, in accordance with many embodiments, is explicated based on reducing the number of crosslinked chains and, consequently, allowing more molecular mobility within the chemically and physically crosslinked macromolecule. Several embodiments of printed biocompatible resin implants demonstrate good mechanical and geometrical stability at relatively higher temperatures, amending the typical properties of neat, amorphous PMMA. This thermomechanical endurance also manifested in, and was most evident in, the loss tangent, with limited activation energy dissipation mechanisms, indicating predominantly elastic behavior and negligible damping. In various embodiments, loss tangent as a function of temperature further confirms the physical and chemical crosslinking duality of biocompatible resins. In accordance with an embodiment of a biocompatible resin with 0 wt.% PMMA, the manifestation of a single peak centered at 97.4°C corresponds to the glass transition temperature of the poly(EGDMA-co-MMA). In some embodiments, two transitions coexist for biocompatible resins > 2.5 wt.% PMMA at 68.2°C (for poly(EGDMA-co-MMA)) and 129.1 °C (for high-molecular-weight PMMA), pointing to a pseudo block copolymer structure.

[0098] In various embodiments, biocompatible resins incorporate antibacterial agents. Biocompatible resins with antibacterial agents, such as silver oxide, exhibit similar thermomechanical behavior to biocompatible resins without antibacterial agents. Figs. 20D to 20F provide the storage modulus (Fig. 20D), loss modulus (Fig. 20E), and loss tangent (Fig. 20F) of printed biocompatible resin implants incorporating silver oxide, in accordance with various embodiments. In some embodiments, similar thermomechanical behavior is due to the monodispersity of the nanoscale particles and the crosslinking duality of the underlying pseudo copolymer. In many embodiments, hybridizing the base resins for advanced bio-functionality proved effective in maintaining thermal (transitions), chemical (spectral peaks), and mechanical (viscoelastic) stabilities for biocompatible resins with or without antibacterial agents. In certain embodiments, silver oxide nanoparticles act as non-impeding pinning sites. The silver oxide nanoparticles, inKPPB Ref: S94-12318.PCT accordance with some embodiments, allow chain mobility afforded by the molecular structure while inducing an antibacterial shield over the printed implants. In various embodiments, the biocompatible resins also incorporate a bioceramic agent.

[0099] Biocompatible resins with an nHAp osteoinductive agent, in accordance with several embodiments, are reduced throughout the thermal history. Figs. 20G to 201 provide the storage modulus (Fig. 20G), loss modulus (Fig. 20H), and loss tangent (Fig. 201) of printed biocompatible resin implants incorporating HAp nanoparticles, in accordance with various embodiments. In many embodiments, the nHAp acts as a stresstransfer inhibitor for nanoscale inclusions. This interaction, in some embodiments, is based on the nonconformable and non-uniform geometry of nHAp particles. The nonconformable nHAp particles, in several embodiments, are substantiated by distinct mechanical properties of nHAp (E = 114 GPa and p = 3.14 g / cm3) compared to the surrounding polymer matrix and their chemical incompatibility. In various embodiments, the nHAp particles remain suspended but unreactive to the polymer. The nHAp particles, in accordance with certain embodiments, have a lower size limit that may also pin the relative molecular motion and positively affect the resistance to deformation. In many embodiments, the non-uniform morphology implies possible poor adhesion between the nHAp particles and the surrounding biocompatible resin. The poor adhesion, in accordance with numerous embodiments, leads to partial or complete debonding such that the osteoinductive fillers resemble voids that compromise the stiffness. The heterogeneous interactions and polydispersity of the filler, in several embodiments, dampen the net effect of hybridization with nHAp.

[0100] Figs. 21A and 21 B provide the nanomechanics of biocompatible resins, in accordance with many embodiments, showing the interrelation between hardness, modulus, and elastic / plastic energy.

