Current 3D Research Articles

Abstract 3838: Engineered hydrogel elucidates contributions of matrix mechanics to esophageal adenocarcinoma and identify matrix-activated therapeutic targets

Abstract INTRODUCTION: Changes in the tumor microenvironment arbitrated by a stiffened ECM are associated with tumor aggression and enable increased propensity towards metastasis. For instance, in vitro (2D) studies have implicated ECM properties in EAC progression. However, these studies are limited by the lack of 3D intercellular interactions, underscoring the need for physiologically relevant 3D culture models, such as patient-derived organoids (PDOs), that better recapitulate human cancer and its microenvironment to elucidate underlying mechanisms. Engineered hydrogels are an evolving and important component of 3D organoid culture systems, especially to introduce tunable physicochemical matrix signals that have been investigated in tumor progression and metastasis. Furthermore, PDOs have become an attractive pre-clinical in vitro model to study cancer biology and evaluate response to therapeutics. METHODS: We have engineered a visible light-mediated hydrogel platform that supports the development of patient derived Barrett's esophagus (BE) organoids, a precursor to esophageal adenocarcinoma (EAC), as well as EAC organoids. This synthetic biomaterial platform allows control over hydrogel stiffness to better recapitulate the mechanically dynamic esophageal cancer microenvironment, and may help identify therapeutic targets in EAC organoids. RESULTS: Our preliminary data have demonstrated that BE and EAC organoid density, size and proliferation can be controlled by synthetic ECM biomechanical properties. Furthermore, our data show that increased matrix stiffness promotes changes in the transcriptional profiles of EAC organoids, as observed via Principal Component Analysis, and gene set enrichment analysis of upregulated genes reveals enrichment of anti-apoptotic pathways. This suggests that the synthetic ECM facilitates activation of mechanotransduction pathways in EAC organoids and that matrix mechanics have a significant role in activation of canonical anti-apoptotic signaling pathways. Ongoing studies involve identifying matrix stiffness-activated therapeutic targets via small molecule inhibition of upregulated genes that are considered prospective biomarkers in GI cancer. SUMMARY: Our work is significant because it establishes a biomaterial platform that overcomes the limitations of current 3D organoid culture methods to elucidate the role of the tumor microenvironment in EAC tumorigenesis and to identify disease-relevant therapeutic targets. This work will also provide an opportunity to further establish the engineered biomaterial as a platform to potentially elucidate the mechanisms of, and therapy targets for, other human adenocarcinomas in the context of changes in matrix biomechanics.FUNDING: NCI P01-CA098101, U54 CA-163004 and Charles H. Revson Senior Fellowships in Biomedical Science. Citation Format: Ricardo Cruz-Acuña, Secunda W. Kariuki, Claudia Loebel, Tatiana Karakasheva, Joel T. Gabre, Jason A. Burdick, Anil K. Rustgi. Engineered hydrogel elucidates contributions of matrix mechanics to esophageal adenocarcinoma and identify matrix-activated therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3838.

Bacterial targeted AIE photosensitizers synergistically promote chemotherapy for the treatment of inflammatory cancer

Tumor-associated components, especially extratumoral bacteria (EB) in the form of biofilms, could exacerbate cancer progression and hinder the effectiveness of antitumor drugs by covering the interstitial tumor space. Although photodynamic therapy (PDT) is a promising modality to kill cancer cells and bacteria with high spatiotemporal precision, the low penetration of light limits its potential in deep tumor therapy. Furthermore, current 2D culture-based preclinical in vitro models failed to reflect the complexity of the tumor microenvironment. Here, we developed an unprecedented “1 + 1 > 2″ combinatorial strategy of PDT and chemotherapy by co-delivering a bacterial-targeted photosensitizer with aggregation-induced emission (AIE) property and an anticancer drug, doxorubicin. The theranostic system could selectively visualize and rapidly kill EB, using a microfluidic-based 3D bladder cancer model. The effect of combinatorial therapy was synergistic, resulting in improved efficacy, as evidenced by at least a 2.5-fold reduction in the half-maximal inhibitory concentration of doxorubicin. Validation using a fish wound infection model further demonstrated the feasibility of AIE photosensitizers for efficient fluorescence imaging-guided PDT in vivo. Overall, we proposed a robust AIE PDT/chemotherapy strategy that shows great potential for rapid and concurrent treatment of bacterially infected cancer patients.

