Does Time Heal All Wounds? – Predicting Accute and Long-term Damage in Blood Vessels
Macroscopic morphology of an aortic tissue together with a view of the complex underlying microscopical organization of smooth muscle cell nuclei (blue), collagen (green), and elastin (yellow), which represent the main constituents of arterial walls. |
A frequent side effect of common surgical interventions (e.g., balloon angioplasty with or without stenting) is mechanical overloading of the affected or surrounding tissue. This may lead to acute damage and, if not immediately problematic, trigger longer-term remodeling that will necessitate re-intervention. Therefore, optimizing surgical techniques and instrument design is imperative. The effectiveness of these techniques and procedures depends on how well injury mechanisms in cardiovascular tissue are understood and how they can be translated into objective engineering design criteria. Hence, the ultimate goal of this project is to create reliable constitutive material models that enable quantifying the long-term effects of mechanically-induced damage to cardiovascular tissue, particularly to atherosclerotic vessels. This requires the characterization of the microstructural organization of collagen fibers and other extracellular matrix structures in combination with the corresponding mechanical tissue properties along the whole tissue remodeling process using innovative imaging and image processing techniques as well as newly developed experimental testing setups. Furthermore, it is essential to understand how smooth muscle cells, in both contractile and synthetic phenotypes, are organized in arterial tissue and how they react to altered cellular and tissue level mechanical loading. These findings will lead to a novel experimentally validated constitutive model for arterial tissue where the active energy contribution of the smooth muscle cells is considered due to changes in wall shear stress and mechanical stretching. The occurring reaction cascades resulting in contraction, relaxation, phenotype switching, and extracellular matrix production will be modeled, where acute and long-term damage capability will be included, leading to a unique biomechanical and mechanobiological model. Finally, this knowledge can then be used to virtually predict the acute damage and vascular remodeling after balloon angioplasty through finite element modeling. It is hypothesized that, given accurate modeling of collagen and smooth muscle damage behavior, a computational model is a robust predictive tool for cardiovascular intervention outcomes. Hence, these models can be used to optimize surgical treatments to minimize acute and long-term damage. Funding: Austrian Science Fund (FWF) |