Abstract

Towards High Content Screening Platforms: Parallelizable Microphysiological Systems as In-vitro Models of Cardiac and Adipose Tissue

Peter Loskill, Attract Group Manager Organ-on-a-Chip, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB

Drug discovery and development to date has relied on animal models, which are useful, but fail to resemble human physiology. The discovery of human induced pluripotent stem (iPS) cells has led to the emergence of a new paradigm of drug screening using human disease-specific organ-models. One promising approach to produce these systems is employing microfluidic devices, which can simulate 3D tissue structure and function. Using microfabrication techniques, we have developed various microphysiological platforms (MPSs) that incorporate in vitro models of human tissue, for instance a heart-on-a-chip and white adipose tissue(WAT)-on-a-chip System. The MPSs consist of three functional components: tissue culture chambers mimicking in vivo geometry and spatial dimension of the respective organs; “vasculature-like” media channels enabling a precise and computationally predictable delivery of soluble compounds (nutrients, drugs, hormones); “endothelial-like” barriers protecting the tissues from shear forces while allowing diffusive transport. All MPSs integrate create physiological micro-tissues that are viable and functional over multiple weeks. They are able to combine human genetic background, physiologically relevant tissue structure and “vasculature-like” perfusion. Due to their small scale, they are amenable for parallelization and integration into a high-content-screening approach. Additionally, utilizing our flexible plug & play multi-organ-integration approach, it is possible to combine individual MPSs into Multi-Organ-chips. The developed systems are extremely versatile and are applicable for pharmaceutical research, toxicity screening as well as mechanistic studies.