3d-printed anatomical models with flexible photopolymerisable coatings, production method thereof and uses of same

Abstract

The present invention relates to 3D-printed anatomical models with flexible photopolymerisable coatings that allow the production of solid hollow models, which may be geometrically highly complex, with high anatomical fidelity and high optical translucency. The piece of the invention mainly acquires these advantageous technical features as a result of the use of coatings that can be photopolymerised by means of step-growth mechanisms or hybrid polymer reactions, as is achieved with thiol–ene chemistry, also called click chemistry or thiol–Michael additions, which may be mediated by free radicals or catalysts.

Description

[0001] 3D-printed anatomical models with flexible light-curing coatings, their manufacturing methods and uses

[0002] Field of Invention

[0003] The present invention relates, in general, to three-dimensionally printed flexible elastomeric atomic models with high optical transparency. Also described is a method for generating said specific anatomical replicas or models of tissues, organs, or any human or animal anatomical structure, or parts of specific anatomical structures, such as examples of hollow parts with irregular geometries, wherein said replicas or models are three-dimensionally printed using light-induced additive manufacturing techniques, for example, stereolithography or digital light processing (DLP). In particular, the method is oriented toward processing digital images of a patient's target organ, generating a digital three-dimensional model, and modifying various parameters before, during, and after printing according to the inherent characteristics of said target organ.The process also includes a post-treatment stage to provide the material with a combination of advantageous characteristics.

[0004] The 3D anatomical model of the present invention seeks to exhibit high fidelity to the specific physiological properties of the target organ of the "patient" or "subject of study" (the source of the imaging); and has applications in the fields of medicine and education, for example, models for testing medical and dental devices, surgical planning, medical and dental demonstrations, teaching, medical and dental research, among others.

[0005] Background of the Invention

[0006] Advanced surgical aids for preoperative planning and rehearsal are a major concern in clinical practice and are increasingly relevant in medicine and dentistry due to the importance of minimizing medical errors, operating times, and rates of infection or postoperative complications. Three-dimensional anatomical models stand out among these due to their ease of manufacture, manipulation, and use in preoperative practice.

[0007] Some of the advantages of these models include improved planning and greater surgical precision, reduced operating time and mortality risk due to postoperative complications, improved teaching and training of students and physicians, and improved patient communication through visual examples, among others.

[0008] 3D printing is a manufacturing process for creating three-dimensional objects by superimposing layers and using a computer-aided design (CAD) program to create a digital model that is cut into very thin cross-sections (layers). Some of the advantages of 3D printing include flexibility and ease of modeling and operation, rapid manufacturing, production of strong and lightweight parts, minimization of waste production, and cost-effectiveness, among others. There are different 3D printing techniques that vary in material selection, surface finish, durability, speed, and manufacturing cost.

[0009] Some of the most commonly used techniques are: stereolithography, electron beam melting (EBM), digital light processing (DLP), PolyJet, Direct Ink Writing (DIW), fused deposition modeling (FDM), among others. The selection of the appropriate printing technique will depend on the desired characteristics of the object to be printed. Sometimes, an additional post-treatment process is performed, which refers to any process or technique performed on a printed part after the 3D printing process, to further improve the quality of the object (appearance and / or consistency). Some examples of post-treatment operations include: sanding, polishing, painting, edge retouching, support removal, etc.

[0010] One example in the medical field where there is greatest interest in developing anatomical models that are highly faithful to the target organs of a "patient" (individual or study subject) is vascular complications, where endovascular repair procedures are currently the preferred approach. However, endograft selection and preprocedural planning remain challenging. Simulation of endovascular procedures and flow studies with medical vascular phantoms aid in endograft selection and surgical planning. However, the implementation of simulation systems has progressed very slowly due to the unsatisfactory properties and characteristics of current medical phantoms.

[0011] An ideal anatomical model in which both the shape and texture and its rheological properties (viscoelastic or mechanical) in general are as similar as possible to the real organ, with which high optical transparency can be very beneficial for endovascular training, simulation and education.

[0012] However, to date, the available state of the art indicates that there is no 3D printing resin that meets all the requirements for these purposes.

[0013] The desired characteristics of anatomical models, such as those for endovascular training, are transparency to allow radiation-free practice, adequate strength to prevent breakage during the training session, and appropriate biomechanics to ensure good navigation of endovascular devices, in addition to faithfully reproducing the anatomy. This represents a major challenge to be solved because current soft 3D printing resins have low strength and insufficient transparency.

[0014] Some anatomical models manufactured by three-dimensional printing are known in the state of the art and are used for preoperative functions and analysis. The methods known within the prior art generally include the steps of obtaining medical images of the target organ of a "patient" or "study subject," creating a computational model, modifying the latter to make it as similar as possible to the target organ, printing, and an additional post-processing step if necessary.However, post-processing steps are often optional and include traditional methods such as those mentioned above, which do not allow obtaining high-fidelity physical and mechanical characteristics to match the target organs because: i) These common post-treatments are designed to improve the appearance and strength of the printed parts, but cannot significantly alter the flexibility or opacity of the materials. i) Most commercially available 3D printing materials are relatively rigid. iii) These common post-treatments are difficult to use on hollow objects, especially those with irregular geometries, and even more so on mechanically soft materials.

[0015] This translates, first, into a lower quality of the anatomical model, in line with the intended purposes; specifically, since transparency is important for educational purposes to demonstrate the surgical process in detail, while flexibility is also important as it helps simulate the actual target organ to a greater degree. This makes the use of conventional manufacturing and post-treatment techniques for creating three-dimensional anatomical models for preoperative purposes inconvenient.

[0016] This represents a significant technical challenge for doctors, patients, hospitals, and educational institutions that require reliable anatomical models that allow them to simulate and practice operations as accurately as possible. Furthermore, the manufacture of any anatomical model is a specialized activity that requires a considerable amount of training; therefore, companies currently dedicated to reproducing 3D anatomical models are few and far between, and the price is very high.

[0017] Such is the case of the anatomical model described in US patent US20210089848 published on March 25, 2022, which describes a method for converting image data into three-dimensional printing data. The method includes adjusting various parameters according to the printer's definition data, such as: the resolution of the image data, the resolution of one or more three-dimensional masks, increasing or decreasing the thickness of the sections to be printed, and creating void areas between layers. The manufacturing process includes post-treatment consisting of smoothing or morphological operations such as thinning or erosion, void filling, and edge removal.

[0018] On the other hand, patent US20220165182, published on May 26, 2022, reveals a surgical operation training simulator, an assembly that anatomically reproduces at least a portion of a human or animal body. It also discloses a manufacturing method for a simulator of the aforementioned type, during which all the elements that make up the assembly are manufactured simultaneously during an additive synthesis stage, preferably by 3D printing. The manufacturing method comprises: a stage of displaying a three-dimensional image of a portion of the human or animal body to be modified, a stage of modifying this three-dimensional image to define a first digital model, and a stage of additive synthesis of the assembly. It does not comprise a post-processing stage.

[0019] For its part, patent WO2021146466, published on July 22, 2021, discloses methods and systems for generating computer models of biological or physiological objects, which do not require extensive user training in the use of complicated design software. Methods and systems for generating libraries of possible 3D models of biological or physiological objects are also disclosed.The process comprises: selecting at least one biological or physiological parameter and at least one printing parameter, using a computer processor to generate a set of parameters, using the set of parameters to generate the computer representation of the three-dimensional biological or physiological object, displaying such representation on a graphical user interface, using said interface to receive input from the user to transmit the computer representation or a derivative thereof to the user or to a 3D printer, which computer representation or derivative thereof is usable to print the 3D biological or physiological object. It is further mentioned that when printing in a liquid medium, a water immersion lens corrected for changes in refractive index may be used to maintain structural fidelity.

