A stretchable human lung-on-chip model of alveolar inflammation for evaluating anti-inflammatory drug response.

This study describes a complex human in vitro model for evaluating anti-inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre-clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co-cultured with macrophages differentiated from the THP-1 cell line, creating a physiological biological microenvironment. To mimic the three-dimensional architecture and dynamic expansion and relaxation of the air-blood-barrier, they are grown on a stretchable microphysiological lung-on-chip.

The physiological interactome of TCR-like antibody therapeutics in human tissues.

Selective binding of TCR-like antibodies that target a single tumour-specific peptide antigen presented by human leukocyte antigens (HLA) is the absolute prerequisite for their therapeutic suitability and patient safety. To date, selectivity assessment has been limited to peptide library screening and predictive modeling. We developed an experimental platform to de novo identify interactomes of TCR-like antibodies directly in human tissues using mass spectrometry.

A multiplex inhalation platform to model like aerosol delivery in a breathing lung-on-chip.

Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from towards the use of alternative human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung.

A New Immortalized Human Alveolar Epithelial Cell Model to Study Lung Injury and Toxicity on a Breathing Lung-On-Chip System.

The evaluation of inhalation toxicity, drug safety and efficacy assessment, as well as the investigation of complex disease pathomechanisms, are increasingly relying on lung models. This is due to the progressive shift towards human-based systems for more predictive and translational research. While several cellular models are currently available for the upper airways, modelling the distal alveolar region poses several constraints that make the standardization of reliable alveolar models relatively difficult.

Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane.

The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane. However, they fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane.

Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip.

The lung alveolar region experiences remodeling during several acute and chronic lung diseases, as for instance idiopathic pulmonary fibrosis (IPF), a fatal disease, whose onset is correlated with repetitive microinjuries to the lung alveolar epithelium and abnormal alveolar wound repair. Although a high degree of mechanical stress (>20% linear strain) is thought to potentially induce IPF, the effect of lower, physiological levels of strain (5-12% linear strain) on IPF pathophysiology remains unknown. In this study, we examined the influence of mechanical strain on alveolar epithelial wound healing.

Medium throughput breathing human primary cell alveolus-on-chip model.

Organs-on-chips have the potential to improve drug development efficiency and decrease the need for animal testing. For the successful integration of these devices in research and industry, they must reproduce in vivo contexts as closely as possible and be easy to use. Here, we describe a 'breathing' lung-on-chip array equipped with a passive medium exchange mechanism that provide an in vivo-like environment to primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells.

A microfluidic bubble trap and oscillator.

A new approach to trap air bubbles before they enter microfluidic systems is presented. The bubble trap is based on the combined interaction of surface tension and hydrodynamic forces. The design is simple, easy to fabricate and straightforward to use.

A lung-on-a-chip array with an integrated bio-inspired respiration mechanism.

We report a lung-on-a-chip array that mimics the pulmonary parenchymal environment, including the thin alveolar barrier and the three-dimensional cyclic strain induced by breathing movements. The micro-diaphragm used to stretch the alveolar barrier is inspired by the in vivo diaphragm, the main muscle responsible for inspiration. The design of this device aims not only at best reproducing the in vivo conditions found in the lung parenchyma but also at making the device robust and its handling easy.

Electrically induced lipid migration in non-lamellar phase.

Inverted hexagonal blocks of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipid adsorbed on a polyethyleneimine (PEI)-coated surface in deionized water transformed its shape upon the application of an electric field, forming lipid objects in a variety of shapes (e.g. lines with a width of 10-50 μm).