{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:14:12Z","timestamp":1790187252944,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014769","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carnegie Mellon University, Mechanical Engineering","award":["Start up fund"],"award-info":[{"award-number":["Start up fund"]}],"id":[{"id":"https:\/\/ror.org\/05x2bcf33","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21HD115115"],"award-info":[{"award-number":["R21HD115115"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Proper placental development is essential for a healthy pregnancy. It depends on the remodeling of the maternal uterine vasculature to meet fetal demands while maintaining physiological intervillous space (IVS) hemodynamics for biochemical exchange. Terminal villi, the primary sites of feto-maternal exchange, exhibit impaired development in pregnancies complicated by intrauterine growth restriction and preeclampsia, which are also associated with incomplete spiral artery (SA) remodeling. Despite this association, the mechanistic link between maternal blood flow and villous development remains unclear. Here, we investigate whether incomplete SA remodeling alters IVS hemodynamics and increases wall shear stress (WSS) on placental villi, potentially impairing terminal villi formation. Computing WSS throughout an entire placentone is challenging due to uncertainty in placental microstructure and the computational cost of resolving microscale hemodynamics. We propose a novel multiscale computational framework to quantify WSS on placental villi at the end of the second trimester, when WSS may affect terminal villi development. A macroscale placentone model is used to compute IVS velocities, which are coupled with microscale models of intermediate villi to estimate villous WSS across physiologically relevant flow conditions. We simulate IVS hemodynamics in healthy pregnancy and varying degrees of incomplete SA remodeling. Our results show that IVS velocity is the primary determinant of mean villous WSS, whereas villous type and orientation have comparatively weaker effects. In healthy placentones, most villi experience a mean WSS of 0.001\u20131 Pa, with higher stresses localized near the free-of-villi cavity. By correlating these estimates with regions naturally devoid of terminal villi, we identify a mean WSS range of approximately 0.71\u20131.44 Pa that may inhibit terminal villi formation. Incomplete SA remodeling significantly increases WSS, reaching levels consistent with villous tissue loss and placental lake formation. These findings suggest a mechanistic link between uteroplacental hemodynamics and villi development, establishing physiological shear-stress thresholds relevant to placental health.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014769","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:48:28Z","timestamp":1789580908000},"page":"e1014769","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiscale computational modeling to quantify how spiral artery remodeling alters wall shear stress on placental villi"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8897-1571","authenticated-orcid":true,"given":"Armita","family":"Najmi","sequence":"first","affiliation":[{"name":"Carnegie Mellon University","place":["Pittsburgh, Pennsylvania, United States of America"],"department":["Department of Mechanical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-4752","authenticated-orcid":true,"given":"Noelia","family":"Grande Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University","place":["Pittsburgh, Pennsylvania, United States of America"],"department":["Department of Mechanical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"pcbi.1014769.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajog.2017.11.577","article-title":"Pathophysiology of placental-derived fetal growth restriction","volume":"218","author":"GJ Burton","year":"2018","journal-title":"Am J Obstet Gynecol"},{"key":"pcbi.1014769.ref002","volume-title":"Benirschke\u2019s pathology of the human placenta","author":"RN Baergen","year":"2021"},{"issue":"3","key":"pcbi.1014769.ref003","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF00234852","article-title":"Classification of human placental villi. 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