[0020] Regarding document W02022066980 published on March 31, 2022, an additive manufacturing method, an additive manufacturing system, a support material for additive manufacturing, an assembly of the support material and a structure material, and a product thereof are described. In this document, the image data is compared with the computer model, and based on the analysis of the comparison, all of the aforementioned are proposed. Likewise, the option of using the curing technique that includes crosslinking is mentioned to selectively increase the rigidity of the overall object or portions thereof. Curing can occur before, during, after, or a combination of both, the removal of the support material. Likewise, mention is made of the use of different printing angles to provide mechanical properties different from the conventional plane.

[0021] On the other hand, patent WO2019021295, published on January 31, 2019, discloses a method for additive manufacturing an object that exhibits the properties of a hard body tissue. The object consists of two materials, each texture element having an interior portion made of said second material at least partially surrounded by a wall portion made of said first material. Furthermore, it also describes the use of supports to support specific areas of the object during construction and to ensure proper vertical placement of subsequent layers of the object. The process may include post-treatment to remove remnants of a "mixed layer" on the surfaces of the objects (i.e., the residual layer of mixed model materials and hardened supports that forms at the interface of both).

[0022] For its part, document WO2022269404 describes a method for manufacturing anatomical models adapted to simulate organs or parts of organs of a patient, through the combined use of additive printing, molding methods, material extrusion, and software technologies to obtain patient-specific organ models. The method comprises a step of selecting or segmenting, by means of a digital image processing software program, the elements of the anatomical structure of an organ or part of an organ from the previously processed images. The necessary and sufficient information that can be associated with the organ model and allow its parameterization is contained in a first software library or materials library and a second software library or manufacturing process library.These libraries are used to select at least one material from the first library and at least one manufacturing method from the second library based on a parameter representative of a measurement or estimate of the hardness of said organ or organ part to be simulated. Acetone smoothing is also mentioned as a post-processing option.

[0023] In contrast, U.S. patent US20190122584, published on April 24, 2019, discloses methods for producing customizable tissue-like materials, as well as organ model systems formed from such methods. Additionally, an electronic device integrated into a surface or structure of the printed geometric structure is added. A sensor measures one or more of the following: pressure, strain, force, contact, deformation of the polymeric body, temperature of the polymeric body, or strain induced in the polymeric body.

[0024] On the other hand, document WO2022117544 published on June 9, 2022 describes a composition comprising one or more commercially available resins for 3D printing, selected from acrylic resins, optionally polyacrylate homo- or co-polymers or mixtures thereof, and silicone resins, mixed with material of plant origin selected from the Solenaceae families, optionally potatoes, eggplants, tomatoes, peppers and in the Fragraría genus, optionally strawberries. And that provides a composite product based on polymers suitable for SLA and / or DLP 3D printing, with sufficient elasticity and flexibility characteristics for the production of realistic organ models, particularly hearts, for teaching and training of medical personnel or the simulation of surgical operations and that withstand multiple cycles of use.

[0025] Finally, European patent EP3483864, published on May 15, 2019, discloses a patient-specific simulator of the aorta and reproductive system, created through 3D printing. The modeling is based on real images of patients' aorta obtained through examinations such as computed tomography and / or magnetic resonance imaging. The purpose is to allow physicians in the field to acquire complex skills and / or perfect their surgical techniques by training in a controlled environment, under appropriate guidance, without exposing the patient to risks.Appropriate post-processing generally depends on the anatomical model and may include one or more of the following: removal of support material using a water jet, repair of breaks that occurred during support removal, exposure of models to ultraviolet (UV) light to improve transparency, iliac arteries reinforced with silicone, or polishing the surface of the object to remove residues of the support material.

[0026] Based on the lessons learned from the state of the art, it is clear that, to date, current elastomeric (soft) 3D printing resins used to manufacture anatomical models have low strength and insufficient transparency. This has led to slow progress in the implementation of simulation systems due to the unsatisfactory properties and characteristics of current medical phantoms. Furthermore, 3D-printed anatomical models require traditional post-treatment processes that do not allow them to provide the models with optimal physical and mechanical characteristics for preoperative applications.

[0027] Therefore, there is a need to provide a method for generating a three-dimensionally printed anatomical model or replica of a patient's target organ, with high optical transparency and physical and mechanical properties that faithfully simulate said target organ. This is intended to improve practice and preoperative planning, minimize medical errors, and enhance surgical safety, teaching, and patient communication, compared to current three-dimensionally printed anatomical models.

[0028] Summary of the Invention

[0029] To overcome the deficiencies of the state of the art, the different aspects of the present invention relate to a method for manufacturing objects, including the generation of a replica or anatomical model of an organ, printed three-dimensionally using light-induced additive manufacturing techniques and a unique post-treatment.

[0030] The anatomical models of the present application are composed in particular of soft (elastomeric) printing resins and coated with a polymeric coating, where the photopolymer coatings for the surface treatment of the anatomical models of the present invention are based on strategies that use "click" chemistry, such as thiol-ene formulations and ternary thiol-ene-acrylate systems by thiol-Michael addition reactions.

[0031] These anatomical models can be used for applications in the fields of medicine, dentistry, and education, for example, models for testing medical devices, surgical planning, demonstrations, teaching, medical and dental research, among others. Some advantages of the present invention lie in obtaining 3D printed anatomical models with high fidelity to the target organs or anatomical structures, being patient-specific, flexible and with high optical translucency. Likewise, the 3D printed and coated objects, which are the object of the present invention, show adequate radio-transparency and echo-lucency characteristics that allow their use in operating rooms under X-rays and in clinics and hospitals under an ultrasound probe.

[0032] In another aspect of the present application, a process for manufacturing the three-dimensional anatomical models of the present invention is also described, which is characterized by being a process that addresses the limitations inherent to SLA printing (low intrinsic optical translucency) and that maintains at the same time the advantages related to this printing method.

[0033] These and other objectives and advantages will become apparent to those skilled in the art from the following description of the figures and the detailed description of the invention; and the appended claims.

[0034] Brief Description of the Fiauras

[0035] Figure 1 shows a scheme showing the three monomers and the photoinitiator used for the example formulation of the coating of the anatomical models of the present application (A), and the scheme of the mechanism of the formation of the ternary system network thiol-allyl ether-acrylate (B).

[0036] Figure 2 shows the FTIR spectra of three coating formulations of the anatomical models of the present application PEGDA / PETMP-AGE before and after exposure to UV light.

[0037] Figure 3 shows the comparison of tensile properties of three categories of samples: i) as printed without modification, ii) post-cured, and iii) coated with the formulations used in the present application PEGDA(50-80%) / PETPM-AGE(10-50%). The data were compared with the properties of human aorta (red block) and PDMS (yellow block), which were cured at room temperature.

[0038] Figure 4 shows the mechanical properties of samples of anatomical models of the present application coated with the thiol-allyl ether-diacrylate formulation compared to samples of parts as originally printed, without modifications.

