02266nas a2200277 4500000000100000008004100001260001500042100002000057700002500077700002100102700001600123700002200139700001600161700001600177700001900193700001700212700002500229700001900254700001300273245012900286856004300415300001600458490000700474520149300481022001401974 2024 d c2024-08-141 aRahul Cherukuri1 aAnanth Kumar Kammala1 aTilu Jain Thomas1 aLeah Saylor1 aLauren Richardson1 aSungjin Kim1 aMarc Ferrer1 aCristina Acedo1 aMin Jae Song1 aAkhilesh K. Gaharwar1 aRamkumar Menon1 aArum Han00aHigh-Throughput 3D-Printed Model of the Feto-Maternal Interface for the Discovery and Development of Preterm Birth Therapies uhttps://doi.org/10.1021/acsami.4c08731 a41892-419060 v163 aSpontaneous preterm birth (PTB) affects around 11% of births, posing significant risks to neonatal health due to the inflammation at the fetal–maternal interface (FMi). This inflammation disrupts immune tolerance during pregnancy, often leading to PTB. While organ-on-a-chip (OOC) devices effectively mimic the physiology, pathophysiology, and responses of FMi, their relatively low throughput limits their utility in high-throughput testing applications. To overcome this, we developed a three-dimensional (3D)-printed model that fits in a well of a 96-well plate and can be mass-produced while also accurately replicating FMi, enabling efficient screening of drugs targeting FMi inflammation. Our model features two cell culture chambers (maternal and fetal cells) interlinked via an array of microfluidic channels. It was thoroughly validated, ensuring cell viability, metabolic activity, and cell-specific markers. The maternal chamber was exposed to lipopolysaccharides (LPS) to induce an inflammatory state, and proinflammatory cytokines in the culture supernatant were quantified. Furthermore, the efficacy of anti-inflammatory inhibitors in mitigating LPS-induced inflammation was investigated. Results demonstrated that our model supports robust cell growth, maintains viability, and accurately mimics PTB-associated inflammation. This high-throughput 3D-printed model offers a versatile platform for drug screening, promising advancements in drug discovery and PTB prevention. a1944-8244