Prótesis Totales Digitales 3D fabricadas por CAD-CAM: Revisión bibliográfica / 3D Digital Denture Complete manufactured by CAD-CAM: Literature review

El artículo se centra en la aplicación de tecnología CAD/CAM en la odontología, específicamente en la fabricación de prótesis dentales totales. Este avance ha transformado la forma en que se diseñan y producen estas prótesis, emergiendo la fabricación de ella mediante capas sucesivas a base de tecnologías de impresión 3D como la estereolitografía, el procesamiento digital de luz y la pantalla de cristal líquido. En la presente revisión se profundizó en aspectos clínicos y biomecánicos, evaluando la retención, adaptación de la base, resistencia a la flexión y límite elástico de las prótesis. Los resultados indican que las prótesis digitales ofrecen mejor retención y adaptación en comparación con los métodos convencionales, aunque no hay diferencias estadísticamente significativas en resistencia a la flexión. También se exploraron aspectos económicos, destacando la reducción de costos y ahorro de tiempo en el proceso clínico con el enfoque digital. Los pacientes experimentan mayor satisfacción con prótesis impresas en 3D en términos de comodidad y eficiencia. Sin embargo, existen limitaciones, como la dificultad en la evaluación estética de prótesis monocromáticas, además de la dependencia de técnicas convencionales para evaluar la funcionalidad del paciente. La tecnología CAD/CAM ha revolucionado la fabricación de prótesis dentales totales, ofreciendo ventajas y beneficios. Este avance tecnológico promete mantener su relevancia en la comunidad científica y odontológica.

The article focuses on the application of CAD/CAM technology in dentistry, specifically in the manufacturing of complete dentures. This advance has transformed the way these dentures are designed and produced, with the manufacturing of layers emerging through successive 3D printing technologies such as stereolithography, digital light processing and liquid crystal display. In the present review clinical and biomechanical aspects were delved into, evaluating retention, adaptation of the base, resistance to flexion and elastic limit of the prostheses. The results indicate that digital prostheses offer better retention and adaptation compared to conventional methods, although there are no statistically significant differences in bending resistance. Economic aspects were also explored, highlighting the cost reduction and time savings in the clinical process with the digital approach. Patients experience greater satisfaction with 3D printed dentures in terms of comfort and efficiency. However, there are limitations, such as the difficulty in the aesthetic evaluation of monochromatic dentures, in addition to the dependence on conventional techniques to evaluate the patient's functionality. CAD/CAM technology has revolutionized the manufacturing of total dental prostheses, offering advantages and benefits. These technological advance promises to maintain its relevance in the scientific and dental community.

Effect of adding ytterbium trifluoride filler particles on the mechanical, physicochemical and biological properties of methacrylate-based experimental resins for 3D printing.

OBJECTIVE: To formulate an experimental methacrylate-based photo-polymerizable resin for 3D printing with ytterbium trifluoride as filler and to evaluate the mechanical, physicochemical, and biological properties. METHODS: Resin matrix was formulated with 60 wt% UDMA, 40 wt% TEGDMA, 1 wt% TPO, and 0.01 wt% BHT. Ytterbium Trifluoride was added in concentrations of 1 (G1 %), 2 (G2 %), 3 (G3 %), 4 (G4 %), and 5 (G5 %) wt%. One group remained without filler addition as control (GC). The samples were designed in 3D builder software and printed using a UV-DLP 3D printer. The samples were ultrasonicated with isopropanol and UV cured for 60 min. The resins were tested for degree of conversion (DC), flexural strength, Knoop microhardness, softening in solvent, radiopacity, colorimetric analysis, and cytotoxicity (MTT and SRB). RESULTS: Post-polymerization increased the degree of conversion of all groups (p < 0.05). G2 % showed the highest DC after post-polymerization. G2 % showed no differences in flexural strength from the G1 % and GC (p > 0.05). All groups showed a hardness reduction after solvent immersion. No statistical difference was found in radiopacity, softening in solvent (ΔKHN%), colorimetric spectrophotometry, and cytotoxicity (MTT) (p > 0.05). G1 % showed reduced cell viability for SRB assay (p < 0.05). SIGNIFICANCE: It was possible to produce an experimental photo-polymerizable 3D printable resin with the addition of 2 % ytterbium trifluoride as filler without compromising the mechanical, physicochemical, and biological properties, comparable to the current provisional materials.

