Three-dimensional Platform Research Articles

Construction of chamber-specific engineered cardiac tissues in vitro with human iPSC-derived cardiomyocytes and human foreskin fibroblasts

Human-induced pluripotent stem cell (hiPSC) technology and directed cardiac differentiation technology can provide a continuous supply of cells for disease modeling, drug screening, and cell therapy. However, two-dimensional (2D) cells often fail to faithfully reflect the physiological structure and function of the heart. Considering the contractile function is the most critical and easy-to-understand function of cardiomyocytes, the engineered cardiac tissues (ECT) with mechanical properties may serve as an appropriate three-dimensional (3D) platform for drug evaluation. At present, there are various methods to generate ECTs, some of which are quite costly. In the present study, we proposed that human foreskin fibroblast (HFF) cells, as a cost-effective and accessible cell source, can promote the compaction and remodeling of ECTs. The HFFs derived ECTs displayed stable structural and functional characteristics with a higher performance-to-price ratio. Moreover, both ECTs made from atrial and ventricular cardiomyocytes showed an excellent drug response, demonstrating that the ECT with HFFs as an easy and reliable platform for drug evaluation.

Two-Dimensional and Three-Dimensional Cartilage Model Platforms for Drug Evaluation and High-Throughput Screening Assays.

Osteoarthritis (OA) is a severely painful and debilitating disease of the joint, which brings about degradation of the articular cartilage and currently has few therapeutic solutions. Two-dimensional (2D) high-throughput screening (HTS) assays have been widely used to identify candidate drugs with therapeutic potential for the treatment of OA. A number of small molecules which improve the chondrogenic differentiation of progenitor cells for tissue engineering applications have also been discovered in this way. However, due to the failure of these models to accurately represent the native joint environment, the efficacy of these drugs has been limited in vivo. Screening systems utilizing three-dimensional (3D) models, which more closely reflect the tissue and its complex cell and molecular interactions, have also been described. However, the vast majority of these systems fail to recapitulate the complex, zonal structure of articular cartilage and its unique cell population. This review summarizes current 2D HTS techniques and addresses the question of how to use existing 3D models of tissue-engineered cartilage to create 3D drug screening platforms with improved outcomes. Impact statement Currently, the use of two-dimensional (2D) screening platforms in drug discovery is common practice. However, these systems often fail to predict efficacy in vivo, as they do not accurately represent the complexity of the native three-dimensional (3D) environment. This article describes existing 2D and 3D high-throughput systems used to identify small molecules for osteoarthritis treatment or in vitro chondrogenic differentiation, and suggests ways to improve the efficacy of these systems based on the most recent research.

High Aspect Ratio and Light-Sensitive Micropillars Based on a Semiconducting Polymer Optically Regulate Neuronal Growth.

Many nano- and microstructured devices capable of promoting neuronal growth and network formation have been previously investigated. In certain cases, topographical cues have been successfully complemented with external bias, by employing electrically conducting scaffolds. However, the use of optical stimulation with topographical cues was rarely addressed in this context, and the development of light-addressable platforms for modulating and guiding cellular growth and proliferation remains almost completely unexplored. Here, we develop high aspect ratio micropillars based on a prototype semiconducting polymer, regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT), as an optically active, three-dimensional platform for embryonic cortical neurons. P3HT micropillars provide a mechanically compliant environment and allow a close contact with neuronal cells. The combined action of nano/microtopography and visible light excitation leads to effective optical modulation of neuronal growth and orientation. Embryonic neurons cultured on polymer pillars show a clear polarization effect and, upon exposure to optical excitation, a significant increase in both neurite and axon length. The biocompatible, microstructured, and light-sensitive platform developed here opens up the opportunity to optically regulate neuronal growth in a wireless, repeatable, and spatio-temporally controlled manner without genetic modification. This approach may be extended to other cell models, thus uncovering interesting applications of photonic devices in regenerative medicine.

Rayleigh Instability-Driven Coaxial Spinning of Knotted Cell-Laden Alginate Fibers as Artificial Lymph Vessels.

