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In this work, a core substituted NMI-conjugated dipeptide (4MNLV) was extensively studied in mixed solvent systems to explore the polarity effect on the self-assembly pattern and their photophysical property. 4MNLV adopted a J- or H- type aggregation pattern depending upon the polarity index of the solvent system chosen. The self-assembly process was achieved through the anti-solvent effect. UV-vis study suggested that if the stock solution of 4MNLV was diluted with a relatively more polar solvent (compared to the stock solvent), then the system acquired J- type of aggregation pattern by showing a red-shift in their absorption maxima (λmax). Conversely, when the stock was diluted by a relatively less polar solvent, H-type of aggregation was observed where blue shift of λmax was noticed. The emission spectra and the lifetime of the self-assembled materials were also influenced by the chosen solvent system. The chirotopic behaviour of these self-assembled materials was studied through CD spectroscopy. Morphological study indicated the formation of helical nanofibrillar structures. The bright green fluorescence of these highly biocompatible naphthalimide-peptide conjugate was used for cell imaging application, indicating its futuristic scope.
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Achieving rapid clotting and clot stability are important unmet goals of clinical management of noncompressible hemorrhage. This study reports the development of a spatiotemporally controlled release system of an antihemorrhagic drug, etamsylate, in the management of internal hemorrhage. Gly-Arg-Gly-Asp-Ser (GRGDS) peptide-functionalized chitosan nanoparticles, with high affinity to bind with the GPIIa/IIIb receptor of activated platelets, were loaded with the drug etamsylate (etamsylate-loaded GRGDS peptide-functionalized chitosan nanoparticles; EGCSNP). Peptide conjugation was confirmed by LCMS, and the delivery system was characterized by DLS, SEM, XRD, and FTIR. In vitro study exhibited 90% drug release till 48 h fitting into the Weibull model. Plasma recalcification time and prothrombin time tests of GRGDS-functionalized nanoparticles proved that clot formation was 1.5 times faster than nonfunctionalized chitosan nanoparticles. The whole blood clotting time was increased by 2.5 times over clot formed under nonfunctionalized chitosan nanoparticles. Furthermore, the application of rheometric analysis revealed a 1.2 times stiffer clot over chitosan nanoparticles. In an in vivo liver laceration rabbit model, EGCSNP spatially localized at the internal injury site within 5 min of intravenous administration, and no rebleeding was recorded up to 3 h. The animals survived for 3 weeks after the injury, indicating the strong potential of the system for the management of noncompressible hemorrhage.
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Coagulação Sanguínea , Quitosana , Modelos Animais de Doenças , Hemorragia , Nanopartículas , Animais , Coelhos , Nanopartículas/química , Quitosana/química , Hemorragia/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/química , Masculino , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/uso terapêuticoRESUMO
Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems. Thus, the present work reports a new salt form of LTP with a docusate counterion to enhance the pharmaceutical properties of the drug (LTP-DOC). NMR spectra showed a downfield shift of the methylene singlet proton from 3.83 and 4.41 ppm, indicating a lowering of electron density on the adjacent nitrogen atom and confirming the formation of amine-sulfonyl salt through the specified basic nitrogen center located adjacent to the furan ring. PXRD diffractograms of LTP-DOC indicated a reduced crystallinity of the prepared salt. The dissolution, equilibrium solubility, lipid excipient solubility, partitioning coefficient, distribution coefficient, tabletability, and in vitro cytotoxicity of the lipophilic salt of LTP were investigated. The equilibrium solubility data showed that LTP-DOC possesses a pH-independent solubility profile in the pH range of 3.5 to 7.4 with a 3.14 times higher permeability coefficient than commercial ditosylate salt. Furthermore, the prepared LTP-DOC salts showed twice higher log P than the free base and 8 times higher than LTP-DTS. The prepared LTP-DOC was found to have 4- to 9-fold higher solubility in lipid excipients like Capmul MCM C8 and Maisine CC compared to the ditosylate salt. The LTP-DOC salt was tabletable and showed approximately 1.2 times lower dissolution than commercial ditosylate salt, indicating extended-release behavior. A cytotoxicity study of LTP-DOC salt showed an approximately 2.5 times lower IC50 value than the LTP-free base and 1.7 times lower than commercial ditosylate salt with an approximately 3 times higher selectivity index. The investigations strongly indicate a high translational potential of the prepared salt form in maintaining solubility-lipophilicity interplay, enhancing the drug's bioavailability, and developing lipidic formulations.