Novel techniques and future developments in minimally invasive pectus repair.

After the paradigm shift in the treatment of excavated deformities caused by the introduction of the Nuss technique in 1998, several innovative technical modifications and new treatment modalities have radically changed the surgical approach of pectus excavatum in the last couple of years. These new trends attain different topics. On one hand, the use of three-dimensional (3D) printing and implant customization surge as a possibility for a wider audience as 3D printers become available with lower costs. They provide the surgeon with new elements that enable precise planning, simulation, and customized prostheses amidst a tendency to abandon standardization and incorporate personalized medicine. Another topic comprises mandatory sternal elevation, in the continuous search for safety first always. Complete thoracic remodeling as a goal of repair instead of addressing only focal depressions, leaving the upper chest or focal protrusions unresolved. Finally, although the current surgical approach has evolved significantly, many groups still use lateral stabilizers or direct implant fixation with sutures or wires to the ribs. These systems continue to prove unreliable in preventing implant displacement. Fortunately, the bridge technique, described in this review, has come to address this sometimes fatal issue with encouraging results. We provide an updated overview of the latest developments regarding these concepts, related to the current state-of-the-art of the treatment of pectus excavatum.

Metamaterial design for aortic aneurysm simulation using 3D printing.

INTRODUCTION: The use of three-dimensional (3D) printed anatomic models is steadily increasing in research and as a tool for clinical decision-making. The mechanical properties of polymers and metamaterials were investigated to evaluate their application in mimicking the biomechanics of the aortic vessel wall. METHODOLOGY: Uniaxial tensile tests were performed to determine the elastic modulus, mechanical stress, and strain of 3D printed samples. We used a combination of materials, designed to mimic biological tissues' properties, the rigid VeroTM family, and the flexible Agilus30™. Metamaterials were designed by tessellating unit cells that were used as lattice-reinforcement to tune their mechanical properties. The lattice-reinforcements were based on two groups of patterns, mainly responding to the movement between links/threads (chain and knitted) or to deformation (origami and diamond crystal). The mechanical properties of the printed materials were compared with the characteristics of healthy and aneurysmal aortas. RESULTS: Uniaxial tensile tests showed that the use of a lattice-reinforcement increased rigidity and may increase the maximum stress generated. The pattern and material of the lattice-reinforcement may increase or reduce the strain at maximum stress, which is also affected by the base material used. Printed samples showed max stress ranging from 0.39 ± 0.01 MPa to 0.88 ± 0.02 MPa, and strain at max stress ranging from 70.44 ± 0.86% to 158.21 ± 8.99%. An example of an application was created by inserting a metamaterial designed as a lattice-reinforcement on a model of the aorta to simulate an abdominal aortic aneurysm. CONCLUSION: The maximum stresses obtained with the printed models were similar to those of aortic tissue reported in the literature, despite the fact that the models did not perfectly reproduce the biological tissue behavior.

Bonding positional accuracy of attachments and marginal adaptation of in-house aligners - A quality improvement laboratory study.

OBJECTIVES: To evaluate the 3D accuracy of attachment positioning and the adaptation of aligners to attachments using in-house templates made with either polyethylene terephthalate glycol (PETG) or ethylene-vinyl acetate (EVA) and either pressure or vacuum thermoforming machines. MATERIALS AND METHODS: Overall, 140 test specimens were resin-printed. Templates for the attachment bonding were made with 1-mm EVA or 0.5-mm PETG laminates. Orthodontic aligners were manufactured with 0.75-mm PETG. The thermoplastification process was carried out using either vacuum or pressure machines. The positional differences between the virtual and bonded attachments were assessed in the X, Y and Z coordinates. The marginal adaptation between the aligners and the attachments was measured. RESULTS: Minor inaccuracies in the positioning of the attachments were observed in all combinations of thermoforming machines and plastic laminates used to fabricate the templates, mainly in the superior-inferior (Z) dimension. PETG performed better than EVA in the anterior region (p < .05). No association was found between thermoplastification machines and the accuracy of the positioning of the attachments (p > .05). While small misadaptations between the aligners and the attachments were observed, the EVA templates performed better than the PETG templates. CONCLUSIONS: The inaccuracy of the attachment positioning and the misadaptation of the aligners to the attachments were slight. The vacuum and pressure thermoplastification machines showed no difference in attachment positioning accuracy. The PETG template was better than the EVA template in the anterior region, but the EVA attachments presented a better adaptation to the aligners than the PETG attachments.