[0101] In many embodiments, the biocompatible resin can be printed in customizable shapes. AM, in accordance with many embodiments, allows for the printed components to be printed in any configuration for the desired application. In several embodiments, the printed biocompatible resin can be designed to mimic the structure of native tissue. The biocompatible resins, in accordance with various embodiments, can be printed withKPPB Ref: S94-12318.PCT specific topologies for each implant. In many embodiments, the structural topography of printed biocompatible resins impacts the mechanical properties of the printed implants. For example, biocompatible resins are designed with topology to mimic the structure of bone. The geometry of bone tissue and its relationship to the topography of the implant, in numerous embodiments, are important to proper osseointegration and prevent detrimental effects, such as (but not limited to) prolonged presence of a fibrous capsule, induced pain, or loosening. Mathematically generated meta-structures, including (but not limited to) triply periodic minimal surface (TPMS) structures, are viable bone surrogate topologies for skeletal implants. In many embodiments, TPMS structures are based on the congruency between computer-generated geometries and natural bone microstructures. TPMS structures, in accordance with several embodiments, comprise an interconnected, porous diploe-like architecture. Figs. 22A to 22D provide examples of TPMS structures, in accordance with many embodiments, that resemble bone microstructure from different anatomical sites. In some embodiments, the TPMS structure is (but not limited to) a gyroid structure (Fig. 22A), a diamond structure (Fig. 22B), an IW- P structure (Fig. 22C), or a Fischer-Koch structure (Fig. 22D). The TPMS structures, in many embodiments, reduce stress concentrations, zero average curvature, and / or open porous structures. In certain embodiments, the attributes of TPMS scaffold porosity facilitate cell migration and / or vascularization, promoting better osseointegration while mitigating stress shielding. A 10 x 10 x 10 mm3printed biocompatible resin with 0.5 wt.% nHAp and 0.5 wt.% silver oxide, in accordance with various embodiments, exhibited a compressive stiffness of 734 ± 7.5 N / m as shown in Fig. 23. The printed biocompatible resin showed a delineated linear response after the initial toe region. The printed biocompatible resins failed at a compressive force of approximately 370 N after nearly 1 mm compressive deflection. In many embodiments, the compression response can be numerically simulated using finite element methods by ascribing comparable boundary conditions to those imposed during experimentation. In several embodiments, the effective modulus can be adjusted for inherent porosity and internal cracks from nanoscale hybridization of nHAp and silver oxide using MacKenzie and Salganik equations, respectively. The adjusted elastic modulus, in accordance with certainKPPB Ref: S94-12318.PCT embodiments, is 1.75 GPa, and Poisson’s ratio is 0.3. Fig. 23 provides the deformation distribution within the printed gyroid biocompatible resin. The finite element analysis model, in accordance with many embodiments, can be extended to account for the effect of other molecular decoration levels on the compressive response. The extended finite element analysis model, in some embodiments, can affirm the stiffening and / or softening effects of decorations, such as (but not limited to) bioceramic agents and antibacterial agents. For example, the finite element analysis model can validate and calibrate a broad range of TPMS geometries. In many embodiments, the finite element analysis model can compare a range of TPMS geometries with native tissue properties, including those from different anatomical locations.

[0102] Fig. 24 provides the compressive stiffness of printed biocompatible implants in gyroid, diamond, IW-P, and Fischer-Koch structures, ranging between 600-1000 N / m. In many embodiments, the printed biocompatible resins in TPMS structures exhibited comparable bone stiffness to skull, vertebra, and femoral trabecular. The finite element analysis model, in certain embodiments, can investigate the sensitivity of the bone microstructure resembling TPMS structure to Poisson’s ratio. As described herein, the mechanical properties of a biocompatible print can be adjusted by adjusting the weight percent of PMMA. In many embodiments, the finite element analysis model can be used to determine the mechanical properties of biocompatible resins with different PMMA weight percentages. For example, repeated finite element analysis model simulations can vary the Poisson’s ratio from (but not limited to) 0.30 to 0.35 to 0.40, or within a range of values known for PMMA. Fig. 25 provides the compressive force-displacement results of a finite element analysis model for different TPMS structures. As shown in Fig. 23, the sensitivity to Poisson’s ratio is dependent on the TPMS geometry. The printed biocompatible resins are sustainable and adaptable for AM of bone surrogates and implants, irrespective of anatomical complexity.ExamplesExample 1KPPB Ref: S94-12318.PCT

