Abstract

Cardiac fibrosis following myocardial infarction (MI) is driven by complex interactions among cardiomyocytes (CMs), cardiac fibroblasts (CFs), and immune cells, particularly macrophages. Current in vitro models often fail to capture the spatial heterogeneity and dynamic immune–cardiac crosstalk that are central to post-MI remodeling. Therefore, we aimed to develop a physiologically relevant cardiac fibrosis-on-a-chip model that integrates spatially patterned cardiac tissue architecture with region-specific immune cell delivery and mimic post-MI fibrosis. We engineered a three-layer microfluidic device seeded with human iPSC-derived CMs and CFs at defined ratios to replicate scar, border, and healthy regions. A valve-actuation system enabled the controlled introduction of iPSC-derived macrophages (iMacs) in a gradient pattern, mimicking their spatial distribution in vivo. TGF-β was used as a comparative …

Date

November 30, 2025

Authors

Jiaying Ji, Mateo Tristan, Frank Ketchum, Wenzheng Kuang, Guosheng Fu, Xiang Ren, Pinar Zorlutuna

Journal

Lab on a Chip

Publisher

Royal Society of Chemistry