Unconventional sourced proteins in 3D and 4D food printing: Is it the future of food processing?

Following consumer trends and market needs, the food industry has expanded the use of unconventional sources to obtain proteins. In parallel, 3D and 4D food printing have emerged with the potential to enhance food processing. While 3D and 4D printing technologies show promising prospects for improving the performance and applicability of unconventional sourced proteins (USP) in food, this combination remains relatively unexplored. This review aims to provide an overview of the application of USP in 3D and 4D printing, focusing on their primary sources, composition, rheological, and technical-functional properties. The drawbacks, challenges, potentialities, and prospects of these technologies in food processing are also examined. This review underscores the current necessity for greater regulation of food products processed by 3D and 4D printing. The data presented here indicate that 3D and 4D printing represent viable, sustainable, and innovative alternatives for the food industry, emphasizing the potential for further exploration of 4D printing in food processing. Additional studies are warranted to explore their application with unconventional proteins.

3D PRINTING IN COMPLEX TIBIAL FRACTURE CLASSIFICATION & PLANNING.

Objective: Tibial plateau fractures are common intra-articular fractures that pose classification and treatment challenges for orthopedic surgeons. Objective: This study examines the value of 3D printing for classifying and planning surgery for complex tibial plateau fractures. Methods: We reviewed 54 complex tibial plateau fractures treated at our hospital from January 2017 to January 2019. Patients underwent preoperative spiral CT scans, with DICOM data processed using Mimics software. 3D printing technology created accurate 1:1 scale models of the fractures. These models helped subdivide the fractures into seven types based on the tibial plateau's geometric planes. Surgical approaches and simulated operations, including fracture reduction and plate placement, were planned using these models. Results: The 3D models accurately depicted the direction and extent of fracture displacement and plateau collapse. They facilitated the preoperative planning, allowing for precise reconstruction strategies and matching intraoperative details with the pre-printed models. Post-surgery, the anatomical structure of the tibial plateau was significantly improved in all 54 cases. Conclusion: 3D printing effectively aids in the classification and preoperative planning of complex tibial plateau fractures, enhancing surgical outcomes and anatomical restoration. Level of Evidence IV, Prospective Study.

Objetivo: As fraturas do planalto tibial são fraturas intra-articulares comuns de classificação e tratamento desafiadores aos cirurgiões ortopédicos. Objetivo: Este estudo investiga o uso de impressão 3D para classificar e planejar a cirurgia de fraturas complexas do planalto tibial. Métodos: 54 fraturas complexas do planalto tibial tratadas em nosso hospital de janeiro de 2017 a janeiro de 2019 foram revisadas. Os pacientes foram submetidos a tomografias computadorizadas em espiral pré-operatórias, com dados DICOM processados usando o software Mimics. A tecnologia de impressão 3D gerou modelos precisos em escala 1:1 das fraturas. Estes modelos ajudaram a subdividir as fraturas em sete tipos com base nos planos geométricos do planalto tibial. As abordagens cirúrgicas e as operações simuladas, incluindo a redução da fratura e a colocação de placa, foram planejadas utilizando estes modelos. Resultados: Os modelos 3D representaram com precisão a direção e a extensão da deslocação da fratura e do colapso do planalto. Os modelos facilitaram o planejamento pré-operatório, viabilizando estratégias de reconstrução precisas e a correspondência dos detalhes intraoperatórios com os modelos pré-impressos. Após a cirurgia, a estrutura anatômica do planalto tibial melhorou significativamente em todos os 54 casos. Conclusão: A impressão 3D ajuda na classificação e no planejamento pré-operatório de fraturas complexas do planalto tibial, melhorando os resultados cirúrgicos e a restauração anatômica. Nível de Evidência IV, Estudo Prospectivo.

