{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:44Z","timestamp":1791348704874,"version":"4.3.1"},"reference-count":175,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006393","name":"Universidad de Granada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Implant Dent Rel Res"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Peri\u2010implantitis, characterized by inflammatory bone loss, is a leading cause of dental implant failure. Current regenerative strategies face limitations due to the persistent inflammatory microenvironment. Mesenchymal stem cell\u2010derived extracellular vesicles (MSC\u2010EVs) have emerged as promising acellular therapeutics with dual osteogenic and immunomodulatory capacities, offering a novel approach to address the complexity of peri\u2010implant bone defects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This narrative review synthesizes preclinical evidence on MSC\u2010EVs for peri\u2010implant bone regeneration. It examines methods for EV isolation from various sources. Furthermore, it analyzes advanced engineered delivery systems, such as peptide\u2010functionalized implant surfaces and bioactive scaffolds, designed to enhance local retention and therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MSC\u2010EVs orchestrate bone regeneration through multifaceted mechanisms. They directly stimulate osteogenesis by transferring pro\u2010osteogenic miRNAs and proteins, activating key pathways like PI3K\/AKT and Wnt\/\u03b2\u2010catenin. Crucially, they modulate the osteoimmune environment by reprogramming macrophages toward a reparative M2 phenotype, suppressing pro\u2010inflammatory Th1\/Th17 responses, and expanding regulatory T cells (Tregs). Concurrently, MSC\u2010EVs inhibit bone resorption by favorably modulating the RANKL\/OPG balance and directly interfering with osteoclast differentiation. They also promote neovascularization, a critical factor for healing in ischemic zones. Preclinical models demonstrate that localized delivery via engineered systems significantly enhances osseointegration, bone\u2010implant contact, and regeneration of functional bone\u2010vessel units.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MSC\u2010EVs represent a promising and multifaceted therapeutic strategy for bone regeneration in peri\u2010implantitis, simultaneously targeting inflammation, bone resorption, and osteogenesis. While robust preclinical evidence supports their role in halting bone loss and promoting structured regeneration, successful clinical translation requires further standardization, optimization of delivery, and validation in human trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cid.70151","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:02:09Z","timestamp":1776920529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Extracellular Vesicles as Orchestrators of Osteoimmunomodulation in Peri\u2010Implantitis: Implications for Bone Regeneration"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9358-6948","authenticated-orcid":false,"given":"Marco","family":"Bonilla","sequence":"first","affiliation":[{"name":"Department of Periodontics School of Dentistry, University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Carretero\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area, GENYO. Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria IBs  Granada Spain"},{"name":"Department of Biochemistry and Molecular Biology I Faculty of Sciences, University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sainz","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area, GENYO. Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria IBs  Granada Spain"},{"name":"Department of Biochemistry and Molecular Biology I Faculty of Sciences, University of Granada  Granada Spain"},{"name":"Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mesa","sequence":"additional","affiliation":[{"name":"Department of Periodontics School of Dentistry, University of Granada  Granada 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