{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:09:09Z","timestamp":1774688949580,"version":"3.50.1"},"reference-count":95,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004060","name":"Preeclampsia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001774","name":"New Jersey Health Foundation","doi-asserted-by":"publisher","award":["PC 44\u201022"],"award-info":[{"award-number":["PC 44\u201022"]}],"id":[{"id":"10.13039\/100001774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006426","name":"State of New Jersey Department of Health","doi-asserted-by":"publisher","award":["COCR22PRG012"],"award-info":[{"award-number":["COCR22PRG012"]}],"id":[{"id":"10.13039\/100006426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["2018266781"],"award-info":[{"award-number":["2018266781"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp; Transla Med"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Placental dysfunction leads to pregnancy\u2010related disorders that affect up to 15% of pregnancies. Several of these, such as preeclampsia, are symptomatically managed but have no curative treatments other than preterm delivery. Placental dysfunction arises from improper placental development, leading to restricted blood vessel formation and a hypoxic placental microenvironment. The development of placental therapeutics is challenging due to the complex physiology that enables the placenta to control uptake and transport. Here, we use a simple culture system that combines hypoxia and trophoblast syncytialization to model the functional syncytiotrophoblast layer of the placenta under hypoxic stress. Using this model, we evaluate the impact of hypoxia on lipid nanoparticle (LNP)\u2010mediated mRNA delivery. Our data show that hypoxia hinders syncytiotrophoblast formation in vitro. Despite this, LNP delivery to syncytiotrophoblasts increases protein translation and secretion, particularly under hypoxic conditions. Further, we show delivery of a therapeutic mRNA, placental growth factor (PlGF), to syncytiotrophoblasts in hypoxia, which restored diminished PlGF levels back to normoxic controls. These findings provide an LNP platform for efficient mRNA delivery to hypoxic trophoblasts and demonstrate the importance of considering hypoxia towards the development of drug delivery platforms for placental therapeutics.<\/jats:p>","DOI":"10.1002\/btm2.70114","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:10:46Z","timestamp":1769145046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the impact of hypoxia and syncytialization on lipid nanoparticle\u2010mediated\n                    <scp>mRNA<\/scp>\n                    delivery to placental cells"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3321-3603","authenticated-orcid":false,"given":"Rachel E.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Vijayakumar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Logan J.","family":"Reilley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krisha","family":"Darji","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diya","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Hofbauer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"},{"name":"Cooper Medical School of Rowan University, Rowan University  Camden New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad\u2010Gabriel","family":"Alameh","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drew","family":"Weissman","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3267-5403","authenticated-orcid":false,"given":"Rachel","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Henry M. Rowan College of Engineering Rowan University  Glassboro New Jersey USA"},{"name":"School of Translational Biomedical Engineering &amp; Sciences, Virtua College of Medicine &amp; Life Sciences of Rowan University  Glassboro New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l2381"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2004.06.008"},{"key":"e_1_2_11_4_1","volume-title":"StatPearls [Internet]","author":"Wardinger JE","year":"2022"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2018.00050"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906\u2010014\u20100473\u20105"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00973"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028663\u20104"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1411582"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0066"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010022\u201004475\u2010z"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.11.018"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.12.007"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189675"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1017\/S204017441900014X"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201086073\u2010w"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081578"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00794.2005"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005\u20100078"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.102723"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090800"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109378(99)70518\u20101"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)64849\u20103"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2020\u201000057"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaab065"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c02584"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c04565"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S125286"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.10.029"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.11.014"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202500148"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1028"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202303568"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008291\u20102"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c12893"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307810121"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.10.047"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153642"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.22904"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c00826"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00064"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.10.028"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b01516"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620874114"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.12.032"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109256118"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010020\u20100669\u20106"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201805097"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5277"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1993.1139"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.06.017"},{"issue":"7","key":"e_1_2_11_53_1","first-page":"1231","article-title":"The establishment of a cell line of human hormone\u2010synthesizing trophoblastic cells in vitro","volume":"28","author":"Pattillo RA","year":"1968","journal-title":"Cancer Res"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02619074"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-102-25149"},{"issue":"13","key":"e_1_2_11_56_1","first-page":"3713","article-title":"Differentiation of choriocarcinoma cell line (JAr)","volume":"52","author":"Hochberg A","year":"1992","journal-title":"Cancer Research (Chicago, Ill)"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201006364\u2010z"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2016.12.007"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.159.3822.1467"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8316"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201012685\u2010w"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2013.01.004"},{"key":"e_1_2_11_63_1","volume-title":"Vascular biology of the placenta. Cell types of the placenta","author":"Wang Y","year":"2010"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2007.10.418"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201010\u20100221"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.11.023"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2020.10.024"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.2c00216"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(90)90310-7"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00484.2008"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11182884"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.134668"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06783"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.07.360"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07286"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052772"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.21819"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010015\u20102069\u2010x"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u20104652(199608)168:2<346::Aid\u2010jcp13>3.0.Co;2\u20101"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0925\u20104439(03)00043\u20107"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2023.03.006"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001681R"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201039426\u20105"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13070945"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929\u2010022\u201000791\u20105"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010022\u201003495\u20106"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.5.C1596"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202301428"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm884"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404\u2010021\u201006186\u20105"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.13360"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2011.08.117"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102567.2008.03019.x"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010023\u201001670\u20100"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.674162"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2005.06.014"}],"container-title":["Bioengineering &amp; Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.70114","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/btm2.70114","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.70114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:47:25Z","timestamp":1774687645000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btm2.70114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":95,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/btm2.70114"],"URL":"https:\/\/doi.org\/10.1002\/btm2.70114","archive":["Portico"],"relation":{},"ISSN":["2380-6761","2380-6761"],"issn-type":[{"value":"2380-6761","type":"print"},{"value":"2380-6761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"assertion":[{"value":"2025-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70114"}}