New scenarios for training in oral radiology: clinical performance and predoctoral students' perception of 3D-printed mannequins.

OBJECTIVES: This study aimed to evaluate the impact of 3D-printed mannequins on the training of predoctoral students. METHODS: Two 3D-printed training models were developed: a traditional model that simulates a sound adult patient and a customized model with pathological and physiological changes (impacted third molar and edentulous region). Students accomplished their pre-clinical training divided into a control group (CG, n = 23), which had access to the traditional model, and a test group (TG, n = 20), which had access to both models. Afterward, they performed a full mouth series on patients and filled out a perception questionnaire. Radiographs were evaluated for technical parameters. Descriptive statistics and the Mann-Whitney test were used to compare the groups. RESULTS: Students provided positive feedback regarding the use of 3D printing. The TG reported a more realistic training experience than the CG (P = .037). Both groups demonstrated good clinical performance (CG = 7.41; TG = 7.52), and no significant differences were observed between them. CONCLUSIONS: 3D printing is an option for producing simulators for pre-clinical training in Oral Radiology, reducing student stress and increasing confidence during clinical care.

Partial Shoulder Arthroplasty Guided by Three-dimensional Prototyping.

Three-dimensional (3D) printing technology is a reality in medicine. In Orthopedics and Traumatology, 3D printing guides a precise and tailored surgical treatment. Understanding and disseminating its applicability, use, and outcomes can foster academicism and improve patient care. This is a report of a rare case of a female young adult patient with osteonecrosis of the humeral head due to avascular necrosis developed in early childhood. The treatment was tailored and optimized with 3D printing, which helped determine the steps for partial humeral arthroplasty.

Custom-made Trabecular Metal Acetabular Component in Total Hip Revision.

The following case report aims to demonstrate a total hip arthroplasty revision surgery (THARS) using a custom-made trabecular metal acetabular component for correction of a severe acetabular defect. Currently, in the literature, there are few complete descriptions of surgical planning and procedures involving customized prostheses. This is due to the inherent technical difficulty of the surgical procedure and the high costs related to the planning and materials.

In Situ Printing of Polylactic Acid/Nanoceramic Filaments for the Repair of Bone Defects Using a Portable 3D Device.

In situ 3D printing is attractive for the direct repair of bone defects in underdeveloped countries and in emergency situations. So far, the lack of an interesting method to produce filament using FDA-approved biopolymers and nanoceramics combined with a portable strategy limits the use of in situ 3D printing. Herein, we investigated the osseointegration of new nanocomposite filaments based on polylactic acid (PLA), laponite (Lap), and hydroxyapatite (Hap) printed directly at the site of the bone defect in rats using a portable 3D printer. The filaments were produced using a single-screw extruder (L/D = 26), without the addition of solvents that can promote the toxicity of the materials. In vitro performance was evaluated in the cell differentiation process with mesenchymal stem cells (MSC) by an alkaline phosphatase activity test and visualization of mineralization nodules; a cell viability test and total protein dosage were performed to evaluate cytotoxicity. For the in vivo analysis, the PLA/Lap composite filaments with a diameter of 1.75 mm were printed directly into bone defects of Wistar rats using a commercially available portable 3D printer. Based on the in vitro and in vivo results, the in situ 3D printing technique followed by rapid cooling proved to be promising for bone tissue engineering. The absence of fibrous encapsulation and inflammatory processes became a good indicator of effectiveness in terms of biocompatibility parameters and bone tissue formation, and the use of the portable 3D printer showed a significant advantage in the application of this material by in situ printing.

From medical imaging to 3D printed anatomical models: a low-cost, affordable 3D printing approach.

