Biomimetic cardiac fibrotic model for anti-fibrotic 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 anti-fibrotic 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-β1 (TGF-β1) further promotes cardiac fibroblast activation and ECM deposition, which makes it a suitable fibrotic model to predict the anti-fibrotic potential of drugs. By using this platform, we demonstrate both Honokiol (HKL) and Pirfenidone (PFD) show potential in anti-fibrosis to some extent. HKL is more efficient in anti-fibrosis 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 anti-fibrotic efficacy of novel drugs.