[0039] Figures 5A and 5B show the graph of the R values. a of the internal and external surface roughness of the samples with and without coating (A), compared with the physical appearance of the samples (especially transparency and visibility) of the hollow cylindrical pieces with and without the coating (B).

[0040] Figures 6A, 6B and 6C show confocal laser scanning microscope images at 20X magnification for samples (A) uncoated inside, uncoated outside (B), and coated (C).

[0041] Figures 7 A and 7B show the contact angle between deionized water and the uncoated 3D printed part with an angle of 85.4 (A) and coated with an angle of 68.5 (B).

[0042] Figures 8A and 8B show the transmission spectra of printed and coated samples for rectangular solid samples (A) and for hollow cuvette / cell samples (B). The blue arrow represents the PIV laser wavelength at 532 cm. -1 .

[0043] Figures 9A-9F show scanning electron microscopy (SEM) images of: (A) As-printed hollow cylindrical shape without modifications, (B) Coated hollow cylindrical shape, (C) Unmodified sample cup surface, (D) Coated sample cup surface, (E) Fractured surface of a 1 mm coated dogbone shaped sample, and (F) a 100 micron magnification section of the coating shown in (E).

[0044] Figures 10A-10P show the morphology and printing layers or patterns of the 3D printed samples cut from a patient-specific abdominal aortic aneurysm (AAA). Specifically, they show the STL file of an AAA model processed from a patient's DICOM prior to 3D printing (A); the surface morphology of the sample cut from the top level of the model at three different scales, 100 pm, 20 pm, and 2 pm, respectively (B, C, and D); the SEM images of the cut samples from the aneurysm sac at three different scales: 100 pm, 10 or 20 pm, and 2 pm (E, F, G, H, I, J), respectively; and the SEM images of the cut samples from the bifurcation area and the femoral artery (K, L, M, N, O, P).

[0045] Figures 11A-11E show the 3D printed coated AAA model printed with Flexible 80A in fluoroscopic view with a guidewire inside (A); the 3D printed coated AAA model printed with Elastic 50A (B); the ultrasound training setup with 3D printed AAA models connected to a pulsatile pump, tested and validated by a vascular surgeon (C); the diameter measurement of a coated aneurysm printed with Elastic 50A (D); and the ultrasound image of a coated AAA printed with Flexible 80A (E).

[0046] Figure 12 shows 3D printed anatomical models, object of the present invention, with coating (A) and without coating (B); said models are complex hollow pieces that correspond to anatomical models of abdominal aotic section, polytheal aortic section, thoracic aorta, femoral aorta.

[0047] Detailed Description of the Invention

[0048] Some aspects of the present invention will now be described in more detail with further reference to the accompanying drawings, which show some embodiments and advantages of the present invention. It will be apparent to one skilled in the art that various embodiments of the invention may be expressed in many different ways and should not be construed as limited to the embodiments described herein; rather, these exemplary embodiments are provided to make this invention clear and complete, and to fully convey the scope of the invention to those skilled in the art. For example, unless otherwise indicated, something described as first, second, or the like should not be construed as implying a particular order. As used in the description and the appended claims, the singular forms "a," "an," "the," include plural referents unless the context clearly dictates otherwise.

[0049] The different aspects of the present invention relate to a three-dimensionally printed anatomical model with a photopolymerizable (flexible) elastomeric coating. Said anatomical models have flexibility values ​​within the range for elastomeric and flexible materials, i.e., Young's modulus values ​​close to or below 10 MPa, an elongation percentage from 40% to 1000%, and optical translucency values ​​from 50% to 100%.

[0050] In a preferred embodiment, the anatomical model of the present invention is a specific model of tissues, organs, or any anatomical structure, or parts of specific anatomical structures, such as examples of hollow parts with irregular geometries. Such models also exhibit high fidelity to the physiological properties of the "patient" or "subject" and are precisely created to reflect the unique characteristics of a particular individual, making them especially suitable for personalized medical applications and surgical procedures.

[0051] According to the above, the "patient" or "subject of study" can be understood as the source subject of the imaging from which the anatomical model is generated, and which can be a human or any other animal.

[0052] In a preferred aspect, the atomic model is manufactured using the stereolithographic additive manufacturing (SLA) technique.

[0053] In a preferred embodiment, the atomic model is manufactured using the additive manufacturing technique of digital light processing (DLP) with a projector or LCD screen. In another preferred embodiment, the photopolymer coatings for surface treatment are composed of systems based on "click" chemistry, such as thiol-ene combinations and thiol-Micael systems, such as thiol-ene-acrylate. The coatings of the present invention allow for increased optical transmission of anatomical models, while maintaining the flexibility of the 3D printing resin and anatomical fidelity, as well as, in some cases, radiopacity and echolucency.

[0054] In a preferred aspect, the appropriate click chemistry-based systems that can be used in the formulation of the coating of the present invention may contain mono or multi-functional thiols (mercaptans) in general: alkylated, adiated, phenolic mercaptans, as well as mercaptan proprionates and glycolates; examples of specific compounds and functional groups are: pentaerythritol tetrakis (3-mercaptopropionate) (PETMP), (mercaptopropyl)methylsiloxane homopolymer, (methacryloxypropyl)methylsiloxane-dimethylsiloxane copolymer 2-4%, thiol-functionalized polyesters, mercaptoethanol, mercaptoglycerol, thioethers, dodecane thiol, 3-mercaptopropionic acid and pentaerythritol tetrakis (2-mercaptoacetate).

[0055] In a preferred aspect, the systems based on click chemistry appropriate that can be used in the formulation of the coating of the present invention, may contain vinyls (enes) in general: with various degrees of electronic density, alkylated, aromatic, among others; where examples of compounds and specific functional groups are: vinyl ethers, allyl ethers, norbornenes, N-alkyl maleimides, hydroxy butyl vinyl ether, vinyl sulfones, acrylamides, acrylates, methacrylates, acrylonitriles, styrene, maleimides, vinyl silacenes, and conjugated dienes;Examples of specific compounds are: trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, vinyl esters, trimethylolpropane diallyl ether, norbornene, allyl ethers, glycoidyl dimethacrylate, Bis-GMA, TEGDMA, UDMA, 2-hydroxypropyl ethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, triallyl triazene, unsaturated ketones, fumarate esters, olefins, cinnamates and crotonates.

[0056] In a preferred aspect, appropriate thiol-Michael addition reaction chemistry systems that can be used in the formulation of the coating of the present invention may contain strong bases and acids, amines, alkyl phosphines, metals, organometallic compounds and Lewis acids.

[0057] In a preferred aspect, appropriate free radical initiated click chemistry based systems that can be used in the formulation of the coating of the present invention may contain Type I and Type II initiators, for example: Irgacure 819, phosphine oxides, benzophenone, thioxanthones.

[0058] In general, any chemical reaction classified as click chemistry can be used, which meets all or some of the distinctive characteristics such as: 1) high reaction yields / conversions, 2) they require small amounts of initiators or catalysts, 3) fast reaction rates at wide concentration ranges, 4) they do not require or require few clean-up steps, 5) they are not inhibited by molecular oxygen or water, 6) they tend to have a single regioselective product, 7) high versatility and availability of precursors, and in terms of materials they typically 8) they form highly homogeneous and close to ideal crosslinked polymers, therefore 9) they present low levels of polymerization-induced stresses and shrinkage.

[0059] In a preferred aspect, the coating of the present invention comprises ternary thiol-allyl ether-acrylate systems, and a vinyl group that undergoes homopolymerization.

