New advances in the life sciences and engineering have enabled researchers to construct increasingly accurate experimental models of in vivo conditions. A logical next step would be to connect these discrete modules into increasingly complex networks forming an integrated, microphysiological model of the human body (a human on a chip or HOC). Such a system would be a powerful tool for probing myriad aspects of human health and disease. However, a generalizable HOC platform would require a rational, top-down design strategy and to date precious little time or energy have been spent examining such a problem. Here, we attempt to construct such an approach in three stages. First, we develop a cell-dense, 3-dimensional model of adipose tissue and demonstrate a functional response as measured by insulin-induced glucose uptake. We then use this microtissue construct to conduct a series of experiments that identify crucial parameters and potential problems for an HOC design strategy including control of cellular metabolism, circulating media or ;;blood” volume, and relative organ sizes. Finally, we address those issues using a variety of workarounds, compromises, and design criteria to induce in vivo-like system behavior, even in the face of apparently strange component values. We close by proposing design strategies for a physiologically relevant, 5-organ HOC that incorporates these lessons.
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Toward an Integrated, Physiologically Relevant Microfluidic Model of the Human Body.
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