Multiscale assessment of human aortic tissues: biaxial extension testing simultaneously applied to two-photon fluorescence microscopy and second harmonic generation imaging to obtain material properties of collagen, elastin and SMC at the micro and macroscales.
Microstructural changes of collagen, elastin and SMCs as a function of macroscopic deformation and stress/loading.
Arteries have a remarkable ability to adapt in response to altered hemodynamics, disease progression, and injury. Altered arterial tissue properties in diseased conditions such as atherosclerosis arise from tissue remodeling which is associated with changes in wall constituents at different length scales.
This project is based on the fact that multiscale biomechanical analyses of healthy and diseased arteries and its modeling can be used to better understand several pathophysiological processes at different length scales. This also allows the identification of relationships between structural alterations and diseases. In this study aortic tissue imaging and mechanical characterization techniques will be combined at the macro-, micro- and nanoscale to develop and validate next generation multiscale constitutive models. Biaxial extension testing and second-harmonic generation/two-photon excited fluorescence imaging will be simultaneously used to obtain properties at the micro- and macroscale of healthy and atherosclerotic human aortas. Moreover, load-dependent ultrastructural characteristics of interfibrillar proteoglycans, and of constituents of collagen (e.g., tropocollagen, fibrils), elastin (e.g., tropoelastin, fibrillin), and smooth muscle cells (e.g., myosin, actin) will be determined by three-dimensional transmission electron microscopy (3D-TEM) which is also known as electron tomography.
The combination of the obtained data is used for the development of novel constitutive models based on multiscale homogenization techniques that explicitly incorporate nanoscale, microscale and macroscale mechanisms as well as their coupling effects. The novelties of this project are the application and development of experimental methods on different hierarchical scales, and the intelligent combination, integration and validation of experimental techniques to give an explanation for the role of important constituents in arterial mechanics, physiology, and pathology.
The pursued approach is a step forward to investigate and understand the development, growth and remodeling principles of biological tissues and their response to pathological conditions. This project approaches well-defined clinical problems from engineering and biological perspectives.
Funding: Austrian Science Fund (FWF)