Magnetic leakage behavior assessment in pipeline stress-concentrated areas using improved force-magnetic coupling model.

Magnetic flux leakage (MFL) technology is remarkable for its capability to detect pipeline geometric deformation and general corrosion defects. However, it cannot characterize the MFL behavior in stress-concentrated areas, thereby greatly challenging the subsequent pipeline maintenance. This study suggests that the MFL characteristics of pipeline in stress-concentrated areas are caused by the combined effect of the face magnetic charge on the deformed end-face and the body magnetic charge of the dislocation stack. In addition, an improved force-magnetic coupling model of the pipeline in stress-concentrated areas is established based on the magnetic dipole model and Jiles-Atherton (J-A) theory. In the verification experiment, the Q235 steel plate is magnetized along the extension direction (axis of the pipeline) through the solenoid coil to obtain the distribution law of the MFL signal in the stress-concentrated area under different excitation intensities. The results show that with the increase in excitation intensity, the deformation of the MFL field signal caused by the end-face of the stress-concentrated area gradually increases to a stable state. Moreover, the internal stress of the MFL field signal generated by the pipe dislocation rapidly increases to a peak value and then decays exponentially to a certain base value. The overall change trend is in good agreement with the calculation results of the established force-magnetic coupling model. Meanwhile, the differentiation research between deformation and internal stress MFL field signals under different magnetic field intensities can provide a reliable theoretical basis for the subsequent accurate identification and quantification of pipeline stress-concentrated areas.

Emerging strategies of engineering retinal organoids and organoid-on-a-chip in modeling intraocular drug delivery: Current progress and future perspectives.

Retinal diseases are a rising concern as major causes of blindness in an aging society; therapeutic options are limited, and the precise pathogenesis of these diseases remains largely unknown. Intraocular drug delivery and nanomedicines offering targeted, sustained, and controllable delivery are the most challenging and popular topics in ocular drug development and toxicological evaluation. Retinal organoids (ROs) and organoid-on-a-chip (ROoC) are both emerging as promising in-vitro models to faithfully recapitulate human eyes for retinal research in the replacement of experimental animals and primary cells. In this study, we review the generation and application of ROs resembling the human retina in cell subtypes and laminated structures and introduce the emerging engineered ROoC as a technological opportunity to address critical issues. On-chip vascularization, perfusion, and close inter-tissue interactions recreate physiological environments in vitro, whilst integrating with biosensors facilitates real-time analysis and monitoring during organogenesis of the retina representing engineering efforts in ROoC models. We also emphasize that ROs and ROoCs hold the potential for applications in modeling intraocular drug delivery in vitro and developing next-generation retinal drug delivery strategies.

Advances in In Vitro Models of Neuromuscular Junction: Focusing on Organ-on-a-Chip, Organoids, and Biohybrid Robotics.

The neuromuscular junction (NMJ) is a peripheral synaptic connection between presynaptic motor neurons and postsynaptic skeletal muscle fibers that enables muscle contraction and voluntary motor movement. Many traumatic, neurodegenerative, and neuroimmunological diseases are classically believed to mainly affect either the neuronal or the muscle side of the NMJ, and treatment options are lacking. Recent advances in novel techniques have helped develop in vitro physiological and pathophysiological models of the NMJ as well as enable precise control and evaluation of its functions. This paper reviews the recent developments in in vitro NMJ models with 2D or 3D cultures, from organ-on-a-chip and organoids to biohybrid robotics. Related derivative techniques are introduced for functional analysis of the NMJ, such as the patch-clamp technique, microelectrode arrays, calcium imaging, and stimulus methods, particularly optogenetic-mediated light stimulation, microelectrode-mediated electrical stimulation, and biochemical stimulation. Finally, the applications of the in vitro NMJ models as disease models or for drug screening related to suitable neuromuscular diseases are summarized and their future development trends and challenges are discussed.

Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease.

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC-macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.

Correction: Elbaz et al. Chitin-Based Anisotropic Nanostructures of Butterfly Wings for Regulating Cells Orientation. Polymers 2017, 9, 386.

In the original publication [...].

Research on the Analytical Model of Improved Magnetic Flux Leakage Signal for the Local Stress Concentration Zone of Pipelines.