[0060] In another preferred aspect, the photopolymerizable solution of the coating is composed of a mixture of three components of PEGDA, which can be in a concentration of 5% to 80%, Thiol, which can be in a composition of 1 to 80% and AGE which can be in a composition of 5 to 90%.

[0061] In a preferred aspect, the morphology of the anatomical models may comprise, but is not limited to, a tubular, cylindrical, spheroidal, globular, elongated, elliptical, branched, polyhedral, toroidal, conical, pyramidal, irregular structure, among others.

[0062] In a preferred aspect, the appropriate anatomic models that can be manufactured from the method of the present invention can be any of the group comprising the aortic arch, thoracic aorta, thoraco-abdominal aorta, abdominal aorta, femoral aorta, popliteal aorta, circle of Willis, peripheral arteries, tumors in general (for example cerebral), carotid arterial vasculature, cerebral vasculature, pulmonary vasculature, among other sections composed of any tissue called "soft".

[0063] Likewise, the aforementioned anatomical models can be negative structures of the same or other organs or parts of anatomical structures. Negative structures are cavities or spaces within the human body that do not contain solid tissue, such as bones, muscles, or organs, but are instead filled with air, fluid, or other materials. These negative structures are important for understanding the anatomy and physiology of the human body, as they play a crucial role in functions such as respiration, blood circulation, digestion, and excretion.

[0064] In a preferred aspect, the appropriate anatomical models of negative structures that can be manufactured from the method of the present invention can be any of the group comprising thoracic cavity, abdominal cavity, cranial cavity, pericardial cavity, joint cavity, spaces of the gastrointestinal tract, among others. In another preferred aspect, the anatomical models object of the present invention can be representations in elastomeric materials of anatomically rigid structures. Anatomically rigid structures are understood as those that are formed by tissues or materials that provide resistance and support, which allows them to maintain their shape and function in a stable manner.A person skilled in the art will understand that some anatomical structures require both rigidity and flexibility, as the combination of these two characteristics allows an organism to adapt to changing environmental demands and daily activities. Cartilage is an example of this combination, as it is a firm connective tissue present in areas such as the joints and the nose. It provides support and protection while maintaining the ability to deform and adapt to the forces and movements necessary for its function.

[0065] In a preferred aspect, the anatomically rigid structures that can be manufactured from the method of the present invention can be any of the group comprising cartilage, synovial joints, ligaments, fascia, epiglottis, among others.

[0066] In a preferred aspect, the appropriate anatomical models that can be manufactured from the method of the present invention may correspond to a target extracted from the negative of any of the aforementioned anatomical structures, for example, dental guards.

[0067] In a preferred aspect, the appropriate anatomical models that can be manufactured from the method of the present invention may correspond to a replica of anatomical structures of animals for laboratory studies in medical, biomedical or veterinary research.

[0068] In one exemplary embodiment, the 3D printed anatomical model is a vascular model of geometrically complex regions.

[0069] In another preferred aspect of the aforementioned exemplary modality, the final vascular models have adequate echogenicity (echolucency) to be used in ultrasound Particle Image Velocimetry (PIV) techniques.

[0070] In another preferred aspect of the aforementioned exemplary modality, the final anatomical models have adequate radiopacity to be used under X-rays for surgical (preoperative) planning.

[0071] On the other hand, the present invention relates to a process for the manufacture of coated anatomical models, which are generally carried out in three stages: i) Processing of medical images;

[0072] i) Manufacturing of the anatomical model; and iii) Post-processing.

[0073] The first step in image processing involves medical image processing, receiving medical imaging files in DICOM, STL, OBJ, or other "native" formats—the formats used for CT, MRI, and sonogram images. This first step also involves collecting and integrating detailed information related to the model's intended use: whether the replica will be solid or hollow, as well as the optical and mechanical properties required for the requested model. This first step continues with file segmentation using open-source platforms, such as Autodesk's 3D Slicer and Meshmixer, or preferably, using Materialise's commercial MIMICS software.The images are then post-processed using a prototype design tool such as Meshmixer or 3-matic, in order to refine and improve model characteristics such as thickness, clean structures, smooth surfaces, etc. To complete this first step, the image file must be converted to one that can be read by the 3D printer, such as STL or OBJ formats.

[0074] During the second step of the procedure, the STL file obtained previously is processed in the PreForm software or any other software provided by the manufacturer of the 3D printers used, where the inventor of the present application develops and generates the appropriate parameters for printing depending on the anatomical model, such as: orientation of the anatomical model, location within the printing platform, density of the supports, architecture of the supports and printing resolution.

[0075] Next, a commercial resin must be selected as the printing material according to the requested requirements, for example, acrylic resins for homo- or co-polymers, polyacrylates or their mixtures, and silicone resins. The model is then printed, and once printed, the supports are completely or partially removed before washing. Solvent washing is the final step in this second phase and is performed in a tub or manual or automatic washing machine.

[0076] Finally, in the third stage, post-curing is carried out depending on the resin and the result obtained at the end of the solvent wash.

[0077] In this post-curing process, the piece is placed in an irradiated chamber to allow the photopolymerization reaction to complete.

[0078] Additionally, depending on the desired characteristics according to the model being treated, additional post-treatment procedures such as coating and / or painting can be performed.

[0079] In a preferred aspect, the aforementioned method of the present invention involves a process for addressing the inherent limitations of SLA (short-lived) printing while maintaining its advantages. To better understand the invention described herein, the following examples are presented. It should be understood that these examples are for illustrative purposes only. Therefore, they should not limit the scope of this invention in any way.

[0080] EXAMPLES

[0081] Samples of anatomical model parts were prepared to study their properties when subjected to post-treatment and coating compared to when they did not involve any of these additional processes after printing the part. Formlabs Flexible 80A and Elastic 50A printing materials were used to manufacture the samples, as they are commonly used soft 3D printing resins. The manufacturer has a standard protocol for the post-processing of each resin. For these resins, it is recommended to wash with IPA for almost 20 minutes in two separate 10-minute sessions with a pause in between. Post-curing is then carried out in a Form Cure UV machine to ensure the parts achieve their optimal mechanical properties. Based on the geometry of each sample, the print settings and post-processing steps were explained in each test.In this study, the samples designated as "Green" were only washed with IPA after printing.

[0082] The “Post-cured” samples were subjected to a standard protocol in a post-curing machine, e.g., Form Cure UV (Formlabs, Massachusetts, USA), after printing, and the “Coated” samples were only bathed with IPA and then dip-coated with a UV curing solution and cured under a 365 nm UV light source.

[0083] On the other hand, the photopolymerizable solution of the coating of the present invention was prepared in a three-component mixture of PEGDA, Thiol and AGE in three different compositions: PEGDA (50-80%) / PETMP-AGE (10-40%), PEGDA (40-70%) / PETMP-AGE (10-50%), PEGDA (20-70%) / PETMP-AGE (20-70%). During the coating process, firstly, PEGDA, AGE and photoinitiator (TPO, 0.5% by weight) were added and magnetically stirred for half an hour. In order to delay the gelation time and due to the high activity of the monomers, a small amount of inhibitor (HQ, 0.01 -2.5%) was added to the solution. Then, PETMP was added to the mixture and magnetically stirred for another 30 minutes. When the precursor solution was ready, the samples previously washed with IPA and free of dust were immersed in the photocurable solution for almost 1 or 2 minutes.The dip-coated 3D printed samples were then removed and hung for a few seconds to allow excess resin to drain away by gravity. Finally, they were cured in a UV curing machine (Dymax MX-150, Dymax, USA) at 365 nm for 1 to 2 minutes, depending on the sample geometry.

