{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:21:50Z","timestamp":1787595710542,"version":"build-2736575974"},"reference-count":225,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009620","name":"Gansu Province Major Special Projects Program","doi-asserted-by":"publisher","award":["26ZDFA003"],"award-info":[{"award-number":["26ZDFA003"]}],"id":[{"id":"10.13039\/501100009620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009620","name":"Gansu Province Key Laboratory for Oral Disease Research","doi-asserted-by":"publisher","award":["SZD202501"],"award-info":[{"award-number":["SZD202501"]}],"id":[{"id":"10.13039\/501100009620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Established oral squamous cell carcinoma (OSCC) remains constrained by local recurrence, inadequate lesion exposure, systemic toxicity, and therapy resistance. This narrative review evaluates a proposed microneedle\u2013small extracellular vesicle (sEV) system for localized adjunctive treatment in three preclinical contexts: postoperative residual-disease control, local immunomodulation\/checkpoint combination, and chemoradiotherapy sensitization. Direct evidence for the combined microneedle\u2013sEV system in OSCC is not yet available; the analysis therefore integrates OSCC-specific sEV mechanisms with oral-mucosal microneedle and cross-disease engineering studies. We focus on whether the proposed microneedle\u2013sEV system can preserve sEV potency, achieve reproducible local delivery, and meet oncologic-safety, manufacturing, and repeated-dose oral-safety requirements. The review provides a preclinical decision framework and comparator-based development criteria rather than a claim of clinical readiness.<\/jats:p>","DOI":"10.3390\/cells15171527","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:20:28Z","timestamp":1787592028000},"page":"1527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Proposed Microneedle\u2013Small Extracellular Vesicle System for Localized Adjunctive Treatment of Established Oral Squamous Cell Carcinoma: A Narrative Review and Preclinical Development Perspective"],"prefix":"10.3390","volume":"15","author":[{"given":"Hai","family":"He","sequence":"first","affiliation":[{"name":"Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, School of Bioengineering, Northwest Minzu University, No. 1 Xibeixincun, Baiyin Road, Chengguan District, Lanzhou 730030, 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