Feasibility study of large-scale mass customization 3D printing framework system with a case study on Nanjing Happy Valley East Gate

At present, the development and implementation of digital transformation are the keys to promoting high-quality industry development. The new digital fabrication method of robotic 3D printing is a research area being studied by many to tackle the issue of the declining productivity of traditional construction methods. Although many studies have been done, most of the current 3D printing projects are facing limitations in terms of scale. In order to bridge the gap, this article proposed a mass customization 3D printing framework system for large-scale projects. This article discusses how mass customization is made possible through the joint operation of the FUROBOT software and 3D printing hardware. By taking the east gate of Nanjing Happy Valley Plaza as a case study, the article demonstrates and studies the feasibility of the large-scale mass customization 3D printing framework system.

3D Culture Modeling of Metastatic Breast Cancer Cells in Additive Manufactured Scaffolds.

Cancer biology research is increasingly moving toward innovative in vitro 3D culture models, as conventional and current 2D cell cultures fail to resemble in vivo cancer biology. In the current study, porous 3D scaffolds, designed with two different porosities along with 2D tissue culture polystyrene (TCP) plates were used with a model breast cancer human cell line. The 3D engineered system was evaluated for the optimal seeding method (dynamic versus static), adhesion, and proliferation rate of MDA-MB-231 breast cancer cells. The expression profiles of proliferation-, stemness-, and dormancy-associated cancer markers, namely, ki67, lamin A/C, SOX2, Oct3/4, stanniocalcin 1 (STC1), and stanniocalcin 2 (STC2), were evaluated in the 3D cultured cells and compared to the respective profiles of the cells cultured in the conventional 2D TCP. Our data suggested that static seeding was the optimal seeding method with porosity-dependent efficiency. Moreover, cells cultured in 3D scaffolds displayed a more dormant phenotype in comparison to 2D, which was manifested by the lower proliferation rate, reduced ki67 expression, increased lamin A/C expression, and overexpression of STCs. The possible relationship between the cell affinity to different extracellular matrix (ECM) proteins and the RANK expression levels was also addressed after deriving collagen type I (COL-I) and fibronectin (FN) MDA-MB-231 filial cell lines with enhanced capacity to attach to the respective ECM proteins. The new derivatives exhibited a more mesenchymal like phenotype and higher RANK levels in relation to the parental cells, suggesting a relationship between ECM cell affinity and RANK expression. Therefore, the present 3D cell culture model shows that cancer cells on printed scaffolds can work as better representatives in cancer biology and drug screening related studies.

3D CFD simulation and analysis of transient flow in a water pipeline

Abstract A three-dimensional (3D) computational fluid dynamics (CFD) approach is developed to elaborate the water-hammer pipe flow and 3D detailed dynamic characteristics of a closing ball valve. The proposed CFD approach considers the water compressibility and the viscous sublayer, which are sometimes neglected in previous studies. Comparisons of the CFD results, the measured pressures and the one-dimensional results, demonstrate that the current 3D CFD approach better reproduces the experimental pressure oscillations while helping to visualize the associated physical processes and to further explore the 3D transient characteristics. The mean velocity distributions in the radial direction significantly change as the pipe transient progresses, which is closely associated with transient shear stress. Mean velocity variations at the valve during the closing process undergo three distinct stages: slight change, then drastic reduction, and finally slowing down. Head loss coefficient and discharge coefficient of the valve change as the valve closing time shortens.