[0084] Example 1. Characterization of photocurable formulations for clear coating

[0085] A detailed description and characterization of the polymeric coatings applied to the 3D models of the present invention will be described below:

[0086] In the present invention, thiol-ene-vinyl systems containing homopolymerization of vinyl monomers such as (meth)acrylate have been presented. The aforementioned compounds were chosen to overcome several of the obstacles present in the prior art.

[0087] For example, step-growth thiol-ene photopolymerization is known to exhibit lower shrinkage stress compared to conventional chain-growth photopolymerization. Photopolymerization-induced shrinkage and the resulting stress are therefore a significant problem in some applications, such as coating. The most destructive consequence of this shrinkage stress is detachment from the polymer / substrate interface.

[0088] The volumetric shrinkage of thiol-ene polymerization (12–15 mL / mol) has been found to be considerably lower than that of conventional methacrylate systems; however, thiol-ene photopolymerization results in a poorly crosslinked network compared to (meth)acrylate systems. As a result, they exhibit low modulus and strength. Furthermore, the volumetric shrinkage of thiol-ene polymerization (12–15 mL / mol) has been found to be considerably lower than that of conventional methacrylate systems; however, thiol-ene photopolymerization results in a poorly crosslinked network compared to (meth)acrylate systems. As a result, they exhibit lower Young’s modulus and strength levels.

[0089] The coating of the present invention, in contrast, employs ternary thiol-allyl ether-acrylate systems and a vinyl group that undergoes homopolymerization. The system of the present application exhibits a combination of chain and step-growth photopolymerization. Furthermore, the photopolymerization mechanism and the resulting network structure are strongly affected by the amount of homopolymerization and the reactivity of the thiyl radicals with respect to the two different double bonds of (meth)acrylate and allyl ether.

[0090] Overall, this ternary system exhibits two distinct polymerization regimes. First, a regime dominated by acrylate homopolymerization with significant chain transfer to the thiol. This is followed by a regime dominated by thiol-ene polymerization.

[0091] These two polymerization regimes and the structure of the monomers used in the formulation are represented in Figure 1.

[0092] The three formulations used in this study are shown in Table 1. The final thiol-ene formulation also showed high transparency and good flexibility suitable for the vascular phantom.

[0093] All formulations showed good surface interaction with the 3D printing resin material. The coating improved transparency in both soft materials (Flexible 80A and Elastic 50A), and varying the thiol / ene ratio resulted in different elasticities, offering the opportunity to fine-tune the final mechanical properties to the target organ.

[0094] Although it is known in the prior art that the thiol / ene ratio directly affects the photocrosslinking rate, the inventor of the present application unexpectedly discovered that the thiol:AGE functional group molar ratio was adjusted to a stoichiometry of 1.5:1 for all formulations, and that it also has a rapid gelation of approximately 1.4 seconds. PEGDA was used in this study because this monomer has high reactivity and good transparency. Furthermore, AGE monomer was added to the formulation to prevent spontaneous gelation between PEGDA and thiol.

[0095] Example 2. Degree of conversion of the clear coating

[0096] In order to measure the degree of conversion of the coating used in the present invention, a drop of monomer precursor solution was placed between two polyethylene films to avoid reduced oxygen inhibition during photopolymerization and irradiated under a UV curing unit at 365 nm. The degree of conversion (GC) of the stretching vibrations of the C=C double bond in PEGDA molecules at 1636 cm was analyzed. -1 and the thiol stretching vibrations (SH) in PETMP at 2560 cm -1 using a Fourier transform infrared (FTIR) spectrometer. The sample's GC was calculated by measuring the absorbance spectra of C=C and SH before and after 60 seconds of UV light exposure. The carbonyl functional spectrum peaked at 1720 cm -1was used as an internal reference. The conversion ratio of C=C or SH was calculated using Eqs. 1 and 2, taking into account the decrease in the peak areas of C=C or SH compared to the peak area of ​​the carbonyl group at 1720 cm -1 . According to the FTIR spectrum the stretching vibration peak of thiol (SH) appeared at 2560 cm -1 and the stretching vibration peaks of acrylate (C=C) were located at 1636 and 1620 cm' 1 . Also, more characteristic absorption peaks were observed in the stretching vibration of the C=C double bonds at 1410 and 810 cm -1 . The conversion was calculated from the C=C peak at ~1636. The aforementioned peaks disappeared after UV irradiation. The area under the peak curve is shown in Table 2, which shows the degree of C=C and SH conversion of the three formulations with and without HQ after 60 seconds of UV exposure.

[0097] The results of the FTIR spectra are shown in Figure 2, where the FTIR spectra of three PEGDA / PETMP-AGE formulations are shown before and after UV exposure.

[0098] Table 2.

[0099] Example 3. Optical properties testing by UV-VIS transmission spectroscopy. UV-VIS spectroscopy (Ocean Insight, Florida, USA) and (Agilent Cary 7000 Universal Measurement Spectrophotometer, Agilent Technologies, Inc. USA) were performed to quantitatively measure optical transparency. First, to measure the transparency of the printed bulk materials, 2 mm thick rectangular strips were printed with Flexible 80A and Elastic 50A resins. To check the effect of print orientation on transparency, samples were printed in three different orientations, 90, 75, and 45 degrees relative to the print platform with both resins. One orientation (90 degrees) was then selected for both resins to check the transparency after coating.Additionally, to measure the transparency of the 3D-printed hollow structure, a rectangular hollow tub design was created using SolidWorks (licensed desktop CAD software) with a 1 mm thickness on each wall to measure the transmittance of a hollow model. Finally, to test the effect of the interface with a fluid instead of air on transparency, a common blood substitute solution composed of purified water and glycerol (WG 40:60) was used. Samples were prepared with a rectangular hollow design adapted to the UV-VIS spectroscope sample holder in two categories: green and coated, and subjected to transmission testing with and without the blood substitute. Samples for the hollow structure were printed with Flexible 80A resin using the Form 3 printer. The print orientation was fixed for all samples at 90 degrees to the print platform.

[0100] Optical imaging is frequently used for cardiovascular flow and biofluid studies. There are several suggested fluids used as blood substitutes in vascular flow studies, consisting of water and glycerol with different compositions.

[0101] In this study, a fluid composed of 40% distilled water and 60% glycerol was tested at room temperature. The optical properties of Flexible 80A resin after printing with and without a blood substitute were studied using UV-VIS spectroscopy. First, the optical properties of this resin as a bulk material were studied. As shown in Figure 8A, transparency increased up to 81% for the coated sample at a wavenumber of 532 cm . -1, which is the wavenumber of lasers for PI V lasers. It was also observed that the coating was able to cover the surface roughness and reduce light scattering, which improved transparency. The results are consistent with the surface roughness values ​​after coating.

[0102] In accordance with exemplary embodiments mentioned herein, where the 3D printed anatomical model is a vascular model of geometrically complex regions, the optical properties of this resin were also investigated when printed in a hollow cell or vat shaped model, Figure 8B. As a result of this study, it was found that the average transparency increased from 10.64% of the unprinted part to 50.55% of the coated one at 532 cm -1. The 3D printed cell / cuvette-shaped parts, which were compatible with the UV-VIS spectroscopy cell, were then examined. They were filled with the blood substitute, and as shown in Figure 8, there was no improvement in the transparency of the printed sample. However, transparency increased in the coated sample to 71.56% at 532 cm -1 once it was filled with the blood substitute.