Local stress concentrations pose a significant hazard to the safe operation of pipelines. However, the classical analytical model of the magnetic flux leakage (MFL) signal is still unable to effectively quantitatively analyze and accurately evaluate the local stress concentration zone of a pipeline. In this paper, based on the Jiles-Atherton model of the magnetomechanical effect, the mathematical relationship between stress and the magnetization of ferromagnetic material under hysteresis conditions is introduced, and an improved analytical model of the MFL signal based on the magnetomechanical model is established. The influence law of stress intensity on the MFL signal in the local stress concentration zone of the pipeline is calculated and analyzed, and the theoretical calculation results are verified through experiments. Simulation and experimental results show that, considering the hysteresis condition, the stress causes a change in the hysteresis loop of the ferromagnetic material, and the magnetization strength of the material decreases with increasing stress; the effect of stress on the magnetization strength of ferromagnetic materials is most obvious when the external magnetic field is approximately 5 KA/m. The MFL signal on the surface of the local stress concentration zone of the pipe changes abruptly, and the amount of change in the axial amplitude and radial peak-to-peak value of the leakage signal of the pipe tends to increase with the increase in the stress intensity of the local stress concentration zone. A comparison of the analysis with the classical analytical model of the MFL signal shows that the improved analytical model of the MFL signal is more suitable for the quantification study of the local stress concentration zone of the pipeline.

Robust Carbonated Structural Color Barcodes with Ultralow Ontology Fluorescence as Biomimic Culture Platform.

Photonic crystal (PC) barcodes are a new type of spectrum-encoding microcarriers used in multiplex high-throughput bioassays, such as broad analysis of biomarkers for clinical diagnosis, gene expression, and cell culture. Unfortunately, most of these existing PC barcodes suffered from undesired features, including difficult spectrum-signal acquisition, weak mechanical strength, and high ontology fluorescence, which limited their development to real applications. To address these limitations, we report a new type of structural color-encoded PC barcodes. The barcodes are fabricated by the assembly of monodisperse polydopamine- (PDA-) coated silica (PDA@SiO2) nanoparticles using a droplet-based microfluidic technique and followed by pyrolysis of PDA@SiO2 (C@SiO2) barcodes. Because of the templated carbonization of adhesive PDA, the prepared C@SiO2 PC beads were endowed with simultaneous easy-to-identify structural color, high mechanical strength, and ultralow ontology fluorescence. We demonstrated that the structural colored C@SiO2 barcodes not only maintained a high structural stability and good biocompatibility during the coculturing with fibroblasts and tumor cells capture but also achieved an enhanced fluorescent-reading signal-to-noise ratio in the fluorescence-reading detection. These features make the C@SiO2 PC barcodes versatile for expansive application in fluorescence-reading-based multibioassays.

Patient-Specific Organoid and Organ-on-a-Chip: 3D Cell-Culture Meets 3D Printing and Numerical Simulation.

The last few decades have witnessed diversified in vitro models to recapitulate the architecture and function of living organs or tissues and contribute immensely to advances in life science. Two novel 3D cell culture models: 1) Organoid, promoted mainly by the developments of stem cell biology and 2) Organ-on-a-chip, enhanced primarily due to microfluidic technology, have emerged as two promising approaches to advance the understanding of basic biological principles and clinical treatments. This review describes the comparable distinct differences between these two models and provides more insights into their complementarity and integration to recognize their merits and limitations for applicable fields. The convergence of the two approaches to produce multi-organoid-on-a-chip or human organoid-on-a-chip is emerging as a new approach for building 3D models with higher physiological relevance. Furthermore, rapid advancements in 3D printing and numerical simulations, which facilitate the design, manufacture, and results-translation of 3D cell culture models, can also serve as novel tools to promote the development and propagation of organoid and organ-on-a-chip systems. Current technological challenges and limitations, as well as expert recommendations and future solutions to address the promising combinations by incorporating organoids, organ-on-a-chip, 3D printing, and numerical simulation, are also summarized.

Artificial intelligence velocimetry and microaneurysm-on-a-chip for three-dimensional analysis of blood flow in physiology and disease.

Understanding the mechanics of blood flow is necessary for developing insights into mechanisms of physiology and vascular diseases in microcirculation. Given the limitations of technologies available for assessing in vivo flow fields, in vitro methods based on traditional microfluidic platforms have been developed to mimic physiological conditions. However, existing methods lack the capability to provide accurate assessment of these flow fields, particularly in vessels with complex geometries. Conventional approaches to quantify flow fields rely either on analyzing only visual images or on enforcing underlying physics without considering visualization data, which could compromise accuracy of predictions. Here, we present artificial-intelligence velocimetry (AIV) to quantify velocity and stress fields of blood flow by integrating the imaging data with underlying physics using physics-informed neural networks. We demonstrate the capability of AIV by quantifying hemodynamics in microchannels designed to mimic saccular-shaped microaneurysms (microaneurysm-on-a-chip, or MAOAC), which signify common manifestations of diabetic retinopathy, a leading cause of vision loss from blood-vessel damage in the retina in diabetic patients. We show that AIV can, without any a priori knowledge of the inlet and outlet boundary conditions, infer the two-dimensional (2D) flow fields from a sequence of 2D images of blood flow in MAOAC, but also can infer three-dimensional (3D) flow fields using only 2D images, thanks to the encoded physics laws. AIV provides a unique paradigm that seamlessly integrates images, experimental data, and underlying physics using neural networks to automatically analyze experimental data and infer key hemodynamic indicators that assess vascular injury.

