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Session: Poster session 2 (Odd numbers)
Session starts: Friday 27 January, 10:00
Presentation starts: 10:00

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Tamar Wissing (Biomedical Engineering, Thorax Center, Erasmus Medical Center & Biomedical Engineering, Eindhoven University of Technology)
Sheila Serra (Biomedical Engineering, Thorax Center, Erasmus Medical Center)
Anthal Smits (Biomedical Engineering, Eindhoven University of Technology)
Carlijn Bouten (Biomedical Engineering, Eindhoven University of Technology)
Frank Gijsen (Biomedical Engineering, Thorax Center, Erasmus Medical Center)
Kim van der Heiden (Biomedical Engineering, Thorax Center, Erasmus Medical Center)

Abstract:
Stroke, one of the leading causes of death worldwide, is caused by rupture of the fibrous cap overlying the atherosclerotic plaque in the carotid artery. Cap rupture is difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. We aim to create a tissue engineered human disease model for atherosclerosis with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between biological composition and mechanical properties to unravel rupture mechanics. Human Vena Saphena Cells (HVSCs) were cultured in 1 x 1.5 cm-sized fibrin-based constrained gels for 21 days according to previously established [1] dynamic culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). After 7 days of static culture, a soft 2 mm ∅ fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. The samples were statically cultured for another week, whereafter they were exposed to an intermittent or continuous straining protocol up till 21 days using the Flexcell FX-40001 (Flexcell Int, McKeesport, PA). Statically cultured samples were included as controls. Samples were exposed to uniaxial tensile tests or analyzed via imaging and immunohistochemistry (IHC) at day 21 to determine mechanical properties and collagen composition (e.g. organization, quantity & type), respectively. Results demonstrate reproducible collagenous tissues, that vary in collagen composition due to the presence of a successfully integrated soft inclusion and the culture protocol applied. All statically cultured samples exhibited an isotropic collagen organization, irrespective of the locus analysed. In contrast, both the samples that were exposed to intermittent as well as the continuous loading demonstrated an isotropic to anisotropic collagen configuration when moving from the top of the construct to the shoulder and mid region. The model mimics the bulk mechanical properties of human caps and can now be deployed to further assess tissue mechanical properties and failure of fibrous caps to better understand fibrous cap rupture and to identify new biomarkers for identification of plaques at risk of rupture.