{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:55:07Z","timestamp":1790218507920,"version":"4.1.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Erasmus MC-Health~Holland TKI-LSH","award":["Grant EMCLSH21004"],"award-info":[{"award-number":["Grant EMCLSH21004"]}]},{"name":"Wenzhou Wangqiao Orthopedic Hospital"},{"name":"Dutch Research Council (NWO)-XS Science","award":["OCENW.XS5.074"],"award-info":[{"award-number":["OCENW.XS5.074"]}]},{"name":"European Union Horizon 2020 Research and Innovation Program","award":["801159"],"award-info":[{"award-number":["801159"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"crossref","award":["202207720011"],"award-info":[{"award-number":["202207720011"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part C: Methods"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>\n                    During development and regeneration, bone is formed by endochondral ossification (EO) through the remodeling of a cartilage template. This complex process involves multiple cell types and interactions that cannot currently be modeled\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . This study aimed to develop a novel tissue-engineered human\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    model of certain aspects of the early stages of EO by integrating cartilage which undergoes mineralization, self-assembled vascular networks, and osteoclasts into a single system. We first studied the dynamics of osteoclastogenesis and vascularization in an\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    model of stromal cell-mediated EO, to inform our\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    system. Next, we aimed to develop a fully human cell-based three-dimensional model of EO by combining pediatric bone marrow stromal cells differentiating into chondrocytes, osteoclasts derived from human CD14+ monocytes, and human umbilical vein endothelial cells and adipose-derived stromal cells as vessel-forming cells. We investigated how mineralizing cartilage affects osteoclast and vessel formation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    through separate cartilage-osteoclasts and cartilage-vessels cocultures. Finally, we combined these elements and established a complex\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    model that supports the functionality of all these cell types and recapitulates chondrogenesis, cartilage mineralization, vessel formation and osteoclastogenesis. This integrated approach reaches unprecedented complexity and will enable new tissue engineering strategies to model skeletal diseases or cancer metastasis to the bone.\n                  <\/jats:p>","DOI":"10.1177\/19373341251378152","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T17:31:34Z","timestamp":1758303094000},"page":"105-120","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of a Complex Human\n                    <i>In Vitro<\/i>\n                    Model of Endochondral Ossification"],"prefix":"10.1177","volume":"32","author":[{"given":"Encheng","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2688-3599","authenticated-orcid":false,"given":"Amaia","family":"Garmendia Urdalleta","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Witte-Bouma","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert-Jan","family":"Kremers","sequence":"additional","affiliation":[{"name":"Optical Imaging Centre, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzia","family":"Di Maggio","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5737-8811","authenticated-orcid":false,"given":"Andrea","family":"Banfi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland."}],"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, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lolli","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-811467-4.00006-1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.21088"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2016.0197"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-811467-4.00006-1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2008.0297"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000302107"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711662105"},{"issue":"6","key":"e_1_3_4_9_2","article-title":"Sinus\/alveolar crest tenting (SACT): A new technique for implant placement in atrophic maxillary ridges without bone grafts or membranes","volume":"23","author":"Winter AA","year":"2003","unstructured":"Winter AA, , Pollack AS, , Odrich RB. 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