{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T13:02:46Z","timestamp":1777813366580,"version":"3.51.4"},"reference-count":30,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Foundation of Educational Department of Liaoning Province","award":["JYTMS20230568"],"award-info":[{"award-number":["JYTMS20230568"]}]},{"name":"Foundation of Educational Department of Liaoning Province","award":["LJ222410161071"],"award-info":[{"award-number":["LJ222410161071"]}]},{"name":"Foundation of Educational Department of Liaoning Province","award":["LJ222410161078"],"award-info":[{"award-number":["LJ222410161078"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100998"],"award-info":[{"award-number":["82100998"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270971"],"award-info":[{"award-number":["82270971"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401094"],"award-info":[{"award-number":["82401094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Fund of Natural Science Foundation of Liaoning Province","award":["2023-MSLH-026"],"award-info":[{"award-number":["2023-MSLH-026"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>Chronic apical periodontitis (CAP), an inflammatory disease of periapical tissues, leads to alveolar bone destruction. Current therapies lack osteoblast-targeting specificity and fail to effectively promote bone repair. Extracellular vesicles (EVs), particularly milk-derived EVs (MEVs), show potential for bone regeneration and have anti-inflammatory effects. We investigated the therapeutic potential of engineered MEVs modified with the osteoblast-targeting peptide DSPE-PEG-Mal-Cys-SDSSD (DPS) in CAP. DPS-MEVs enhanced osteogenic capacity and exhibited greater osteoblast targeting compared with unmodified MEVs through oxidative phosphorylation (OXPHOS) activation, driven by Kruppel-like factor 4 (KLF4)\u2013mediated upregulation of NADH dehydrogenase 1 alpha subcomplex 4 (Ndufa4) in vivo and in vitro. We also transplanted DPS-MEVs into a CAP model of dogs through apical microsurgery and found that DPS-MEVs enhanced bone repair and reduced inflammation by promoting polarization of M2 macrophages. These findings highlighted the potential of engineered DPS-MEVs as a dual-functional therapy for CAP, combining immunomodulation and tissue repair to advance precision treatment for inflammatory bone diseases.<\/jats:p>","DOI":"10.1177\/00220345251368767","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:19:18Z","timestamp":1760782758000},"page":"505-515","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Milk EVs Promote Apical Periodontitis Bone Repair via Osteoblast Targeting"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5717-4296","authenticated-orcid":false,"given":"S.-X.","family":"Wu","sequence":"first","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1064-4431","authenticated-orcid":false,"given":"Q.-Y.","family":"Song","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.-R.","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z.-R.","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2129-8905","authenticated-orcid":false,"given":"L.-N.","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8759-4498","authenticated-orcid":false,"given":"M.","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8880-1301","authenticated-orcid":false,"given":"W.-D.","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,10,18]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2021.10.020"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12351"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.02.048"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/2041731418776819"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1590\/1807-3107bor-2019.vol33.0047"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0520-2_8"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517722761"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2016.11.015"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.09.003"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202402579"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.52570"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.04.042"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0312751"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25116012"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25105543"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.03.020"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.07.042"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2020.0141"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b07828"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-03955-2"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.0c00233"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13467"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.62046"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13769"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.09.024"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202300951"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-017-2123-1"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307761"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.133422"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2023.2169414"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251368767","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345251368767","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251368767","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:09:37Z","timestamp":1777496977000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345251368767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,18]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1177\/00220345251368767"],"URL":"https:\/\/doi.org\/10.1177\/00220345251368767","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,18]]}}}