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Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17\u03b2-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2\u2019s clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo\u2013cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion\/relapse model, this functionalized E2\/ND\/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2\/ND\/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2\/ND\/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.<\/jats:p>","DOI":"10.1073\/pnas.1704027114","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T20:50:24Z","timestamp":1502743824000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen\u2013nanodiamond hydrogel"],"prefix":"10.1073","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9123-7737","authenticated-orcid":false,"given":"Christine","family":"Hong","sequence":"first","affiliation":[{"name":"Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayoung","family":"Song","sequence":"additional","affiliation":[{"name":"Section 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90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Lee","sequence":"additional","affiliation":[{"name":"Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Deng","sequence":"additional","affiliation":[{"name":"Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Hadaya","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Lim","family":"Lee","sequence":"additional","affiliation":[{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Advanced Prosthodontics, School of Dentistry, University of 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