Tissue-engineered collagenous fibrous cap models to systematically elucidate atherosclerotic plaque rupture

A significant amount of vascular thrombotic events are associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event....

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Bibliographic Details
Published in:Scientific reports 2022-03, Vol.12 (1), p.5434-5434, Article 5434
Main Authors: Wissing, T. B., Van der Heiden, K., Serra, S. M., Smits, A. I. P. M., Bouten, C. V. C., Gijsen, F. J. H.
Format: Article
Language:English
Subjects:
631/1647/767/1657
639/166/985
692/4019/592
Arteriosclerosis
Atherosclerosis
Collagen
Fibrin
Fibrosis
Heterogeneity
Humanities and Social Sciences
Humans
Mechanical properties
multidisciplinary
Plaque, Atherosclerotic
Plaques
Rupture
Science
Science (multidisciplinary)
Stochasticity
Tissue engineering
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Summary:A significant amount of vascular thrombotic events are associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 × 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, 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. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of a successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-08425-4