Biomechanical Investigation of Arterial Damage

LAESIO, on which engineers will work with the support of medical doctors, biologists, and mathematicians, is trying to clarify what happens from a biomechanical and structural point of view when stents damage blood vessels rather than treat them. Vascular damage during coronary stent implantation (CSI) needs to be reduced since it is proven to be the most potent stimulus for in-stent restenosis. For this purpose, engineers need precise and verified mathematical material damage models (MDM) which can describe the mechanical behavior of arterial walls during CSI. This MDM can be used later for computer simulations to develop improved stents or new vascular therapies. The central hypothesis of LAESIO states, that a precise MDM for stent optimization is only achievable through the correlation of the load on the artery during the CSI with the severity of the resulting vascular damage and the cell proliferation. The overall objective is to develop such an experimentally verified MDM to mathematically describe so called damage mechanisms (DM) inside the arterial wall on the macro-. micro- and nano-levels as well as cell proliferation during the process of the CSI. As a fundament for all investigations, the mechanical interplay between stent and blood vessel during a CSI is simulated in an experiment outside the organism. Inside a testing chamber, a specimen from a human coronary artery (CA) is stretched in two perpendicular directions. In Parallel, a stamp in shape of a stent-strut is pressed onto the specimen in thickness direction. This allows to add artifical injuries to the arterial wall, similar to the injuries generated during a CSI. To simulate the blood flow and pressure inside a CA, the testing chamber is connected to an artificial heart. In addition, a bioreactor with nutrient solution enables long-term testing over several days. Throughout the experiment, the stress/strain behavior of the arterial wall is measured, which allows a unique insight of the changes in the material characteristics between healthy and injured blood vessels. Histological and 3D imaging methods are performed to investigate the damage to the respective structural components of the artery, such as collagen fibers and muscle cells. Furthermore, the time- and load-dependent cell proliferation is analyzed. High-resolution microscopes are used, which enable observations of the arterial wall at nano-scale. The obtained data are then statistical analyzed and mathematically linked to each other. The resulting equations are able to mathematical describe DMs and cell proliferation during CSI. LAESIO provides with the unique MDM a powerful tool for manufactures of stents and scientists, which makes it possible to estimate the negative effects of stent prototypes via computer simulations. The findings from this project will also improve the understanding of CA in the physiological and pathological condition.

When doctors insert stents to keep coronary arteries open, the procedure can also injure the vessel walls. Such injuries are one of the main reasons why vessels may narrow again after treatment. But how exactly do these damages occur - and why does the tissue sometimes become softer? To find out, we examined coronary arteries from pigs and applied pressure with a tool shaped like part of a stent. Using a specially developed device called LAESIO, we measured how the vessel wall changed before and after the load. We then used advanced 3D imaging to compare the damaged areas with healthier regions farther away. Our results show that the type and extent of damage - such as compression, softening, or changes in the fine fiber structure - depend on the direction, intensity, and exact location of the load. Light microscopy images revealed locally pronounced, longitudinally oriented bundles of smooth muscle cells in the intima, accompanied by a duplicated internal elastic membrane. In stamped samples, we observed significant tissue compression under the indentation, elongated cell nuclei at the lesion sides, bulging at the lesion edges, and structural weaknesses in both the intima and media. Fluorescence microscopy analysis in MATLAB identified molecularly unfolded, mechanically damaged collagen, which was quantified using a threshold value and qualitatively assessed through local contrast enhancement. We also examined the surface and internal structures of a coronary artery using specialized electron microscopes. These investigations showed that the inner layer of the artery (the intima) cannot withstand the pressure of stent struts and is especially damaged at their ends. Furthermore, the artery can better tolerate stress around its circumference than along its length. Transmission electron microscopy revealed severe damage to muscle cells located beneath and next to the stent strut. In addition, important structural components of the tissue - the so-called proteoglycans - were found to realign after mechanical loading. This knowledge may help improve computer models of stent implantation, making future treatments safer and more effective.