{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:22:25Z","timestamp":1785882145636,"version":"3.56.0"},"reference-count":50,"publisher":"AIP Publishing","issue":"3","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"tdm","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["18360"],"award-info":[{"award-number":["18360"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1063\/5.0168087","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T17:11:38Z","timestamp":1696007498000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture"],"prefix":"10.1063","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5791-5220","authenticated-orcid":false,"given":"Imke","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam 1 , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-8989","authenticated-orcid":false,"given":"Hanneke","family":"Crielaard","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam 1 , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Wissing","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam 1 , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1035-5094","authenticated-orcid":false,"given":"Carlijn","family":"Bouten","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Eindhoven University of Technology 2 , Eindhoven, The Netherlands"},{"name":"Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology 3 , Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5246-9060","authenticated-orcid":false,"given":"Frank","family":"Gijsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam 1 , Rotterdam, The Netherlands"},{"name":"Department Biomechanical Engineering, Delft University of Technology 4 , Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5900-0425","authenticated-orcid":false,"given":"Ali C.","family":"Akyildiz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam 1 , Rotterdam, The Netherlands"},{"name":"Department Biomechanical Engineering, Delft University of Technology 4 , Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6886-6693","authenticated-orcid":false,"given":"Eric","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam 5 , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"van der Heiden","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Thorax Center Erasmus MC, University Medical Center Rotterdam 1 , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"2023092917112667500_c1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jbiomech.2019.03.005","article-title":"Calcifications in atherosclerotic plaques and impact on plaque biomechanics","volume":"87","year":"2019","journal-title":"J. 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