Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model
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 c...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1629285/full |
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| author | Imke L. Jansen Deniz Șahin Frank J. H. Gijsen Frank J. H. Gijsen Eric Farrell Kim van der Heiden |
| author_facet | Imke L. Jansen Deniz Șahin Frank J. H. Gijsen Frank J. H. Gijsen Eric Farrell Kim van der Heiden |
| author_sort | Imke L. Jansen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-882ddc6fece8464b82828bec8e5a60b3 |
| institution | Kabale University |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-882ddc6fece8464b82828bec8e5a60b32025-08-20T05:32:31ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-08-011210.3389/fcvm.2025.16292851629285Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap modelImke L. Jansen0Deniz Șahin1Frank J. H. Gijsen2Frank J. H. Gijsen3Eric Farrell4Kim van der Heiden5Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Biomechanical Engineering, Delft University of Technology, Delft, NetherlandsDepartment of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsAtherosclerotic 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.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1629285/fullatherosclerosishuman disease modelcalcificationtissue engineeringmechanical testing |
| spellingShingle | Imke L. Jansen Deniz Șahin Frank J. H. Gijsen Frank J. H. Gijsen Eric Farrell Kim van der Heiden Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model Frontiers in Cardiovascular Medicine atherosclerosis human disease model calcification tissue engineering mechanical testing |
| title | Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model |
| title_full | Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model |
| title_fullStr | Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model |
| title_full_unstemmed | Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model |
| title_short | Investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue-engineered atherosclerotic cap model |
| title_sort | investigating the impact of microcalcification size and volume on collagenous matrix and tissue mechanics using a tissue engineered atherosclerotic cap model |
| topic | atherosclerosis human disease model calcification tissue engineering mechanical testing |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1629285/full |
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