[0103] A bioactive antimicrobial printable resin is prepared using a polymer mix of methyl methacrylate (MMA) monomers, a crosslinking agent ethylene glycol dimethacrylate (EGDMA), and poly(methyl methacrylate) (PMMA) powder, the MMA, EGDMA, and PMMA in a ratio of 45.5 to 45.5 to 9 weight percent. The polymer mix is mechanically mixed in a specific sequence wherein the MMA and EGDMA are homogenized, and then the PMMA powder is dissolved in the homogenized MMA- EGDMA at a controlled temperature ranging between 40-60 °C for 30-60 minutes. Next, the photo-initiator, e.g., BAPO, is added at less than 0.5 wt. %, and the polymer-initiator mix is subjected to UV light to form poly(MMA-EGDMA) resin.Example 2

[0104] A bioactive antimicrobial printable resin is prepared using a polymer mix of methyl methacrylate (MMA) monomers, a crosslinking agent ethylene glycol dimethacrylate (EGDMA), and poly(methyl methacrylate) (PMMA) powder, the MMA, EGDMA, and PMMA in a ratio of 45.5 to 45.5 to 9 weight percent. The polymer mix is mechanically mixed in a specific sequence wherein the MMA and EGDMA are homogenized, and then the PMMA powder is dissolved in the homogenized MMA- EGDMA at a controlled temperature ranging between 40-60 °C for 30-60 minutes. Next, the photo-initiator, e.g., BAPO, is added at less than 0.5 wt.% %, along with an osteoinductive agent, e.g., hydroxyapatite powder, and the polymer-initiator- osteoinductive mix is subjected to UV light to form poly(MMA-EGDMA) osteoinductive resin.Example 3

[0105] A bioactive antimicrobial printable resin is prepared using a polymer mix of methyl methacrylate (MMA) monomers, a crosslinking agent ethylene glycol dimethacrylate (EGDMA), and poly(methyl methacrylate) (PMMA) powder, the MMA, EGDMA, and PMMA in a ratio of 45.5 to 45.5 to 9 weight percent. The polymer mix is mechanically mixed in a specific sequence wherein the MMA and EGDMA are homogenized, and then the PMMA powder is dissolved in the homogenized MMA-KPPB Ref: S94-12318.PCTEGDMA at a controlled temperature ranging between 40-60 °C for 30-60 minutes. Next, the photo-initiator, e.g., BAPO, is added at less than 0.5 wt.%, along with an osteoinductive agent, e.g., hydroxyapatite powder, and an antimicrobial agent, e.g., silver oxide nanoparticles, and the polymer-initiator-osteoinductive-antimicrobial mix is subjected to UV light to form poly(MMA-EGDMA) osteoinductive-antimicrobial resin.Example 4

[0106] A process for curing a polymeric orthopedic implant is illustrated and comprises the following steps: a) photo-polymerizing a bioactive antimicrobial printable resin in the presence of a photo-initiator using UV light compatible with the photo-initiator; b) printing an orthopedic implant using additive processing; c) washing the printed orthopedic implant to obtain a finished orthopedic implant.Example 5

[0107] An additive process of making an orthopedic implant is illustrated and comprises the following steps: a) printing an orthopedic implant using a 3D printer, extruding the resin described herein, wherein the additive process is vat photo-polymerization, fused filament fabrication, or direct ink writing.Example 6

[0108] Fused filament fabrication is performed through the manufacturing of the fusing filaments of the composite filaments of the resin(s) described herein, and is carried out as follows. A fuse fabrication printer, e.g., 3NTR A4v3, is used to print the poly(MMA- EGDMA) osteoinductive-antimicrobial resin orthopedic implant. Orthopedic implants are printed using a polymer-appropriate nozzle temperature, typically between 250 - 450°C, with a lower print bed temperature typically 90-150°C and a print chamber temperature typically 50-100°C. The layers of the orthopedic implant are printed at a thickness rangingKPPB Ref: S94-12318.PCT from 0.1 mm to 1.0 mm. Some aspects may vary and be printed at different thicknesses than other aspects.Example 7

