ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Heart Valve Disease
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1629285
This article is part of the Research TopicBiomechanics and Mechanotransduction in Cardiovascular CalcificationView all 3 articles
Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model
Provisionally accepted
- 1Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
- 2Department of Oral and Maxillofacial Surgery Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
- 3Department of Biomechanical Engineering, Delft University of Technology, Delft, Netherlands
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Atherosclerotic plaque rupture can lead to thrombotic cardiovascular events such as stroke and myocardial infarction. Computational models have shown that microcalcifications (calcified particles with a diameter < 50 μm) in the atherosclerotic plaque cap can increase cap tissue stresses and consequently contribute to plaque rupture. Microcalcification characteristics, such as particle size and volume fraction, have been implicated to affect cap stresses. However, the effect of these characteristics on tissue mechanics within a collagenous matrix, has not been investigated experimentally. In this study, we employ a tissue-engineered model of the atherosclerotic plaque cap with human myofibroblasts to assess the impact of microcalcification size and volume fraction on cap mechanics and rupture. To mimic human microcalcification size and volume, hydroxyapatite microparticles, in two size ranges (diameter up to 5 μm or up to 50 μm) and two volumes (1 v/v% and 5 v/v%) were incorporated homogenously throughout the tissue-engineered model. 5 v/v% of particles caused a significant lowering of the mechanical properties as was shown by a decrease in stiffness and ultimate tensile stress under uniaxial tensile loading. Additionally, the 5 v/v% of hydroxyapatite particles, in both size ranges, caused a reduced tissue compaction during culture. This might indicate that hydroxyapatite particles influence mechanobiological processes governing tissue organisation and consequent tissue mechanics. These experimental data support computational findings regarding the detrimental role of microcalcifications on cap rupture risk and highlight the importance of volume fraction. Furthermore, this study indicates an additional importance to look at the interplay between calcification, its effect on plaque cap-resident cells and the consequent effect on tissue mechanics.
Keywords: Atherosclerosis, Human disease model, calcification, Tissue Engineering, mechanical testing Data availability
Received: 15 May 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Jansen, Șahin, Gijsen, Farrell and Van Der Heiden. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Imke Lisanne Jansen, Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
Eric Farrell, Department of Oral and Maxillofacial Surgery Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
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