Bulk density-calibrated fiber networks reveal local weakness as the driver of protease-dependent aortic failure.

The mechanical integrity of the aortic wall depends on the microstructural organization of its collagen and elastin networks, which together maintain load-bearing capacity under hemodynamic stress. When this structure becomes heterogeneous through disease or proteolytic degradation, localized stress concentrations can precipitate failure, yet the mechanisms linking microscale density variations to macroscopic failure remain poorly defined. In this study, we combined density-driven finite element modeling and spatial statistical analysis to investigate how microstructural disorder contributes to mechanical failure in porcine aortic tissue. Representative volume elements incorporating experimentally derived collagen and elastin distributions were constructed and subjected to uniaxial loading simulations. Protease treatments (collagenase and elastase) were modeled by selectively degrading collagen or elastin fibers, respectively. Moran's I analysis was used to quantify spatial autocorrelation of modeled fiber-density fields and to assess changes in microstructural spatial coherence. Protease treatment reduced fiber volume fraction and decreased positive Moran's I, indicating a shift from more spatially clustered fiber organization toward less spatially correlated density fields. Finite element analysis revealed that protease-informed reductions in local fiber density altered load sharing, produced localized stress amplification, and promoted earlier damage initiation in the model. These findings support a mechanistic link between spatial fiber-density organization and local mechanical vulnerability in aortic tissue.