[0109] Additive manufacturing can be accomplished according to following steps: (i) providing a polymer resin of MMA-EGDMA-PMMA-osteoinductive-antimicrobial resin material and a photoinitiator for promoting photocrosslinking of the polymer; (ii) providing a stereolithography instrument comprising a UV laser for activating the photoinitiator and photocrosslinking the polymer; (iii) providing a CAD image of the desired three- dimensional orthopedic implant, wherein said CAD image is readable by the stereolithography instrument; (iv) depositing the polymer in successive layers on a build platen in the stereolithography instrument; and (v) photocrosslinking the polymer in each of the successive layers according to corresponding cross-sectional patterns derived from the CAD image. The fabrication method may further comprise an earlier step of scanning a bone to be duplicated to provide data and converting the data into a three-dimensional CAD image.

[0110] It will be understood that the components of the embodiments, as generally described herein and illustrated in the appended figures, may be arranged and designed in a variety of different configurations. Thus, the following more detailed description of various embodiments, as represented in the figures, is not intended to limit the scope of the present disclosure but is merely representative of various embodiments. While various aspects of the embodiments are presented in drawings, the drawings are not necessarily drawn to scale unless specifically indicated.

[0111] The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The embodiments described are to be considered in all respects only as illustrative and not restrictive.

[0112] Reference throughout this specification to features, advantages, or similar language does not imply that all of the features and advantages that may be realized with the present invention should be or are in any single embodiment of the invention. Rather, language referring to the features and advantages is understood to mean that a specificKPPB Ref: S94-12318.PCT feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the present invention. Thus, discussions of the features and advantages and similar language throughout this specification may, but do not necessarily, refer to the same embodiment.

[0113] Furthermore, the described features, advantages, and characteristics of the invention may be combined in any suitable manner in one or more embodiments. One skilled in the relevant art will recognize, in light of the description herein, that the invention can be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments of the invention.

[0114] Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the indicated embodiment is included in at least one embodiment. Thus, the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may but do not necessarily all refer to the same embodiment.DOCTRINE OF EQUIVALENTS

[0115] This description of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form described, and many modifications and variations are possible in light of the teaching above. The embodiments were chosen and described in order to best explain the principles of the invention and its practical applications. This description will enable others skilled in the art to best utilize and practice the invention in various embodiments and with various modifications as are suited to a particular use. The scope of the invention is defined by the following claims.

[0116] As used herein, the singular terms “a,” “an,” and “the,” may include plural referents unless the context clearly dictates otherwise. Reference to an object in the singular is not intended to mean “one and only one” unless explicitly so stated, but rather “one or more.”KPPB Ref: S94-12318.PCT

[0117] As used herein, the terms “approximately” and “about” are used to describe and account for small variations. When used in conjunction with an event or circumstance, the terms can refer to instances in which the event or circumstance occurs precisely as well as instances in which the event or circumstance occurs to a close approximation. When used in conjunction with a numerical value, the terms can refer to a range of variation of less than or equal to ± 10% of that numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1 %, less than or equal to ±0.5%, less than or equal to ±0.1 %, or less than or equal to ±0.05%.

[0118] Additionally, amounts, ratios, and other numerical values may sometimes be presented herein in a range format. It is to be understood that such a range format is used for convenience and brevity and should be understood flexibly to include numerical values explicitly specified as limits of a range, but also to include all individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly specified. Where ranges are described, the range should be understood to include the endpoints of the ranges, and the endpoints of such ranges are also contemplated to stand on their own as inventive, individual data points and to form the endpoints of other ranges. For example, a ratio in the range of about 1 to about 200 should be understood to include the explicitly recited limits of about 1 and about 200, but also to include individual ratios such as about 2, about 3, and about 4, sub-ranges such as about 1 to about 10, about 10 to about 50, about 20 to about 100, about 100 to about 200, and so forth, and related ranges such as greater than about 1 or less than about 200.

