A functional placenta-on-chip model for maternal-fetal transport

Area of Science:

• Obstetrics and Gynecology
• Biomedical Engineering
• Developmental Biology

Background:

• The human placenta is a complex barrier crucial for fetal development, but studying its function is challenging due to limited tissue access and complex in vitro models.
• Existing models often fail to fully recapitulate the structural and functional intricacies of the in vivo human placental barrier.

Purpose of the Study:

• To develop and validate a static, two-chamber placenta-on-a-chip platform that recreates key attributes of the human placental barrier.
• To provide an experimentally accessible model for investigating placental transport, metabolic regulation, and barrier integrity.

Main Methods:

• A two-chamber device separated by a microporous membrane coated with extracellular matrix was designed.
• The platform was engineered to support trophoblast syncytialization, hormone secretion, and selective barrier function.
• Experiments assessed macromolecular restriction, small solute diffusion, glucose transport, urea exchange, and response to hyperglycemic conditions.

Main Results:

• The engineered placental barrier restricted macromolecular transport while allowing controlled diffusion of small solutes.
• Glucose transport was sensitive to cellular configuration and endothelial layer presence, yielding in vivo-comparable fetal-to-maternal ratios.
• The platform demonstrated directional urea transfer and increased glucose transport under hyperglycemia without barrier breakdown.

Conclusions:

• The developed placenta-on-a-chip platform offers a scalable and robust model for studying placental barrier function, transport, and metabolism.
• This model provides a valuable tool for advancing research in placental biology, pregnancy-associated pathologies, and the safety assessment of drugs during pregnancy.