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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.
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.
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.
A method that quantifies signal reductions in proton magnetic resonance spectroscopy resulting from the replacement of 1H with 2H after the administration of a deuterated substrate can be used to monitor the turnover of cellular metabolites in vivo.
A macroporous material encapsulating an immune-cell-activating cytokine, an adjuvant and tumour-associated antigens elicits prophylactic immunity to acute myeloid leukaemia in mice, and eradicates the disease when combined with chemotherapy.
Optimized adeno-associated viruses delivering split cytosine base editors and adenine base editors with trans-splicing inteins can edit brain, liver, retina, heart and skeletal-muscle tissues at therapeutically relevant efficiencies.
A comparison of compatibilities in protospacer adjacent motifs and of on-target and off-target activities of Streptococcus pyogenes Cas9 variants at endogenous sites in human cells enables the editing of new genomic sites associated with genetic diseases.
Structural and functional analyses of the remodelling of intact lymphatic vasculature after the ligation of a hind-limb lymphatic vessel in sheep reveal the adaptations to the changes in fluid load that occur after lymphatic injury.
An optical-imaging instrument that integrates a visible multispectral imaging system with the detection of near-infrared fluorescence in the first and second windows aids the fluorescence-guided surgical resection of liver tumours in patients.
Machine-learning algorithms trained with retinal fundus images, with subject metadata or with both data types, predict haemoglobin concentration with mean absolute errors lower than 0.75 g dl–1 and anaemia with areas under the curve in the range of 0.74–0.89.
A cellular-nanoporation method produces large quantities of exosomes containing therapeutic mRNAs and targeting peptides that restore tumour-suppressor function in mice with orthotopically implanted phosphatase and tensin homologue (PTEN)-deficient brain gliomas.
Micropatterned nitinol (a nickel titanium alloy) thin films loaded with human CAR-T cells and implanted into tumours foster the expansion of the cells and extend animal survival in mouse models of human tumours.
The local delivery of a calcium channel blocker and a Rho-kinase inhibitor, determined by screening for small molecules that cause ureteral relaxation, significantly reduce ureteral contraction in pigs.
A wireless device designed to be conformally placed on the suprasternal notch can continuously provide real-time information of essential vital signs as well as talking time, swallow counts and sleep patterns.
The serial assessment of the functional parameters of leukocytes isolated via an inertial microfluidic system from 50 μl of peripheral blood from sepsis patients provides significantly more prognostic information than leukocyte counting.
This Perspective summarizes the most recent developments in the bioprinting of cartilage, bone and skin for clinical applications, and discusses translational challenges and opportunities in the fabrication of complex 3D-printed tissues and organs.
Attaching a syndecan-binding domain to vascular endothelial and platelet-derived growth factor variants enhances their binding to syndecans and triggers tonic signalling for enhanced bone regeneration and wound repair in mice.
A computational approach for the design of self-assembling antibody–drug conjugates via affinity ligands for specific conserved amino acid residues in antibodies yields homogenous and stable antibody–drug conjugates that form in less than 8 min.
Functionalized multi-walled carbon nanotubes twisted into helical fibre bundles that mimic the hierarchical structure of muscle can be used for the long-term monitoring of multiple disease biomarkers in vivo.
A deep-learning model trained to map 2D projection views of a patient to the corresponding 3D anatomy can subsequently generate volumetric tomographic X-ray images of the patient from a single projection view.
The analysis of behavioural patterns from standardized video recordings of infants with varying degrees of visual impairment enables, via deep learning, classification of the infants by visual-impairment severity and by ophthalmological condition.
Decellularized whole porcine livers revascularized with human endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleens had been removed can sustain perfusion for up to 15 days.
The loss of residual strains in the intervertebral disc alters the microenvironment and instigates aberrant tissue remodelling and the adoption of atypical cellular phenotypes, promoting disease progression.
The overexpression of β-catenin and the transcription factor Gata4 in skin fibroblasts induces these cells to secrete reparative exosomes, as shown in mice models of myocardial infarction and Duchenne muscular dystrophy.
A reconfigurable microfluidic cell-culture system that facilitates the assembly of 3D tissue models by stacking layers containing preconditioned microenvironments enables the modelling of the spatiotemporal dynamics of paracrine signalling.
This Perspective overviews immunotherapies leveraging engineering approaches, including the design of biomaterials, delivery strategies and nanotechnology solutions, for the realization of individualized cancer treatments.
Bioresorbable photonic devices for the spectroscopic characterization of tissues and biofluids can continuously monitor cerebral temperature, oxygenation and neural activity in the brains of freely moving mice before they are fully resorbed.
Smartphone-controlled soft optofluidic probes with replaceable plug-like drug cartridges enable chronic in vivo pharmacology and optogenetics for the selective wireless manipulation of brain circuits in rodents.
The polymer encapsulation of the monoclonal antibody rituximab and the ligand-mediated targeting of metastases in the central nervous system significantly improve antitumour efficacy in mouse models of metastatic non-Hodgkin lymphoma.
Dextran nanoparticles loaded with a chemotherapeutic agent and bound to phages that eliminate a pro-tumoural gut bacterium and promote the growth of anticancer-compound-producing bacteria boost chemotherapy responses in mouse models of colorectal cancer.
A parameter derived from the collective order of monolayers of corneal endothelial cells makes for a non-invasive quantitative biomarker of the quality of the cells in culture and of the long-term prognosis of corneal restoration in patients.
Orthologous therapeutic proteins can elude the adaptive immune system and allow for effective repeated dosing, as shown for CRISPR gene editing with orthologues of adeno-associated viral capsids and of the Cas9 protein.
In a 3D model of breast cancer, a stiff extracellular matrix promotes a tumorigenic phenotype through broad changes in chromatin accessibility and in the activity of histone deacetylases and the transcription factor Sp1.
The detection of small tumours with PET is significantly enhanced by temporal integration of the imaging signals, triggered by the acidic milieu of cancers, from pH-sensitive positron-emitting polycationic polymers.