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However, effective strategies are still lacking for tissue regeneration in complicated conditions, such as the periodontal bone defect. Here, human dental follicle stem cells (hDFSCs) and their aggregates (hDFSCA) are cultured and characterized, which are formed based on the inherent property of these stem cells self\u2010assembly into compact spheroid\u2010like structures, mimicking mesenchymal condensation in development. A periodontal tissue\u2010specific microenvironment simulation material is then established, human decellularized alveolar bone matrix particles (hDABMPs), which possess favorable physicochemical and biological properties for regenerative use. hDFSCs co\u2010cultured with hDABMPs exhibit improved cell function, and hDFSCA\u2010hDABMP co\u2010aggregates are subsequently constructed, which activate the developmental gene expression in hDFSCA and initiate hypoxic adaptation mechanisms for tissue regeneration. Indeed, hDFSCA\u2010hDABMP co\u2010aggregates significantly promote regeneration after implantation in alveolar bone defects with good biosafety. Interestingly, during the early stages of implantation, hDABMPs enhance hDFSC survival and expansion, thereby providing a sufficient source of cells for tissue regeneration. Collectively, this study reveals a development\u2010inspired, engineered cell\u2010niche co\u2010aggregation strategy for enhancing CA therapeutic potential by simulating tissue\u2010specific microenvironments, offering novel insights for functional tissue regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202501550","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T05:27:11Z","timestamp":1747373231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development\u2010Inspired Biomimetic Cell\u2010Niche Coaggregates Safeguard Tooth Stem Cell\u2010Based Functional Tissue Regeneration"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiao\u2010Hui","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center 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