{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:51Z","timestamp":1786977951584,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201065"],"award-info":[{"award-number":["82201065"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Periodontitis\u2010induced inflammatory microenvironment compromises the function of periodontal ligament stem cells (PDLSCs) and significantly impedes the regeneration of periodontal tissues. Meanwhile, the clinical application of extracellular vesicles (EVs) is constrained by their low yield and high production costs. For the first time, this study systematically compares the functional differences between intracellular vesicles (IVs) and EVs derived from human PDLSCs (hPDLSCs) in promoting bone regeneration under inflammatory conditions, while also elucidating their underlying molecular mechanisms. IVs were produced with 6.9\u2010fold higher efficiency and exhibited superior cellular uptake compared to EVs. In vitro, under lipopolysaccharide (LPS)\u2010induced inflammatory environment, IVs outperformed EVs in enhancing the hPDLSCs proliferation, suppressing the secretion of pro\u2010inflammatory cytokines (IL\u20106 and TNF\u2010\u03b1) and upregulating osteogenic markers through Yes\u2010associated protein (YAP)\/transcriptional coactivator with PDZ\u2010binding motif (TAZ) activation, thereby promoting calcium nodule formation. Proteomic and functional analyses identified laminin subunit alpha 4 (LAMA4) as a key effector enriched in IVs, which is essential for activating YAP\/TAZ signalling and osteogenesis. Correspondingly, in vivo, IVs\u2010loaded gel effectively promoted bone regeneration in rat periodontal bone defects without organ toxicity. This study establishes IVs as a superior, high\u2010yield cell\u2010free therapeutic and delineates an LAMA4\u2010dependent mechanism via YAP\/TAZ activation for inflammatory bone regeneration.<\/jats:p>","DOI":"10.1002\/jev2.70267","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:42:44Z","timestamp":1774528964000},"source":"Crossref","is-referenced-by-count":1,"title":["Application of Intracellular Vesicles Surpass Extracellular Vesicles in Regenerative Repair of Inflammatory Bone Defects via the LAMA4\u2010Mediated YAP\/TAZ Signalling"],"prefix":"10.1002","volume":"15","author":[{"given":"Haotian","family":"Liu","sequence":"first","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, 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