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However, the lack of standardized purification methods and limited scalability remain critical bottlenecks for the practical application and industrial translation of LDEVs. In this study, we developed an electrophoretic oscillation-assisted tangential flow filtration (EPOTF) platform using a SiNx membrane nanofilter for the scalable and high-purity purification of structurally intact LDEVs. The EPOTF process effectively suppressed membrane cake formation and membrane fouling, enabling stable size-selective purification under large-volume conditions. EPOTF-purified LDEVs exhibited stable physicochemical characteristics, high recovery yield, and excellent batch-to-batch reproducibility. Cryo-TEM analysis confirmed preservation of a distinct lipid bilayer structure and near-ideal spherical morphology with low spherical deviation, indicating minimal structural damage during purification. Furthermore, EPOTF-purified LDEVs significantly enhanced hydration, antioxidant activity, skin barrier recovery, and anti-inflammatory responses in an ex vivo human skin explant model. Taken together, these findings establish EPOTF as a robust and scalable purification platform for the biomanufacturing of high-quality LDEVs, with strong potential for cosmetic and skin-engineering applications.<\/jats:p>","DOI":"10.1021\/acsabm.6c01073","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:02:31Z","timestamp":1787115751000},"page":"10220-10231","source":"Crossref","is-referenced-by-count":0,"title":["EPOTF-Enabled Scalable Production of Structurally Intact Lemon-Derived Extracellular Vesicles with Enhanced Bioactivity"],"prefix":"10.1021","volume":"9","author":[{"given":"Minji","family":"Ko","sequence":"first","affiliation":[{"name":"Kookmin University , , ,","place":["Seoul, Republic of Korea, 02707"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejin","family":"Jung","sequence":"additional","affiliation":[{"name":"Kookmin University , , ,","place":["Seoul, Republic of Korea, 02707"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoung","family":"Shin","sequence":"additional","affiliation":[{"name":"Incospharm Corp. , , ,","place":["Daejeon, Republic of Korea, 34000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Incospharm Corp. , , ,","place":["Daejeon, Republic of Korea, 34000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyong Nam","family":"Lee","sequence":"additional","affiliation":[{"name":"Kookmin University , , ,","place":["Seoul, Republic of Korea, 02707"]},{"name":"Archevita Biosystems Co., Ltd. , , ,","place":["Seoul, Republic of Korea, 02731"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-6357","authenticated-orcid":true,"given":"Young Kwang","family":"Lee","sequence":"additional","affiliation":[{"name":"San Diego State University , , , ,","place":["San Diego, California, United States, 92182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekyoo","family":"Jeong","sequence":"additional","affiliation":[{"name":"Incospharm Corp. , , ,","place":["Daejeon, Republic of Korea, 34000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0580-4628","authenticated-orcid":true,"given":"Young Rag","family":"Do","sequence":"additional","affiliation":[{"name":"Kookmin University , , ,","place":["Seoul, Republic of Korea, 02707"]},{"name":"Archevita Biosystems Co., Ltd. , , ,","place":["Seoul, Republic of Korea, 02731"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026110201073801800_cit1","doi-asserted-by":"publisher","first-page":"4598","DOI":"10.7150\/thno.97096","article-title":"Exosome-like nanoparticles derived from fruits, vegetables, and herbs: innovative strategies of therapeutic and drug delivery","volume":"14","author":"Zhao","year":"2024","journal-title":"Theranostics"},{"key":"2026110201073801800_cit2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0296259","article-title":"Isolation of plant-derived exosome-like nanoparticles (PDENs) from Solanum nigrum L. berries and Their Effect on interleukin-6 expression as a potential anti-inflammatory agent","volume":"19","author":"Emmanuela","year":"2024","journal-title":"PLoS One"},{"issue":"1","key":"2026110201073801800_cit3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ymthe.2020.11.030","article-title":"Plant exosome-like nanovesicles: emerging therapeutics and drug delivery nanoplatforms","volume":"29","author":"Dad","year":"2021","journal-title":"Mol. 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