The Impact of Regional Mechanics and Tissue Structure on Scar Formation Following Myocardial Infarction

Like many mechanically loaded tissues, the heart responds to ischemic injury such as myocardial infarction (MI) by forming a stiff, collagen-rich scar. The mechanical and structural properties of this scar play a critical role in determining heart function and subsequent patient outcomes post-MI. Experimental data and computational models both suggest that regional mechanics (local strains or stresses) are a key determinant of collagen structure in healing infarcts. At the same time, other studies suggest that the collagen fiber structure determines evolving infarct mechanical properties – and therefore the strains in the infarct. Thus, structure and deformation appear to be coupled: as the collagen structure is formed in a healing infarct, deformation is altered, which in turn would result in a change in collagen structure. While there is strong correlative evidence that this relationship exists, some aspects of this coupling have not been definitively proven, and the quantitative relationships between structure and mechanics in healing infarcts have not been adequately mapped. In order to fully understand and quantify this dynamic relationship, we used model-driven experiments to test the impact of perturbing local mechanics on collagen structure and turnover. We also mechanically tested scars with varying collagen structure to measure how factors such as collagen alignment and collagen content affect passive infarct mechanical properties. Using these data, we then developed and experimentally validated a constitutive law for myocardial scar for open source use in finite element models of fiber-based tissue. Better understanding and modeling of these mechanisms will provide needed guidance in the design of therapies that seek to treat post-MI patients by means of altering infarct mechanics or structure.