[0103] The transmission spectra of the samples used in this study are shown in Figure 8.

[0104] Example 4. Tensile test

[0105] The mechanical properties of SLA 3D printed soft materials were evaluated using a standard materials testing apparatus (Instron 3365, Instron Company, USA) equipped with a 1 kN load cell and a constant displacement test at 10 mm / min. The dog bone-shaped specimen was designed in SolidWorks according to ASTM D635, with 73 mm length, 54 mm gauge length, 10 mm width, 5 mm gauge width, and 3 mm thickness. Five specimens from each category were used. The printing orientation was set for all specimens at 75 degrees to the printing platform, with a printing thickness of 0.01 mm. The dog bone-shaped specimens were prepared with two 3D printing resins: Flexible 80A and Elastic 50A, in three categories: Green, Standard Post-Cure, and Coated.To see the effect of SLA 3D printing using low-force stereolithography (LFS), a set of test specimens were also printed on the Form 2 printer, using Flexible 80A resin with the same printing parameters.

[0106] Although Formlabs lists the basic mechanical properties of its 3D printing resins, elastic moduli are not included. The main difference between printing on the Form 2 and Form 3 printers is the low-force stereolithography (LFS) technology, which greatly reduces peel forces to significantly increase print quality and printer reliability. Overall, samples printed on the Form 3 had a higher elastic modulus and ultimate tensile strength (UTS). Furthermore, compared to the Form 2, the results from the Form 3 were closer to the data provided by the supplier. On the other hand, to investigate the effect of the coating on the mechanical properties of Flexible 80A, specimens printed on the Form 3 printer were used to achieve the best print quality. Detailed data for UTS, elongation at break (emax), and Young's modulus (E) are shown in Table 3.As the thiol-ene content increases, more carbon-sulfur-carbon or thioether bonds are created in the network, leading to an increase in the distance between crosslinking sites and thus greater flexibility in the system. Therefore, Young's modulus decreases with increasing thiol-ene content. The maximum stress defines the UTS that a material can withstand while being stretched before it breaks or fails. As the thiol-ene content increases, the zone of plasticity, or UTS, increases. Therefore, the specimen has a greater elongation before failure.

[0107] The stress-strain curves of the coated samples according to the present application and those printed without modification are shown in Figure 4. The mechanical properties of the PEGDA / PETMP-AGE formulation can be easily tuned by changing the monomer / oligomer stoichiometry.

[0108] The results of the tensile test are promising when compared with the data from human abdominal aortic aneurysm (AAA) and polydimethylsiloxane (PDMS) tensile tests reported in the literature.

[0109] Currently available 3D printing materials cannot mimic the mechanical properties of soft tissue under large deformations (stresses). When interacting with cardiovascular equipment, the models behave very differently than real tissue. This is due to the complexity of soft tissue composition, which contains collagen and elastin fibers that make it more resilient depending on the applied stress, known as "strain-hardening behavior," where stiffness increases with increasing strain. Meanwhile, 3D printing polymers or resins are characterized by stress-strain curves that display "strain-softening behavior," where the opposite is true: a decrease in uniaxial stress with increasing strain.

[0110] The Sylgard® 184 silicone elastomer kit is the most widely used commercial PDMS in many applications, including vascular phantoms. PDMS exhibits varying mechanical properties depending on the curing temperature. Phantom fabrication is mostly done at room temperature due to handling. The tensile properties of PDMS at room temperature and the tensile properties of aneurysmal and non-aneurysmal human aorta were used to evaluate the mechanical properties of the coated samples.

[0111] The PEGDA70 / PETMP-AGE30 coating formulation exhibited the most similar properties to those of the human abdominal aorta. The results indicated that the standard post-cured Flexible 80A printed specimen had a higher UTS and elongation than the human abdominal aorta. Furthermore, the unmodified printed specimens also had a lower Young's modulus compared to human tissue data. It can be inferred that the PEGDA70 / PETMP-AGE30 coating layer optimized the properties, as the combination of the coating and the bulk part had more tissue-like properties.

[0112] The tensile test results, i.e., the stress-strain curves of the coated and unmodified printed samples are shown in Figure 4. Example 5. Thickness measurement and morphology study of samples using scanning electron microscopy (SEM).

[0113] Scanning electron microscopy (SEM) images were taken to measure the coating thickness and study the surface morphology. To study the surface morphology of these 3D printing soft materials, three types of samples were used. A hollow rectangular shape similar to the transmission test sample (Flexible 80A), a hollow cylindrical shape design similar to a blood vessel with an outer diameter of 12 mm and a thickness of 1.5 mm (Flexible 80A), and finally, some rectangular samples with a thickness of 1.5 mm which were cut from random locations from a soft AAA 3D ​​printed by SLA (with two resins Flexible 80A and Elastic 50A). The morphology and printing layer of the first and second categories of samples were further evaluated with the coating or uncoating.To measure the coating thickness, the fractured surface of the dog-bone shaped samples coated with Flexible 80A was used from the tensile test.

[0114] According to the results obtained from this test, the hollow cylindrical designs of the printed morphology without modification and coated were similar to the images of the confocal laser microscope, confirming the smoothed fine surface as a result of the coating, Figure 9. An average thickness of 59.17 ± 6.84 was measured. The thickness is low enough to not modify the anatomical details inside the model in the practice model or in the aneurysm. In addition, it was also verified that the thickness of the coating directly depends on the coating techniques.

[0115] Scanning electron microscope (SEM) images prepared in this study are shown in Figure 9.

[0116] Example 6. Measurement of surface roughness

[0117] The surface roughness of the test specimens was quantitatively characterized using a confocal laser microscope (Zeiss Axio CSM 700, Carl Zeiss, Germany) and a Mitutoyo surface roughness gauge (SJ-210, Mitutoyo, Japan). Flexible 80A resin was used for this characterization. Similar to the transmission test specimen, the hollow rectangular test specimens were printed with Flexible resin using Form 2 and Form 3 printers. To measure the surface roughness of a geometry such as human blood vessels, a hollow cylindrical shape with a thickness of 1.5 mm was designed. Vessel-shaped samples were also followed by the green and coated categories. A print orientation of 90 degrees to the print platform and a layer thickness of 0.05 mm were used for all samples.The average surface roughness (Ra) of the outer and inner surfaces of green and coated samples printed with Form 2 and Form 3 printers was measured. Two samples were printed in each category. In each category, two test specimens were tested, and two positions on each test specimen were measured four times for each point. Confocal laser scanning provided qualitative images of the morphology and surface roughness of each test specimen.

[0118] The average surface roughness (Ra) of the printed and coated specimens is shown in Figure 5A. The surface roughness of parts printed with the Form 3 printer was lower than that of the Form 2 specimens at both tilt angles. The surface roughness created by the printing layers is shown in confocal microscopy images in Figure 6. The image shows that the coating layer covered the roughness of the part, resulting in a smooth and uniform surface. The coating layer could significantly reduce the surface roughness from the range of 1 - 2.5 microns of the as-printed sample to 80-100 nanometers. The coating layer reduces the staircase effect of the 3D printer and the surface roughness of the exterior and interior. The surface roughness of the cup-shaped sample before and after coating was observed by confocal laser microscope.Where it could be noted that the staircase effect, causing surface roughness, was softened, and the R. a average of 3.59 ± 0.97 was reduced to 0.077 ± 0.05 after coating.

