Mechanical strain-enabled reconstitution of dynamic environment in organ-on-a-chip platforms: A review

Abstract

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ-or tissue-level functionality at a small scale instead of replicating the entire human organ. This pro-vides an alternative to animal models for drug development and environmental toxicology screen-ing. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demon-strated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC proto-types leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require minia-turization and specialized designs. As such, this review proposes to summarize innovative micro-fluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.