Chitin-Based Anisotropic Nanostructures of Butterfly Wings for Regulating Cells Orientation.

In recent years, multiple types of substrates have been applied for regulating cell orientation. Among them, surface topography patterns with grooves or ridges have been widely utilizing for cell culturing. However, this construction is still complicated, low cost-effective and exhibits some technological limitations with either "top-down" or "bottom-up" approaches. Here, a simple and green method was developed by utilizing butterfly wings (Morpho menelaus, Papilio ulysses telegonus and Ornithoptera croesus lydius) with natural anisotropic nanostructures to generate cell alignment. A two-step chemical treatment was proposed to achieve more hydrophilic butterfly wings preceding cell culturing. Furthermore, calcein acetoxymethyl ester (Calcein-AM) staining and Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay results demonstrated the appropriate viability of NIH-3T3 fibroblast cells on those butterfly wings. Moreover, the cells displayed a high degree of alignment in each specimen of these wings. We anticipate that those originating from natural butterfly wings will pose important applications for tissue engineering.

Cells Cultured on Core-Shell Photonic Crystal Barcodes for Drug Screening.

The development of effective drug screening platforms is an important task for biomedical engineering. Here, a novel methacrylated gelatin (GelMA) hydrogel-encapsulated core-shell photonic crystal (PhC) barcode particle was developed for three-dimensional cell aggregation culture and drug screening. The GelMA shells of the barcode particles enable creation of a three-dimensional extracellular matrix (ECM) microenvironment for cell adhesion and growth, while the PhC cores of the barcode particles provide stable diffraction peaks that can encode different cell spheroids during culture and distinguish their biological response during drug testing. The applicability of this cell spheroids-on-barcodes platform was investigated by testing the cytotoxic effect of tegafur (TF), a prodrug of 5-fluorouracil (5-FU), on barcode particle-loaded liver HepG2 and HCT-116 colonic tumor cell spheroids. The cytotoxicity of TF against the HCT-116 tumor cell spheroids was enhanced in systems using cocultures of HepG2 and NIH-3T3 cells, indicating the effectiveness of this multiple cell spheroids-on-barcodes platform for drug screening.

Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems.

"Organ-on-a-chip" systems integrate microengineering, microfluidic technologies, and biomimetic principles to create key aspects of living organs faithfully, including critical microarchitecture, spatiotemporal cell-cell interactions, and extracellular microenvironments. This creative platform and its multiorgan integration recapitulating organ-level structures and functions can bring unprecedented benefits to a diversity of applications, such as developing human in vitro models for healthy or diseased organs, enabling the investigation of fundamental mechanisms in disease etiology and organogenesis, benefiting drug development in toxicity screening and target discovery, and potentially serving as replacements for animal testing. Recent advances in novel designs and examples for developing organ-on-a-chip platforms are reviewed. The potential for using this emerging technology in understanding human physiology including mechanical, chemical, and electrical signals with precise spatiotemporal controls are discussed. The current challenges and future directions that need to be pursued for these proof-of-concept studies are also be highlighted.

Surfactant-free HEMA crystal colloidal paint for structural color contact lens.

Structural color originates from physical interactions of light with submicron ordered structures. Structural color is also the optimal candidate as a method for coloring contact lenses because of its vivid iridescence and being free of pigment. Here, we report a facile approach for fabricating a novel structural color contact lens by decorating with structural color paint through UV polymerization in a mould. The paints were fabricated by dispersing poly(methyl methacrylate-hydroxyethyl methacrylate) (PMH) nanoparticles in 2-hydroxyethyl methacrylate (HEMA) solvent without additional surfactants. The obtained structural color contact lenses showed high light transmission as well as gorgeous structural color, varying by adjusting the particle sizes. Moreover, cell viability assay and cell morphology observation revealed that the structural color contact lenses are cytocompatible. With high light transmission, gorgeous structural color, as well as good cytocompatibility, the structural color contact lenses are very promising as potential substitutes of traditional color contact lenses dyed by chemical pigments.

Self-assembled coffee-ring colloidal crystals for structurally colored contact lenses.

A circlular structural-colored contact lens is reported, which is fabricated by replicating self-assembled colloidal photonic crystal templates. The structural-colored contact lenses not only display variable and brilliant color under light illumination, but also avoid the addition of any colorants to the hydrogel lenses and prevent the potential harm posed by traditional colored contact lenses.

Aptamer-functionalized barcode particles for the capture and detection of multiple types of circulating tumor cells.

