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 provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated 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 prototypes 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 miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.
Highlights
Laboratory preclinical testing is an important step in the validation and evaluation of new drug candidates before further human clinical trials, and is expected to reduce the emergency medical events caused by adverse drug reactions [1]
The convergence of microfluidic technologies and traditional cell culture protocol give rise to the blooming development of 3D cell dynamic culture to realise the concept of organ-on-a-chip (OOC), offering a vast opportunity for providing an alternative to animal models in preclinical drug screening
A 3D microfluidic vascular chip was derived from the lungon-a-chip design and was used to investigate the signalling between co-cultured human aortic endothelial cells (ECs) and aortic vascular smooth muscle cells (VSMCs) under the reproduced mechanical vascular microenvironment [85]
Summary
Laboratory preclinical testing is an important step in the validation and evaluation of new drug candidates before further human clinical trials, and is expected to reduce the emergency medical events caused by adverse drug reactions [1]. The convergence of microfluidic technologies and traditional cell culture protocol give rise to the blooming development of 3D cell dynamic culture to realise the concept of organ-on-a-chip (OOC), offering a vast opportunity for providing an alternative to animal models in preclinical drug screening. Actuators that can stretch and compress play an important role in mimicking in vivo physiologies in OOC technology with dynamic cell culture environments. Systems for providing mechanical strains are more complicated and may require specialized designs to generate proper levels of stimuli to tissues To this end, this review seeks to highlight exciting microfluidic OOC platforms that are stimulated by mechanical strains. The review offers a perspective on the opportunities and challenges in developing OOC actuators for yielding future clinical advances
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