{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:05:38Z","timestamp":1790679938068,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,25]]},"group-title":"Bioengineering","reference-count":86,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Fibrotic strictures are among the most disabling complications of Crohn\u2019s disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn\u2019s disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 2\n                  <jats:sup>5<\/jats:sup>\n                  design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smoothmuscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn\u2019s disease.\n                <\/jats:p>","DOI":"10.64898\/2026.09.20.752998","type":"posted-content","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:35:14Z","timestamp":1790368514000},"source":"Crossref","is-referenced-by-count":0,"title":["Wall stiffening is a primary contributor to motility loss in crohn\u2019s disease: an electromechanical modeling study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3591-1327","authenticated-orcid":false,"given":"Ahilan","family":"Anantha Krishnan","sequence":"first","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masah","family":"Abubaker","sequence":"additional","affiliation":[{"name":"Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA"},{"name":"Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"1","key":"2026092903501257000_2026.09.20.752998v1.1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(19)30333-4","article-title":"The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"5","year":"2020","journal-title":"The Lancet gastroenterology & hepatology"},{"key":"2026092903501257000_2026.09.20.752998v1.2","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.2000.1069"},{"key":"2026092903501257000_2026.09.20.752998v1.3","doi-asserted-by":"crossref","unstructured":"Anantha Krishnan, A. , P. 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