The primary goal of this project is to develop in vitro placental model with real-time sensing capabilities for study of human placental pathologies, using microfluidics, placenta-on-a-chip and microsensing technologies. We will demonstrate the capabilities of the proposed platform with Plasmodium falciparum placental malaria model. Important pathological events, including sequestration of infected erythrocytes (IE), placental trophoblast inflammatory and perfusion responses will be evaluated and monitored in real time and under flow conditions. To accomplish this goal, we propose two specific aims to prototype and evaluate this platform.
Aim 1 is to develop a 2D placental model with impedimetric sensing and evaluate two pathological events of placental malaria, including IE sequestration and trophoblast inflammatory responses in real time. The analysis will include microscopic imaging of IE sequestration and corresponding electrical impedance sensing of IE passage and adhesion, as well as electrical impedance sensing of trophoblast integrity combined with measurements of cytokines levels and immunofluorescence microscopy to test for trophoblast inflammatory responses.
Aim 2 is to develop a 3D placental model with electrochemical sensing for oxygen and glucose perfusion through the placental barrier. Pathological events of IE sequestration and impacted placental barrier perfusion response will be associated with the measured parameters. Furthermore, in both aims, we will evaluate the influences of anti- adhesion interventions, including anti-PfEMP1 antibodies and known anti-adhesion molecules on those pathological events. Proof-of-the-concept study of this placental sensing platform using placental malaria model is essential for future studies to elucidate the molecular details of placental malaria pathology and other placental pathologies, as well as to develop novel therapeutics to prevent or alleviate placental inflammatory and adverse perfusion responses.
New approaches to study human placenta pathologies and evaluate new drug therapies to improve pregnancy outcome are urgently needed. This project will apply microfluidic organ-on-a-chip technology and biosensing technologies to develop novel placenta-on-a-chip sensing platform. This platform can not only recapitulate essential features of placental barrier but also monitor its biophysiological functions, thereby providing real time measurements of interactions between maternal blood flow and fetal circulation under influences of blood pathology and drug therapies.
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