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The colon serves as a primary target for pharmaceutical compound screening and disease modelling. To better study colon diseases and develop treatments, engineered in vitro models with colon-specific physiological features are required. Existing colon models lack integration of colonic crypt structures with underlying perfusable vasculature, where vascular–epithelial crosstalk is affected by disease progression. We present a colon epithelium barrier model with vascularized crypts that recapitulates relevant cytokine gradients in both healthy and inflammatory conditions. Using our previously published IFlowPlate384 platform, we initially imprinted crypt topography and populated the patterned scaffold with colon cells. Proliferative colon cells spontaneously localized to the crypt niche and differentiated into epithelial barriers with a tight brush border. Toxicity of the colon cancer drug, capecitabine, was tested and showed a dose-dependent response and recovery from crypt-patterned colon epithelium exclusively. Perfusable microvasculature was then incorporated around the colon crypts followed by treatment with pro-inflammatory TNFα and IFNγ cytokines to simulate inflammatory bowel disease (IBD)-like conditions. We observed in vivo-like stromal basal-to-apical cytokine gradients in tissues with vascularized crypts and gradient reversals upon inflammation. Taken together, we demonstrated crypt topography integrated with underlying perfusable microvasculature has significant value for emulating colon physiology and in advanced disease modelling. [ABSTRACT FROM AUTHOR]

Stem cell-derived organoids are a promising tool to model native human tissues as they resemble human organs functionally and structurally compared to traditional monolayer cell-based assays. For instance, colon organoids can spontaneously develop crypt-like structures similar to those found in the native colon. While analyzing the structural development of organoids can be a valuable readout, using traditional image analysis tools makes it challenging because of the heterogeneities and the abstract nature of organoid morphologies. To address this limitation, we developed and validated a deep learning-based image analysis tool, named D-CryptO, for the classification of organoid morphology. D-CryptO can automatically assess the crypt formation and opacity of colorectal organoids from brightfield images to determine the extent of organoid structural maturity. To validate this tool, changes in organoid morphology were analyzed during organoid passaging and short-term forskolin stimulation. To further demonstrate the potential of D-CryptO for drug testing, organoid structures were analyzed following treatments with a panel of chemotherapeutic drugs. With D-CryptO, subtle variations in how colon organoids responded to the different chemotherapeutic drugs were detected, which suggest potentially distinct mechanisms of action. This tool could be expanded to other organoid types, like intestinal organoids, to facilitate 3D tissue morphological analysis. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip systems that recapitulate tissue-level functions have been proposed to improve in vitro–in vivo correlation in drug development. Significant progress has been made to control the cellular microenvironment with mechanical stimulation and fluid flow. However, it has been challenging to introduce complex 3D tissue structures due to the physical constraints of microfluidic channels or membranes in organ-on-a-chip systems. Inspired by 4D bioprinting, we develop a subtractive manufacturing technique where a flexible sacrificial material can be patterned on a 2D surface, swell and shape change when exposed to aqueous hydrogel, and subsequently degrade to produce perfusable networks in a natural hydrogel matrix that can be populated with cells. The technique is applied to fabricate organ-specific vascular networks, vascularized kidney proximal tubules, and terminal lung alveoli in a customized 384-well plate and then further scaled to a 24-well plate format to make a large vascular network, vascularized liver tissues, and for integration with ultrasound imaging. This biofabrication method eliminates the physical constraints in organ-on-a-chip systems to incorporate complex ready-to-perfuse tissue structures in an open-well design. [ABSTRACT FROM AUTHOR]

