{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:16:38Z","timestamp":1786115798306,"version":"build-2736575974"},"reference-count":148,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Extracellular vesicles (EVs) are nanoscale membrane\u2010bound structures that play a pivotal role in intercellular communication by transporting bioactive molecules, including proteins, lipids, nucleic acids, and organelles, between cells. Originating from the endosomal pathway, EVs reflect the physiological and pathological status of their parent cells and participate in a broad range of biological processes, such as immune regulation, tissue regeneration, and disease progression. This review provides a comprehensive overview of EVs' biology, covering their biogenesis, biochemical composition, isolation strategies, and characterization methodologies. Recent advances in quantitative, qualitative, and single\u2010vesicle analytical techniques are discussed, highlighting both their advantages and technical limitations. Emphasis is placed on the functional roles of EVs in cancer, cardiovascular diseases, autoimmune disorders, intestinal fibrosis, and neural repair, with a focus on their contributions to disease pathogenesis, biomarker discovery, and therapeutic resistance. Furthermore, emerging strategies employing both natural and engineered EVs as therapeutic delivery platforms are examined. Special attention is given to EVs\u2010integrated hydrogel systems designed to improve bioavailability, enhance retention at target sites, and enable controlled therapeutic release. Despite their considerable therapeutic potential, several challenges remain, including the need for standardized isolation protocols, scalable production, management of vesicle heterogeneity, and successful clinical translation. Overall, this review highlights the multifaceted biological significance of EVs and underscores their increasing potential as diagnostic biomarkers and next\u2010generation therapeutic platforms across a wide range of disease conditions.<\/jats:p>","DOI":"10.1002\/bit.70334","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:37:58Z","timestamp":1785994678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles\u2010Based Biological Macromolecule Delivery Systems: Biogenesis, Characterization, and Emerging Clinical Applications"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-0067","authenticated-orcid":false,"given":"Emine \u0130ncilay","family":"Toruno\u011flu","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Medical Biochemistry Necmettin Erbakan University Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-7673","authenticated-orcid":false,"given":"Zeynep Bet\u00fcl","family":"Sar\u0131","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Basic Medical Sciences, Medical Biology Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Emin","family":"Sar\u0131","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Medical Biology Necmettin Erbakan University Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-0183","authenticated-orcid":false,"given":"Erdi Can","family":"Aytar","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Department of Horticulture Usak University U\u015fak T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2024.177236","article-title":"Recent Advances in the Application of Engineered Exosomes From Mesenchymal Stem Cells for Regenerative Medicine","volume":"989","author":"Abbasi R.","year":"2025","journal-title":"European Journal of Pharmacology"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neulet.2016.11.025","article-title":"The Role of Morphine on Rat Neural Stem Cells Viability, Neuro\u2010Angiogenesis and Neuro\u2010Steroidgenesis Properties","volume":"636","author":"Abdyazdani N.","year":"2017","journal-title":"Neuroscience Letters"},{"key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10571-016-0366-z","article-title":"Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake","volume":"36","author":"Abels E. 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