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Extracellular vesicles (EVs) are nanoparticles containing RNAs, metabolites, lipids, and proteins that have surfaced as vital paracrine regulators able to coordinate these intricate mechanisms without the intrinsic risks associated with cell transplantation. This review synthesizes extensive in vivo evidence and evolving clinical findings highlighting that EVs from immune cells, mesenchymal stem cells, dental stem cells, and engineered origins regulate periodontal and dental pulp regeneration, peri-implant osseointegration, temporomandibular joint disorders, root resorption, orthodontic tooth movement, and craniomaxillofacial bone repair. EVs function as context-based biological regulators: regenerative EVs enhance M2 (anti-inflammatory) macrophage polarization, neurogenesis, angiogenesis, and odonto-osteogenesis, while EVs from pathogenic, mechanically stressed, or inflamed cells can initiate inflammation, osteoclastogenesis, and tissue damage. EV long noncoding RNAs and microRNAs play a critical part in dictating reparative versus destructive outcomes by regulating the TGF-\u03b2\/SMAD, PI3K\/protein kinase B, NF-\u03baB, and immune-metabolic cascades. Biomaterial-based delivery platforms and engineered EVs, such as surface-modified dental implants, scaffolds, and hydrogels, consistently improved local retention, efficacy, and multi-tissue repair. Crucially, human studies indicate clinically significant enhancements in periodontal and alveolar bone regeneration, emphasizing their translational promise. Nonetheless, clinical implementation is restricted by heterogeneity in EV origins, cargo variability, manufacturing methods, dosage, and delivery approaches, together with an incomplete comprehension of how to predict their bioactivity. Future advances will mandate Minimal Information for Studies of Extracellular Vesicles (MISEV)\u2013guided optimization, functional release criteria, localized delivery systems, potency-driven classification, and scalable Good Manufacturing Practices production. Overall, current evidence positions EVs as cell-free, adaptable mediators with transformative potential for precision-guided craniofacial therapy and regenerative dentistry.<\/jats:p>","DOI":"10.1177\/00220345261448514","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T08:15:03Z","timestamp":1780906503000},"page":"1112-1125","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Extracellular Vesicles in Regenerative Dentistry"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9482-1957","authenticated-orcid":false,"given":"P.","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Oral Biology, Rutgers School of Dental Medicine, The State University of New Jersey, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.E.","family":"Estrin","sequence":"additional","affiliation":[{"name":"College of Dentistry and Dental Clinics, The University of Iowa, Iowa City, IA, USA"},{"name":"School of Dental Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.J.","family":"Miron","sequence":"additional","affiliation":[{"name":"Department of Periodontology, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Abdelgawad LM Nghnughi MH Abdelgwad M. 2022. 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