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Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.
Assuntos
Bioimpressão , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Córnea , Bioimpressão/métodos , Impressão Tridimensional , Alicerces Teciduais/química , Hidrogéis/químicaRESUMO
As the most commonly used additive manufacturing technology, fused deposition modeling (FDM) still faces some technical issues caused by temperature change-induced unsteady thermal stress and warping. These issues can further lead to the deformation of printed parts and even terminate the printing process. In response to these issues, this article established a numerical model of temperature field and thermal stress field for FDM by finite element modeling and "birth-death element" technique to predict the deformation of the part. What makes sense in this process is that the logic of elements sort based on ANSYS Parametric Design Language (APDL) was proposed to sort the meshed elements, which was aimed to perform FDM simulation quickly on the model. In this work, the effects of the sheets shape and infill line directions (ILDs) on the distortion during FDM were simulated and verified. From the analysis of stress field and deformation nephogram, the simulation results indicated that ILD had greater effects on the distortion. Moreover, the sheet warping became most serious when the ILD was aligned with the diagonal of the sheet. The simulation results matched well with the experimental results. Thus, the proposed method in this work can be used to optimize the printing parameters for FDM process.
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Surgery is the most frequent treatment for patients with brain tumors. The construction of full-scale human brain models, which is still challenging to realize via current manufacturing techniques, can effectively train surgeons before brain tumor surgeries. This paper aims to develop a set of three-dimensional (3D) printing approaches to fabricate customized full-scale human brain models for surgery training as well as specialized brain patches for wound healing after surgery. First, a brain patch designed to fit a wound's shape and size can be easily printed in and collected from a stimuli-responsive yield-stress support bath. Then, an inverse 3D printing strategy, called "peeling-boiled-eggs," is proposed to fabricate full-scale human brain models. In this strategy, the contour layer of a brain model is printed using a sacrificial ink to envelop the target brain core within a photocurable yield-stress support bath. After crosslinking the contour layer, the as-printed model can be harvested from the bath to photo crosslink the brain core, which can be eventually released by liquefying the contour layer. Both the brain patch and full-scale human brain model are successfully printed to mimic the scenario of wound healing after removing a brain tumor, validating the effectiveness of the proposed 3D printing approaches.
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Heart valve disease has become a serious global health problem, which calls for numerous implantable prosthetic valves to fulfill the broader needs of patients. Although current three-dimensional (3D) bioprinting approaches can be used to manufacture customized valve prostheses, they still have some complications, such as limited biocompatibility, constrained structural complexity, and difficulty to make heterogeneous constructs, to name a few. To overcome these challenges, a sacrificial scaffold-assisted direct ink writing approach has been explored and proposed in this work, in which a sacrificial scaffold is printed to temporarily support sinus wall and overhanging leaflets of an aortic valve prosthesis that can be removed easily and mildly without causing any potential damages to the valve prosthesis. The bioinks, composed of alginate, gelatin, and nanoclay, used to print heterogenous valve prostheses have been designed in terms of rheological/mechanical properties and filament formability. The sacrificial ink made from Pluronic F127 has been developed by evaluating rheological behavior and gel temperature. After investigating the effects of operating conditions, complex 3D structures and homogenous/heterogenous aortic valve prostheses have been successfully printed. Lastly, numerical simulation and cycling experiments have been performed to validate the function of the printed valve prostheses as one-way valves.
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Bioimpressão , Tinta , Humanos , Valva Aórtica , Impressão Tridimensional , Alicerces Teciduais/química , Bioimpressão/métodos , Engenharia Tecidual/métodos , Hidrogéis/químicaRESUMO
Yield-stress support bath-enabled three-dimensional (3D) printing has been widely used in recent years for diverse applications. However, current yield-stress fluids usually possess single microstructures and still face the challenges of on-demand adding and/or removing support bath materials during printing, constraining their application scope. This study aims to propose a concept of stimuli-responsive yield-stress fluids with an interactive dual microstructure as support bath materials. The microstructure from a yield-stress additive allows the fluids to present switchable states at different stresses, facilitating an embedded 3D printing process. The microstructure from stimuli-responsive polymers enables the fluids to have regulable rheological properties upon external stimuli, making it feasible to perfuse additional yield-stress fluids during printing and easily remove residual fluids after printing. A nanoclay-Pluronic F127 nanocomposite is studied as a thermosensitive yield-stress fluid. The key material properties are characterized to unveil the interactions in the formed dual microstructure and microstructure evolutions at different stresses and temperatures. Core scientific issues, including the filament formation principle, surface roughness control, and thermal effects of the newly added nanocomposite, are comprehensively investigated. Finally, three representative 3D structures, the Hall of Prayer, capsule, and tube with changing diameter, are successfully printed to validate the printing capability of stimuli-responsive yield-stress fluids for fabricating arbitrary architectures.