OBJECTIVE: To share our experience in creating precise anatomical models using available open-source software. METHODS: An affordable method is presented, where from a DICOM format of a computed tomography, a segmentation of the region of interest is achieved. The image is then processed for surface improvement and the DICOM format is converted to STL. Error correction is achieved and the model is optimized to be printed by stereolithography with a desktop 3D printer. RESULTS: Precise measurements of the dimensions of the DICOM file (CT), the STL file, and the printed model (3D) were carried out. For the C6 vertebra, the dimensions of the horizontal axis were 55.3 mm (CT), 55.337 mm (STL), and 55.3183 mm (3D). The dimensions of the vertebral body were 14.2 mm (CT), 14.551 mm (STL), and 14.8159 mm (3D). The length of the spinous process was 18.2 mm (CT), 18.283 mm (STL), and 18.2266 mm (3D), while its width was 8.5 mm (CT), 8.3644 mm (STL), and 8.3226 mm (3D). For the C7 vertebra, the dimensions of the horizontal axis were 58.6 mm (CT), 58.739 mm (STL), and 58.7144 mm (3D). The dimensions of the vertebral body were 14 mm (CT), 14.0255 mm (STL), and 14.2312 mm (3D). The length of the spinous process was 18.7 mm (CT), 18.79 mm (STL), and 18.6458 mm (3D), and its width was 8.9 mm (CT), 8.988 mm (STL), and 8.9760 mm (3D). CONCLUSION: The printing of a 3D model of bone tissue using this algorithm is a viable, useful option with high precision.

OBJETIVO: Compartir nuestra experiencia para crear modelos anatómicos precisos utilizando software con licencia abierta disponibles. MÉTODOS: Se presenta un método asequible, en donde a partir de un formato DICOM de una tomografía computarizada se logra una segmentación de la región de interés. Posteriormente se procesa la imagen para una mejora de superficie y se realiza la conversión de formato DICOM a STL. Se logra la corrección de errores y se optimiza el modelo para luego ser impreso por medio de estereolitografía con una impresora 3D de escritorio. RESULTADOS: Se efectuaron mediciones precisas de las dimensiones del archivo DICOM (TC), del archivo STL y del modelo impreso (3D). Para la vértebra C6, las dimensiones del eje horizontal fueron 55.3 mm (TC), 55.337 mm (STL) y 55.3183 mm (3D). Las dimensiones del cuerpo vertebral fueron 14.2 mm (TC), 14.551 mm (STL) y 14.8159 mm (3D). La longitud de la apófisis espinosa fue de 18.2 mm (TC), 18.283 mm (STL) y 18.2266 mm (3D), mientras que su ancho fue de 8.5 mm (TC), 8.3644 mm (STL) y 8.3226 mm (3D). Para la vértebra C7, las dimensiones del eje horizontal fueron 58.6 mm (TC), 58.739 mm (STL) y 58.7144 mm (3D). Las dimensiones del cuerpo vertebral fueron 14 mm (TC), 14.0255 mm (STL) y 14.2312 mm (3D). La longitud de la apófisis espinosa fue de 18.7 mm (TC), 18.79 mm (STL) y 18.6458 mm (3D), y su ancho fue de 8.9 mm (TC), 8.988 mm (STL) y 8.9760 mm (3D). CONCLUSIÓN: La impresión de un modelo en 3D de tejido óseo mediante este algoritmo resulta una opción viable, útil y con una alta precisión.

3D printed benznidazole tablets based on an interpolyelectrolyte complex by melting solidification printing process (MESO-PP): An innovative strategy for personalized treatment of Chagas disease.

3D printing technology is revolutionizing pharmaceuticals, offering tailored solutions for solid dosage forms. This innovation is particularly significant for conditions like Chagas disease, which require weight-dependent treatments. In this work, a formulation of benznidazole (BNZ), the primary treatment for this infection, was developed to be utilized with the Melting Solidification Printing Process (MESO-PP) 3D printing technique. Considering the limited aqueous solubility of BNZ, an interpolyelectrolyte complex (IPEC), composed of chitosan and pectin, was integrated to improve its dissolution profile. The formulations, also called inks in this context, with and without IPEC were integrally characterized and compared. The printing process was studied, the release of BNZ from 3D-prints (3DP) was exhaustively analyzed and a physiologically based pharmacokinetic model (PKPB) was developed to forecast their pharmacokinetic performance. 3DP were successfully achieved loading 25, 50 and 100 mg of BNZ. The presence of the IPEC in the ink caused a decrease in the crystalline domain of BNZ and facilitated the printing process, reaching a print success rate of 83.3 %. Interestingly, 3DP-IPEC showed accelerated release dissolution profiles, releasing over 85 % of BNZ in 90 min, while 3DP took up to 48 h for doses above 25 mg. The PBPK model demonstrated that 3DP-IPEC tablets would present high bioavailability (0.92), higher than 3DP (0.36) and similar to the commercial product. This breakthrough holds immense potential for improving treatment outcomes for neglected diseases.

