Biowire Model of Interstitial and Focal Cardiac Fibrosis

This paper presents a human cardiac fibrosis disease model built on the Biowire II heart-on-a-chip platform, where engineered cardiac tissues are suspended between elastic POMaC wires that enable noninvasive, repeated functional readouts based on wire deflection. By tuning cardiomyocyte–fibroblast composition to generate normal vs fibrotic tissues, the authors recapitulate hallmark fibrosis phenotypes including increased collagen deposition, myofibroblast activation, elevated passive tension, reduced active force, and electrophysiological dysfunction/arrhythmogenic behavior. The study also constructs an integrated scar–myocardium (heteropolar) model combining healthy and fibrotic tissue compartments to mimic regional heterogeneity (scar, border zone, adjacent myocardium). Finally, the platform is used for proof-of-concept antifibrotic compound evaluation (furin inhibition), using functional biomechanics (especially passive tension) plus collagen readouts to assess treatment timing effects.