CoSyR: A novel beam dynamics code for the modeling of synchrotron radiation effects

The self-consistent nonlinear dynamics of a relativistic charged particle beam interacting with its complete self-fields is a fundamental problem underpinning many of the accelerator design issues in high brightness beam applications, as well as the development of advanced accelerators. Particularly, synchrotron radiation induced effects in a magnetic dispersive beamline element can lead to collective beam instabilities and emittance growth. A novel beam dynamics code is developed based on a Lagrangian method for the calculation of the particles’ radiation near-fields using wavefront/wavelet meshes via the Green’s function of the Maxwell equations. These fields are then interpolated onto a moving mesh for dynamic update of the beam. This method allows radiation co-propagation and self-consistent interaction with the beam in 2D/3D simulations at greatly reduced numerical errors. Multiple levels of parallelisms are inherent in this method and implemented in our code CoSyR to enable at-scale simulations of nonlinear beam dynamics on modern computing platforms using MPI, multi-threading, and GPUs. The current 2D implementation of CoSyR has been used to evaluate the transverse and longitudinal coherent radiation effects on the beam and to investigate beam optics designs proposed for mitigation of beam brightness degradation in a magnetic bunch compressor. In this paper, the design of CoSyR, as well as the benchmark with other coherent synchrotron radiation models, are described and discussed. Extension of the core algorithms to 3D is possible and planned.

Ultra-low turn-off current 2D material heterojunction selectors: first-principle calculations

Selector is important for emerging non-volatile memory arrays to settle the sneak path problem and inhibit the array leakage current. The turn-off current of the selector determines the ability of selector to inhibit the leakage current. Here, selector models with the structure of graphene/g-GaN/graphene show ultra-low turn-off current. First, combining the plane electrostatic potential and the current–voltage characteristic of switch layers of heterojunctions, it can be concluded that the resistance switching mechanism is based on Schottky barrier at the interface. Moreover, three selector models with different switch layers (model A, B, C) are explored to study the influence of the switch layer structure on the device. The plane average electrostatic potential of selectors shows that the different structures of the switch layer result in the difference of the threshold voltage (V th), owing to the different interface barrier. Finally, the electronic transmission shows each selector have an ultra-low turn-off current (I off) and high nonlinearity, which could better suppress the leakage current in array. This work supplies a potential implementation scheme for the selector with ultra-low turn-off current.

Omnidirectional camera pose estimation and projective texture mapping for photorealistic 3D virtual reality experiences

<p class="Abstract">Modern applications in virtual reality require a high level of fruition of the environment as if it was real. In applications that have to deal with real scenarios, it is important to acquire both its three-dimensional (3D) structure and details to enable the users to achieve good immersive experiences. The purpose of this paper is to illustrate a method to obtain a mesh with high quality texture combining a raw 3D mesh model of the environment and 360 <em>°</em> images. The main outcome is a mesh with a high level of photorealistic details. This enables both a good depth perception thanks to the mesh model and high visualization quality thanks to the 2D resolution of modern omnidirectional cameras. The fundamental step to reach this goal is the correct alignment between the 360 ° camera and the 3D mesh model. For this reason, we propose a method that embodies two steps: 1) find the 360 <em>° </em>cameras pose within the current 3D environment; 2) project the high-quality 360 <em>° </em>image on top of the mesh. After the method description, we outline its validation in two virtual reality scenarios, a mine and city environment, respectively, which allows us to compare the achieved results with the ground truth.</p>

A data-driven machine learning approach for the 3D printing process optimisation

ABSTRACT 3D printing has become highly applicable in modern life recently. The industry has brought a facelift to most others. However, this technology still exists some shortcomings, and it therefore has not been generalised to bring the best benefits to users. In this paper, based on multilayer perceptron and convolution neural network models, we propose a new data-driven machine learning platform for predicting optimised parameters of the 3D printing process from a model design to a complete product. This finding can open up great advances in the current 3D printing technology. Accordingly, the results obtained allow us to predict quickly and accurately some decisive parameters of the traditional 3D printing process such as time, weight and length while the input was fuzzy with a part of the initial information missing. The proposed approach does not need to account for the shape, size and material of the printed object, but it can perform the process automatically without other extra factors. After completing the model, a configurator is proposed to set the parameters for the respective printer types, which makes the 3D printing process simple and fast.