3D printed ventilation tubes and their effect on biological models.

BACKGROUND: Acute otitis media (AOM) causes inflammation and hearing loss. Ventilation tubes are key in treatment. 3D printing improves prostheses in otorhinolaryngology, offering precision and greater adaptability. MATERIALS AND METHODS: An experimental study was conducted with Wistar rats from July to December 2020. 3D tympanostomy tube models were designed, with technical specifications and tests performed on inexpensive 3D printers. The tympanostomy tube was inserted endoscopically. RESULTS: Procedures were performed on five rats with implants in both ears. Pre-intervention pathologies, such as atical retraction and glue ear, were found. The PLA-printed tympanostomy tube showed improvement after adjustments. Histopathological results revealed significant middle and inner ear damage. CONCLUSION: In our study, the design and 3D printing of implants fulfilled the desired functions when modified, with a height of 5 mm. Complications included PLA degradation and ear damage. There were no adverse events during observation, highlighting the need for further research on 3D-printed implants.

SimuVet: a preliminary study of the innovative development of a simulator for epidural anesthesia training in dogs.

Epidural anesthesia in dogs is a locoregional anesthesia technique used in veterinary medicine, becoming an important integrated application in the anesthetic protocol to provide safer and more effective analgesia to patients. For this, professionals must adhere to rigorous guidelines and possess technical skills. In this context, in veterinary education, the development of practical clinical skills represents a crucial aspect in the training of these professionals. However, traditional teaching methods have proven insufficient to ensure a consistent level of competence among recent graduates. The introduction of non-animal alternatives for educational purposes has contributed to the development of simulation-based teaching, an innovative and accessible field capable of enhancing pre-clinical proficiency in students and reducing the use of live animals and cadavers. Despite its application in various areas of veterinary education, there are no conclusive results regarding the development of accessible simulators capable of effectively enhancing training in epidural anesthesia in dogs. Therefore, this article represents a pioneering study aimed at sharing a method for creating SimuVet, a realistic simulator for training epidural anesthesia in dogs. The simulator was fully developed by veterinary researchers with limited experience in 3D printing and, after preliminary analysis, demonstrated excellent performance and ultrasonographic anatomy. Future work will focus on the formal validation of this simulator with the aim of improving the teaching and learning process for students and experts in performing epidural anesthesia in companion animals.

The role of 3D printing in chest wall reconstruction.

Technology is advancing fast, and chest wall surgery finds particular benefit in the broader availability of three-dimensional (3D) reconstruction and printing. An increasing number of reports are being published on the use of these resources in virtual 3D reconstructions of chest walls in computed tomography (CT) scans, virtual surgeries, 3D printing of real-size models for surgical planning, practice, and education, and of note, the manufacture of customized 3D printed implants, changing the fundamental conception from a surgery that fits all, to a surgery for each patient. In this review, we explore the evidence published on simple chest wall reconstruction, including the use of 3D technology to assist in the improvement of the repair of the most frequent chest wall deformities: pectus excavatum and carinatum. Current studies are oriented to the automatization and customization of transthoracic implants, as well as education on real-size models. Next, we investigate the implementation of 3D printing in the repair of complex chest wall reconstruction, comprised of infrequent chest wall deformities such as pectus arcuatum and Poland syndrome. These malformations are very heterogeneous resulting in a high degree of improvisation during the surgical repair. In this setting, 3D technology plays a role in the standardization of a process that contemplates customization, concepts that may seem contradictory. Finally, 3D printing with biocompatible materials is rapidly becoming the first choice for the reconstruction of wide chest wall oncological resections. In this work, we review the first and most important current publications on the subject.

Oral Films Printed with Green Propolis Ethanolic Extract.