Claims

KPPB Ref: S94-12318.PCTWHAT IS CLAIMED IS:1 . A biocompatible resin comprising: a base resin polymer comprising a methyl methacrylate (MMA) monomer, a crosslinking agent, and a poly(methyl methacrylate) (PMMA) powder.

2. The biocompatible resin of claim 1 , wherein the crosslinking agent is an ethylene glycol dimethacrylate (EGDMA).

3. The biocompatible resin of claims 1 or 2, further comprising an antibacterial agent.

4. The biocompatible resin of claim 3, wherein the antibacterial agent is selected from at least one of: silver oxide, copper oxide, or cupronickel.

5. The biocompatible resin of claims 3 or 4, wherein the antibacterial agent has a weight percent less than 0.5 wt.%.

6. The biocompatible resin of any one of the claims 1 to 4, further comprising a bioceramic.

7. The biocompatible resin of claim 6, wherein the bioceramic is a hydroxyapatite.

8. The biocompatible resin of claims 6 or 7, wherein the bioceramic has a weight percent less than 0.5 wt.%.

9. The biocompatible resin of any one of the claims 1 to 7, wherein a ratio of the MMA monomers, the crosslinking agent, and the PMMA powder is 45.5:45.5:9 wt.%.KPPB Ref: S94-12318.PCT10. The biocompatible resin of any one of the claims 1 to 9, further comprising a photoinitiator.11 . The biocompatible resin of claim 10, wherein the photoinitiator is compatible with an exposure wavelength of an additive manufacturing process.

12. The biocompatible resin of claims 10 or 11 , wherein the photoinitiator is a phenylbis (2,4,6-trimethylbenzoyl)-phosphine oxide (BAPO).

13. The biocompatible resin of any one of the claims 10 to 12, wherein the photoinitiator has a weight percent less than 0.5 wt.%.

14. The biocompatible resin of any one of the claims 1 to 13, wherein the biocompatible resin is configured for an additive manufacturing process.

15. The biocompatible resin of claim 14, wherein the additive manufacturing process is selected from at least one of: fused filament fabrication, vat photo polymerization, and direct ink writing.

16. A method of synthesizing a biocompatible resin, comprising: forming a base resin comprising: mixing a methyl methacrylate (MMA) monomer and a crosslinking agent; and dissolving a poly(methyl methacrylate) (PMMA) powder in the MMA monomer and the crosslinking agent.

17. The method of claim 16, wherein the crosslinking agent is an ethylene glycol dimethacrylate (EGDMA).KPPB Ref: S94-12318.PCT18. The method of claims 16 or 17, wherein a ratio of the MMA monomers, the crosslinking agent, and the PMMA powder is 45.5:45.5:9 wt.%.

19. The method of any one of the claims 16 to 18, further comprising: mixing an antibacterial agent in the base resin.

20. The method of claim 19, wherein the antibacterial agent is selected from at least one of: silver oxide, copper oxide, or cupronickel.21 . The method of claims 19 or 20, wherein the antibacterial agent has a weight percent of less than 0.5 wt.%.

22. The method of anyone of the claims 16 to 21 , further comprising mixing a bioceramic in the base resin.

23. The method of claim 22, wherein the bioceramic is a hydroxyapatite powder.

24. The method of claims 22 to 23, wherein the bioceramic has a weight percent less than 0.5 wt.%.

25. The method of any one of the claims 16 to 24, further comprising preparing the biocompatible resin for an additive manufacturing process.

26. The method of claim 25, wherein the additive manufacturing process is a vat photopolymerization.

27. The method of claim 26, further comprising mixing a photoinitiator in the base resin.KPPB Ref: S94-12318.PCT28. The method of claim 27, wherein the photoinitiator is compatible with an exposure wavelength of the vat photopolymerization.

29. The method of claims 27 or 28, wherein the photoinitiator is a phenylbis (2,4,6- trimethylbenzoyl)-phosphine oxide (BAPO).

30. The method of claims 27 to 29, wherein the photoinitiator has a weight percent less than 0.5 wt.%.31 . The method of claim 25, wherein the additive manufacturing process is a fused filament fabrication.

32. The method of claim 25, wherein the additive manufacturing process is a direct ink writing.

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