Mechanical regulation of fibroblast migration and collagen remodelling in healing myocardial infarcts

•  After myocardial infarction, fibroblasts infiltrate the necrotic myocardium, deposit collagen, and remodel collagen, forming scar tissue. •  Mechanical, structural, and chemical guidance cues have all been shown to regulate alignment of fibroblasts and collagen in vitro. •  We developed a computational model of infarct healing with parameters closely tied to published data, ran simulations with different combinations of guidance cues, and successfully predicted measured collagen structures in rat infarct scars. •  We determined that a mechanical guidance cue was the most important determinant of collagen alignment in healing myocardial infarcts. •  Since anisotropy of infarct scar tissue is an important determinant of cardiac function, our model represents a potentially powerful tool for testing the effects of post‐infarction therapies on scar anisotropy and designing new therapies that modulate infarct healing by controlling the mechanical stimuli acting on the infarct region or the response of fibroblasts to those stimuli.