Biomimetic Cardiac Fibrotic Model for Antifibrotic Drug Screening

Cardiac fibrosis is characterized by pathological proliferation and activation of cardiac fibroblasts to myofibroblasts. Inhibition and reverse of transdifferentiation of cardiac fibroblasts to myofibroblasts is a potential strategy for cardiac fibrosis. Despite substantial progress, more effort is needed to discover effective drugs to improve and reverse cardiac fibrosis. The main reason for the slow development of antifibrotic drugs is that the traditional polystyrene culture platform does not recapitulate the microenvironment where cells reside in tissues. In this study, we propose an in vitro cardiac fibrotic model by seeding electrospun yarn scaffolds with cardiac fibroblasts. Our results show that yarn scaffolds allow three-dimensional growth of cardiac fibroblasts, promote extracellular matrix (ECM) deposition, and induce the transdifferentiation of cardiac fibroblasts to myofibroblasts. Exogenous transforming growth factor-beta 1 further promotes cardiac fibroblast activation and ECM deposition, which makes it a suitable fibrotic model to predict the antifibrotic potential of drugs. By using this platform, we demonstrate that both Honokiol (HKL) and Pirfenidone (PFD) show potential in antifibrosis to some extent. HKL is more efficient in antifibrosis than PFD as revealed by biochemical composition, gene, and molecular analyses as well as histological and biomechanical analysis. The electrospun yarn scaffold provides a novel platform for constructing in vitro fibrotic models to study cardiac fibrosis and to predict the antifibrotic efficacy of novel drugs. Impact statementCardiac fibrosis is a significant challenge in the clinic and could result in impaired cardiac function and heart failure. In this study, we report an in vitro cardiac fibrotic model by biomimetic electrospun yarn scaffold with cardiac fibroblasts. Our fibrous yarn scaffold supports three-dimensional growth of cardiac fibroblasts, which replicates the microenvironment where cells reside in the native cardiac extracellular matrix. Upon the activation of exogenous growth factor, it exhibits characteristics of cardiac fibrosis and becomes an effective model to predict the antifibrotic efficacy of novel drugs. Our findings might provide a reliable platform for screening antifibrotic drugs.