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In contrast to existing models, which focus primarily on hematopoietic or stromal compartments, our system recapitulates key aspects of functional bone remodeling and enables the maintenance of mature immune cells (up to 42 days), with preserved functional responsiveness at defined time points during culture. Dynamic flow and sequential cell seeding facilitated osteoclast\u2010mediated resorption, osteoblast\u2010driven matrix formation, and the maintenance of donor\u2010specific immune profiles over extended culture periods. The balance between bone cell activity and immune cell persistence was further optimized by controlled temperature modulation. The BOAC model preserves key features of bone and bone marrow physiology, including extracellular matrix formation, soluble factor signaling, and cellular heterogeneity. The bone scaffold provides a physiologically relevant 3D architecture derived from decellularized human trabecular bone. Single\u2010nucleus RNA sequencing confirmed the presence of major donor\u2010specific immune and bone cell populations. This 3D human in vitro system provides a robust platform for translational research and personalized medicine.<\/jats:p>","DOI":"10.1002\/advs.202518224","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T12:47:17Z","timestamp":1783342037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A 3D Human Bone and Bone Marrow\u2010on\u2010a\u2010Chip Model for In Vitro Bone Remodeling and Immune Cell Maintenance"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-5694","authenticated-orcid":false,"given":"Nina","family":"Stelzer","sequence":"first","affiliation":[{"name":"BIH\u2010Center for Regenerative Therapies Berlin Institute of Health at Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Julius Wolff Institute Berlin Institute of Health at Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin 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