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Excipientes , Lapatinib , Solubilidade , Lapatinib/química , Humanos , Excipientes/química , Lipídeos/química , Sais/química , Disponibilidade Biológica , Concentração de Íons de Hidrogênio , Química Farmacêutica/métodos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Liberação Controlada de FármacosRESUMO
Background and Aim: To compare the effects of probiotics on liver stiffness and steatosis in obese and non-obese patients with nonalcoholic fatty liver disease (NAFLD),the pragmatic clinical trial included 50 obese body mass index (BMI) ≥25 kg/m2 and 50 non-obese NAFLD BMI <25 kg/m2 age and sex-matched patients. Materials and Methods: Fibroscan with controlled attenuated parameter (CAP) was done at day 0 and at the end of 6 months. Probiotics supplementation was provided for both groups for 6 months along with lifestyle modifications. Results: At inclusion, both groups had comparable characteristics except BMI, metabolic syndrome and waist circumference (WC). Beneficial changes occurred in BMI (p=0.024), WC (p=0.045), ALT (p=0.024), total cholesterol (p=0.016), LDL (p=0.025) and triglyceride (p=0.021) of obese group, systolic blood pressure (p=0.003) and LDL level (p=0.018) in non-obese group. No significant change was observed in liver enzymes and glycemic profiles. Significant improvement in CAP was observed in both groups. But after adjusting for changes in BMI and WC, the change in CAP among non-obese participants were significantly higher compared to obese, mean change of 19.33±48.87 and 16.02±51.58 dB/m in non-obese and obese patients, respectively; p=0.044). Conclusion: Probiotics improve CAP/ steatosis in both obese and non-obese NAFLD patients and improvement was higher in non-obese, irrespective of BMI change.
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Supramolecular nanostructured based delivery systems are emerging as a meaningful approach in the treatment of cancer, offering controlled drug release and improved therapeutic efficacy. The self-assembled structures can be small molecules, polymers, peptides, or proteins, which can be used and functionalized to achieve tailored release and target specific cells, tissues, or organs. These structures can improve the solubility and stability of drugs having low aqueous solubility by encapsulating and protecting them from degradation. Alongside, peptides as natural biomolecules have gained increasing attention as potential candidates in cancer treatment because of their biocompatibility, low cytotoxicity, and high specificity toward tumor cells. The amino acid sequences in peptide molecules are tunable, efficiently controlling the morphology of peptide-based self-assembled nanosystems and offering flexibility to form supramolecular nanostructures (SNs). It is evident from the current literature that the supramolecular nanostructures based delivery of peptide for cancer treatment hold great promise for future cancer therapy, offering potential strategies for personalized medicine with improved patient outcomes. SIGNIFICANCE STATEMENT: This review focuses on fundamentals and various drug delivery mechanisms based on SNs. Different SN approaches and recent literature reviews on peptide delivery are also presented to the readers.
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Nanoestruturas , Neoplasias , Humanos , Peptídeos/química , Proteínas , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , Sequência de Aminoácidos , Preparações Farmacêuticas , Neoplasias/tratamento farmacológicoRESUMO
Three-dimensional (3D) bioprinting offers promising solutions to the complex challenge of vascularization in biofabrication, thereby enhancing the prospects for clinical translation of engineered tissues and organs. While existing reviews have touched upon 3D bioprinting in vascularized tissue contexts, the current review offers a more holistic perspective, encompassing recent technical advancements and spanning the entire multistage bioprinting process, with a particular emphasis on vascularization. The synergy between 3D bioprinting and vascularization strategies is crucial, as 3D bioprinting can enable the creation of personalized, tissue-specific vascular network while the vascularization enhances tissue viability and function. The review starts by providing a comprehensive overview of the entire bioprinting process, spanning from pre-bioprinting stages to post-printing processing, including perfusion and maturation. Next, recent advancements in vascularization strategies that can be seamlessly integrated with bioprinting are discussed. Further, tissue-specific examples illustrating how these vascularization approaches are customized for diverse anatomical tissues towards enhancing clinical relevance are discussed. Finally, the underexplored intraoperative bioprinting (IOB) was highlighted, which enables the direct reconstruction of tissues within defect sites, stressing on the possible synergy shaped by combining IOB with vascularization strategies for improved regeneration.