Constructing artificial lymph vessels, which play a key role in the immune response, can provide new insights into immunology and disease pathologies. An immune tissue is a highly complex network that consists of lymph vessels, with a "beads-on-a-string" knotted structure. Herein, we present the facile and rapid fabrication of beads-on-a-string knotted cell-laden fibers using coaxial spinning of alginate by exploiting the Plateau-Rayleigh instability. It is shown how alterations in the flow rate and alginate concentration greatly affect the beads-on-a-string structure, rooted in the Plateau-Rayleigh instability theory. Biocompatibility was confirmed by the lactate dehydrogenase (LDH) assay and live/dead staining of the encapsulated human white blood cells. Finally, the encapsulated white blood cells were still functional as indicated by their anti-CD3 activation to secrete interleukin 2. The rapid fabrication of a cell-laden beads-on-a-string three-dimensional (3D) culture platform enables a crude mimicry of the lymph vessel structure. With joint expertise in immunology, microfluidics, and bioreactors, the technology may contribute to the mechanistic assay of human immune response in vitro and functional replacement.

Biofilm-Infected Human Clusteroid Three-Dimensional Coculture Platform to Replace Animal Models in Testing Antimicrobial Nanotechnologies.

Microbial biofilms are a major concern in wound care, implant devices, and organ infections. Biofilms allow higher tolerance to antimicrobial drugs, can impair wound healing, and potentially lead to sepsis. There has been a recent focus on developing novel nanocarrier-based delivery vehicles to enhance the biofilm penetration of traditional antibacterial drugs. However, a feasible in vitro human skin model to mimic the biofilm formation and its treatment for clearance have not yet been reported. This study describes the benefits of using an innovative bacterial biofilm-infected keratinocyte clusteroid model for the first time. It paves a new way for testing innovative nanomedicine delivery systems in a rapid and reproducible way on a realistic human cell-based platform, free of any animal testing. Herein, we have developed a novel composite 3D biofilm/human keratinocyte clusteroid coculture platform, which was used to measure biofilm clearance efficiency of nanoparticle (NP)-based therapeutics. We tested this model by treating the biofilm-infected 3D coculture layers by a ciprofloxacin-loaded Carbopol nanogel particles, surface-functionalized by the cationic protease Alcalase. We measured the antibacterial efficiency of the NP treatment on clearing Staphylococcus aureus and Pseudomonas aeruginosa biofilms on the 3D keratinocyte clusteroid/biofilm coculture model. Our experiments showed that these bacteria can infect the 3D layer of keratinocyte clusteroids and produce a stable biofilm. The biofilms were efficiently cleared by treatment with a formulation of 0.0032 wt % ciprofloxacin-loaded in 0.2 wt % Carbopol NPs surface-functionalized with 0.2 wt % Alcalase. Taken together, these promising results demonstrate that our coculture model can be exploited as a novel platform for testing the biofilm-eliminating efficiency of various NP formulations emulating skin and wound infections and could have wider applicability to replace animal models in similar experiments. This 3D cell culture-based platform could help in developing and testing of more effective antibacterial agents for clinical applications of antiplaque dental treatments, implants, infection control, and wound dressings.

Discussion on the Application of Three-dimensional Real Scene Safety Production Platform Based on Mine Surface and Underground

Discussion on the Application of Three-dimensional Real Scene Safety Production Platform Based on Mine Surface and Underground

Construction of polydopamine-coated three-dimensional graphene-based conductive network platform for amperometric detection of dopamine

An effectively sensitive and selective electrochemical sensor based on polydopamine (PDA)-coated material was fabricated for the dopamine (DA) amperometric detection. The coated compounds were synthesized through incorporating carbon black (CB) nanoparticles into graphene oxide (GO) sheets via spray-drying technique to obtain three-dimensional (3D) CB-GO microsphere structure (CG). Electrochemical characterizations of the PDA-CG modified Pt electrode (PDA-CG/Pt) were carried out through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), revealing an excellent conductivity activity against other electrodes in this study, which comes down to the synergistic effect of the introduction of CB nanoparticles and the presence of PDA layer. The sensor prepared by this facile approach without containing any metal elements also shows superior catalytic performance towards oxidation of DA, regardless of the existence of other interference including glucose (Glu), uric acid (UA) and ascorbic acid (AA). The linear range for amperometric detection of DA was from 0.2 to 63 μM, and the detection limit was 0.048 μM (S/N = 3). Furthermore, this modified biosensor could be successfully applied to determine DA in biological fluids of human serums with satisfying results.

Displacement and temperature sensor based on whispering gallery effect within unsymmetrical U-type fiber structure

We experimentally demonstrate displacement and temperature sensing based on the whispering gallery effect (WGE) within an unsymmetrical U-shaped tapered-fiber. The tapered-fiber (TF) is created by heat pulling a single-mode fiber (SMF) and bent in the region transition using the three-dimensional control platform to form an unsymmetrical U-shaped. Due to the light leaks into the cladding, most of the light is transmitted along the inner wall of the cladding in the form of WME. The Mach-Zehnder interference (MZI) fringes are caused by the cladding mode and the core mode. The can be used in a small space within 2.3 mm. The proposed sensor can achieve displacement measurement in the micron scale and has a maximum displacement sensitivity of about 38 pm/μm and 0.048 dB/μm over a displacement range of 10−60 μm at room temperature. The temperature sensitivity reaches 10.1 pm/°C when the waist diameter is 2.3 μm at the range of 20−60 °C. The device is compact, robust in mechanical strength, simple in fabrication, and can be easily used in small space physical measurements.

