There is a critical need for improved systems to model the effects of chemical and biological agents on the body.1,2 Currently, animal models serve as gold standards for testing, but the drawbacks associated with such models are high costs and uncertainties in interpretation of the results. Interspecies differences and variability means that animal models are often poor predictors of human efficacy and toxicology. In vitro systems that use human tissues would be preferable; however, for these systems to serve as tools that reflect human biology, key physiological features and toxicology endpoints need to be included in their design for informative and reliable efficacy, pharmocokinetic, and toxicity testing. Traditional in vitro 2D cultures, currently the norm for early drug compound screening, fail to recapitulate the 3D microenvironment of in vivo tissues.3,4 Tissue culture dishes have three major differences from native tissue microenvironments: surface topography, surface stiffness, and most importantly, a 2D rather than 3D architecture. As a consequence, 2D culture places a selective pressure on cells, substantially altering their original phenotypic properties. Drug diffusion kinetics are not accurately modeled in 2D tissue culture,

13.1 Introduction .................................................................................................. 271 13.2 Single versus Multiple Organoid Function ................................................... 272

13.2.1 Cancer ............................................................................................... 272 13.2.2 Drug Testing/Toxicology .................................................................. 274 13.2.3 Disease Modeling ............................................................................. 274

13.3 Biofabricating a Highly Physiologically Accurate Multi-Organoid Platform .....274 13.3.1 Overview of ECHO Platform Organoids .......................................... 275 13.3.2 Microfluidic Hardware Integration ................................................... 278 13.3.3 Common Media Development .......................................................... 279 13.3.4 Miniaturization and High-Throughput .............................................280