Organ-on-a-chip systems for modeling tumor and normal tissue microenvironments in radiotherapy research

Radiation therapy (RT) precisely targets tumors with ionizing radiation, aiming to achieve local control while minimizing collateral damage to surrounding healthy tissues. Radiation research is often carried out in animal models, but these suffer from ethical issues, high cost of operation, low throughput, and low correlation to responses in humans. The advent of microfluidic organ-on-a-chip (OoC) technology offers a promising alternative to precisely and reproducibly model the physiology of different tissues in a laboratory setting. Furthermore, organ-on-a-chip models can be constructed from patient-specific tissues to tailor therapies while enabling fine control over relevant microenvironmental factors. In this review, we highlight emerging research at the intersection of radiation biology and microphysiological models, with a focus on the unique capabilities enabled by these advanced technologies.