Doppler shifts of spectral lines formed in the solar transition region and corona

Context. Emission lines formed in the transition region and corona dominantly show redshifts and blueshifts, respectively. Aims. We investigate the Doppler shifts in a 3D radiation magnetohydrodynamic (MHD) model of the quiet Sun and compare these to observed properties. We concentrate on Si IV 1394 Å originating in the transition region and examine the Doppler shifts of several other spectral lines at different formation temperatures. Methods. We constructed a radiation MHD model extending from the upper convection zone to the lower corona using the MURaM code. In this quiet Sun model, the magnetic field is self-consistently maintained by the action of a small-scale dynamo in the convection zone, and it is extrapolated to the corona as an initial condition. We synthesized the profiles of several optically thin emission lines, which formed at temperatures from the transition region into the corona. We investigated the spatial structure and coverage of redshifts and blueshifts and how this changes with the line-formation temperature. Results. The model successfully reproduces the observed change of average net Doppler shifts from redshifted to blueshifted from the transition region into the corona. In particular, the model shows a clear imbalance of area coverage of redshifts versus blueshifts in the transition region of ca. 80% to 20%, even though it is even a bit larger on the real Sun. We determine that (at least) four processes generate the systematic Doppler shifts in our model, including pressure enhancement in the transition region, transition region brightenings unrelated to coronal emission, boundaries between cold and hot plasma, and siphon-type flows. Conclusions. We show that there is not a single process that is responsible for the observed net Doppler shifts in the transition region and corona. Because current 3D MHD models do not yet fully capture the evolution of spicules, which is one of the key ingredients of the chromosphere, most probably these have yet to be added to the list of processes responsible for the persistent Doppler shifts.

Defining Soft Tissue: Bitmap Printing of Soft Tissue for Surgical Planning.

Nearly all applications of 3D printing for surgical planning have been limited to bony structures and simple morphological descriptions of complex organs due to the fundamental limitations in accuracy, quality, and efficiency of the current modeling paradigms and technologies. Current approaches have largely ignored the constitution of soft tissue critical to most surgical specialties where multiple high-resolution variations transition gradually across the interior of the volume. Differences in the scales of organization related to unique organs require special attention to capture fine features critical to surgical procedures. We present a six-material bitmap printing technique for creating 3D models directly from medical images, which are superior in spatial and contrast resolution to current 3D modeling methods, and contain previously unachievable spatial fidelity for soft tissue differentiation. A retrospective exempt IRB was obtained for all data through the Colorado Multiple Institution Review Board #21-3128.

4D imaging of turbulent flames with improved multi-camera calibration method and processing speed

4D imaging measurements in turbulent flames have been long desired to better understand the complex phenomena involved in the combustion process. Such 4D measurements provide the information of turbulent flames in all three spatial coordinates and time sequences. Tomographic reconstruction has been recently demonstrated as a promising approach for 4D flame diagnostics. However, two critical issues remain in the current 4D tomographic measurements: the accuracy of multi-camera calibration and the processing time of the tomographic program. Therefore, this work aims to address the two issues by developing a new multi-camera calibration method and a parallel tomographic reconstruction program. As shown in this work, the new multi-camera calibration method can significantly improve the angle calibration accuracy; and the parallel program reduces the processing time for 1000 tomographic reconstructions from 10 days to ~12 h. Such enhanced accuracy and processing speed are expected to benefit a range of combustion researches, and a specific example is demonstrated involving 4D imaging of a subsonic diffusion flame.

Statistical shape models of the posterior cranial fossa and hindbrain volumes may provide a more robust clinical metric for Chiari malformation