An active and stable bi-functional catalyst for the hydrogen oxidation reaction (HOR) and hydrogen evolution reaction (HER) is highly desirable for clean energy conversion devices, such as anion exchange membrane fuel cells (AEMFCs) and magnesium (Mg)–seawater batteries. Herein, DFT analysis predicates that the amine-ligand modulation manipulates the d-band center of ruthenium (Ru) downshift from the Fermi level, resulting in optimized hydrogen and hydroxide bonding energies (HBE and OHBE), and thus lowering the limiting energy of the HOR/HER. We elaborately fabricate NH2-ligand modulated Ru nanoclusters (Ru/PEI-XC), taking advantage of the abundant –NH2 groups of polyethylene imine (PEI). The optimal Ru/PEI-XC catalyst exhibits a superior HOR activity of 423.3 A gmetal−1 at an overpotential (η) of 50 mV and a specific exchange current density of 687.1 μA cmmetal−2, which are about 1.7 and 3.6 fold those of the commercial Pt/C catalyst. Ru/PEI-XC presents an overwhelming advantage for the HER in a wide pH range, especially in alkaline electrolyte, with η = 13 mV at −10 mA cm−2, which is 20 mV lower than that of Pt/C. Both the potentiostatic and accelerated degradation tests manifest the excellent long-term stability of Ru/PEI-XC in catalyzing the HOR and HER. Furthermore, Ru/PEI-XC as the anode of an AEMFC delivers a peak power density of 1.4 W mgPGM−1, comparable with that of its Pt/C-based counterpart. A proof-of-concept rechargeable Mg–seawater battery could also be driven by the Ru/PEI-XC cathode, delivering a maximum discharging power density of 18.9 mW cm−2, with low charging voltage and good cycling properties. This study reveals that ligand modulation is an effective strategy to manipulate the d-band center of metals and tune the reactivity, which paves an avenue for designing advanced hydrogen electrocatalysts. [ABSTRACT FROM AUTHOR]

A Cu2O/Pt/BiVO4 heterojunction was prepared by successively depositing Pt and Cu2O nanoparticles on {010} facets of BiVO4, showing much higher photocatalytic activity in hydrogen evolution than that constructed by random deposition of Cu2O on all facets of BiVO4 particles. Photoluminescence spectroscopy revealed that the facet-selective Cu2O/Pt/BiVO4 arrays effectively promoted charge separation of the BiVO4 host. A band alignment was consequently presented to illustrate the interface charge flow in the heterojunction. This work demonstrates the roles that facets played in semiconductor heterojunctions applied to photocatalytic reactions. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) tissue models such as epithelial spheroids or organoids have become popular for pre-clinical drug studies. In contrast to 2D monolayer culture, the characterization of 3D tissue models from non-invasive brightfield images is a significant challenge. To address this issue, here we report a deep-learning uncovered measurement of epithelial networks (Deep-LUMEN) assay. Deep-LUMEN is an object detection algorithm that has been fine-tuned to automatically uncover subtle differences in epithelial spheroid morphology from brightfield images. This algorithm can track changes in the luminal structure of tissue spheroids and distinguish between polarized and non-polarized lung epithelial spheroids. The Deep-LUMEN assay was validated by screening for changes in spheroid epithelial architecture in response to different extracellular matrices and drug treatments. Specifically, we found the dose-dependent toxicity of cyclosporin can be underestimated if the effect of the drug on tissue morphology is not considered. Hence, Deep-LUMEN could be used to assess drug effects and capture morphological changes in 3D spheroid models in a non-invasive manner. [ABSTRACT FROM AUTHOR]

A rod-like Ta3N5 thin film was synthesized by calcining a vacuum-sealed mixture of Ta metal plates and NH4Cl powder. Photoelectrochemical water oxidation results showed that an anodic photocurrent of 3.2 mA cm−2 at 1.23 V (vs. RHE) with a faradaic efficiency of unity for O2 evolution could be achieved by employing the as-prepared Ta3N5/Ta as a photoanode. [ABSTRACT FROM AUTHOR]

Most kidney diseases begin with abnormalities in glomerular podocytes, motivating the need for podocyte models to study pathophysiological mechanisms and new treatment options. However, podocytes cultured in vitro face a limited ability to maintain appreciable extents of differentiation hallmarks, raising concerns over the relevance of study results. Many key properties such as nephrin expression and morphology reach plateaus that are far from the in vivo levels. Here, we demonstrate that a biomimetic topography, consisting of microhemispheres arrayed over the cell culture substrate, promotes podocyte differentiation in vitro. We define new methods for fabricating microscale curvature on various substrates, including a thin porous membrane. By growing podocytes on our topographic substrates, we found that these biophysical cues augmented nephrin gene expression, supported full-size nephrin protein expression, encouraged structural arrangement of F-actin and nephrin within the cell, and promoted process formation and even interdigitation compared to the flat substrates. Furthermore, the topography facilitated nephrin localization on curved structures while nuclei lay in the valleys between them. The improved differentiation was also evidenced by tracking barrier function to albumin over time using our custom topomembranes. Overall, our work presents accessible methods for incorporating microcurvature on various common substrates, and demonstrates the importance of biophysical stimulation in supporting higher-fidelity podocyte cultivation in vitro. [ABSTRACT FROM AUTHOR]