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Bioimpressão , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
Effective vascularization during wound healing remains a critical challenge in the regeneration of skin tissue. On the other hand, mesenchymal stem cell (MSC) to endothelial phenotype transition (MEnDoT) is a potential phenomenon grossly underexplored in vascularized skin tissue engineering. Vitamin D3 has a proven role in promoting MEnDoT. Hence, a D3-incorporated scaffold made with biocompatible materials such as chitosan, collagen and fibrinogen should be able to promote endothelial lineage transition in vitro for tissue engineering purposes. In this study, we developed vitamin D3 incorporated chitosan-collagen-fibrinogen (CCF-D3) scaffolds physically crosslinked under UV and conducted thorough physicochemical and biological assays on it compared to a control scaffold without vitamin D3. Our study for the first time reports the potential vascularization property of the CCF-D3 scaffold by inducing the transitions of dental pulp MSC to endothelial lineage via the HIF-1/IGF-1/VEGF pathways. MSC seeded on UV-exposed CCF-D3 scaffolds had higher cell viability and transitioned towards endothelial lineage was observed by elevated proliferative and endothelial-specific gene expressions and flow cytometric analysis of SCA-1+ antibody. The difference in VEGF-A and α-SMA expressions was also observed in the D3-CCF scaffold compared to the scaffolds without D3.
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Quitosana , Hemostáticos , Células-Tronco Mesenquimais , Quitosana/química , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fibrinogênio/metabolismo , Polpa Dentária/metabolismo , Colágeno/química , Engenharia Tecidual , Hemostáticos/farmacologiaRESUMO
Computing, since its inception, has been processor-centric, with memory separated from compute. Inspired by the organic brain and optimized for inorganic silicon, NorthPole is a neural inference architecture that blurs this boundary by eliminating off-chip memory, intertwining compute with memory on-chip, and appearing externally as an active memory chip. NorthPole is a low-precision, massively parallel, densely interconnected, energy-efficient, and spatial computing architecture with a co-optimized, high-utilization programming model. On the ResNet50 benchmark image classification network, relative to a graphics processing unit (GPU) that uses a comparable 12-nanometer technology process, NorthPole achieves a 25 times higher energy metric of frames per second (FPS) per watt, a 5 times higher space metric of FPS per transistor, and a 22 times lower time metric of latency. Similar results are reported for the Yolo-v4 detection network. NorthPole outperforms all prevalent architectures, even those that use more-advanced technology processes.
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Objective: Loosening of dental implants due to resorption of the surrounding bone is one of the challenging clinical complications in prosthetic dentistry. Generally, stiffness mismatch between an implant and its surrounding bone is one of the major factors. In order to prevent such clinical consequences, it is essential to develop implants with customized stiffness. The present study investigates the computational and experimental biomechanical responses together with cytocompatibility studies of three-dimensional (3D)-printed Ti-6Al-4V-based porous dental implants with varied stiffness properties. Methods: Additive manufacturing (direct metal laser sintering, DMLS) was utilized to create Ti-6Al-4V implants having distinct porosities and pore sizes (650 and 1000 µm), along with a nonporous (solid) implant. To validate the compression testing of the constructed implants and to probe their biomechanical response, finite element models were employed. The cytocompatibility of the implants was assessed using MG-63 cells, in vitro. Results: Both X-ray microcomputed tomography (µ-CT) and scanning electron microscopy (SEM) studies illustrated the ability of DMLS to produce implants with the designed porosities. Biomechanical analysis results revealed that the porous implants had less stiffness and were suitable for providing the appropriate peri-implant bone strain. Although all of the manufactured implants demonstrated cell adhesion and proliferation, the porous implants in particular supported better bone cell growth and extracellular matrix deposition. Conclusions: 3D-printed porous implants showed tunable stiffness properties with clinical translational potential.
