Assessing immune hepatotoxicity of troglitazone with a versatile liver-immune-microphysiological-system.

Drug-induced liver injury is a prevalent adverse event associated with pharmaceutical agents. More significantly, there are certain drugs that present severe hepatotoxicity only during the clinical phase, consequently leading to the termination of drug development during clinical trials or the withdrawal from the market after approval. The establishment of an evaluation model that can sensitively manifest such hepatotoxicity has always been a challenging aspect in drug development. In this study, we build a liver-immune-microphysiological-system (LIMPS) to fully demonstrate the liver injury triggered by troglitazone (TGZ), a drug that was withdrawn from the market due to hepatotoxicity. Leveraging the capabilities of organ-on-chip technology allows for the dynamic modulation of cellular immune milieu, as well as the synergistic effects between drugs, hepatocytes and multiple immune cells. Through the LIMPS, we discovered that 1) TGZ can promote neutrophils to adhered hepatocytes, 2) the presence of TGZ enhances the crosstalk between macrophages and neutrophils, 3) the induction of damage in hepatocytes by TGZ at clinically relevant blood concentrations not observed in other in vitro experiments, 4) no hepatotoxicity was observed in LIMPS when exposed to rosiglitazone and pioglitazone, structurally similar analogs of TGZ, even at the higher multiples of blood drug concentration levels. As an immune-mediated liver toxicity assessment method, LIMPS is simple to operate and can be used to test multiple drug candidates to detect whether they will cause severe liver toxicity in clinical settings as early as possible.

Physiological and Disease Models of Respiratory System Based on Organ-on-a-Chip Technology.

The pathogenesis of respiratory diseases is complex, and its occurrence and development also involve a series of pathological processes. The present research methods are have difficulty simulating the natural developing state of the disease in the body, and the results cannot reflect the real growth state and function in vivo. The development of microfluidic chip technology provides a technical platform for better research on respiratory diseases. The size of its microchannel can be similar to the space for cell growth in vivo. In addition, organ-on-a-chip can achieve long-term co-cultivation of multiple cells and produce precisely controllable fluid shear force, periodically changing mechanical force, and perfusate with varying solute concentration gradient. To sum up, the chip can be used to analyze the specific pathophysiological changes of organs meticulously, and it is widely used in scientific research on respiratory diseases. The focus of this review is to describe and discuss current studies of artificial respiratory systems based on organ-on-a-chip technology and to summarize their applications in the real world.

Hydroxyethyl Cellulose As a Rheological Additive for Tuning the Extrusion Printability and Scaffold Properties.

Bioink, a key element of three-dimensional (3D) bioprinting, is frequently engineered to achieve improved printing performance. Viscoelasticity related to rheological properties is correlative of the printability of bioink for extrusion bioprinting, which affects the complexity of printing 3D structures. This article shows the use of hydroxyethyl cellulose (HEC) as a rheological additive for engineering bioink to improve the printability without reducing the biocompatibility. Different concentrations of HEC were added to four types of bioink, namely, reagent-crosslinked, temperature-dependent phase change, ultraviolet-polymerized, and composite hydrogel bioinks, to investigate the effect on the viscoelasticity properties, print fidelity, and other printed scaffold properties. The results indicate that HEC is able to increase the rheological properties by 100 times to stabilize complex structures and improve the printing fidelity to narrow the gap between the design value and theoretical value, even converting nonviscous ink into directly printable ink, as well as tune the swelling ratio for better molecular permeability. The degradation of bioink can also be tuned by the addition of HEC. Moreover, this bioink is biocompatible for cell lines and primary cells. HEC is expected to be widely used in 3D extrusion-based bioprinting.

Establishment and Application of Peristaltic Human Gut-Vessel Microsystem for Studying Host-Microbial Interaction.

Intestinal floras influence a lot of biological functions of the organism. Although animal model are strong tools for researches on the relationship between host and microbe, a physiologically relevant in vitro human gut model was still required. Here, a novel human gut-vessel microfluidic system was established to study the host-microbial interaction. Peristaltic motion of the cells on the chip was driven by a pneumatic pump. When intestinal epithelial cells (Caco2) were co-cultured with vascular endothelial cells (HUVECs) on the peristaltic microfluidic chip, Caco2 showed normal barrier and absorption functions after 5 days cultivation, which generally took 21 days in static Transwell models. Intestinal microvilli and glycocalyx layer were seen after 4 days cultivation, and Lactobacillus casei was successfully co-cultured for a week in the intestinal cavity. A model for intestinal damage and inflammatory responses caused by E. coli was set up on this chip, which were successfully suppressed by Lactobacillus casei or antibiotic. In summary, this human gut-vessel microfluidic system showed a good potential for investigating the host-microbial interaction and the effect and mechanism of microbiome on intestinal diseases in vitro.

Picomolar detection of carcinoembryonic antigen in whole blood using microfluidics and surface-enhanced Raman spectroscopy.

Carcinoembryonic antigen (CEA) is a wide-spectrum biomarker. Clinically, we generally use serum sample to detect CEA, which needs to be centrifuged to pretreat the raw blood sample. In this study, we realized direct CEA detection in raw blood samples exploiting microfluidics. The LOD was as low as 10(-12) M.