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Conventional treatment strategies show limited efficacy in promoting regeneration of damaged periodontal tissues. Here, a delivery platform is developed for small extracellular vesicles (sEVs) derived from gingival mesenchymal stem cells (GMSCs) to treat periodontitis. EVs can achieve comparable therapeutic effects to their cells of origin. However, the short half\u2010lives of EVs after their administration along with their rapid diffusion away from the delivery site necessitate frequent administration to achieve therapeutic benefits. To address these issues, \u201cdual delivery\u201d microparticles are engineered enabling microenvironment\u2010sensitive release of EVs by metalloproteinases at the affected site along with antibiotics to suppress bacterial biofilm growth. GMSC sEVs are able to decrease the secretion of pro\u2010inflammatory cytokines by monocytes\/macrophages and T cells, suppress T\u2010cell activation, and induce the formation of T regulatory cells (Tregs) in vitro and in a rat model of periodontal disease. One\u2010time administration of immunomodulatory GMSC sEV\u2010decorated microparticles leads to a significant improvement in regeneration of the damaged periodontal tissue. This approach will have potential clinical applications in the regeneration of a variety of tissues.<\/jats:p>","DOI":"10.1002\/adhm.202102593","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T10:07:07Z","timestamp":1645524427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Engineered Delivery of Dental Stem\u2010Cell\u2010Derived Extracellular Vesicles for Periodontal Tissue Regeneration"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-9997","authenticated-orcid":false,"given":"Jana","family":"Zarubova","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of California  420 Westwood Plaza, 5121 Engineering V Los Angeles CA 90095\u20101600 USA"},{"name":"Department of Biomaterials and Tissue Engineering Institute of Physiology of the Czech Academy of Sciences  Prague 14220 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mahdi","family":"Hasani\u2010Sadrabadi","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California  420 Westwood Plaza, 5121 Engineering V Los Angeles CA 90095\u20101600 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erfan","family":"Dashtimoghadam","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of North Carolina at Chapel Hill  Chapel Hill NC 27599\u20103290 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California  420 Westwood Plaza, 5121 Engineering V Los Angeles CA 90095\u20101600 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Ansari","sequence":"additional","affiliation":[{"name":"Weintraub Center for Reconstructive Biotechnology Division of Advanced Prosthodontics School of Dentistry University of California  Los Angeles CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California  420 Westwood Plaza, 5121 Engineering V Los Angeles CA 90095\u20101600 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-6202","authenticated-orcid":false,"given":"Alireza","family":"Moshaverinia","sequence":"additional","affiliation":[{"name":"Weintraub Center for Reconstructive Biotechnology Division of Advanced Prosthodontics School of Dentistry University of California  Los Angeles CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"72","volume":"11","author":"Nazir M. 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