Modeling reproductive and pregnancy-associated tissues using organ-on-chip platforms: challenges, limitations, and...

Area of Science:

• Biotechnology and Biomedical Engineering
• Reproductive Biology and Toxicology

Background:

• Organ-on-chip (OOC) technology, also known as microphysiological systems or tissue chips, has significantly advanced in vitro physiological and pathological modeling and pharmaceutical drug assessment.
• Regulatory shifts, like the FDA Modernization Act 2.0, encourage the use of non-animal models, including OOC platforms and in silico simulations, for preclinical in vitro drug trial data, driving growth in microfluidics.
• These regulatory changes have profound implications for developing therapeutics for use during pregnancy, an area where OOC platforms show particular promise.

Purpose of the Study:

• To review existing reproductive and pregnancy-related OOC platforms and their current methodologies for generating endpoint datasets.
• To identify and describe the limitations hindering the progress of the OOC field, including device constraints and assay shortfalls.
• To highlight novel approaches and engineering adaptations needed to overcome current challenges and realize the full potential of OOC technology.

Main Methods:

• Review of available literature on reproductive and pregnancy-related Organ-on-chip platforms.
• Description of current methodologies for endpoint data generation, including microscopic imaging, immunocytochemistry, real-time polymerase chain reaction, and cytokine multiplex analysis.
• Discussion of novel approaches such as spatial transcriptomics, imaging cytometry by time of flight, and exosome analysis using Exoview.

Main Results:

• Identified limitations in current OOC platforms, including reduced cell numbers, low supernatant volumes, and fabrication material restrictions.
• Described various OOC platforms relevant to reproductive health and pregnancy, alongside established data generation techniques.
• Highlighted emerging techniques designed to overcome existing OOC platform limitations and enhance data acquisition.

Conclusions:

• Organ-on-chip platforms are poised to deliver biologically relevant and clinically translatable data, revolutionizing in vitro modeling, drug discovery, and toxicologic risk assessment.
• Engineering adaptations to increase device throughput (e.g., device arrays) and biological advancements to improve data processing are crucial for OOC technology to reach its full potential.
• The integration of advanced OOC systems is essential for advancing therapeutic development, particularly for pregnancy-related applications, in alignment with regulatory modernization.