Materials for blood brain barrier modeling in vitro.

Brain homeostasis relies on the selective permeability property of the blood brain barrier (BBB). The BBB is formed by a continuous endothelium that regulates exchange between the blood stream and the brain. This physiological barrier also creates a challenge for the treatment of neurological diseases as it prevents most blood circulating drugs from entering into the brain. In vitro cell models aim to reproduce BBB functionality and predict the passage of active compounds through the barrier. In such systems, brain microvascular endothelial cells (BMECs) are cultured in contact with various biomaterial substrates. However, BMEC interactions with these biomaterials and their impact on BBB functions are poorly described in the literature. Here we review the most common materials used to culture BMECs and discuss their potential impact on BBB integrity in vitro. We investigate the biophysical properties of these biomaterials including stiffness, porosity and material degradability. We highlight a range of synthetic and natural materials and present three categories of cell culture dimensions: cell monolayers covering non-degradable materials (2D), cell monolayers covering degradable materials (2.5D) and vascularized systems developing into degradable materials (3D).

Effect of E Cigarette Emissions on Tracheal Cells Monitored at the Air-Liquid Interface Using an Organic Electrochemical Transistor.

E-cigarettes have been suggested as a potentially healthier alternative to cigarettes based on studies using cell viability, DNA damage, and transcriptional response assays. However, little is known about the effect of e-cigarette aerosols on the integrity of the tracheal epithelium, specifically with respect to barrier resistance. This is partly due to the lack of methods for monitoring epithelia at the air-liquid interface (ALI), i.e., under physiological conditions. Here, it is shown that an organic electrochemical transistor can be adapted for the measurement of barrier resistance at the ALI. This technology enables accurate, continuous quantification of tracheal barrier integrity through the use of a conformable gate electrode placed on top of the cell-secreted mucus, obviating the need for addition of culture medium or buffer as a conductance medium for rigid electrodes. This platform allows for the detection of a dose-dependent, rapid decrease in barrier resistance of an in vitro model of human bronchial epithelium (MucilAir) after E-cigarette aerosols exposure. The system represents a powerful tool to study tissue responses of the human airway epithelium to inhaled smoke. The same technology will have broad applications for toxicology studies on other tissues with ALI, including other airway tissues and skin.

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring.

Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are two-fold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.