Integrating Organs-on-Chips: Multiplexing, Scaling, Vascularization, and Innervation

Major considerations for integrating organs-on-chips (OoCs) include scaling and interconnection via vascularization and innervation. Scaling rules are crucial for predicting events that occur in vivo, but so far, there are no optimal scaling rules for microsystems. To develop scaling rules for microsystems, data should be acquired using mesoscale approaches by using in vitro tissues fabricated by bioreactors or 3D printing. Beyond numerous OoC models of vascularization, organ-specific microvasculature and the main connections between each organ part should also be considered for mimicking the in vivo vascular system. There are still few examples of on-chip innervation, but innervated OoCs and neuronal connections between each part in vitro will give new insights into corresponding in vivo behavior. Organs-on-chips (OoCs) have attracted significant attention because they can be designed to mimic in vivo environments. Beyond constructing a single OoC, recent efforts have tried to integrate multiple OoCs to broaden potential applications such as disease modeling and drug discoveries. However, various challenges remain for integrating OoCs towards in vivo-like operation, such as incorporating various connections for integrating multiple OoCs. We review multiplexed OoCs and challenges they face: scaling, vascularization, and innervation. In our opinion, future OoCs will be constructed to have increased predictive power for in vivo phenomena and will ultimately become a mainstream tool for high quality biomedical and pharmaceutical research. Organs-on-chips (OoCs) have attracted significant attention because they can be designed to mimic in vivo environments. Beyond constructing a single OoC, recent efforts have tried to integrate multiple OoCs to broaden potential applications such as disease modeling and drug discoveries. However, various challenges remain for integrating OoCs towards in vivo-like operation, such as incorporating various connections for integrating multiple OoCs. We review multiplexed OoCs and challenges they face: scaling, vascularization, and innervation. In our opinion, future OoCs will be constructed to have increased predictive power for in vivo phenomena and will ultimately become a mainstream tool for high quality biomedical and pharmaceutical research. the process of making new blood vessels from pre-existing vessels through sprouting endothelial cells from existing vessels. a device containing tens to thousands of microelectrodes to obtain neural signals or stimulate neurons on the neuron-electronic circuit interfaces. a specific environment that controls how stem cells in tissue would participate in regeneration, maintenance, and repair. a receptor found in the central and peripheral nervous system muscle. It is responsible for motor nerve–muscle communication that regulates muscle contraction. the process by which mesenchymal stem cells differentiate into osteoblasts. a value used to measure the tissue integrity of an in vitro cultured cell monolayer. It measures the integrity of the tight junction and quantifies barrier functions. A higher TEER value corresponds with a stronger barrier, which means that diffusion is finely regulated through the cell monolayer. the process of blood vessel formation in the embryo.