Research on the Construction of Substation Equipment Model Library Based on BIM Three-Dimensional Modeling

Substation equipment has a large amount of heterogeneous information during its life cycle. However, when Autodesk Revit is used as the modeling software to build a BIM model of traction substation equipment, due to the limited type of model attribute parameters and parameter grouping methods, the model cannot meet the requirements. Requirements for information integration in the entire life cycle of equipment. Based on this, the thesis uses the MVC model of three-dimensional modeling platform and the technical support of synchronous calculation to propose a BIM-based substation equipment graphics calculation system. Taking the common cable trench, cover plate and foundation earthwork calculation in substation station engineering as an example, the realization method of main technology is explained.

Three-Dimensional Ex Vivo Culture for Drug Responses of Patient-Derived Gastric Cancer Tissue.

Gastric cancer (GC) is one of the most common malignancies with high mortality and substantial morbidity. Although the traditional treatment strategies for GC revolve around surgery, radiotherapy, and chemotherapy, none have been able to optimally treat most affected patients. To improve clinical outcomes and overcome potential GC resistance, we established a three-dimensional (3D) culturing platform that accurately predicts drug responses in a time- and cost-effective manner. We collected tumor tissues from patients following surgeries and cultured them for 3 days using our protocol. We first evaluated cell proliferation, viability, and apoptosis using the following markers: Ki67 and cleaved caspase 3 (Cas3). We demonstrated that cell viability was maintained for 72 h in culture and that the tumor microenvironments and vascular integrities of the tissues were intact throughout the culture period. We then administered chemotherapeutics to assess drug responses and found differential sensitivity across different patient-derived tissues, enabling us to determine individualized medication plans. Overall, our study validated this rapid, cost-effective, scalable, and reproducible protocol for GC tissue culture that can be employed for drug response assessments. Our 3D culture platform paves a new way for personalized medication in GC and other tumors and can greatly impact future oncological research.

Development and Application of 3D Visualization Platform for Flood Evolution in Le’an River Basin of Wuyuan

With the rapid development of computer network technology, virtual display technology has become a typical representative of modern information technology, which can provide more efficient and intuitive technical means for flood prevention and risk assessment of water conservancy departments, and make more innovations and breakthroughs in the field of 3D simulation. This paper takes the area of Wuyuan County in the upper reaches of Le’an River in Poyang Lake as an example. Based on WebGIS technology, spatial database technology, CTS virtual display technology and combined with TOPMODEL semi-distributed hydrological model and IFMS domestic flood analysis software, it uses computer languages such as C#.NET and Java to carry out secondary development, explore and build a three-dimensional immersive hydrological multi-element virtual reality platform with real-time interactive display function, and realize the dynamics simulation display of three-dimensional data query, water and rain monitoring, flood evolution, submergence analysis, disaster assessment and other scenes under the three-dimensional perspective. It also provides an auxiliary decision-making platform for flood control and disaster reduction in the river basin, and further improves the guarantee level of water safety in the river basin.

3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study

Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study, different three-dimensional (3D) printing platforms were used to establish novel 3D cell cultures enriched in CSCs from non-small cell lung cancer (NSCLC) patients and cell lines. Rigid scaffolds with an elevated compressive modulus and uniform pores and channels were produced using different filaments. Hydrogel-based scaffolds were printed with a more irregular distribution of pores and a lower compressive modulus. As a 3D model of reference, suspension spheroid cultures were established. Therein, cancer cell lines exhibited enhanced proliferation profiles on rigid scaffolds compared to the same cells grown on either hydrogel scaffolds or tumor spheres. Meanwhile, primary cancer cells grew considerably better on hydrogel scaffolds or in tumor sphere culture, compared to cells grown on rigid scaffolds. Gene expression analysis confirmed that tumor spheres and cells seeded on hydrogel scaffolds significantly overexpress most of stemness and invasion promoters tested compared to control cells grown in 2D culture. A different phenomenon was observed within cells growing on the rigid scaffolds, where fewer significant variations in gene expression were detected. Our findings provide strong evidence for the advantageous usage of 3D printed models, especially those which use GelMA-PEGDA hydrogels as the primary scaffold material, for studying lung CSCs. The results demonstrated that the 3D printed scaffolds were better to mimic tumor complexity and regulate cancer cell behavior than in vivo 2D culture models.

