(592f) Invited Talk: Engineering "Time" into in Vitro Models, Using Microfluidic Tools to Implement Biorhtyhms-on-Chip.

Our bodies are driven by different rhythms and consequently biological clocks. One of the most common rhythms we think about is the circadian rhythm, which is driven by a master clock in the brain. While this drives intrinsic function, the master clock is directly influenced by environmental cues, such as the light/dark cycles, and impacts the rhythmic circulation of molecules in our body such as hormones. These signals in turn orchestrate cellular, tissue, and organ-level entrainment, maturation and function across our bodies. The disruption of these clocks, and biorhythms, has been linked with higher likelihood of developing different disease and poor health outcomes. In the Lesher-Pérez Research Group we have developed various microfluidic tools to to integrate and apply biorhythms, and effectively engineer time into microphysiological models systems. In this talk we describe the implementation of autonomous microfluidic circuits that leverage the electrohydraulic analogy to apply biorhythmic stimulus of key peripheral molecules to in vitro and ex vivo cultures to recapture key biological processes relevant for cells. Furthermore, we can couple granular hydrogels to ensure 3D culture environments for spheroids and other engineered tissue structures. By leveraging these two technologies, microfluidic circuits and granular gels, our research group is producing a method to engineer "time" into complex tissue cultures and generate 4D tissue engineered systems. We aim to implement these systems as a new microphysiological model platform for drug testing and disease modeling.