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Tetrahedral DNA nanostructures (TDN), promising nucleic acid nanomaterials, have garnered attention for their potential in osteoporotic mandibular regeneration owing to their ability to enhance cellular activity and promote osteogenic differentiation. Osteoblasts play a critical role in bone regeneration; however, intracellular delivery of TDN into osteoblasts remains difficult. In this study, a novel osteoblast\u2010targeted CH6 aptamer\u2010functionalized TDN (TDN\u2010CH6) is aimed to develop for osteoporotic mandibular regeneration. This results demonstrated that TDN\u2010CH6 exhibits superior osteoblast specificity and efficient recruitment to bone fracture sites. Furthermore, TDN\u2010CH6 significantly enhances cellular activity and osteogenic differentiation compared to TDN alone. Notably, Gelatin Methacryloyl (GelMA) hydrogels incorporating TDN and TDN\u2010CH6 shows improved biological performance and are favorable for osteoporotic mandibular regeneration, suggesting that this platform represents a promising strategy for addressing complex bone defects.<\/jats:p>","DOI":"10.1002\/mabi.202400471","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T02:01:21Z","timestamp":1737511281000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["GelMA Hydrogels Integrated With aptamer CH6\u2010Functionalized Tetrahedral DNA Nanostructures for Osteoporotic Mandibular Regeneration"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-3354","authenticated-orcid":false,"given":"Shebin","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Oral &amp; Cranio\u2010Maxillofacial Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical Sciences  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; 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