Three-dimensional cell-culture platform based on hydrogel with tunable microenvironmental properties to improve insulin-secreting function of MIN6 cells

Pancreatic β-cells have been reported to be mechanosensitive to cellular microenvironments, and subjecting the cells to more physiologically relevant microenvironments can produce better results than when subjecting them to the conventional two-dimensional (2D) cell-culture conditions. In this work, we propose a novel three-dimensional (3D) strategy for inducing multicellular spheroid formation based on hydrogels with tunable mechanical and interfacial properties. The results indicate that MIN6 cells can sense the substrates and form tightly clustered monolayers or multicellular spheroids on hydrogels with tunable physical properties. Compared to the conventional 2D cell-culture system, the glucose sensitivities of the MIN6 cells cultured in the 3D culture model is enhanced greatly and their insulin content (relative to the amount of protein) is increased 7.3–7.9 folds. Moreover, the relative gene and protein expression levels of some key factors such as Pdx1, NeuroD1, Piezo1, and Rac1 in the MIN6 cells are significantly higher on the 3D platform, compared to the 2D control group. We believe that this 3D cell-culture system developed for the generation of multicellular spheroids will be a promising platform for diabetes treatment in clinical islet transplantation.

Current Advances in 3D Tissue and Organ Reconstruction.

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.

Evaluation of PAMAM Dendrimers (G3, G4, and G5) in the Construction of a SPR-based Immunosensor for Cardiac Troponin T.

An immunosensor was developed using a SAM of an alkanethiol associated with PAMAM(G4) dendrimers based on surface plasmon resonance (SPR) to enhance the sensitivity for troponin T detection in blood samples. The feasibility of using three-dimensional platforms based on dendrimers for the development of immunosensors was demonstrated by evaluating three different generations of these dendrimers (G3, G4, and G5) to detect troponin T. The results showed the efficiency of these 3D platforms in anchoring biomolecules, amplifying the detection of troponin T. The sandwich assay showed good performance for troponin T detection, using secondary monoclonal antibodies, in the concentration range of 5 - 300 ng mL-1 (0.14 - 8.67 nmol L-1), R2 = 0.991, with the LOD of 3.6 ng mL-1. The sandwich assay's applicability was demonstrated by evaluating a secondary polyclonal antibody's performance in the concentration range of 3 - 30 ng mL-1, R2 = 0.998, with the LOD of 0.98 ng mL-1. The immunosensor was applied to determine troponin T in blood plasma samples from healthy patients, with an average recovery of 88 to 104%. The performance of the SPR-based immunosensor indicates reliable results and is expected to contribute to the rapid diagnosis of heart attack, with reduced costs.

Research on Transmission and Transformation Engineering Cost System Based on BIM 3D Modelling Technology

Taking the concept of service-oriented design as the concept, the paper designs the digital platform architecture based on the integrated application ideas and technical methods of the IFC standard and the three-dimensional geospatial engineering cost information platform, and builds a 3DGIS+BIM digital power engineering cost based on the B/S network architecture. information platform. Combined with the application value of BIM technology in the field of engineering cost, the applicability of BIM technology in the management of transmission and transformation engineering cost is first analysed; then the BIM technology is studied layer by layer from the aspects of graphical calculation, three-dimensional design and full process management Promoting strategies for application of engineering cost management; Finally, from the perspective of policy guidance, industry standards, BIM platform construction, and training of BIM talents, the application guarantee mechanism of BIM technology in transmission and transformation project cost management is proposed, with a view to BIM technology in transmission and transformation projects Provide reference for application promotion in cost management.

Kinematic effects of different gait speeds during gait initiation movement.

[Purpose] We investigated the influence of gait speed on the movement strategy during gait initiation. [Participants and Methods] This study included 21 young healthy individuals (11 males and 10 females; mean age, 21.7 ± 0.5 years; mean height, 166.1 ± 9.8 cm; and mean weight, 57.3 ± 11.2 kg). A three-dimensional motion analyzer and strain gauge force platform were used in this study. The measurement task consisted of gait initiation from the quiet stance; the two measurement conditions were normal gait and the highest speed. The analysis interval was from the start of the center of pressure migration to the heel contact at the first step of the swing limb. The center of gravity, center of pressure, joint movements, step length, and step time during the anticipatory postural control (from the start of center of pressure migration to swing leg-heel off) and swing (swing leg-heel off to swing leg-heel contact) phases were analyzed. [Results] Significant differences were observed in the center of gravity, center of pressure, hip flexion, abduction movement, stance-limb ankle dorsiflexion movement during the anticipatory postural control phase, and step time during the anticipatory postural control and swing phases. The stance-limb ankle plantar flexion movement and step length did not differ significantly in the swing phase. [Conclusion] When the gait speed increases, fluctuations in the joint movements increase as the center of pressure displacement increases, thus requiring complex control.