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Fluid bath-assisted three-dimensional (3D) printing is an innovative 3D printing strategy that extrudes liquid ink materials into a fluid bath to form various 3D configurations. Since the support bath can provide in situ support, extruded filaments are able to freely construct complex 3D structures. Meanwhile, the supporting function of the fluid bath decreases the dependence of the ink material's cross-linkability, thus broadening the material selections for biomedical applications. Fluid bath-assisted 3D printing can be divided into two subcategories: embedded 3D printing and support bath-enabled 3D printing. This review will introduce and discuss three main manufacturing processes, or stages, for these two strategies. The stages that will be discussed include preprinting, printing, and postprinting. In the preprinting stage, representative fluid bath materials are introduced and the bath material preparation methods are also discussed. In addition, the design criteria of fluid bath materials including biocompatibility, rheological properties, physical/chemical stability, hydrophilicity/hydrophobicity, and other properties are proposed in order to guide the selection and design of future fluid bath materials. For the printing stage, some key technical issues discussed in this review include filament formation mechanisms in a fluid bath, effects of nozzle movement on printed structures, and design strategies for printing paths. In the postprinting stage, some commonly used postprinting processes are introduced. Finally, representative biomedical applications of fluid bath-assisted 3D printing, such as standalone organoids/tissues, biomedical microfluidic devices, and wearable and bionic devices, are summarized and presented.
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Microfluídica , Impressão Tridimensional , Organoides , ReologiaRESUMO
Pediatric orbital trapdoor fractures are common in children and adolescents and usually require emergency surgical intervention. Herein, a personalized 3D printing-assisted approach to surgical treatment is proposed, serving to accurately and effectively repair pediatric orbital trapdoor fractures. We first investigated stress distribution in external force-induced orbital blowout fractures via numerical simulation, determining that maximum stresses on inferior and medial walls exceed those on superior and lateral walls and thus confer higher probability of fracture. We also examined 36 pediatric patients treated for orbital trapdoor fractures between 2014 and 2019 to verify our theoretical construct. Using 3D printing technique, we then created orbital models based on computed tomography (CT) studies of these patients. Absorbable implants were tailor-made, replicating those of 3D-printed models during surgical repairs of fractured orbital bones. As follow-up, we compared CT images and clinical parameters (extraocular movements, diplopia, enophthalmos) before and 12 months after operative procedures. There were only two patients with diplopia and six with enophthalmos >2 mm at 12 months, attesting to the efficacy of our novel 3D printing-assisted strategy.
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Polymeric parts have been increasingly used in various engineering fields. The performance of polymeric parts is significantly affected by working-environment-induced aging. In this paper, an ultrasonic-vibration-assisted injection molding system was designed and utilized to fabricate polymeric parts from isotactic polypropylene (iPP) using different processing conditions. The natural aging experiments were performed to age the fabricated iPP parts for one year. The effects of key process parameters as well as ultrasound power on the microstructures and the mechanical properties of the iPP parts after aging were systematically investigated using X-ray diffraction analysis, Fourier transform infrared analysis, scanning electron microscope imaging, and tensile testing. It is found that both the microstructures and the tensile strength of the iPP parts deteriorate with the increasing aging time. In addition, the crystallinity and the tensile strength decrease with the increasing melt temperature but increase with the increasing mold temperature in a given range and holding pressure. The increase in ultrasound power leads to an increase in crystallinity. However, when the ultrasound power is over 200 W, the tensile strength of the aged iPP parts decreases, which indicates that high ultrasound power may not form optimal condensed microstructures with excellent anti-aging capacity.
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This paper presents a group of new experiments on human olfactory threshold measurement. It is a successful educational reform in teaching of genetic experiment. It considered not only training students' skills in the research on population genetics and investigating local population's olfactory allelic frequency, but also class experiments and research out of the class.