Abstract

Multiscale Computational Tools for Model-guided PK/PD Simulations on Human Body-on-Chips (HuBoC)

Andrzej Przekwas, Chief Technology Officer, CFD Research Corp

Static in vitro cell cultures and animal models serve as gold standard platforms for conducting preclinical drug testing. Unfortunately, these platforms do not adequately recapitulate the human in vivo conditions. Microfluidic-based organ-on-a-chip (µOoC) cell culture technology developed under a DARPA grant using human primary or stem cells, has been used to reproduce in vivo like conditions in in vitro in order to model disease states and predict clinically relevant drug efficacy and safety. Multiple OoC devices containing endothelium-lined vascular channels can be connected in a physiologically-consistent form via a synthetic cardiovascular circulation system to create a Human Body-on-Chips (HuBoC). This paper presents computational framework, CoBi, for 3D high-fidelity design of in vitroOoC and HuBoC platforms and complementary reduced order PBPK-like model for extrapolation of on-chip data to in vivo human conditions. The multiscale model formulation accounts for convective-diffusive-reactive plug flow reactors rather than commonly used well-stirred reactors (0D) to accurately predict spatiotemporal drug distribution, residence times and organ perfusion in vivo. The model has been validated on several OoC devices developed by Wyss Institute and used for design and analytics of various OoC devices. We will describe the model formulation, illustrate the simulation results for traces in various OoC devices, discuss model validation on selected compounds and preliminary simulations of multi-organ HuBoC platform developed in collaboration with the Wyss Institute.