A Biomimetic Cardiac Fibrosis-on-a-Chip as a Visible Disease Model for Evaluating Mesenchymal Stem Cell-Derived Exosome Therapy

Abstract

Cardiac fibrosis acts as a serious worldwide health issue due to its prevalence in numerous forms of cardiac disease and its essential link to cardiac failure. Considering the efficiency of stem cell therapy for cardiac fibrosis, great efforts have been dedicated to developing accurate models for investigating their underlying therapeutic mechanisms. Herein we present an elaborate biomimetic cardiac fibrosis-on-a-chip based on Janus structural color film (SCF) to provide microphysiological visuals for stem cell therapeutic studies. By coculturing cardiomyocytes (CMs) and cardiac fibroblasts (FBs) on Janus SCF with fibrosis induction, the chip can recreate physiological intercellular crosstalk within the fibrotic microenvironment, elucidating the physiological alterations of fibrotic hearts. In particular, the Janus structural color film possesses superior perceptual capabilities for capturing and responding to a weak cardiac force, demonstrating synchronized structural color shifts. Based on these features, we have not only explored the dynamic relationship between color mapping and the evaluated disease phenotype but also demonstrated the self-reporting capacity of the cardiac fibrosis-on-a-chip for the assessment of mesenchymal stem cell-derived exosome therapy. These features suggest that such a chip can potentially facilitate the evolution of precision medicine strategies and create a protocol for preclinical cardiac drug screening.