Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.
In this paper, we developed a three-dimensional brain-on-a-chip with an interstitial level of flow. The chip contains an osmotic micropump system for providing interstitial flow and a concave microwell array for mimicking the brain's 3D cytoarchitecture.
Heterotypic functional materials with compositional and topographical properties that vary spatiotemporally on the micro- or nanoscale are common in nature. However, fabricating such complex materials in the laboratory remains challenging. Here we describe a method to continuously create microfibres with tunable morphological, structural and chemical features using a microfluidic system consisting of a digital, programmable flow control that mimics the silk-spinning process of spiders. With this method we fabricated hydrogel microfibres coded with varying chemical composition and topography along the fibre, including gas micro-bubbles as well as nanoporous spindle-knots and joints that enabled directional water collection. We also explored the potential use of the coded microfibres for tissue engineering applications by creating multifunctional microfibres with a spatially controlled co-culture of encapsulated cells.
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