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Here, we report a rectally administered, sprayable, thermo\u2010responsive hyaluronic acid\u2010based copolymer platform for the localized co\u2010delivery of probiotic\u2010derived extracellular vesicles (ProEVs) and 5\u2010aminosalicylic acid. This system enables enhanced retention and sustained presentation of therapeutics at inflamed colonic sites. The combined formulation demonstrates improved therapeutic efficacy compared to individual treatments, promoting mucosal recovery and intestinal homeostasis. Mechanistically, the platform modulates inflammatory responses, supports epithelial barrier function, and contributes to microbiota rebalancing. Notably, extracellular vesicles provide a more effective and consistent therapeutic modality compared to live probiotics. Importantly, the formulation is designed for clinical translation, offering localized administration, minimal toxicity, and stability upon lyophilization, enabling off\u2010the\u2010shelf use. These findings highlight the potential of integrating extracellular vesicles with biomaterial\u2010based delivery systems as a multifunctional therapeutic strategy for inflammatory bowel disease.<\/jats:p>","DOI":"10.1002\/advs.76585","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:03:30Z","timestamp":1784322210000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Probiotic\u2010Derived Vesicles Rectally Delivered via Thermo\u2010Gelling Copolymer Promote Mucosal Healing and Reduce Inflammation in Ulcerative Colitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Ayushi","family":"Mairal","sequence":"first","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur  Kanpur UP India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ubaid","family":"Tariq","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur  Kanpur UP India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur  Kanpur UP India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-9928","authenticated-orcid":false,"given":"Saravanan","family":"Matheshwaran","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur  Kanpur UP India"},{"name":"Centre For Environmental Science and Engineering Indian Institute of Technology Kanpur  Kanpur UP India"},{"name":"The Mehta Family Centre For Engineering in Medicine Indian Institute of Technology Kanpur  Kanpur UP India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Marsal","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University and Sk\u00e5ne University Hospital  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur  Kanpur UP India"},{"name":"Centre For Environmental Science and Engineering Indian Institute of Technology Kanpur  Kanpur UP India"},{"name":"The Mehta Family Centre For Engineering in Medicine Indian Institute of Technology Kanpur  Kanpur UP India"},{"name":"Centre of Excellence for Materials in Medicine Gangwal School of Medical Sciences and Technology Indian Institute of Technology Kanpur  Kanpur UP India"},{"name":"Centre For Nanosciences Indian Institute of Technology Kanpur  Kanpur UP India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otad055"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2018.1463897"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2014.08.350"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.15.1.79\u201094.2002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i15.1708"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016\u20105085(98)70381\u20106"},{"issue":"6","key":"e_1_2_9_8_1","article-title":"Advancements in Inflammatory Bowel Disease: A Narrative Review of Diagnostics, Management, Epidemiology, Prevalence, Patient Outcomes, Quality of Life, and Clinical Presentation","author":"Muzammil M. 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