Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution ofin-vitroliver technologies

Abstract

The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism’s toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop “organs-on-a-chip”. One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results.

Recent advances in nonbiofouling PDMS surface modification strategies applicable to microfluidic technology

“…Dangla et al studied the microchannel deformation of PDMS through changes in the channel height using a synthetic Schlieren method when PDMS was in contact with swelling solvents 66 . Although swelling is desirable in a few applications such as extraction of contaminants from bulk PDMS and changing the surface properties of PDMS 40 , channel deformation due to swelling often causes inaccurate measurements of flow rates and pressure drops.…”

Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture

“…Compared to conventional co-culture approaches (e.g. transwell plate) 210–213 , hydrogel microcapsules not only offers robust cell microniches with tunable structures and ECM properties, but also significantly reduces the requirement of cell number for co-culture compared to the bulk co-culture approaches due to decreased spatial distance and enhanced cellular interaction in miniaturized environment of microcapsules.…”

4 in 1: Antibody‐free protocol for isolating the main hepatic cells from healthy and cirrhotic single rat livers

“…For these and additional reasons, it is generally accepted that a combination of both tools is required in pre‐clinical translational research. In this regard, multi‐cell in vitro liver cultures such as liver‐on‐a‐chip devices, organoids or precision cut liver slices are becoming popular as they combine the versatility of in vitro cultures while partially simulating the in vivo microenvironment, showing improved function and drug‐response over conventional cultures.…”