Keynote Presentation: Multi-Organ Human on a Chip Systems for Preclinical Efficacy and Toxicity Evaluations with Live Q&A

One of the primary limitations in drug discovery and toxicology research is the lack of good model systems between the single cell level and animal or human systems. This is especially true for neurodegenerative diseases such as ALS, Alzheimer’s, and spinal cord injury. In addition, with the banning of animals for toxicology testing in many industries body-on-a-chip systems to replace animals with human mimics is essential for product development and safety testing. Our research focus is on the establishment of functional in vitro systems to address this deficit where we seek to create organs and subsystems to model motor control, muscle function, myelination and cognitive function, as well as cardiac and other subsystems. The idea is to integrate microsystems fabrication technology and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems. Our advances in culturing adult rat, mouse and human mammalian spinal cord, hippocampal neurons, muscle and cardiac cells in a defined serum-free medium, suggest outstanding potential for answering questions related to maturation, aging, neurodegeneration and injury. We are using this ability to manipulate the biological systems and integrate it with silicon-based systems to create functional organ mimics for high content drug discovery. We are also using what we learn for a more fundamental understanding of cellular development, protein adsorption and neuronal regeneration. Examples will be given of some of the more advanced human-on-a-chip systems being developed as well as the results of six workshops held at NIH to explore what is needed for validation and qualification of these systems.