Chiari malformation is characterised by the herniation of the cerebellar tonsils through the foramen magnum. However, tonsillar herniation and other 2D morphometric measurements of the posterior cranial fossa (PCF) have a weak association with patients’ symptoms and clinical outcomes. This study aimed to contrast current 2D metrics with a novel 3D shape analysis of the PCF and the hindbrain, to determine if 3D measurements provides further insight into the pathophysiology of Chiari. The cranium of 12 controls and 21 Chiari malformation patients with (N = 9) and without (N = 12) a syrinx were scanned. The morphology of the PCF was quantified with typical 2D measurements. Additionally, a correspondence-based shape model that normalised the PCF volume, was used to find 3D differences in the shape of the PCF, and the distance of the hindbrain from the inner surfaces of the PCF. Shape analysis showed that, compared to controls, the caudal (p = 0.007; 2.3 mm, IQR: 1.6–3.3 mm) and anterior (p = 0.027; 1.3 mm,IQR: 1.1–1.6 mm) surfaces of the hindbrain were closer to the PCF in patients with and without a syrinx, respectively. However, there were negligible differences in the shape of the PCF between patient groups (p > 0.39). Current morphometric measures should be normalised for variation in PCF volume, so that shape measures are not biased. The reduced CSF space between the hindbrain and PCF will alter CSF dynamics, which may compress cerebellar vasculature and contribute to patient symptomatology.

Design and evaluation of an intelligent reduction robot system for the minimally invasive reduction in pelvic fractures

IntroductionPelvic fracture is a severe high-energy injury with the highest disability and mortality of all fractures. Traditional open surgery is associated with extensive soft tissue damages and many complications. Minimally invasive surgery potentially mitigates the risks of open surgical procedures and is becoming a new standard for pelvic fracture treatment. The accurate reduction has been recognized as the cornerstone of minimally invasive surgery for pelvic fracture. At present, the closed reduction in pelvic fractures is limited by the current sub-optimal 2D intra-operative imaging (fluoroscopy) and by the high forces of soft tissue involved in the fragment manipulation, which might result in fracture malreduction. To overcome these shortcomings and facilitate pelvic fracture reduction, we developed an intelligent robot-assisted fracture reduction (RAFR) system for pelvic fracture.MethodsThe presented method is divided into three parts. The first part is the preparation of 20 pelvic fracture models. In the second part, we offer an automatic reduction algorithm of our robotic reduction system, including Intraoperative real-time 3D navigation, reduction path planning, control and fixation, and robotic-assisted fracture reduction. In the third part, image registration accuracy and fracture reduction accuracy were calculated and analyzed.ResultsAll 20 pelvic fracture bone models were reduced by the RAFR system; the mean registration error E1 of the 20 models was 1.29 ± 0.57 mm. The mean reduction error E2 of the 20 models was 2.72 ± 0.82 mm. The global error analysis of registration and reduction results showed that higher errors are mainly located at the edge of the pelvis, such as the iliac wing.ConclusionThe accuracy of image registration error and fracture reduction error in our study was excellent, which could reach the requirements of the clinical environment. Our study demonstrated the precision and effectiveness of our RAFR system and its applicability and usability in clinical practice, thus paving the way toward robot minimally invasive pelvic fracture surgeries.

235 Analysiss of TNBC Cell Lines Cultured a Novel Translational Breast Cancer Microphysiological System (BC-MPS)

OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

As-Rigid-as-Possible Shape Servoing

Shape servoing is the problem of controlling the shape of a deformable object via robotic manipulation, exploiting sensory feedback. In many shape servoing scenarios of practical interest, the object has a natural tendency to preserve local rigidity. Motivated by this observation, we propose to use the As-Rigid-As-Possible deformation model for shape servoing. Specifically, we propose a novel control scheme based on a deformation Jacobian computed from this model. The proposed scheme drives the object to a desired 3D shape using as feedback the object’s measured current 3D shape. The scheme is simple to implement, and it avoids some typical requirements in existing work: specifically, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(i)</i> we do not need to know the object’s mechanical deformation parameters, and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(ii)</i> we do not use a Jacobian computed from data collected over a time window while the robots move. We test the proposed scheme in bi-arm shape servoing experiments with a variety of deformable objects of different material (paper, rubber, plastic). Tracking of the deformable object’s surface in 3D is performed in our experiments via an algorithm based on monocular vision. The experimental results validate the practicality of our scheme.

