3D Bioprinting of feto-maternal barrier tissue models

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

This project includes several research areas: A collaboration with Drs. Ramkumar Menon and Arum Han with a grant awarded from RFA-TR-21-015 to create models of the fetal maternal interface (FMi) to model inflammation in pre-term birth (PTB). We have constructed a 3D biofabricated a FMi tissue model in a 96- multi well plate format including amnion epithelial cells and decidual cells derived from healthy pregnancies. The biofabricated FMi model features two cell culture chambers (maternal and fetal cells) interlinked via an array of microfluidic channels. This biofabricated FMi model has been thoroughly validated to ensure cell viability, metabolic activity, and cell-specific markers. Furthermore, when the the maternal chamber was exposed to lipopolysaccharides (LPS) to induce an inflammatory state, proinflammatory cytokines in the culture supernatant were detected, both in the maternal and fetal side. The efficacy of anti-inflammatory agents in mitigating LPS-induced inflammation was tested and demonstrated that pharmacological validity of the model. Results demonstrated that our model supports robust cell growth, maintains viability, and accurately mimics preterm birth-associated inflammation. The assay is now used at NCATS to implement a repurposing and anti-inflmaatory screen of ~1000 compounds. We are also developing a biofabricated placenta model using primary cells, in a 96-well trans well plate. This placenta model includes primary trophoblasts and vasculature with endothelial cells and using conditions that mimic early and late-stage pregnancy. The two placenta models have been validated for cell markers, hormone secretion, nutrient uptake and barrier function. We are now exploring inflammatory conditions to model preeclampsia.