[0119] The roughness values ​​Ra for the samples are displayed in Figure 5 and the images showing the roughness by confocal microscopy images are displayed in Figure 6.

[0120] Example 7. Contact Angle The interaction of the surface of soft 3D printing resin with water and how this wettability can be altered by surface treatment was identified by applying the sessile or recumbent drop method. For this test, 80A flexible resin was used. For consistent results, the same samples were used for transmission, and surface roughness was used for this test. A 10 pl drop of water was applied to the surface of the green and coated samples, and an image of the drop was taken after 5 seconds. The contact angle of each drop was measured using the Drop Analysis LB-ADSA plugin in ImageJ software. In addition, the surface roughness of the internal flow channel was measured to measure the model's roughness. Hollow rectangular cubic and hollow cylindrical containers were used to measure the roughness of the exterior and interior.This is important because the roughness of the exterior and interior surfaces can also affect transparency. The surface roughness of samples printed on the Form 2 and Form 3 was measured to assess the differences between these two generations. Printing parameters such as print orientation and layer thickness can alter surface roughness, so the samples were printed at two different angles (85.4° and 68.5°).

[0121] The result of measuring the water contact angle before and after coating reveals the changes in the surface, Figure 7. The average contact angle of the uncoated samples was 85.20 ± 2.5, while after coating it was reduced to 68.25 ± 1.7.

[0122] The above demonstrates that the organ samples in this application exhibit superior hydrophilic and wettability properties after coating. It has been previously reported that wettability can be affected by changes in surface roughness, as well as the addition of certain components that can alter the chemistry of the part, making it, for example, hydrophilic and facilitating protein adhesion.

[0123] In the present invention, a combination of both effects occurs: a reduction in surface roughness and a change in the chemistry of the 3D-printed part, resulting in a decrease in wettability and surface tension. This wettability behavior after coating is favorable for the PIV experiment, as human tissue also has similar hydrophilic characteristics.

[0124] The contact angle images and values ​​obtained for the samples in this study are displayed in Figure 6.

[0125] Example 8. Manufacturing a 3D printed patient-specific phantom

[0126] The manufacturing process of these anatomical models follows the steps previously described in the description: Image acquisition, image segmentation, optimization of 3D digital models, printing and post-processing.

[0127] For the study corresponding to example 8, anatomical models, including that of an abdominal aortic aneurysm (AAA), were reconstructed from a computed tomography in DICOM (Digital Imaging and Communications in Medicine) format using the 3D slicer software (www.slicer.org), an open source program.

[0128] Regions of interest were isolated from surrounding tissue using Hounsfield units (150–400 for the abdominal aorta) to select a specific pixel intensity. Digital models were optimized using the cropping and smoothing algorithms provided by the 3D slicer. Models were also hollowed out to an appropriate wall thickness using another software program (3-matic, Materialise Co., Leuven, Belgium).

[0129] The digital constructions were then exported in stereolithographic (STL) file format and imported into another computer-aided design program, Meshmixer (www.meshmixer.com). This software inspected the hollow model for all possible surface defects, and reconstructed the triangular surface mesh.

[0130] The final STL file of the 3D model was exported to the open-source software Preform, provided by the printer manufacturer, which features an algorithm to automatically adjust the print layer thickness, print orientation, and support distribution. However, when using soft resins for printing complex hollow structures, printing parameters were typically adjusted manually. Prior art suggests that print orientation and layer thickness can alter the properties of 3D printed parts. A study by Kenneth I. Aycock et al. showed the effect of print orientation from 90° to 45° on the transparency and laser penetration of a 3D-printed SLA vascular phantom for laser PIV.However, defining a specific orientation for 3D printing of patient-specific soft vascular models is not easy due to the printing challenges of these materials, their dimensions, and their inherent complexity. Figure 10 shows how the surface roughness of a patient-specific 3D-printed AAA can vary, as seen in micrographs of cut sections from randomly selected portions of the phantoms printed in the flexible material. When it comes to anatomical 3D printing, layers and print orientations can be more difficult to distinguish. Therefore, the coating of the present invention could be more beneficial as a surface treatment technique than simply adjusting the print orientation.

[0131] Example 9. Applications of vascular models (vascular training - pre-procedure planning and eco-compatibility of 3D printed SLA soft materials).

[0132] To test the use of the parts of the present invention as anatomical models, AAA phantoms were printed with Flexible 80A and Elastic 50A, followed by standard post-processing and / or coating steps, and then placed inside a medical phantom. The specimens were manipulated and tested prior to procedure planning on a free-floating angiography table to verify fluoroscopic visibility of the anatomical phantoms.

[0133] Likewise, to verify the acoustic properties of the vascular phantoms, an echo-compatibility test was performed for both resins (Flexible 80A and Elastic 50A), in which a 3D-printed AAA model was integrated into a flow setup. The AAA phantom was fitted within a container connected to a peristaltic pump (100 series canned pump, Watson Marlow, UK). The pump generated a continuous flow from the inlet to the outlet of the model in a closed circuit, and a routine BMF (Fluid Media Block) formulation composed of water and glycerol at room temperature was used. The BMF solution was flowed into the phantom by the peristaltic pump at a constant flow rate of 200 ml / s. An ultrasound system (GE Vivid T8 ultrasound machine, General Electric, USA) was used with standard parameters.

[0134] Unlike computer simulators, the cost of 3D printers has decreased in recent years, making them increasingly affordable for educational institutions. 3D printing-based endovascular simulators are a cost-effective solution for medical practice, providing haptic feedback and allowing physicians to practice with guidewires, catheters, and stent grafts to simulate the actual procedure in operating room-like conditions.

[0135] Fluoroscopic visibility of the fabricated vascular phantoms was checked using a pair of soft resin models that included a soft liner. The AAA phantoms were tested with and without the liner to ensure that the liner layer did not interfere with X-ray visibility. A fluoroscopic image of a coated AAA model with a guidewire inside is shown in Figure 1 1A. The coated AAA vascular phantom was used for preoperative planning.

[0136] Furthermore, these soft SLA 3D-printed resins could be a good option for phantom manufacturing, allowing for more cost-effective simulation of vascular procedures. The mechanical characteristics of these soft resins allow for more realistic practice compared to phantoms made from rigid materials. It's worth noting that the final cost of these models is significantly lower than that of models printed with PolyJet.

[0137] Pre-procedural planning is an essential part of endovascular procedures. With this in mind, pre-procedural planning using the specific coated 3D-printed model of the present invention is more beneficial, as it provides flexibility closer to vascular tissue, while having adequate transparency to clearly view the guidewires and catheter within the model without the need for fluoroscopy, as shown in Figure 11 B.

[0138] On the other hand, echogenicity testing is important in 3D-printed vascular models, as echogenicity is beneficial for vascular applications such as training and education of medical residents and ultrasound-based flow visualization and quantification techniques. The echogenicity of Flexible 80A is well known in the prior art. However, in the study conducted by the inventor of the present application, it was shown that the AAA printed in Elastic 50A also exhibits good echogenicity for ultrasound imaging (Figure 11 C); thus, it is clear that the coating layer did not present ultrasound interference. This observation is important, as it means that the use of Echo-PIV in phantoms similar to those of Laser-PIV may now be possible.Furthermore, it can be a practical tool for medical students to practice, analyzing complex and rare cases, measuring the diameters of aneurysms, Figures 1 1 D and 1 1 E.