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Loading configuration of hip joint creates resultant bending effect on femoral implants. So, the lateral side of femoral implant which is under tension retracts from periimplant bone due to positive Poisson's ratio. This retraction of implant leads to load shielding and gap opening in proximal-lateral region, thereby allowing entry of wear particle to implant-bone interface. Retraction of femoral implant can be avoided by introducing auxetic metamaterial to the retracting side. This allows the implant to push periimplant bone under tensile condition by virtue of their auxetic (negative Poisson's ratio) nature. To develop such implants, a patient-specific conventional solid implant was first designed based on computed-tomography scan of a patient's femur. Two types of metamaterials (2D: type-1) and (3D: type-2) were employed to design femoral meta-implants. Type-1 and type-2 meta-implants were fabricated using metallic 3D printing method and mechanical compression testing was conducted. Three finite element (FE) models of the femur implanted with solid implant, type-1 meta-implant and type-2 meta-implant were developed and analysed under compression loading. Significant correlation (R2 = 0.9821 and R2 = 0.9977) was found between the experimental and FE predicted strains of the two meta-implants. In proximal-lateral region of the femur, an increase of 7.1% and 44.1% von-Mises strain was observed when implanted with type-1 and type-2 meta-implant over the solid implant. In this region, bone remodelling analysis revealed 2.5% bone resorption in case of solid implant. While bone apposition of 0.5% and 7.7% was observed in case of type-1 and type-2 meta-implants, respectively. The results of this study indicates that concept of introduction of metamaterial to the lateral side of femoral implant can prove to provide higher osseointegration-friendly environment in the proximal-lateral region of femur.
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Fêmur , Próteses e Implantes , Humanos , Fêmur/cirurgia , Osseointegração , Remodelação Óssea , Extremidade Inferior , Análise de Elementos FinitosRESUMO
This study aimed to perform quantitative biomechanical analysis for probing the effect of varying thread shapes in an implant for improved primary stability in prosthodontics surgery. Dental implants were designed with square (SQR), buttress (BUT), and triangular (TRI) thread shapes or their combinations. Cone-beam computed tomography images of mandible molar zones in human subjects belonging to three age groups were used for virtual implantation of the designed implants, to quantify patient-specific peri-implant bone microstrain, using finite element analyses. The in silico analyses were carried out considering frictional contact to simulate immediate loading with a static masticatory force of 200 N. To validate computational biomechanics results, compression tests were performed on three-dimensional printed implants having the investigated thread architectures. Bone/implant contact areas were also quantitatively assessed. It was observed that, bone/implant contact was maximum for SQR implants followed by BUT and TRI implants. For all the cases, peak microstrain was recorded in the cervical cortical bone. The combination of different thread shapes in the middle or in the apical part (or both) was demonstrated to improve peri-implant microstrain, particularly for BUT and TRI. Considering 1500-2000 microstrain generates in the peri-implant bone during regular physiological functioning, BUT-SQR, BUT-TRI-SQR, TRI-SQR-BUT, SQR, and SQR-BUT-TRI design concepts were suitable for younger; BUT-TRI-SQR, BUT-SQR-TRI, TRI-SQR-BUT, SQR-BUT, SQR-TRI for middle-aged, and BUT-TRI-SQR, BUT-SQR-TRI, TRI-BUT-SQR, SQR, and SQR-TRI for the older group of human patients.
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Implantes Dentários , Fenômenos Biomecânicos , Força de Mordida , Simulação por Computador , Análise do Estresse Dentário , Análise de Elementos Finitos , Humanos , Pessoa de Meia-Idade , Estresse MecânicoRESUMO
3D Bioprinting is fast advancing to offer capabilities to process living cells into geometrically and functionally complex tissue and organ substitutes. As bioprinted constructs are making their way into clinic, the bioprinting community needs to consider the responsible innovation and translation of the bioprinted tissues and organs.
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Bioimpressão , Engenharia Tecidual , Impressão Tridimensional , Alicerces TeciduaisRESUMO
Needle insertion is executed in numerous medical and brachytherapy events. Exact needle insertion into inhomogeneous soft biological tissue is of useful importance due to its significance in clinical diagnosis (especially percutaneous) and treatments. The surgical needles used in such processes can deflect during the percutaneous process. Needle deflecting which affects needle - soft tissue interface and needle controllability have a crucial role in establishment precision. In this paper, we have analyzed a mechanics-based model both rotational and non-rotational needle insertion, and studied the deflection phenomenon in both insertion cases, we validated it with a real-time nonlinear Dassault Systèmes® ABAQUS simulation model. For definite contact force, the maximum the contact stiffness was, the minimum it inserted, the cohesive surface model was used to investigate the needle insertion analysis, where the fracture point was defined by a failure strain and with the help of the in, the fully failed components would be removed. Using living tissue comparable PVA gel materials, the needle insertion force model is developed from insertion experimentations with the help of two different processes (rotational and non-rotational needle insertion). In a rotational needle, deflection is less than in a non-rotational needle. The preliminary insertion was observed in the rotational needle at 1.261 mm (experiment), and 1.538 mm (simulation), and for non-rotational needle insertion, the initial insertion was noticed at 1.756 mm (experiment) and 1.982 mm (simulation). The main aim of this study is to navigate the surgical needle in an accurate way to reduce the erroneousness for a clinical diagnosis like anesthesia, brachytherapy, biopsy, and modern microsurgery operation.
