3D microphysiological systems: from modeling, to drug discovery, developmental biology, and space research

Riccardo Gottardi
Center for Cellular and Molecular Engineering, University of Pittsburgh, PA, USA
Thursday 20th October 2016
Aula Seminari "Saleri" VI Piano Mox Dipartimento di Matematica - Politecnico di Milano
A growing research in recent years focused on the development of next generation bioreactors capable of generating engineered constructs that mimic at least some of the physiological functions of native organ systems. Such microphysiological systems rely on the combination of microfluidic and tissue engineering to generate a high number of identical 3D organoid models that can be used for drug and toxicological screening. Moreover, the ultimate aim is to be able to connect multiple tissues within an organ system and from there multiple organ systems among themselves to better recapitulate the complexity and interconnection of human physiology, going from organ-on-a-chip to humans-on-a-chip. The effective development of these devices requires a solid understanding of their interconnected fluidics to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this lecture, the focus will be on a specific model of bioreactor developed at the Center for Cellular and Molecular Engineering (CCME), with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilaginous in nature, while the other is osseous. Some of the challenges at the level of computational modelling of the system will be described, such as addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media, and coupling of fluid dynamics with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living constructs. The same design and modelling approach is applicable to multi-chamber, interconnected system. In particular, it may be applied to human-on-chip devices. To this end, a lumped parameter approach to predict the behavior of multi-unit bioreactor systems with modest computational effort, will also be described. Furthermore, the lecture will present a comparison of the modeling outcomes with the experimental results and will introduce some of the opportunities opened by the possibility of using microphysiological systems to understand human physiology in challenging environments, such as microgravity on board the International Space Station, which is the object of a recent grant obtained by CCME. Finally, the lecture will outline some open problems where a modelling and computational approach can help guide the experimental development of microphysiological systems, such as understanding the processes of limb morphogenesis, digit patterning, and segmentation, and their translation to a regenerative approach. contact: christian.vergara@polimi.it