Deterministic Approach to Achieve Full-Polarization Cloak.

Achieving full-polarization (σ) invisibility on an arbitrary three-dimensional (3D) platform is a long-held knotty issue yet extremely promising in real-world stealth applications. However, state-of-the-art invisibility cloaks typically work under a specific polarization because the anisotropy and orientation-selective resonant nature of artificial materials made the σ-immune operation elusive and terribly challenging. Here, we report a deterministic approach to engineer a metasurface skin cloak working under an arbitrary polarization state by theoretically synergizing two cloaking phase patterns required, respectively, at spin-up (σ+) and spin-down (σ−) states. Therein, the wavefront of any light impinging on the cloak can be well preserved since it is a superposition of σ+ and σ− wave. To demonstrate the effectiveness and applicability, several proof-of-concept metasurface cloaks are designed to wrap over a 3D triangle platform at microwave frequency. Results show that our cloaks are essentially capable of restoring the amplitude and phase of reflected beams as if light was incident on a flat mirror or an arbitrarily predesigned shape under full polarization states with a desirable bandwidth of ~17.9%, conceiving or deceiving an arbitrary object placed inside. Our approach, deterministic and robust in terms of accurate theoretical design, reconciles the milestone dilemma in stealth discipline and opens up an avenue for the extreme capability of ultrathin 3D cloaking of an arbitrary shape, paving up the road for real-world applications.

The impact of culture dimensionality on behavioral epigenetic memory contributing to pluripotent state of iPS cells.

Three-dimensional (3D) culture platforms have been explored to establish physiologically relevant cell culture environment and permit expansion scalability; however, little is known about the mechanisms underlying the regulation of pluripotency of human induced pluripotent stem cells (hiPSCs). This study elucidated epigenetic modifications contributing to pluripotency of hiPSCs in response to 3D culture. Unlike two-dimensional (2D) monolayer cultures, 3D cultured cells aggregated with each other to form ball-like aggregates. 2D cultured cells expressed elevated levels of Rac1 and RhoA; however, Rac1 level was significantly lower while RhoA level was persisted in 3D aggregates. Compared with 2D monolayers, the 3D aggregates also exhibited significantly lower myosin phosphorylation. Histone methylation analysis revealed remarkable H3K4me3 upregulation and H3K27me3 maintenance throughout the duration of 3D culture; in addition, we observed the existence of naïve pluripotency signatures in cells grown in 3D culture. These results demonstrated that hiPSCs adapted to 3D culture through alteration of the Rho-Rho kinase-phospho-myosin pathway, influencing the epigenetic modifications and transcriptional expression of pluripotency-associated factors. These results may help design culture environments for stable and high-quality hiPSCs.

Nanofibrous Tubular Three-Dimensional Platform for Single Dental Pulp Stem Cell Polarization.

Dental pulp stem cells (DPSCs) are the primary stem cell source for regenerative endodontics. DPSCs need to undergo a polarization process and retain the permanent polarization status to perform the function of odontoblasts. However, the factors that control DPSC polarization and its underlying mechanism remain unknown. In this study, we established a unique nanofibrous tubular three-dimensional (3D) platform to explore DPSC polarization. The 3D platform has a "clean" background and confines one single DPSC in each microisland of the platform; therefore, it is capable of deciphering any signal that initiates or regulates DPSC polarization. Using the biomimetic platform, we identified that the nanofibrous tubular architecture is the crucial factor to initiate DPSC polarization. Dynamic morphological observation showed that the cellular process of the polarized DPSCs continuously extended and reached a plateau at 72 h. Meanwhile, Golgi apparatus, a cell polarization marker, continuously moved from a juxtanuclear region, passed the nucleus, and eventually settled down at a final position that was a few micrometers away from the nucleus. Inhibition of microfilament and microtubule polymerization demonstrated the indispensable role of cytoskeleton reorganization in modulating DPSC polarization. In addition, cell tension was involved in the regulation of DPSC polarization. The findings of this work expand the in-depth understanding of DPSC polarization, which helps design new bioinspired materials for regenerative endodontics.