[0139] Example 12. Manufacturing of hollow parts in flexible materials with a wider transparency range

[0140] One of the most difficult challenges of light-induced additive manufacturing is the fabrication of parts in elastic, flexible, or soft materials. To date, there are several reports in scientific articles detailing 3D printing in silicone-based resins. However, the printable geometries are limited. The problems are exacerbated when the objects to be printed are hollow and have irregular geometries, as is the case with specific anatomical structures of human or animal patients.

[0141] As can be seen in Figure 12, the hollow parts object of the present invention, unlike prior art, do not have limited geometries, but rather can be complex parts with reliefs and branches. Furthermore, as can be seen in Figure 12 and as has been verified throughout this document, they possess flexibility and high optical transparency. These characteristics are desirable in anatomical models for applications such as practice and preoperative planning, medical teaching and research, or as a demonstration model.

[0142] Many modifications and other embodiments of the invention will come to mind to one skilled in the art to which the invention pertains, having the benefit of the teachings presented in the foregoing descriptions and associated drawings. Therefore, it should be understood that the invention should not be limited to the specific and exemplary embodiments described, but that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are used herein, they are used only in a generic and descriptive sense and not for limiting purposes. Furthermore, it should be understood that the raw materials from which the various components comprising the invention described herein and other elements can be manufactured may vary without departing from the scope and spirit of the invention, and therefore, the embodiments referred to should not be considered limiting.

Claims

CLAIMS 1. A three-dimensionally printed anatomical model, characterized in that it is coated with a thiol-ene-based polymer solution, and that it has Young's modulus values ​​below 10 MPa, an elongation percentage from 40% to 1000% and optical translucency values ​​from 50% to 100%.

2. The three-dimensionally printed anatomical model according to claim 1, characterized in that it has a geometric structure selected from the group comprising tubular, cylindrical, spheroidal, globular, elongated, elliptical, branched structures, regular or irregular geometric structures, and / or any combination thereof.

3. The three-dimensionally printed anatomical model according to claim 1, wherein the anatomical model is a model of the aorta, aortic arch, thoracic aorta, thoraco-abdominal aorta, abdominal aorta, femoral aorta, popliteal aorta, circle of Willis, peripheral arteries, tumors in general (for example, cerebral), carotid arterial vasculature, cerebral vasculature, pulmonary vasculature, among other sections composed of any tissue called "soft".

4. The three-dimensionally printed anatomical model according to claim 3, wherein the anatomical model is a negative structure of the same structures or of other organs or parts of anatomical structures.

5. The three-dimensionally printed anatomical model according to claim 4, wherein the negative structure is a thoracic cavity, abdominal cavity, cranial cavity, pericardial cavity, joint cavity and spaces of the gastrointestinal tract.

6. The three-dimensionally printed anatomical model according to claim 1, wherein the anatomical model is a representation in elastomeric materials of anatomically rigid structures.

7. The three-dimensionally printed anatomical model according to claim 6, wherein the rigid anatomical structure is cartilage, synovial joints, ligaments, fascia, and epiglottis.

8. A polymeric coating for the surface treatment of 3D printing products, wherein the coating comprises a combination of binary or ternary thiol-ene systems and thiol-Michael systems, obtained by synthesis of “click” chemistry systems.

9. The coating according to claim 8, wherein the click chemistry systems contain mono or multi-functional thiols (mercaptans) and vinyls (enes).

10. The coating according to claim 9, wherein suitable mono or multi-functional thiols (mercaptans) comprise pentaerythritol tetrakis (3-mercaptopropionate) (PETMP), (mercaptopropyl)methylsiloxane homopolymer, (methacryloxypropyl)methylsiloxane-dimethylsiloxane copolymer 2-4%, thiol-functionalized polyesters, mercaptoethanol, mercaptoglycerol, thioethers, dodecane thiol, 3-mercaptopropionic acid and pentaerythritol tetrakis (2-mercaptoacetate).

11. The coating according to claim 9, wherein suitable vinyl(enes) comprise vinyl ethers, allyl ethers, norbornenes, N-alkyl maleimides, hydroxy butyl vinyl ether, vinyl sulfones, acrylamides, acrylates, methacrylates, acrylonitriles, styrene, maleimides, vinyl silacenes, and conjugated dienes; Examples of specific compounds are: trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, vinyl esters, trimethylolpropane diallyl ether, norbornene, allyl ethers, glycidyl dimethacrylate, Bis-GMA, TEGDMA, UDMA, 2-hydroxypropyl ethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, triallyl triazene, unsaturated ketones, fumarate esters, olefins, cinnamates and crotonates.

12. The coating according to claim 8, wherein the appropriate thiol-Michael addition reaction chemistry systems contain strong bases and acids, amines, alkyl phosphines, metals, organometallic compounds and Lewis acids.

13. The coating according to claim 8, wherein the free radical initiators of the appropriate click chemistry systems are Type I and Type II initiators.

14. The coating according to claim 13, wherein the Type I and Type II initiators are Irgacure 819, phosphine oxides, benzophenone, thioxanthones.

15. The coating according to claim 8, characterized in that it comprises ternary systems thiol-allyl, ether-acrylate, and a vinyl group having homopolymerization.

16. The coating according to claim 8, wherein the coating composition comprises a mixture of PEGDA, which may be in a concentration of 5% to 80%, Thiol, which may be in a composition of 1 to 80% and AGE which may be in a composition of 5 to 90%.

17. A method for manufacturing the anatomical model as claimed in claim 1, the process comprising the following steps: i) Obtaining and processing medical image data and complementary medical information; i) Manufacturing the anatomical model using a 3D printing technique; and wherein the process is characterized in that it comprises: iii) Carrying out post-treatment of the anatomical model obtained;iv) Coating the anatomical model, wherein said coating step comprises coating the obtained model with a polymeric solution based on any chemical reaction classified as based on click chemistry systems, which meets all or some of the distinctive characteristics such as: 1) high reaction yields / conversions, 2) require small amounts of initiators or catalysts, 3) fast reaction rates at wide ranges of concentrations, 4) do not require or require few cleaning steps, 5) are not inhibited by molecular oxygen or water, 6) tend to have a single regioselective product, 7) high versatility and availability of precursors, and in terms of materials typically 8) form highly homogeneous and close to ideal crosslinked polymers, therefore 9) present low levels of stress and shrinkage induced by polymerization.; 18. The method according to claim 17, wherein the data that is obtained and processed comes from imaging techniques that generate DICOM type files.

19. The method according to claim 17, wherein the data that is obtained and processed comes from an impression or negative mold of an anatomical structure.

20. The method according to claim 17, wherein the 3D printing technique is selected from the group comprising additive manufacturing techniques by photopolymerization where a liquid resin and light are used to induce a polymerization process by which an object is built layer by layer.

21. The method according to claim 20, wherein the 3D printing technique is stereolithographic additive manufacturing (SLA) and / or digital light processing (DLP) additive manufacturing.

22. Use of an anatomical model as claimed in any of claims 1 to 7, for practice and preoperative planning, medical and dental teaching and research, or as a demonstration model.

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