Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications.

The drug development process can greatly benefit from liver-on-a-chip platforms aiming to recapitulate the physiology, mechanisms, and functionalities of liver cells in an in vitro environment. The liver is the most important organ in drug metabolism investigation. Here, we report the development of a hybrid cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) microfluidic (HCP) platform to culture a Huh7 hepatoma cell line in dynamic conditions towards the development of a liver-on-a-chip system. The microfluidic platform is comprised of a COC bottom layer with a microchannel and PDMS-based flat top layer sandwiched together. The HCP device was applied for culturing Huh7 cells grown on a collagen-coated microchannel. A computational fluid dynamics modeling study was conducted for the HCP device design revealing the presence of air volume fraction in the chamber and methods for optimizing experimental handling of the device. The functionality and metabolic activity of perfusion culture were assessed by the secretion rates of albumin, urea, and cell viability visualization. The HCP device hepatic culture remained functional and intact for 24 h, as assessed by resulting levels of biomarkers similar to published studies on other in vitro and 2D cell models. The present results provide a proof-of-concept demonstration of the hybrid COC-PDMS microfluidic chip for successfully culturing a Huh7 hepatoma cell line, thus paving the path towards developing a liver-on-a-chip platform.

Liver microphysiological platforms for drug metabolism applications.

Drug development is a costly and lengthy process with low success rates. To improve the efficiency of drug development, there has been an increasing need in developing alternative methods able to eliminate toxic compounds early in the drug development pipeline. Drug metabolism plays a key role in determining the efficacy of a drug and its potential side effects. Since drug metabolism occurs mainly in the liver, liver cell-based alternative engineering platforms have been growing in the last decade. Microphysiological liver cell-based systems called liver-on-a-chip platforms can better recapitulate the environment for human liver cells in laboratory settings and have the potential to reduce the number of animal models used in drug development by predicting the response of the liver to a drug in vitro. In this review, we discuss the liver microphysiological platforms from the perspective of drug metabolism studies. We highlight the stand-alone liver-on-a-chip platforms and multi-organ systems integrating liver-on-a-chip devices used for drug metabolism mimicry in vitro and review the state-of-the-art platforms reported in the last few years. With the development of more robust and reproducible liver cell-based microphysiological platforms, the drug development field has the potential of reducing the costs and lengths associated with currently existing drug testing methods.

The impact of frying aerosol on human brain activity.

Knowledge on the impact of the exposure to indoor ultrafine particles (UFPs) on the human brain is restricted. Twelve non-atopic, non-smoking, and healthy adults (10 female and 7 male, in average 22 years old) were monitored for brain physiological responses via electroencephalographs (EEGs) during cooking. Frying ground beef meat in sunflower oil using electric stove without ventilation was conducted. UFPs, particulate matter (PM) (PM1, PM2.5, PM4, PM10), CO2, indoor temperature, RH, oil and meat temperatures were monitored continuously throughout the experiments. The UFP peak concentration was recorded to be approximately 2.0 × 105 particles/cm3. EEGs were recorded before exposure, at end of cooking when PM peak concentrations were observed, and 30 min after the end of the cooking session (post-exposure). Brain electrical activity statistically significantly changed during post-exposure compared to the before exposure, suggesting the translocation of UFPs to the brain, occurring solely in the frontal and temporal lobes of the brain. Study participants older than 25 were more susceptible to UFPs compared to those younger than 25. Also, the brain abnormality was mainly driven by male rather than female study participants. The brain slow-wave band (delta) decreased while the fast-wave band (Beta3) increased similar to the pattern found in the literature for the exposure to smoking fumes and diesel exhaust.