Design of multi-material sound transmission blocker using additive manufacturing

Additive manufacturing is most commonly done through 3D printing, which can print in multiple materials. This enables the design and construction of new structures that can block sound transmission, such as a periodic array of TPU plastic cylinders embedded in a matrix of PLA plastic. The difference in wave speed between the plastics can cause reflections and interference inside the material. However, printing in multimaterials provides distinct challenges for the current 3D printing technology. When printing with multiple nozzles, the inactive nozzle can clog, and getting the two materials to fuse can yield warping and separation. We addressed these problems to fabricate a sample of TPU cylinders (1.8 cm diameter, 8.6 cm height) embedded in PLA (20 cm × 10 cm × 2 cm) and measured the change in STL relative to a block of PLA. We discovered an improved attenuation of about 5.5 dB at 6300 Hz.

Automated Brain Volumetry in Patients With Memory Impairment: Comparison of Conventional and Ultrafast 3D T1-Weighted MRI Sequences Using Two Software Packages.

BACKGROUND. Isotropic 3D T1-weighted imaging has long acquisition times, potentially leading to motion artifact and altered brain volume measurements. Acquisition times may be greatly shortened using an isotropic ultrafast 3D echo-planar imaging (EPI) T1-weighted sequence. OBJECTIVE. The purpose of this article was to compare automated brain volume measurements between conventional 3D T1-weighted imaging and ultrafast 3D EPI T1-weighted imaging. METHODS. This retrospective study included 36 patients (25 women, 11 men; mean age, 68.4 years) with memory impairment who underwent 3-T brain MRI. Examinations included both conventional 3D T1-weighted imaging using inversion recovery gradient-recalled echo sequence (section thickness, 1.0 mm; acquisition time, 3 minutes 4 seconds) and, in patients exhibiting motion, an isotropic ultrafast 3D EPI T1-weighted sequence (section thickness, 1.2 mm; acquisition time, 30 seconds). The 36-patient sample excluded five patients in whom severe motion artifact rendered the conventional sequence of insufficient quality for volume measurements. Automated brain volumetry was performed using NeuroQuant (version 3.0, CorTechs Laboratories) and FreeSurfer (version 7.1.1, Harvard University) software. Volume measurements were compared between sequences for nine regions in each hemisphere. RESULTS. Volumes showed substantial to almost perfect agreement between the two sequences for most regions bilaterally. However, most regions showed significant mean differences between sequences, and Bland-Altman analyses showed consistent systematic biases and wide limits of agreement (LOA). For example, for the left hemisphere using NeuroQuant, volume was significantly greater for the ultrafast sequence in four regions and significantly greater for the conventional sequence in three regions, whereas standardized effect size between sequences was moderate for four regions and large for one region. Using NeuroQuant, mean bias (ultrafast minus conventional) and 95% LOA were greatest in cortical gray matter bilaterally (-50.61 cm3 [-56.27 cm3, -44.94 cm3] for the left hemisphere; -50.02 cm3 [-54.88 cm3, -45.16 cm3] for the right hemisphere). The variation between the two sequences was observed in subset analyses of 16 patients with and 20 patients without Alzheimer disease. CONCLUSION. Brain volume measurements show significant differences and systematic biases between the conventional and ultrafast sequences. CLINICAL IMPACT. In patients in whom severe motion artifact precludes use of the conventional sequence, the ultrafast sequence may be useful to enable brain volume-try. However, the current conventional 3D T1-weighted sequence remains preferred in patients who can tolerate the standard examination.

Design, simulation, and experiments for direct thixotropic metal 3D printing

Compared with current powder-based 3D metal printing, thixotropic metal 3D printing has great potentials and advantages in equipment cost, product quality, and process efficiency. In this paper, detailed problem statement, technique challenge, and development method regarding thixotropic metal 3D printing are discussed. A shear mixing and extruding prototype machine for thixotropic alloy fabrication was designed. We developed a direct thixotropic metal 3D printing machine and conducted a modeling and simulation process for the system. The printability of this direct metal 3D printing machine was studied. At the end, conclusions and future directions are also presented.

Current Advances in 3D Bioprinting for Cancer Modeling and Personalized Medicine.

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.