To curb the high cost of drug development, there is an urgent need to develop more predictive tissue models using human cells to determine drug efficacy and safety in advance of clinical testing. Recent insights gained through fundamental biological studies have validated the importance of dynamic cell environments and cellular communication to the expression of high fidelity organ function. Building on this knowledge, emerging organ-on-a-chip technology is poised to fill the gaps in drug screening by offering predictive human tissue models with methods of sophisticated tissue assembly. Organ-on-a-chip start-ups have begun to spawn from academic research to fill this commercial space and are attracting investment to transform the drug discovery industry. This review traces the history, examines the scientific foundation and envisages the prospect of these renowned organ-on-a-chip technologies. It serves as a guide for new members of this dynamic field to navigate the existing scientific and market space. [ABSTRACT FROM AUTHOR]

Tissue engineering enables the generation of three-dimensional (3D) functional cardiac tissue for pre-clinical testing in vitro, which is critical for new drug development. However, current tissue engineering methods poorly recapitulate the architecture of oriented cardiac bundles with supporting capillaries. In this study, we designed a microfabricated bioreactor to generate 3D micro-tissues, termed biowires, using both primary neonatal rat cardiomyocytes and human embryonic stem cell (hESC) derived cardiomyocytes. Perfusable cardiac biowires were generated with polytetrafluoroethylene (PTFE) tubing template, and were integrated with electrical field stimulation using carbon rod electrodes. To demonstrate the feasibility of this platform for pharmaceutical testing, nitric oxide (NO) was released from perfused sodium nitroprusside (SNP) solution and diffused through the tubing. The NO treatment slowed down the spontaneous beating of cardiac biowires based on hESC derived cardiomyocytes and degraded the myofibrillar cytoskeleton of the cardiomyocytes within the biowires. The biowires were also integrated with electrical stimulation using carbon rod electrodes to further improve phenotype of cardiomyocytes, as indicated by organized contractile apparatus, higher Young's modulus, and improved electrical properties. This microfabricated platform provides a unique opportunity to assess pharmacological effects on cardiac tissue in vitro by perfusion in a cardiac bundle model, which could provide improved physiological relevance. [ABSTRACT FROM AUTHOR]

Correction for 'Deep-LUMEN assay – human lung epithelial spheroid classification from brightfield images using deep learning' by Lyan Abdul et al., Lab Chip, 2020, DOI: 10.1039/d0lc01010c. [ABSTRACT FROM AUTHOR]

Several important neurotransmitter precursors were hyperpolarized via homogeneous hydrogenation with parahydrogen. Polarization enhancement was achieved for 1H and 13C spins by several orders of magnitude compared to thermal spectra. Such large signal enhancements of these molecules could facilitate neurotransmitter studies. [ABSTRACT FROM AUTHOR]

A rod-like Ta 3 N 5 thin film was synthesized by calcining a vacuum-sealed mixture of Ta metal plates and NH 4 Cl powder. Photoelectrochemical water oxidation results showed that an anodic photocurrent of 3.2 mA cm -2 at 1.23 V (vs. RHE) with a faradaic efficiency of unity for O 2 evolution could be achieved by employing the as-prepared Ta 3 N 5 /Ta as a photoanode.

Dynamics of complex signaling networks are important to many biological problems. Quantitative data at early time points after cellular stimulation are necessary for accurate model generation. However, the large amount of data needed is often extremely time-consuming and expensive to acquire with conventional methods. We present a two-module microfluidic platform for simultaneous multi-time point stimulation and lysis of T cells for early time point signaling activation with a resolution down to 20 s using only small amounts of cells and reagents. The key design features are rapid mixing of reagents and uniform splitting into eight channels for simultaneous collection of multi-time point data. Chaotic mixing was investigated via computational fluid dynamic modeling, and was used to achieve rapid and complete mixing. This modular device is flexible-with easy adjustment of the setup, a wide range of time points can be achieved. We show that treatment in the device does not elicit adverse cellular stress in Jurkat cells. The activation of six important proteins in the signaling cascade was quantified upon stimulation with a soluble form of alpha-CD3. The dynamics from device and conventional methods are similar, but the microdevice exhibits significantly less error between experiments. We envision this high-throughput format to enable simple and fast generation of large sets of quantitative data, with consistent sample handling, for many complex biological systems.