Platform design of hybrid microphysiological system integrating in vitro and in silico models for reproducing insulin-regulated glucose metabolism

This study presents a hybrid platform for microphysiological systems (MPS) that combines in vitro organ-on-a-chip (OoC) technology and an in silico model. In this platform, in silico models act as virtual organs that interact with real OoCs, enabling the stimulation of multi-organ interactions without physically preparing all surrounding OoCs. Generally, replicating organ interactions in the body requires the preparation of various cultured cell types. However, co-culturing cells results in complex specifications and methods for the MPS. In contrast, this study proposes a hybrid design of real OoCs and in silico models for multi-organ applications. An OoC model of skeletal muscle (SM) integrated with an in silico insulin controller was developed for a glucose metabolism system that responds to insulin action. The platform consists of a real SM OoC and an in silico insulin control model. A lab-on-a-chip device was designed for the real SM OoC that enables feedback control by automated culture, insulin dosing, and glucose monitoring. An in silico architecture was developed to enable the installation of various mathematical models into an in silico controller. The proposed cybernetic MPS platform facilitates the efficient preparation of multiorgan models that enhance in vitro drug testing.