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Microcalcifications (&lt;50 \u00b5m) have been shown, in computational models, to affect the biomechanical stability of the cap. The current study aims to develop a tissue\u2010engineered model of the atherosclerotic fibrous cap with microcalcifications produced by mesenchymal stromal cells (MSCs). Human MSCs are seeded in fibrin gels and cultured for 2 weeks in medium supplemented with TGF\u2010\u03b21 to induce smooth muscle cell differentiation and collagenous matrix formation. Afterward, mineralizing medium stimulates microcalcification formation for an additional 4 weeks. Tissue\u2010engineered structures are imaged after culture with second harmonic generation microscopy with a hydroxyapatite probe, showing collagenous matrix with microcalcifications. Mechanical characterization shows the effect of microcalcifications on global tissue mechanics, as the ultimate stress at rupture of the tissue is significantly lower compared to control tissues. The amount of calcification, determined by histological analysis, is correlated to the decrease in ultimate tensile stress, with a higher amount of microcalcification resulting in weakened mechanical properties. The developed tissue\u2010engineered plaque cap model with biologically formed collagenous matrix and microcalcifications offers valuable insight into the impact of microcalcifications on biomechanical stability.<\/jats:p>","DOI":"10.1002\/adbi.202500106","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T14:59:26Z","timestamp":1752073166000},"source":"Crossref","is-referenced-by-count":3,"title":["Modelling Atherosclerotic Plaque Cap Mechanics: Microcalcifications Reduce Mechanical Properties in Mesenchymal Stromal Cell\u2010Based Model"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5791-5220","authenticated-orcid":false,"given":"Imke L.","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Thorax Center Erasmus MC University Medical Center Rotterdam  Rotterdam 3015 GD The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Erasmus MC University Medical Center Rotterdam  Rotterdam 3015 GD The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.H.","family":"Gijsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Thorax Center Erasmus MC University Medical Center Rotterdam  Rotterdam 3015 GD The Netherlands"},{"name":"Department of Biomechanical Engineering Delft University of Technology  Delft 2628 CD The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Erasmus MC University Medical Center Rotterdam  Rotterdam 3015 GD 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  Rotterdam 3015 GD The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2019.03.005"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307611"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0051-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.179739"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.10.065"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(91)90235-U"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300128"},{"key":"e_1_2_9_8_1","first-page":"1","volume":"101","author":"Moss A. 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