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Effective interventions to minimize these fetal responses are limited as drugs do not usually cross the feto\u2013maternal interface (FMi) barrier, and reliable models to test drug efficacy and other pharmacologic parameters have not been available. We leveraged New Approach Methods (NAMs), including employing extracellular vesicles (exosomes of 30\u2013200\u2009nm) to deliver the anti\u2010inflammatory cytokine interleukin (IL)\u201010 and using a high\u2010throughput 3D\u2010printed FMi model to test the efficacy of this delivery. IL\u201010 encapsulated exosomes were prepared by encapsulating recombinant IL\u201010 (rIL\u201010) using electroporation (eIL\u201010) or by transfecting RAW264.7 cells with an IL\u201010\u2010expression plasmid (tIL\u201010) that enabled the expression of IL\u201010 in the cells during exosome biogenesis, which was then collected. Using a biocompatible polymer resin, we 3D printed a two\u2010chambered FMi scaffold to mimic the amnion\u2013decidual (feto\u2013maternal) interface. Microchannels were integrated into the lower portions of the scaffold to facilitate intercellular communication. The device was composed of a mix of cells and gelatin methacrylate hydrogel material (lower part) and cell\u2010specific culture medium (upper part). We showed that empty exosomes and IL\u201010\u2010loaded exosomes delivered to the maternal side of the scaffold were able to cross to the fetal side of our FMi device. Furthermore, the effectiveness of eIL\u201010 and tIL\u2010100 (500\u2009ng) in reducing LPS\u2010induced FMi inflammation on both the maternal and fetal sides was demonstrated by measuring pro\u2010inflammatory IL\u20106 and IL\u20108 concentrations via multiplex assays at 6\u2009h and 24\u2009h timepoints. We determined that our 3D\u2010printed two\u2010chamber FMi model enabled the propagation of IL\u201010 encapsulated exosomes between the interconnected chambers. LPS treatment to the maternal decidua induced expression of pro\u2010inflammatory IL\u20106 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and IL\u20108 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) in both decidua and amnion compared with healthy (control) conditions. Co\u2010treatment of LPS along with IL\u201010\u2010loaded exosomes, regardless of its formulation, significantly reduced levels of the maternal and fetal inflammatory cytokines IL\u20106 and IL\u20108 at both 6 and 24\u2009h after delivery. A high\u2010throughput 3D\u2010printed FMi model was used to show that IL\u201010 encapsulated exosomes can reduce infection\u2010induced FMi inflammation. We describe two NAMs with the potential to significantly improve perinatal medicine: (1) an exosomal drug delivery method that protects the drug and can cross feto\u2013maternal barriers and (2) a 3D\u2010printed device that can be used for high\u2010throughput drug screening.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500545r","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T03:25:08Z","timestamp":1747106708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exosomal Delivery of Interleukin\u201010 Reduces Infection\u2010Associated Inflammation in a\n                    <scp>3D<\/scp>\n                    \u2010Printed Model of a Humanized Feto\u2013Maternal Interface"],"prefix":"10.1096","volume":"39","author":[{"given":"Leah M.","family":"Saylor","sequence":"first","affiliation":[{"name":"Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology The University of Texas Medical Branch at Galveston  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Cherukuri","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-2083","authenticated-orcid":false,"given":"Ananth K.","family":"Kammala","sequence":"additional","affiliation":[{"name":"Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology The University of Texas Medical Branch at Galveston  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology The University of Texas Medical 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