Скачать или смотреть Multi-Scale Modeling of Scar Formation: Towards In Situ Design of Better Scar

Jeffrey Holmes, University of Virginia

May 21, 2014

Following myocardial infarction (heart attack), damaged muscle is replaced by scar tissue, and the structure and mechanical properties of that scar are key determinants of the risk of a range of serious complications, including infarct rupture and heart failure. Contrary to expectations, we recently showed that highly anisotropic scar that is very stiff in the longitudinal direction but relatively soft in the circumferential direction can significantly improve pump function of the heart. Yet this scar structure has never been observed in naturally healing infarcts! Furthermore, reported structural and mechanical anisotropy vary in different animal models of infarction for reasons that are poorly understood. In order to better understand the development of scar anisotropy, we developed an agent-based computational model of scar formation. Using a combination of simulations and model-driven experiments, we have shown that mechanical environment guides the development of scar anisotropy in the heart, and have begun to understand when and why mechanical cues overcome other alignment cues present in healing wounds. We are now coupling our cell-level agent-based model to tissue-level finite-element models and sub-cellular network models of fibrosis signaling pathways to design novel approaches for manipulating scar formation in situ.