{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T20:30:28Z","timestamp":1766435428828,"version":"3.48.0"},"posted":{"date-parts":[[2025,12,19]]},"group-title":"Bioengineering","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100009730","name":"Stand Up To Cancer","doi-asserted-by":"crossref","award":["Convergence Program 3.1416,"],"award-info":[{"award-number":["Convergence Program 3.1416,"]}],"id":[{"id":"10.13039\/100009730","id-type":"DOI","asserted-by":"crossref"}]},{"name":"D. K. Ludwig Fund for Cancer Research"},{"name":"MIT Center for Precision Cancer Medicine"},{"name":"National Cancer Institute","award":["Koch Institute Support (core) Grant P30-CA014051"],"award-info":[{"award-number":["Koch Institute Support (core) Grant P30-CA014051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Oxygen gradients organize tissue architecture and metabolism\n                  <jats:sup>1,2<\/jats:sup>\n                  , yet their precise spatial profiles and mechanistic roles remain poorly understood because both\n                  <jats:italic>in vivo<\/jats:italic>\n                  measurement and\n                  <jats:italic>in vitro<\/jats:italic>\n                  control are technically challenging\n                  <jats:sup>3,4<\/jats:sup>\n                  . Here, we quantify the oxygen landscape of the mammalian intestine using microscale sensors, revealing a steep luminal\u2013basal gradient of approximately 10-60 \u00b5M mm\n                  <jats:sup>\u2212<\/jats:sup>\n                  <jats:sup>1<\/jats:sup>\n                  that collapses under antibiotic perturbation. We then recreate this physiological range\n                  <jats:italic>ex vivo<\/jats:italic>\n                  with a submerged chemostat microfluidic platform that fixes the oxygen boundary condition by coupling an oxygen-permeable PDMS chip to an external scavenger reservoir and integrating embedded optical sensors for real-time readout. This architecture suppresses ambient oxygen ingress and sustains programmable gradients of 10-20 \u00b5M mm\n                  <jats:sup>\u2212<\/jats:sup>\n                  <jats:sup>1<\/jats:sup>\n                  across three-dimensional colorectal cancer organoid cultures while remaining compatible with live imaging and endpoint retrieval. The platform bridges quantitative\n                  <jats:italic>in vivo<\/jats:italic>\n                  oxygen mapping with controlled\n                  <jats:italic>ex vivo<\/jats:italic>\n                  modeling, establishing a generalizable approach to interrogate how spatial oxygen dynamics govern epithelial organization and disease progression.\n                <\/jats:p>","DOI":"10.64898\/2025.12.16.694730","type":"posted-content","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T05:25:18Z","timestamp":1766208318000},"source":"Crossref","is-referenced-by-count":0,"title":["Reconstructing physiological oxygen gradients reveals the role of hypoxia in colon epithelial organization"],"prefix":"10.64898","author":[{"given":"Jiaquan","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicia H.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco L.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella Y.","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth K.","family":"Benitez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karuna","family":"Ganesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5223-9433","authenticated-orcid":false,"given":"Scott R.","family":"Manalis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025122210002617000_2025.12.16.694730v1.1","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1089\/ten.tea.2012.0592","article-title":"Directed oxygen gradients initiate a robust early remodeling response in engineered vascular grafts","volume":"19","year":"2013","journal-title":"Tissue Eng. 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