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A central challenge is designing membranes that reproduce the biochemical and biophysical cues of the native intestinal microenvironment. Here, we report a nanofiber\u2010supported decellularized extracellular matrix (NaDE) membrane engineered to emulate these key features. Specifically, a colon\u2010specific NaDE (C\u2010NaDE) membrane is fabricated by integrating porcine colon\u2010derived decellularized extracellular matrix (CdECM) hydrogel with an ultra\u2010thin nanofiber scaffold. The resulting membrane preserves a collagen\u2010rich extracellular matrix (ECM) composition and exhibits basement membrane\u2010level stiffness (\u223c230\u00a0kPa), thereby providing a supportive niche for intestinal epithelial reconstruction. Colon organoid\u2010derived epithelium cultured on the C\u2010NaDE membrane shows enhanced expression of genes associated with stem cell maintenance and epithelial proliferation. Notably, the C\u2010NaDE membrane also increases markers related to secretory epithelial lineages that are typically underrepresented in conventional synthetic stiff membrane systems, including enteroendocrine, tuft, and Paneth cell populations. These findings demonstrate that integrating organ\u2010specific matrix composition with tissue\u2010relevant mechanics can improve membrane\u2010based intestinal epithelial models. The C\u2010NaDE membrane, therefore, provides a physiologically enhanced platform for studying intestinal biology, disease mechanisms, barrier function, and drug responses.<\/jats:p>","DOI":"10.1002\/adhm.202501510","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:15:08Z","timestamp":1784175308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanofiber\u2010Supported Decellularized Matrix Membrane Creates a Biomimetic Biochemical and Biophysical Niche for Intestinal Organoid Epithelium"],"prefix":"10.1002","volume":"15","author":[{"given":"Jaeseung","family":"Youn","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"},{"name":"Department of Medical Science, School of Medicine CHA University Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam","family":"Than","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhyeok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jangwon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dohui","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Cleveland OH USA"},{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4780-9635","authenticated-orcid":false,"given":"Dong Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"},{"name":"Graduate School of Convergence Science and Technology Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"},{"name":"Division of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522193112"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201020052\u2010z"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.08.015"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102724\u20108"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010023\u201001556\u20101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55567-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.11.016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u201000665\u2010z"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122875"},{"key":"e_1_2_8_11_1","article-title":"Integrin\u2010Activating Yersinia Protein Invasin Sustains Long\u2010Term Expansion of Primary Epithelial Cells as 2D Organoid Sheets","volume":"122","author":"Wetering J. 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