Oral film (OF) research has intensified due to the effortless administration and advantages related to absorption in systemic circulation. Chitosan is one of the polymers widely used in the production of OFs; however, studies evaluating the maintenance of the active principles' activity are incipient. Propolis has been widely used as an active compound due to its different actions. Printing techniques to incorporate propolis in OFs prove to be efficient. The objective of the present study is to develop and characterize oral films based on chitosan and propolis using printing techniques and to evaluate the main activities of the extract incorporated into the polymeric matrix. The OFs were characterized in relation to the structure using scanning and atomic force electron microscopy; the mechanical properties, disintegration time, wettability, and stability of antioxidant activity were evaluated. The ethanolic extract of green propolis (GPEE) concentration influenced the properties of the OFs. The stability (phenolic compounds and antioxidant activity) was reduced in the first 20 days, and after this period, it remained constant.

A 3D-printed tumor-on-chip: user-friendly platform for the culture of breast cancer spheroids and the evaluation of anti-cancer drugs.

Tumor-on-chips (ToCs) are useful platforms for studying the physiology of tumors and evaluating the efficacy and toxicity of anti-cancer drugs. However, the design and fabrication of a ToC system is not a trivial venture. We introduce a user-friendly, flexible, 3D-printed microfluidic device that can be used to culture cancer cells or cancer-derived spheroids embedded in hydrogels under well-controlled environments. The system consists of two lateral flow compartments (left and right sides), each with two inlets and two outlets to deliver cell culture media as continuous liquid streams. The central compartment was designed to host a hydrogel in which cells and microtissues can be confined and cultured. We performed tracer experiments with colored inks and 40 kDa fluorescein isothiocyanate dextran to characterize the transport/mixing performances of the system. We also cultured homotypic (MCF7) and heterotypic (MCF7-BJ) spheroids embedded in gelatin methacryloyl hydrogels to illustrate the use of this microfluidic device in sustaining long-term micro-tissue culture experiments. We further demonstrated the use of this platform in anticancer drug testing by continuous perfusion of doxorubicin, a commonly used anti-cancer drug for breast cancer. In these experiments, we evaluated drug transport, viability, glucose consumption, cell death (apoptosis), and cytotoxicity. In summary, we introduce a robust and friendly ToC system capable of recapitulating relevant aspects of the tumor microenvironment for the study of cancer physiology, anti-cancer drug transport, efficacy, and safety. We anticipate that this flexible 3D-printed microfluidic device may facilitate cancer research and the development and screening of strategies for personalized medicine.

3D printed scaffolds of biosilica and spongin from marine sponges: analysis of genotoxicity and cytotoxicity for bone tissue repair.

Biosilica (BS) and spongin (SPG) from marine sponges are highlighted for their potential to promote bone regeneration. Moreover, 3D printing is introduced as a technology for producing bone grafts with optimized porous structures, allowing for better cell attachment, proliferation, and differentiation. Thus, this study aimed to characterize the BS and BS/SPG 3D printed scaffolds and to evaluate the biological effects in vitro. The scaffolds were printed using an ink containing 4 wt.% of sodium alginate. The physicochemical characteristics of BS and BS/SPG 3D printed scaffolds were analyzed by SEM, EDS, FTIR, porosity, evaluation of mass loss, and pH measurement. For in vitro analysis, the cellular viability of the MC3T3-E1 cell lineage was assessed using the AlamarBlue® assay and confocal microscopy, while genotoxicity and mineralization potential were evaluated through the micronucleus assay and Alizarin Red S, respectively. SEM analysis revealed spicules in BS, the fibrillar structure of SPG, and material degradation over the immersion period. FTIR indicated peaks corresponding to silicon oxide in BS samples and carbon oxide and amine in SPG samples. BS-SPG scaffolds exhibited higher porosity, while BS scaffolds displayed greater mass loss. pH measurements indicated a significant decrease induced by BS, which was mitigated by SPG over the experimental periods. In vitro studies demonstrated the biocompatibility and non-cytotoxicity of scaffold extracts. .Also, the scaffolds promoted cellular differentiation. The micronucleus test further confirmed the absence of genotoxicity. These findings suggest that 3D printed BS and BS/SPG scaffolds may possess desirable morphological and physicochemical properties, indicating in vitro biocompatibility.

3D printed scaffolds as delivery devices for nanocrystals: A proof of concept loading Atorvastatin with enhanced properties for sublingual route of administration.

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.