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Microneedles (MNs) have emerged as a promising minimally invasive platform for localized drug delivery, offering advantages in patient compliance, controlled release, and reduced systemic side effects. In this study, we developed a detachable, hierarchical-release MN patch integrating mesoporous silica nanoparticles (MSNs) within a supramolecular CMC-MPP\u2282CB[8] hydrogel for the sustained, localized delivery of receptor activator of nuclear factor kappa-B ligand (RANKL) to accelerate OTM. The resulting MSN@CMC-MPP\u2282CB[8] MN patches exhibited excellent biocompatibility and sufficient mechanical strength for gingival penetration. In vitro, MSN encapsulation significantly attenuated the initial burst release, providing sustained RANKL delivery while preserving its bioactivity to induce robust osteoclastogenesis in RAW 264.7 cells. In a rat OTM model, RANKL-loaded MSN MN patches accelerated tooth movement and enhanced alveolar bone remodeling comparably to direct RANKL injection. Crucially, the MN delivery demonstrated significantly less root resorption than direct RANKL injection, indicating better safety through localized and controlled delivery. This minimally invasive MN platform, enabling sustained biomolecule release, represents a significant advancement for safely enhancing orthodontic treatment efficiency.<\/jats:p>","DOI":"10.1177\/00220345261446540","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T08:47:46Z","timestamp":1779871666000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustained-Release RANKL Microneedles for Safe Orthodontic Acceleration"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-6618","authenticated-orcid":false,"given":"W.","family":"Qu","sequence":"first","affiliation":[{"name":"Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Zhan","sequence":"additional","affiliation":[{"name":"Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Yan","sequence":"additional","affiliation":[{"name":"Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3667-6023","authenticated-orcid":false,"given":"C.","family":"McGrath","sequence":"additional","affiliation":[{"name":"Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-1092","authenticated-orcid":false,"given":"B.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Peking University, Beijing, China"},{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4220-0919","authenticated-orcid":false,"given":"Z.","family":"Ye","sequence":"additional","affiliation":[{"name":"Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2614-9159","authenticated-orcid":false,"given":"Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Alaa S Fouda AM Grawish ME Abdelnaby YL. 2023. 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