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Braquiterapia , Agulhas , Simulação por Computador , Fenômenos Mecânicos , Modelos AnatômicosRESUMO
The surgical needle insertion process is widely applied in medical interference. During the insertion process, the inhomogeneity and denseness of the soft tissues make it tough to detect the essential tissue damage, a rupture occurs that contains huge forces and material deformations. This study is very important, as all the above-mentioned factors are very significant for modern invasive surgery so that the success rate of the surgery can increase and the patient recovers smoothly. This investigation intends to perform minimally invasive surgical (MIS) procedures and reduce the living tissue damage while performing the biopsy, PCNL, etc. A fracture mechanics method was analyzed to create a needle insertion model which can estimate the needle insertion force during inset in tissue-like PVA gel. The force model was calculated by needle insertion experimentally, and also estimated the needle tip geometry, and diameter influences the fracture toughness. Validate exp. results with simulation results and other papers. It is observed that needle diameter has a significant effect on fracture toughness, whereas the insertion velocity has a slight impact on the fracture toughness. During the rotational needle insertion process, the winds-up of the gel occurs and the diameter of the hole was increasing with increased rpm. Maximum insertion force was noticed in the 27 G needle at 5 mm/s. The interaction function will be less at the maximum fracture development region.
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Materiais Biocompatíveis , Agulhas , Humanos , Fenômenos Mecânicos , Simulação por Computador , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Biofabricated tissues have found numerous applications in tissue engineering and regenerative medicine in addition to the promotion of disease modeling and drug development and screening. Although three-dimensional (3D) printing strategies for designing and developing customized tissue constructs have made significant progress, the complexity of innate multicellular tissues hinders the accurate evaluation of physiological responses in vitro. Cellular aggregates, such as spheroids, are 3D structures where multiple types of cells are co-cultured and organized with endogenously secreted extracellular matrix and are designed to recapitulate the key features of native tissues more realistically. 3D Bioprinting has emerged as a crucial tool for positioning of these spheroids to assemble and organize them into physiologically- and histologically-relevant tissues, mimicking their native counterparts. This has triggered the convergence of spheroid fabrication and bioprinting, leading to the investigation of novel engineering methods for successful assembly of spheroids while simultaneously enhancing tissue repair. This review provides an overview of the current state-of-the-art in spheroid bioprinting methods and elucidates the involved technologies, intensively discusses the recent tissue fabrication applications, outlines the crucial properties that influence the bioprinting of these spheroids and bioprinted tissue characteristics, and finally details the current challenges and future perspectives of spheroid bioprinting efforts in the growing field of biofabrication.
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Bioimpressão , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Medicina Regenerativa , Matriz Extracelular , Alicerces Teciduais/química , Esferoides CelularesRESUMO
Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC-EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Terapia Baseada em Transplante de Células e Tecidos , MicroRNAs/genética , MicroRNAs/metabolismo , BioengenhariaRESUMO
The insertion of the surgical needle in soft tissue has involved significant interest in the current time because of its purpose in minimally invasive surgery (MIS) and percutaneous events like biopsies, PCNL, and brachytherapy. This study represents a review of the existing condition of investigation on insertion of a surgical needle in biological living soft tissue material. As observes the issue from numerous phases, like, analysis of the cutting forces modeling (insertion), tissue material deformation, analysis of the needle deflection for the period of the needle insertion, and the robot-controlled insertion procedures. All analysis confirms that the total needle insertion force is the total of dissimilar forces spread sideways the shaft of the insertion needle for example cutting force, stiffness force, and frictional force. Various investigations have analyzed all these kinds of forces during the needle insertion process. The force data in several measures are applied for recognizing the biological tissue materials as the needle is penetrated or for path planning. The deflection of the needle during insertion and tissue material deformation is the main trouble for defined needle placing and efforts have been prepared to model them. Applying existing models numerous insertion methods are established that are discussed in this review.
