Mortality from liver disease conditions continues to be very high. As liver diseases manifest and progress silently, prompt measures after diagnosis are essential in the treatment of these conditions. Microfluidic organs-on-chip platforms have significant potential for the study of the pathophysiology of liver diseases in vitro. Different liver-on-a-chip microphysiological platforms have been reported to study cell-signaling pathways such as those activating stellate cells within liver diseases. Moreover, the drug efficacy for liver conditions might be evaluated on a cellular metabolic level. Here, we present a comprehensive review of microphysiological platforms used for modelling liver diseases. First, we briefly introduce the concept and importance of organs-on-a-chip in studying liver diseases in vitro, reflecting on existing reviews of healthy liver-on-a-chip platforms. Second, the techniques of cell cultures used in the microfluidic devices, including 2D, 3D, and spheroid cells, are explained. Next, the types of liver diseases (NAFLD, ALD, hepatitis infections, and drug injury) on-chip are explained for a further comprehensive overview of the design and methods of developing liver diseases in vitro. Finally, some challenges in design and existing solutions to them are reviewed

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 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.

Here, we report a fluorescent electrospun nanofiber membrane for integration with microfluidic chips towards lung-on-a-chip applications complemented with computational fluid dynamics modelling. Created with https://BioRender.com.

Organ-on-a-chip (OoC) technology has experienced exponential growth driven by the need for a better understanding of in-organ processes and the development of novel approaches. This paper investigates and compares the flow behavior and filling characteristics of two microfluidic liver-on-a-chip devices using Computational Fluid Dynamics (CFD) analysis and experimental cell culture growth based on the Huh7 cell line. The conducted computational analyses for the two chips showed that the elliptical chamber chip proposed herein offers improved flow and filling characteristics in comparison with the previously presented circular chamber chip. Huh7 hepatoma cells were cultured in the microfluidic devices for 24 h under static fluidic conditions and for 24 h with a flow rate of 3 μL·min⁻¹. Biocompatibility, continuous flow, and biomarker studies showed cell attachment in the chips, confirming the cell viability and their consistent cell growth. The study successfully analyzed the fluid flow behavior, filling characteristics, and biocompatibility of liver-on-a-chip prototype devices, providing valuable insights to improve design and performance and advance alternative methods of in vitro testing.

Microfluidic organs-on-chips or microphysiological systems (MPS) are promising tools that can potentially replace animal testing in drug development. MPS are platforms with microchannels seeded with certain organ cells used to emulate in vivo environments in laboratory conditions. Among them, platforms seeded with lung cells called lung-on-chip devices can evaluate the influence of toxic particles, gases, and chemicals on lung tissue in vitro. Lung-on-chip devices allow the mimicry of healthy lung conditions and a wide range of dis-eases (asthma, cancer, autoimmune, infections). This review focuses on the use of electrospun nanofiber membranes as a functional basement membrane which plays a central role in the development of lung-on-a-chip platforms. Here, we briefly introduce microfluidic devices, MPS, and lung-on-chip devices. Existing basement membrane models, such as thin-film and gel-based membranes, and their challenges/disadvantages are discussed. Next, the concepts of electrospinning and nanofiber membranes are introduced. Finally, the nanofiber membranes used in lung-on-chip devices are reviewed. Implementation of different polymer mate-rials used to synthesize the nanofiber membranes and different methods for incorporation of the membrane inside the device are discussed. Electrospun nanofiber membranes provide good mechanical properties, allow transmigration of the immune cells, and withstand the physiological strain without affecting the cell viability