TY - JOUR
AU - Rahul Cherukuri
AU - Ananth Kumar Kammala
AU - Tilu Jain Thomas
AU - Leah Saylor
AU - Lauren Richardson
AU - Sungjin Kim
AU - Marc Ferrer
AU - Cristina Acedo
AU - Min Jae Song
AU - Akhilesh K. Gaharwar
AU - Ramkumar Menon
AU - Arum Han
AB - Spontaneous 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.
BT - ACS Applied Materials & Interfaces
DA - 2024-08-14
DO - 10.1021/acsami.4c08731
IS - 32
N2 - Spontaneous 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.
PY - 2024
SP - 41892
EP - 41906
T2 - ACS Applied Materials & Interfaces
TI - High-Throughput 3D-Printed Model of the Feto-Maternal Interface for the Discovery and Development of Preterm Birth Therapies
UR - https://doi.org/10.1021/acsami.4c08731
VL - 16
Y2 - 2026-06-03
SN - 1944-8244
ER -