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Braquiterapia , Agulhas , Braquiterapia/métodos , Fricção , Fenômenos Mecânicos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
This study aimed to understand the effect of physiological and dental implant-related parameter variations on the osseointegration for an implant-supported fixed prosthesis. Eight design factors were considered (implant shape, diameter, and length; thread pitch, depth, and profile; cantilever [CL] length and implant-loading protocol). Total 36 implantation scenarios were simulated using finite element method based on Taguchi L36 orthogonal array. Three patient-specific bone conditions were also simulated by scaling the density and Young's modulus of a mandible sample to mimic weak, normal, and strong bones. Taguchi method was employed to determine the significance of each design factor in controlling the peri-implant cortical bone microstrain. For normal bone condition, CL length had the maximum contribution (28%) followed by implant diameter (18%), thread pitch (14%), implant length (8%), and thread profile (5%). For strong bone condition, CL and implant diameter had equal contribution (32%) followed by thread pitch (7%) and implant length (5%). For weak bone condition, implant diameter had the highest contribution (31%) followed by CL length (30%), thread pitch (11%) and implant length (8%). The presence of distal CL in dental framework was found to be the most influential design factor, which can cause high strain in the cervical cortical bone. It was seen that implant diameter had more effect compared to implant length toward peri-implant bone biomechanical response. Implant-loading time had no significant effect towards peri-implant bone biomechanical response, signifying immediate loading is possible with sufficient mechanical retention.
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Implantes Dentários , Fenômenos Biomecânicos , Planejamento de Prótese Dentária , Análise do Estresse Dentário , Módulo de Elasticidade , Análise de Elementos Finitos , Humanos , Mandíbula , Osseointegração , Estresse MecânicoRESUMO
In the last decade, bioprinting has emerged as a facile technique for fabricating tissues constructs mimicking the architectural complexity and compositional heterogeneity of native tissues. Amongst different bioprinting modalities, extrusion-based bioprinting (EBB) is the most widely used technique. Coaxial bioprinting, a type of EBB, enables fabrication of concentric cell-material layers and enlarges the scope of EBB to mimic several key aspects of native tissues. Over the period of development of bioprinting, tissue constructs integrated with vascular networks, have been one of the major achievements made possible largely by coaxial bioprinting. In this review, current advancements in biofabrication of constructs with coaxial bioprinting are discussed with a focus on different bioinks that are particularly suitable for this modality. This review also expounds the properties of different bioinks suitable for coaxial bioprinting and then analyses the key achievements made by the application of coaxial bioprinting in tissue engineering, drug delivery and in-vitro disease modelling. The major limitations and future perspectives on the critical factors that will determine the ultimate clinical translation of the versatile technique are also presented to the reader.
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Bioprinting using cell-laden bioink is a rapidly emerging additive manufacturing method to fabricate engineered tissue constructs and in vitro models of disease biology. Amongst different bioprinting modalities, extrusion-based bioprinting is the most conveniently adopted technique due to its affordability. Bioinks consisting of living cells are suspended in hydrogels and extruded through syringe-needle assemblies, which subsequently undergo gelation at the collector plate. During the process, pressure is exerted on living cells which may cause cell deaths. Thus, for selected combination of cell and hydrogel, exerted pressure and the extrusion play key roles in determining the cell viability. Experimental evaluation to characterise stresses experienced by the cells in a bioink during bioprinting is a tedious exercise. Herein, computational modelling can be applied efficiently for rapid screening of bioinks. In the present study, a smoothed particle hydrodynamics model is developed for the analysis of stresses exerted on the cells during bioprinting process. Cells are modelled by assigning different mechanical properties to nucleus, cytoskeleton and cell membrane regions of the cell to get a more realistic understanding of cell deformation. The cytoplasm and nucleus are modelled as finite element meshes and a spring model of the cell membrane is coupled to the finite element model to develop a three-compartment model of the cell. Cell deformation is taken as a potential indicator of cell death. Effect of different process parameters such as flow rate, syringe-nozzle geometry and cell density are investigated. A submodeling approach is further introduced to predict deformation with higher resolution in a unit volume containing 104 to 108 cells. Results suggest that the generated bioink flow dynamic model can be a useful tool for the computational study of fluid flow involving cell suspensions during a bioprinting process.