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

T. B. Wissing, K. Van der Heiden, S. M. Serra, A. I.P.M. Smits, C. V.C. Bouten, F. J.H. Gijsen*

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number5434
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 31 Mar 2022

Bibliographical note

Funding Information:
We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organization for Scientific Research (024.003.013) and Kim van Gaalen, Sylvia Dekker and Mark van Turnhout for their contribution with the analyses. Kim van der Heiden is funded by an NWO-Vidi Grant 18360.

Publisher Copyright:
© 2022, The Author(s).

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