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Novak, Lin et al. use AI computational drug prediction and CRISPR-enabled in vivo disease modeling to identify therapeutic strategies for the treatment of Rett syndrome. Findings reveal the therapeutic efficacy of vorinostat in a mouse model of Rett syndrome.

Vascular permeability is increased by inflammation and in disorders such as acute respiratory distress syndrome. Mammoto et al. show that lung vascular permeability is controlled by the stiffness of the extracellular matrix and identify lysyl oxidase as a regulator of vascular leakage in pulmonary oedema in mice.

Mechanical forces that are exerted on surface-adhesion receptors can be channelled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus. How do these forces act at a distance to induce mechanochemical conversion in the nucleus, and what effects can they have on the cell?

Human cervical mucosa and its interactions with the microbiome play a central role in female reproductive tract health and disease. Here, the authors develop physiological models of the human cervix using Organ-on-a-Chip technology that produce mucus, and respond to hormonal, environmental, and microbial cues similar to the living cervix.

It is vital but challenging to develop coating technologies for addressing reliability and durability issues of electrochemical sensors when exposed to diverse and complex biological environments. Here, the authors report a micrometer-thick, porous and robust nanocomposite coating that enables highly sensitive and stable electrochemical sensors.

Acute exposure to radiation can lead to acute pneumonitis, fibrosis or death. Here the authors develop an alveolus-on chip model to study the molecular characteristics of radiation induced lung injury, better understand radiation induced lung disease and facilitate drug screening.

A 3D-printed lab-on-a-chip allows for the concurrent rapid electrochemical detection of SARS-CoV-2 RNA in saliva and of anti-SARS-CoV-2 antibodies in saliva spiked with blood plasma.

Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.

A human intestine-on-a-chip lined by intestinal epithelium derived from patients with environmental enteric dysfunction and cultured in nutrient-deficient medium recapitulates essential features of intestinal dysfunction associated with the disease.

Patients treated with Aurora kinase inhibitors experience dose-limiting neutropenia while other cytopenias are rare. Here, Chou et al. show that this cell-type specific side effect is partly explained by loss of drug efflux pump expression during neutrophil differentiation.

A microfluidic bronchial-airway-on-a-chip lined by human bronchial-airway epithelium and pulmonary endothelium can be used to rapidly identify antiviral therapeutics and prophylactics with repurposing potential.

Microscopic oil droplets with defined mechanical properties are used to measure forces exerted within living tissue.

Rho signalling is shown to regulate angiogenesis in response to mechanical signals such as extracellular matrix elasticity, or the angiogenic factor VEGF. The pathway modulates the antagonistic functions of two transcription factors, TFII-I and GATA2, which regulate the expression of VEGFR2.

Mass cytometry with signal amplification enables measurement of low-abundance proteins.

In vitro blood-brain barrier (BBB) models do not fully recapitulate the in vivo barrier function. Here the authors develop an organ-on-a-chip BBB model using iPS-derived human brain endothelial cells differentiated under hypoxia, primary human pericytes and astrocytes, which maintains in vivo-like BBB barrier and shuttling functions for a week.

An efficient and chemically defined protocol for the differentiation of human induced pluripotent stem cells into podocytes enables the recapitulation of the differential clearance of the human kidney glomerulus in an organ-on-a-chip.

A recent advance has led to the development of microfluidically linked microphysiological culture systems that mimic the complex dynamics and interdependent physiology of the various organs that comprise the female reproductive tract. This microfluidic culture platform offers an unprecedented way to study female reproductive biology and develop new reproductive therapeutics.

Mechanical forces in lungs facilitate breathing motions. Here the authors use a microfluidic human lung alveolus chip to study influenza infection and find that mechanical forces from active chips also induce innate inflammatory responses via, at least partially, signaling from TRPV4 and RAGE, thereby implicating them as potential therapeutic targets for lung inflammation.

Physiological modelling of first-pass metabolism using data from a robotic instrument that fluidically links relevant organ chips predicts human pharmacokinetic parameters for orally administered nicotine and for intravenously injected cisplatin.

Even in clonal populations of cells, there is significant phenotypic variation from cell to cell: Huang and colleagues analyse the behaviour of an 'outlier', which had very high expressions of the stem cell marker Sca-1, and conclude that clonal heterogeneity of gene expression level is a manifestation of metastable states of a slowly fluctuating transcriptome. These fluctuations may govern the reversible, stochastic priming of multipotent progenitor cells in cell fate decision. (See Nature Reports Stem Cells).

An antifouling coating for electrodes that consists of a three-dimensional porous matrix of cross-linked bovine serum albumin supported by a network of conductive nanomaterials enables robust affinity-based electrochemical biosensing in complex biological fluids.

The current hemostasis assays are unable to predict thrombotic or bleeding risk in clinics. Here, Jain et al. present a novel microfluidic device mimicking stenosed arterioles that determines clotting times in vitroand in extracorporeal circuits, offering a simple and reliable monitoring of blood homeostasis and platelet function.

A system employing liquid-handling robotics and an integrated mobile microscope enables the automated culture, sample collection and in situ microscopy imaging of up to ten fluidically coupled organ chips within a standard tissue-culture incubator.

Bone marrow formed in a cylindrical PDMS device implanted in a mouse can be surgically removed and cultured for a week in vitro without losing any of the hallmarks of in vivo bone marrow niches.

A vascularized human bone-marrow-on-a-chip improves the maintenance of patient-derived CD34⁺ cells, and recapitulates clinically relevant aspects of bone marrow injury as well as key haematopoietic defects of patients with a rare genetic disorder.

Injectable biomaterial vaccines designed to magnetically capture pathogen-associated molecular patterns protect mice and pigs against septic shock from lethal bacterial infections.

A microfluidic intestine-on-a-chip that allows the control of physiologically relevant oxygen gradients, enables the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota.

DNA can self-assemble into prestressed tensegrity nanostructures composed of compressed bundles of double helices and tense linking segments of single-stranded DNA.

Differentiation of mouse myoblasts is coordinated with glycolysis, calcium/calcineurin signaling, chromatin acetylation and cholesterol biosynthesis. This is consistent with profiling of the intracellular metabolites that accompany myogenic differentiation and points to new targets for cancer differentiation therapy of rhabdomyosarcoma.

In this Opinion article, Brocket al. analyse how intrinsic variability in gene expression in proliferating cells, as well as microenvironmental signals, can drive cells to transform into a neoplastic state or revert to a normalized state.

Three linked microfluidic chips model transport across the blood–brain barrier.

A non-stick surface coating makes medical devices anti-thrombogenic and resistant to biofilm growth.

The small airway-on-a-chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Matrix elasticity, which has been shown to regulate the fate of mesenchymal stem cells in vitro, can also be harnessed to therapeutically control bone formation.

Studying human physiology and pathophysiology in preclinical animal models has drawbacks. Developments in organ-on-a-chip (organ chip) technology have opened up new ways to model human intestinal physiology. This Review discusses intestinal organ chips as disease models and preclinical tools and their potential for personalized medicine.