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To investigate these mechanisms, we developed a novel double osteotomy model in mice, involving transplantation of a 2-mm bone graft between genetically distinct fluorescent reporter lines (yellow fluorescent protein and red fluorescent protein). This approach enabled precise tracking of cellular migration and vascularization over 3, 7, and 14 d post-transplantation. Our findings revealed directed migration of host-derived proximal bone marrow cells into the graft, starting at day 3 and leading to complete host cell infiltration by day 14. CD146-positive blood vessels, mainly originating from the proximal host marrow, invaded the graft coinciding with graft marrow remodeling. Marrow disintegration within the graft occurred prior to vascular and cellular invasion, with subsequent reconstitution progressing from the proximal side. Flushing the graft marrow cavity prior to transplantation resulted in more extensive marrow niche formation by day 14 suggesting that marrow reconstitution can proceed more rapidly without the need for prior remodeling. This study introduces a new model to dissect the spatial and temporal coordination of cellular migration and vessel invasion during bone regeneration. Our results uncover the directional nature of healing and underscore the critical role of marrow reconstitution in guiding regenerative processes\u2014insights that may inform surgical and biomaterial strategies to enhance bone repair.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf162","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:30:10Z","timestamp":1761222610000},"source":"Crossref","is-referenced-by-count":1,"title":["Directed vascularization in bone regeneration requires bone marrow reconstitution"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-7142","authenticated-orcid":false,"given":"Julia","family":"Mehl","sequence":"first","affiliation":[{"name":"Julius Wolff Institute, Berlin Institute of Health at Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 13353,","place":["Germany"]},{"name":"Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 13353 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Thiele","sequence":"additional","affiliation":[{"name":"Julius Wolff Institute, Berlin Institute of Health at Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 13353,","place":["Germany"]},{"name":"Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 13353 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Ellinghaus","sequence":"additional","affiliation":[{"name":"Julius Wolff Institute, Berlin Institute of Health at Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 13353 ,","place":["Germany"]},{"name":"Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 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