Aptamer-functionalized barcode particles are employed to capture and detect various types of circulating tumor cells (CTCs). The particles are spherical colloidal crystal clusters, and the reflection properties that arise from their structures are how their codes are evaluated. Aptamer functionalization (with TD05, Sgc8, and Sgd5) make the particles interact with specific CTC types; dendrimers are used to amplify the effect of the aptamers, allowing for increased sensitivity, reliability, and specificity in CTC capture, detection, and subsequent release.

Hybrid inverse opals for regulating cell adhesion and orientation.

Cell adhesion and alignment are two important considerations in tissue engineering applications as they can regulate the subsequent cell proliferation activity and differentiation program. Although many effects have been applied to regulate the adhesion or alignment of cells by using physical and chemical methods, it is still a challenge to regulate these cell behaviors simultaneously. Here, we present novel substrates with tunable nanoscale patterned structures for regulating the adhesion and alignment of cells. The substrates with different degrees of pattern orientation were achieved by customizing the amount of stretching applied to polymer inverse opal films. Cells cultured on these substrates showed an adjustable morphology and alignment. Moreover, soft hydrogels, which have poor plasticity and are difficult to cast into patterned structures, were applied to infiltrate the inverse opal structure. We demonstrated that the adhesion ratio of cells could be regulated by these hybrid substrates, as well as adjusting the cell morphology and alignment. These features of functional inverse opal substrates make them suitable for important applications in tissue engineering.

Bioinspired multicompartmental microfibers from microfluidics.

Bioinspired multicompartmental microfibers are generated by novel capillary microfluidics. The resultant microfibers possess multicompartment body-and-shell compositions with specifically designed geometries. Potential use of these microfibers for tissue-engineering applications is demonstrated by creating multifunctional fibers with a spatially controlled encapsulation of cells.

Photonic crystal encoded microcarriers for biomaterial evaluation.

Photonic crystal encoded biomaterials microcarriers made from silica-hybrid photonic crystal beads are reported. The characteristic reflection peak originating from the physical periodic structure is used as the code of the microcarriers. They are stable during cell adhesion and culture on their surface. Based on this method, Different biomaterials are incorporated into different PCBs and used as encoded microcarriers for the multiplex evaluation of the interaction of cells and materials in a single culture experiment. These encoded microcarriers are ideal for multiplex bioevaluation of biomaterials or drug applications.

Controlled release and antibacterial activity of antibiotic-loaded electrospun halloysite/poly(lactic-co-glycolic acid) composite nanofibers.

Fabrication of nanofiber-based drug delivery system with controlled release property is of general interest in biomedical sciences. In this study, we prepared an antibiotic drug tetracycline hydrochloride (TCH)-loaded halloysite nanotubes/poly(lactic-co-glycolic acid) composite nanofibers (TCH/HNTs/PLGA), and evaluated the drug release and antibacterial activity of this drug delivery system. The structure, morphology, and mechanical properties of the formed electrospun TCH/HNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. We show that the incorporation of TCH-loaded HNTs within the PLGA nanofibers is able to improve the tensile strength and maintain the three-dimensional structure of the nanofibrous mats. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the fibrous scaffolds demonstrate that the developed TCH/HNTs/PLGA composite nanofibers are cytocompatible. More importantly, the TCH/HNTs/PLGA composite nanofibers are able to release the antibacterial drug TCH in a sustained manner for 42 days and display antimicrobial activity solely associated with the encapsulated TCH drug. With the improved mechanical durability, sustained drug release profile, good cytocompatibility, and non-compromised therapeutic efficacy, the developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for tissue engineering and drug delivery applications.

Characterization and antibacterial activity of amoxicillin-loaded electrospun nano-hydroxyapatite/poly(lactic-co-glycolic acid) composite nanofibers.

We report a facile approach to fabricating electrospun drug-loaded organic/inorganic hybrid nanofibrous system for antibacterial applications. In this study, nano-hydroxyapatite (n-HA) particles loaded with a model drug, amoxicillin (AMX) were dispersed into poly(lactic-co-glycolic acid) (PLGA) solution to form electrospun hybrid nanofibers. The loading of AMX onto n-HA surfaces (AMX/n-HA) and the formation of AMX/n-HA/PLGA composite nanofibers were characterized using different techniques. We show that AMX can be successfully adsorbed onto the n-HA surface and the formed AMX/n-HA/PLGA composite nanofibers have a uniform and smooth morphology with improved mechanical durability. Cell viability assay and cell morphology observation reveal that the formed AMX/n-HA/PLGA composite nanofibers are cytocompatible. Importantly, the loaded AMX within the n-HA/PLGA hybrid nanofibers shows a sustained release profile and a non-compromised activity to inhibit the growth of a model bacterium, Staphylococcus aureus. With the significantly reduced burst-release profile, good cytocompatibility, improved mechanical durability, as well as the remained antibacterial activity, the developed AMX/n-HA/PLGA composite nanofibers should find various potential applications in the fields of tissue engineering and pharmaceutical science.