A tissue-engineered model of the atherosclerotic plaque cap

Title

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture

 Author

Jansen, Imke (Erasmus MC)
Crielaard, Hanneke (Erasmus MC)
Wissing, Tamar (Erasmus MC)
Bouten, Carlijn (Eindhoven University of Technology)
Gijsen, F.J.H. (TU Delft Medical Instruments & Bio-Inspired Technology; Erasmus MC)
Akyildiz, A.C. (TU Delft Medical Instruments & Bio-Inspired Technology; Erasmus MC)
Farrell, Eric (Erasmus MC)
van der Heiden, Kim (Erasmus MC)

Date

2023

 Abstract

Rupture of the cap of an atherosclerotic plaque can lead to thrombotic cardiovascular events. It has been suggested, through computational models, that the presence of microcalcifications in the atherosclerotic cap can increase the risk of cap rupture. However, the experimental confirmation of this hypothesis is still lacking. In this study, we have developed a novel tissue-engineered model to mimic the atherosclerotic fibrous cap with microcalcifications and assess the impact of microcalcifications on cap mechanics. First, human carotid plaque caps were analyzed to determine the distribution, size, and density of microcalcifications in real cap tissue. Hydroxyapatite particles with features similar to real cap microcalcifications were used as microcalcification mimics. Injected clusters of hydroxyapatite particles were embedded in a fibrin gel seeded with human myofibroblasts which deposited a native-like collagenous matrix around the particles, during the 21-day culture period. Second harmonic multiphoton microscopy imaging revealed higher local collagen fiber dispersion in regions of hydroxyapatite clusters. Tissue-engineered caps with hydroxyapatite particles demonstrated lower stiffness and ultimate tensile stress than the control group samples under uniaxial tensile loading, suggesting increased rupture risk in atherosclerotic plaques with microcalcifications. This model supports previous computational findings regarding a detrimental role for microcalcifications in cap rupture risk and can further be deployed to elucidate tissue mechanics in pathologies with calcifying soft tissues.


 To reference this document use:

http://resolver.tudelft.nl/uuid:7e264513-2d82-45d8-9409-eae63bccd9d8

 DOI

https://doi.org/10.1063/5.0168087

 Source

APL Bioengineering, 7 (3)

 Part of collection

Institutional Repository

 Document type

journal article

 Rights

© 2023 Imke Jansen, Hanneke Crielaard, Tamar Wissing, Carlijn Bouten, F.J.H. Gijsen, A.C. Akyildiz, Eric Farrell, Kim van der Heiden
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