Pregnancy-associated organs-on-chips

Abstract

Pregnancy involves constant structural and functional remodelling of maternal and fetal tissues, driven by dynamic interactions between cells, extracellular matrix and tightly regulated biochemical and mechanical cues. These microenvironmental changes, such as cell differentiation, tissue remodelling and perfusion, are essential for fetal development and healthy pregnancy outcomes. However, the physiological complexity and temporal changes of such dynamic gestational events are difficult to reproduce in conventional in vitro models, limiting their physiological relevance for studying pregnancy-related disorders and testing potential therapies. Pregnancy-associated organs-on-chips (PAOOCs) are microphysiological systems that recreate key features of gestational tissues to enable investigations of the underlying mechanisms, progression and treatment of pregnancy-related conditions. These models integrate relevant cell types within engineered extracellular matrices and controlled perfusion to reproduce tissue–tissue interfaces, biochemical gradients and mechanical cues; for example, to model the placental barrier, fetal membrane and transport of drugs and xenobiotics between maternal and fetal systems. However, improving physiological fidelity introduces trade-offs in device complexity, feasibility, scalability and reproducibility. In this Review, we analyse PAOOC technologies, focusing on design parameters that enhance their fidelity to model pregnancy physiology and pathology. We discuss how microenvironmental changes during gestation inform device engineering and provide an application-driven perspective linking biology with design, reproducibility and scalability considerations. By discussing challenges and opportunities of PAOOC design, this Review highlights their potential as platforms for elucidating the mechanisms of gestational diseases, assessing drug efficacy and safety during pregnancy, and advancing reproductive bioengineering for maternal and fetal health. Pregnancy-associated organs-on-chips (PAOOCs) are microphysiological systems that model gestational tissues to unveil the mechanisms of obstetric conditions and evaluate drug safety and efficacy during pregnancy in vitro. In this Review, we discuss the biological and mechanical components of PAOOCs and propose design recommendations to improve their physiological fidelity, reproducibility and accessibility.